TY - JOUR A1 - Zetzl, Teresa A1 - Renner, Agnes A1 - Pittig, Andre A1 - Jentschke, Elisabeth A1 - Roch, Carmen A1 - van Oorschot, Birgitt T1 - Yoga effectively reduces fatigue and symptoms of depression in patients with different types of cancer JF - Supportive Care in Cancer N2 - Purpose Examine the effects of an 8-week yoga therapy on fatigue in patients with different types of cancer. Methods A total of 173 cancer patients suffering from mild to severe fatigue were randomly allocated to yoga intervention (n = 84) (IG) versus waitlist control group (CG) (n = 88). Yoga therapy consisted of eight weekly sessions with 60 min each. The primary outcome was self-reported fatigue symptoms. Secondary outcomes were symptoms of depression and quality of life (QoL). Data were assessed using questionnaires before (T0) and after yoga therapy for IG versus waiting period for CG (T1). Results A stronger reduction of general fatigue (P = .033), physical fatigue (P = .048), and depression (P < .001) as well as a stronger increase in QoL (P = .002) was found for patients who attended 7 or 8 sessions compared with controls. Within the yoga group, both higher attendance rate and lower T0-fatigue were significant predictors of lower T1-fatigue (P ≤ .001). Exploratory results revealed that women with breast cancer report a higher reduction of fatigue than women with other types of cancer (P = .016) after yoga therapy. Conclusion The findings support the assumption that yoga therapy is useful to reduce cancer-related fatigue, especially for the physical aspects of fatigue. Women with breast cancer seem to benefit most, and higher attendance rate results in greater reduction of fatigue. Trial registration German Clinical Trials Register DRKS00016034 KW - yoga KW - complementary alternative medicine KW - mind-body intervention KW - fatigue KW - depression KW - quality of live Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235415 SN - 0941-4355 VL - 29 ER - TY - JOUR A1 - Morimoto, Yoshiro A1 - Shimada-Sugimoto, Mihoko A1 - Otowa, Takeshi A1 - Yoshida, Shintaro A1 - Kinoshita, Akira A1 - Mishima, Hiroyuki A1 - Yamaguchi, Naohiro A1 - Mori, Takatoshi A1 - Imamura, Akira A1 - Ozawa, Hiroki A1 - Kurotaki, Naohiro A1 - Ziegler, Christiane A1 - Domschke, Katharina A1 - Deckert, Jürgen A1 - Umekage, Tadashi A1 - Tochigi, Mamoru A1 - Kaiya, Hisanobu A1 - Okazaki, Yuji A1 - Tokunaga, Katsushi A1 - Sasaki, Tsukasa A1 - Yoshiura, Koh-ichiro A1 - Ono, Shinji T1 - Whole-exome sequencing and gene-based rare variant association tests suggest that PLA2G4E might be a risk gene for panic disorder JF - Translational Psychiatry N2 - Panic disorder (PD) is characterized by recurrent and unexpected panic attacks, subsequent anticipatory anxiety, and phobic avoidance. Recent epidemiological and genetic studies have revealed that genetic factors contribute to the pathogenesis of PD. We performed whole-exome sequencing on one Japanese family, including multiple patients with panic disorder, which identified seven rare protein-altering variants. We then screened these genes in a Japanese PD case–control group (384 sporadic PD patients and 571 controls), resulting in the detection of three novel single nucleotide variants as potential candidates for PD (chr15: 42631993, T>C in GANC; chr15: 42342861, G>T in PLA2G4E; chr20: 3641457, G>C in GFRA4). Statistical analyses of these three genes showed that PLA2G4E yielded the lowest p value in gene-based rare variant association tests by Efficient and Parallelizable Association Container Toolbox algorithms; however, the p value did not reach the significance threshold in the Japanese. Likewise, in a German case–control study (96 sporadic PD patients and 96 controls), PLA2G4E showed the lowest p value but again did not reach the significance threshold. In conclusion, we failed to find any significant variants or genes responsible for the development of PD. Nonetheless, our results still leave open the possibility that rare protein-altering variants in PLA2G4E contribute to the risk of PD, considering the function of this gene. KW - clinical genetics KW - medical genetics Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224192 VL - 8 ER - TY - JOUR A1 - Mergl, Roland A1 - Koburger, Nicole A1 - Heinrichs, Katherina A1 - Székely, András A1 - Tóth, Mónika Ditta A1 - Coyne, James A1 - Quintão, Sónia A1 - Arensman, Ella A1 - Coffey, Claire A1 - Maxwell, Margaret A1 - Värnik, Airi A1 - van Audenhove, Chantal A1 - McDaid, David A1 - Sarchiapone, Marco A1 - Schmidtke, Armin A1 - Genz, Axel A1 - Gusmão, Ricardo A1 - Hegerl, Ulrich T1 - What Are Reasons for the Large Gender Differences in the Lethality of Suicidal Acts? An Epidemiological Analysis in Four European Countries JF - PLoS ONE N2 - Background In Europe, men have lower rates of attempted suicide compared to women and at the same time a higher rate of completed suicides, indicating major gender differences in lethality of suicidal behaviour. The aim of this study was to analyse the extent to which these gender differences in lethality can be explained by factors such as choice of more lethal methods or lethality differences within the same suicide method or age. In addition, we explored gender differences in the intentionality of suicide attempts. Methods and Findings Methods. Design: Epidemiological study using a combination of self-report and official data. Setting: Mental health care services in four European countries: Germany, Hungary, Ireland, and Portugal. Data basis: Completed suicides derived from official statistics for each country (767 acts, 74.4% male) and assessed suicide attempts excluding habitual intentional self-harm (8,175 acts, 43.2% male). Main Outcome Measures and Data Analysis. We collected data on suicidal acts in eight regions of four European countries participating in the EU-funded "OSPI-Europe"-project (www.ospi-europe.com). We calculated method-specific lethality using the number of completed suicides per method * 100 /(number of completed suicides per method + number of attempted suicides per method). We tested gender differences in the distribution of suicidal acts for significance by using the \(\chi\)\(^{2}\)-test for two-by-two tables. We assessed the effect sizes with phi coefficients (φ). We identified predictors of lethality with a binary logistic regression analysis. Poisson regression analysis examined the contribution of choice of methods and method-specific lethality to gender differences in the lethality of suicidal acts. Findings Main Results Suicidal acts (fatal and non-fatal) were 3.4 times more lethal in men than in women (lethality 13.91% (regarding 4106 suicidal acts) versus 4.05% (regarding 4836 suicidal acts)), the difference being significant for the methods hanging, jumping, moving objects, sharp objects and poisoning by substances other than drugs. Median age at time of suicidal behaviour (35-44 years) did not differ between males and females. The overall gender difference in lethality of suicidal behaviour was explained by males choosing more lethal suicide methods (odds ratio (OR) = 2.03; 95% CI = 1.65 to 2.50; p < 0.000001) and additionally, but to a lesser degree, by a higher lethality of suicidal acts for males even within the same method (OR = 1.64; 95% CI = 1.32 to 2.02; p = 0.000005). Results of a regression analysis revealed neither age nor country differences were significant predictors for gender differences in the lethality of suicidal acts. The proportion of serious suicide attempts among all non-fatal suicidal acts with known intentionality (NFSAi) was significantly higher in men (57.1%; 1,207 of 2,115 NFSAi) than in women (48.6%; 1,508 of 3,100 NFSAi) (\(\chi\)\(^{2}\) = 35.74; p < 0.000001). Main limitations of the study Due to restrictive data security regulations to ensure anonymity in Ireland, specific ages could not be provided because of the relatively low absolute numbers of suicide in the Irish intervention and control region. Therefore, analyses of the interaction between gender and age could only be conducted for three of the four countries. Attempted suicides were assessed for patients presenting to emergency departments or treated in hospitals. An unknown rate of attempted suicides remained undetected. This may have caused an overestimation of the lethality of certain methods. Moreover, the detection of attempted suicides and the registration of completed suicides might have differed across the four countries. Some suicides might be hidden and misclassified as undetermined deaths. Conclusions Men more often used highly lethal methods in suicidal behaviour, but there was also a higher method-specific lethality which together explained the large gender differences in the lethality of suicidal acts. Gender differences in the lethality of suicidal acts were fairly consistent across all four European countries examined. Males and females did not differ in age at time of suicidal behaviour. Suicide attempts by males were rated as being more serious independent of the method used, with the exceptions of attempted hanging, suggesting gender differences in intentionality associated with suicidal behaviour. These findings contribute to understanding of the spectrum of reasons for gender differences in the lethality of suicidal behaviour and should inform the development of gender specific strategies for suicide prevention. KW - case fatality rates KW - behavior KW - multicenter KW - depression KW - deaths KW - alliance KW - states Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151547 VL - 10 IS - 7 ER - TY - JOUR A1 - Iotzov, Vassil A1 - Weiß, Martin A1 - Windmann, Sabine A1 - Hein, Grit T1 - Valence framing induces cognitive bias JF - Current Psychology N2 - Valence framing effects refer to inconsistent choice preferences in response to positive versus negative formulation of mathematically equivalent outcomes. Here, we manipulate valence framing in a two-alternative forced choice dictator game using gains and losses as frames to investigate the cognitive mechanisms underlying valence framing. We applied a Drift-Diffusion Model (DDM) to examine whether gain (i.e., “take” money) and loss (i.e., “give” money) frames evoke a cognitive bias as previous research did not consistently reveal framing effects using reaction times and response frequency as dependent variables. DDMs allow decomposing the decision process into separate cognitive mechanisms, whereby a cognitive bias was repeatedly associated with a shift in the starting point of the model. Conducting both a laboratory (N = 62) and an online study (N = 109), female participants allocated money between themselves and another person in a prosocial or selfish way. In each study, one group was instructed to give money (give frame), the other to take money (take frame). Consistent with previous studies, no differences were found in response times and response frequencies. However, in both studies, substantial bias towards the selfish option was found in the take frame groups, captured by the starting point of the DDM. Thus, our results suggest that valence framing induces a cognitive bias in decision processing in women, even when no behavioral differences are present. KW - valence framing KW - cognitive bias KW - decision making KW - drift-diffusion modeling KW - laboratory and online studies Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324824 SN - 1046-1310 VL - 42 IS - 34 ER - TY - JOUR A1 - Albrecht, Franziska A1 - Mueller, Karsten A1 - Ballarini, Tommaso A1 - Lampe, Leonie A1 - Diehl-Schmid, Janine A1 - Fassbender, Klaus A1 - Fliessbach, Klaus A1 - Jahn, Holger A1 - Jech, Robert A1 - Kassubek, Jan A1 - Kornhuber, Johannes A1 - Landwehrmeyer, Bernhard A1 - Lauer, Martin A1 - Ludolph, Albert C. A1 - Lyros, Epameinondas A1 - Prudlo, Johannes A1 - Schneider, Anja A1 - Synofzik, Matthis A1 - Wiltfang, Jens A1 - Danek, Adrian A1 - Otto, Markus A1 - Schroeter, Matthias L. T1 - Unraveling corticobasal syndrome and alien limb syndrome with structural brain imaging JF - Cortex N2 - Alien limb phenomenon is a rare syndrome associated with a feeling of non-belonging and disowning toward one's limb. In contrast, anarchic limb phenomenon leads to involuntary but goal-directed movements. Alien/anarchic limb phenomena are frequent in corticobasal syndrome (CBS), an atypical parkinsonian syndrome characterized by rigidity, akinesia, dystonia, cortical sensory deficit, and apraxia. The structure function relationship of alien/anarchic limb was investigated in multi centric structural magnetic resonance imaging (MRI) data. Whole-group and single subject comparisons were made in 25 CBS and eight CBS-alien/anarchic limb patients versus controls. Support vector machine was used to see if CBS with and without alien/anarchic limb could be distinguished by structural MRI patterns. Whole-group comparison of CBS versus controls revealed asymmetric frontotemporal atrophy. CBS with alien/anarchic limb syndrome versus controls showed frontoparietal atrophy including the supplementary motor area contralateral to the side of the affected limb. Exploratory analysis identified frontotemporal regions encompassing the pre-/and postcentral gyrus as compromised in CBS with alien limb syndrome. Classification of CBS patients yielded accuracies of 79%. CBS-alien/anarchic limb syndrome was differentiated from CBS patients with an accuracy of 81%. Predictive differences were found in the cingulate gyrus spreading to frontomedian cortex, postcentral gyrus, and temporoparietoocipital regions. We present the first MRI-based group analysis on CBS-alien/anarchic limb. Results pave the way for individual clinical syndrome prediction and allow understanding the underlying neurocognitive architecture. (C) 2019 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). KW - Alien limb syndrome KW - Anarchic limb syndrome KW - Corticobasal syndrome KW - Diagnosis prediction KW - Support vector machine Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221040 VL - 117 ER - TY - JOUR A1 - Bürger, Arne A1 - Schoenfeld, Cornelia von A1 - Scheiner, Christin A1 - Seidel, Alexandra A1 - Wasserscheid, Antonia A1 - Gad, Doreya A1 - Kittel-Schneider, Sarah A1 - Romanos, Marcel A1 - Reiter, Andrea M. F. T1 - Universal prevention for non-suicidal self-injury in adolescents is scarce - A systematic review JF - Frontiers in Psychiatry N2 - Non-suicidal self-injury (NSSI) during adolescence is a high-risk marker for the development and persistence of mental health problems and has been recognized as a significant public health problem. Whereas targeted prevention has indeed shown to be effective in reducing NSSI and improve mental health problems, access to such programs is limited. By face validity, universal prevention of NSSI seems an ideal starting point for a stepped-care model to circumvent a lack of resources in the medical care system. However, it is yet unclear how effective such approaches are. Here, we provide a summary of existing work on universal prevention of NSSI in adolescents younger than 21 years based on a systematic literature search. We found that only seven studies are available. None of the programs evaluated was found to be effective in reducing the incidence or frequency of NSSI. After providing a comprehensive summary of the existing work, we evaluate the fact that existing work primarily focusses on selected/targeted prevention and on psychoeducational methods. We derive implications for future directions in the field of universal prevention of NSSI. KW - non-suicidal self-injury KW - NSSI KW - emotion regulation KW - prevention KW - universal prevention KW - adolescence KW - mental health Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357490 VL - 14 ER - TY - JOUR A1 - Gorlova, Anna A1 - Svirin, Evgeniy A1 - Pavlov, Dmitrii A1 - Cespuglio, Raymond A1 - Proshin, Andrey A1 - Schroeter, Careen A. A1 - Lesch, Klaus-Peter A1 - Strekalova, Tatyana T1 - Understanding the role of oxidative stress, neuroinflammation and abnormal myelination in excessive aggression associated with depression: recent input from mechanistic studies JF - International Journal of Molecular Sciences N2 - Aggression and deficient cognitive control problems are widespread in psychiatric disorders, including major depressive disorder (MDD). These abnormalities are known to contribute significantly to the accompanying functional impairment and the global burden of disease. Progress in the development of targeted treatments of excessive aggression and accompanying symptoms has been limited, and there exists a major unmet need to develop more efficacious treatments for depressed patients. Due to the complex nature and the clinical heterogeneity of MDD and the lack of precise knowledge regarding its pathophysiology, effective management is challenging. Nonetheless, the aetiology and pathophysiology of MDD has been the subject of extensive research and there is a vast body of the latest literature that points to new mechanisms for this disorder. Here, we overview the key mechanisms, which include neuroinflammation, oxidative stress, insulin receptor signalling and abnormal myelination. We discuss the hypotheses that have been proposed to unify these processes, as many of these pathways are integrated for the neurobiology of MDD. We also describe the current translational approaches in modelling depression, including the recent advances in stress models of MDD, and emerging novel therapies, including novel approaches to management of excessive aggression, such as anti-diabetic drugs, antioxidant treatment and herbal compositions. KW - major depressive disorder (MDD) KW - aggression KW - neuroinflammation KW - oxidative stress KW - insulin receptor KW - myelination Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304917 SN - 1422-0067 VL - 24 IS - 2 ER - TY - JOUR A1 - Lichter, Katharina A1 - Paul, Mila Marie A1 - Pauli, Martin A1 - Schoch, Susanne A1 - Kollmannsberger, Philip A1 - Stigloher, Christian A1 - Heckmann, Manfred A1 - Sirén, Anna-Leena T1 - Ultrastructural analysis of wild-type and RIM1α knockout active zones in a large cortical synapse JF - Cell Reports N2 - Rab3A-interacting molecule (RIM) is crucial for fast Ca\(^{2+}\)-triggered synaptic vesicle (SV) release in presynaptic active zones (AZs). We investigated hippocampal giant mossy fiber bouton (MFB) AZ architecture in 3D using electron tomography of rapid cryo-immobilized acute brain slices in RIM1α\(^{−/−}\) and wild-type mice. In RIM1α\(^{−/−}\), AZs are larger with increased synaptic cleft widths and a 3-fold reduced number of tightly docked SVs (0–2 nm). The distance of tightly docked SVs to the AZ center is increased from 110 to 195 nm, and the width of their electron-dense material between outer SV membrane and AZ membrane is reduced. Furthermore, the SV pool in RIM1α\(^{−/−}\) is more heterogeneous. Thus, RIM1α, besides its role in tight SV docking, is crucial for synaptic architecture and vesicle pool organization in MFBs. KW - active zone KW - acute brain slices KW - CA3 KW - electron tomography KW - high-pressure freezing KW - hippocampal mossy fiber bouton KW - RIM1α KW - SV pool KW - synaptic ultrastructure KW - presynaptic Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300913 VL - 40 IS - 12 ER - TY - JOUR A1 - Lesch, K. P. A1 - Stöber, Gerald A1 - Balling, U. A1 - Franzek, Ernst A1 - Li, S. H. A1 - Ross, C. A. A1 - Newman, M. A1 - Beckmann, H. A1 - Riederer, P. T1 - Triplet repeats in clinical subtypes of schizophrenia: variation at the DRPLA (B37 CAG repeat) locus is not associated with periodic catatonia N2 - Clinical evidence for a dominant mode of inheritance and anticipation in periodic catatonia, a distinct subtype of schizophrenia, indicates that genes with triplet repeat expansions or other unstable repetitive elements affecting gene expression may be involved in the etiology of this disorder. Because patients affected with dentatorubral-pallidoluysian atrophy (DRPLA) may present with "schizophrenic" symptoms, we have investigated the DRPLA (B 37 CAG repeat) locus on chromosome 12 in 41 patients with periodic catatonia. The B 37 CAG repeat locus was highly polymorphic but all alleles in both the patient and control group had repeat sizes within the normal range. We conclude that variation at the DRPLA locus is unlikely to be associated with periodic catatonia. The evidence for dominant inheritance and anticipation as well as the high prevalence of human brain genes containing trinucleotide repeats justifies further screening for triplet repeat expansions in periodic catatonia. KW - Schizophrenie KW - Association study KW - B 37 CAG repeat locus KW - chromosome 12 KW - schizophrenia KW - periodic catatonia Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63369 ER - TY - JOUR A1 - Kittel-Schneider, Sarah A1 - Felice, Ethel A1 - Buhagiar, Rachel A1 - Lambregtse-van den Berg, Mijke A1 - Wilson, Claire A. A1 - Banjac Baljak, Visnja A1 - Vujovic, Katarina Savic A1 - Medic, Branislava A1 - Opankovic, Ana A1 - Fonseca, Ana A1 - Lupattelli, Angela T1 - Treatment of peripartum depression with antidepressants and other psychotropic medications: a synthesis of clinical practice guidelines in Europe JF - International Journal of Environmental Research and Public Health N2 - This study examined (1) the availability and content of national CPGs for treatment of peripartum depression, including comorbid anxiety, with antidepressants and other psychotropics across Europe and (2) antidepressant and other psychotropic utilization data as an indicator of prescribers' compliance to the guidelines. We conducted a search using Medline and the Guidelines International Network database, combined with direct e-mail contact with national Riseup-PPD COST ACTION members and researchers within psychiatry. Of the 48 European countries examined, we screened 41 records and included 14 of them for full-text evaluation. After exclusion of ineligible and duplicate records, we included 12 CPGs. Multiple CPGs recommend antidepressant initiation or continuation based on maternal disease severity, non-response to first-line non-pharmacological interventions, and after risk-benefit assessment. Advice on treatment of comorbid anxiety is largely missing or unspecific. Antidepressant dispensing data suggest general prescribers' compliance with the preferred substances of the CPG, although country-specific differences were noted. To conclude, there is an urgent need for harmonized, up-to-date CPGs for pharmacological management of peripartum depression and comorbid anxiety in Europe. The recommendations need to be informed by the latest available evidence so that healthcare providers and women can make informed, evidence-based decisions about treatment choices. KW - clinical practice guideline KW - depression KW - anxiety KW - antidepressant KW - psychotropic medications KW - peripartum Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262130 SN - 1660-4601 VL - 19 IS - 4 ER - TY - JOUR A1 - Lechermeier, Carina G. A1 - Zimmer, Frederic A1 - Lüffe, Teresa M. A1 - Lesch, Klaus-Peter A1 - Romanos, Marcel A1 - Lillesaar, Christina A1 - Drepper, Carsten T1 - Transcript analysis of zebrafish GLUT3 genes, slc2a3a and slc2a3b, define overlapping as well as distinct expression domains in the zebrafish (Danio rerio) central nervous system JF - Frontiers in Molecular Neuroscience N2 - The transport of glucose across the cell plasma membrane is vital to most mammalian cells. The glucose transporter (GLUT; also called SLC2A) family of transmembrane solute carriers is responsible for this function in vivo. GLUT proteins encompass 14 different isoforms in humans with different cell type-specific expression patterns and activities. Central to glucose utilization and delivery in the brain is the neuronally expressed GLUT3. Recent research has shown an involvement of GLUT3 genetic variation or altered expression in several different brain disorders, including Huntington’s and Alzheimer’s diseases. Furthermore, GLUT3 was identified as a potential risk gene for multiple psychiatric disorders. To study the role of GLUT3 in brain function and disease a more detailed knowledge of its expression in model organisms is needed. Zebrafish (Danio rerio) has in recent years gained popularity as a model organism for brain research and is now well-established for modeling psychiatric disorders. Here, we have analyzed the sequence of GLUT3 orthologs and identified two paralogous genes in the zebrafish, slc2a3a and slc2a3b. Interestingly, the Glut3b protein sequence contains a unique stretch of amino acids, which may be important for functional regulation. The slc2a3a transcript is detectable in the central nervous system including distinct cellular populations in telencephalon, diencephalon, mesencephalon and rhombencephalon at embryonic and larval stages. Conversely, the slc2a3b transcript shows a rather diffuse expression pattern at different embryonic stages and brain regions. Expression of slc2a3a is maintained in the adult brain and is found in the telencephalon, diencephalon, mesencephalon, cerebellum and medulla oblongata. The slc2a3b transcripts are present in overlapping as well as distinct regions compared to slc2a3a. Double in situ hybridizations were used to demonstrate that slc2a3a is expressed by some GABAergic neurons at embryonic stages. This detailed description of zebrafish slc2a3a and slc2a3b expression at developmental and adult stages paves the way for further investigations of normal GLUT3 function and its role in brain disorders. KW - glucose transporter KW - nervous system KW - brain disorders KW - psychiatric disorders KW - brain development KW - GABA KW - GAD1 Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201797 VL - 12 IS - 199 ER - TY - JOUR A1 - Herrmann, Martin J. A1 - Beier, Jennifer S. A1 - Simons, Bibiane A1 - Polak, Thomas T1 - Transcranial Direct Current Stimulation (tDCS) of the Right Inferior Frontal Gyrus Attenuates Skin Conductance Responses to Unpredictable Threat Conditions JF - Frontiers in Human Neuroscience N2 - Patients with panic and post-traumatic stress disorders seem to show increased psychophysiological reactions to conditions of unpredictable (U) threat, which has been discussed as a neurobiological marker of elevated levels of sustained fear in these disorders. Interestingly, a recent study found that the right inferior frontal gyrus (rIFG) is correlated to the successful regulation of sustained fear during U threat. Therefore this study aimed to examine the potential use of non-invasive brain stimulation to foster the rIFG by means of anodal transcranial direct current stimulation (tDCS) in order to reduce psychophysiological reactions to U threat. Twenty six participants were randomly assigned into an anodal and sham stimulation group in a double-blinded manner. Anodal and cathodal electrodes (7 * 5 cm) were positioned right frontal to target the rIFG. Stimulation intensity was I = 2 mA applied for 20 min during a task including U threat conditions (NPU-task). The effects of the NPU paradigm were measured by assessing the emotional startle modulation and the skin conductance response (SCR) at the outset of the different conditions. We found a significant interaction effect of condition × tDCS for the SCR (F(2,48) = 6.3, p < 0.01) without main effects of condition and tDCS. Post hoc tests revealed that the increase in SCR from neutral (N) to U condition was significantly reduced in verum compared to the sham tDCS group (t(24) = 3.84, p < 0.001). Our results emphasize the causal role of rIFG for emotional regulation and the potential use of tDCS to reduce apprehension during U threat conditions and therefore as a treatment for anxiety disorders. KW - transcranial direct current stimulation KW - emotional regulation KW - sustained fear KW - right inferior frontalgyrus KW - NPU Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146486 VL - 10 IS - 352 ER - TY - JOUR A1 - Gram, Maximilian A1 - Albertova, P. A1 - Schirmer, V. A1 - Blaimer, M. A1 - Gamer, M. A1 - Herrmann, M. J. A1 - Nordbeck, P. A1 - Jakob, P. M. T1 - Towards robust in vivo quantification of oscillating biomagnetic fields using Rotary Excitation based MRI JF - Scientific Reports N2 - Spin-lock based functional magnetic resonance imaging (fMRI) has the potential for direct spatially-resolved detection of neuronal activity and thus may represent an important step for basic research in neuroscience. In this work, the corresponding fundamental effect of Rotary EXcitation (REX) is investigated both in simulations as well as in phantom and in vivo experiments. An empirical law for predicting optimal spin-lock pulse durations for maximum magnetic field sensitivity was found. Experimental conditions were established that allow robust detection of ultra-weak magnetic field oscillations with simultaneous compensation of static field inhomogeneities. Furthermore, this work presents a novel concept for the emulation of brain activity utilizing the built-in MRI gradient system, which allows REX sequences to be validated in vivo under controlled and reproducible conditions. Via transmission of Rotary EXcitation (tREX), we successfully detected magnetic field oscillations in the lower nano-Tesla range in brain tissue. Moreover, tREX paves the way for the quantification of biomagnetic fields. KW - functional magnetic resonance imaging KW - Rotary EXcitation (REX) KW - oscillating biomagnetic fields Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300862 VL - 12 IS - 1 ER - TY - JOUR A1 - Gerber, Bertram A1 - König, Christian A1 - Fendt, Markus A1 - Andreatta, Marta A1 - Romanos, Marcel A1 - Pauli, Paul A1 - Yarali, Ayse T1 - Timing-dependent valence reversal: a principle of reinforcement processing and its possible implications JF - Current Opinion in Behavioral Sciences N2 - Punishment feels bad, but relief upon its termination feels good. As a consequence of such timing-dependent valence reversal, memories of opposite valence can result from associating stimulus A with, for example, the occurrence of punishment (A-) versus punishment termination (-A): A- training results in aversive memory, but -A training in appetitive memory (corresponding effects exist for reward occurrence and termination). Whereas learning through the occurrence of punishment is well studied, much less is known about learning through its termination. Current research investigates how dopaminergic system function contributes to these processes in Drosophila, rats and humans. We argue that dopamine-related psychopathology may entail distortions in learning through punishment termination, and that this may contribute, for example, to non-suicidal self-injury or post-traumatic stress disorder. Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232933 VL - 26 ER - TY - JOUR A1 - Gorlova, Anna A1 - Pavlov, Dmitrii A1 - Anthony, Daniel C. A1 - Ponomarev, Eugene D. A1 - Sambon, Margaux A1 - Proshin, Andrey A1 - Shafarevich, Igor A1 - Babaevskaya, Diana A1 - Lesch, Klaus-Peter A1 - Bettendorff, Lucien A1 - Strekalova, Tatyana T1 - Thiamine and benfotiamine counteract ultrasound-induced aggression, normalize AMPA receptor expression and plasticity markers, and reduce oxidative stress in mice JF - Neuropharmacology N2 - The negative societal impacts associated with the increasing prevalence of violence and aggression is increasing, and, with this rise, is the need to understand the molecular and cellular changes that underpin ultrasound-induced aggressive behavior. In mice, stress-induced aggression is known to alter AMPA receptor subunit expression, plasticity markers, and oxidative stress within the brain. Here, we induced aggression in BALB/c mice using chronic ultrasound exposure and examined the impact of the psychoactive anti-oxidant compounds thiamine (vitamin B1), and its derivative benfotiamine, on AMPA receptor subunit expression, established plasticity markers, and oxidative stress. The administration of thiamine or benfotiamine (200 mg/kg/day) in drinking water decreased aggressive behavior following 3-weeks of ultrasound exposure and benfotiamine, reduced floating behavior in the swim test. The vehicle-treated ultrasound-exposed mice exhibited increases in protein carbonyl and total glutathione, altered AMPA receptor subunits expression, and decreased expression of plasticity markers. These ultrasound-induced effects were ameliorated by thiamine and benfotiamine treatment; in particular both antioxidants were able to reverse ultrasound-induced changes in GluA1 and GluA2 subunit expression, and, within the prefrontal cortex, significantly reversed the changes in protein carbonyl and polysialylated form of neural cell adhesion molecule (PSA-NCAM) expression levels. Benfotiamine was usually more efficacious than thiamine. Thus, the thiamine compounds were able to counteract ultrasound-induced aggression, which was accompanied by the normalization of markers that have been showed to be associated with ultrasound-induced aggression. These commonly used, orally-active compounds may have considerable potential for use in the control of aggression within the community. This article is part of the Special Issue entitled ‘Current status of the neurobiology of aggression and impulsivity’. KW - aggression KW - emotional stress KW - brain oxidative stress KW - plasticity KW - thiamine KW - mice Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227439 VL - 156 ER - TY - JOUR A1 - Taurines, R. A1 - Fekete, S. A1 - Preuss-Wiedenhoff, A. A1 - Warnke, A. A1 - Wewetzer, C. A1 - Plener, P. A1 - Burger, R. A1 - Gerlach, M. A1 - Romanos, M. A1 - Egberts, K. M. T1 - Therapeutic drug monitoring in children and adolescents with schizophrenia and other psychotic disorders using risperidone JF - Journal of Neural Transmission N2 - Risperidone is commonly used to treat different psychiatric disorders worldwide. Knowledge on dose–concentration relationships of risperidone treatment in children and adolescents with schizophrenia or other psychotic disorders is, however, scarce and no age-specific therapeutic ranges have been established yet. Multicenter data of a therapeutic drug monitoring service were analyzed to evaluate the relationship between risperidone dose and serum concentration of the active moiety (risperidone (RIS) plus its main metabolite 9-hydroxyrisperidone (9-OH-RIS)) in children and adolescents with psychotic disorders. Patient characteristics, doses, serum concentrations and therapeutic outcomes were assessed by standardized measures. The study also aimed to evaluate whether the therapeutic reference range for adults (20–60 ng/ml) is applicable for minors. In the 64 patients (aged 11–18 years) included, a positive correlation between daily dose and the active moiety (RIS\(_{am}\)) concentration was found (r\(_s\) = 0.49, p = 0.001) with variation in dose explaining 24% (r\(_s\)\(^2\) = 0.240) of the variability in serum concentrations. While the RIS\(_{am}\) concentration showed no difference, RIS as well 9-OH-RIS concentrations and the parent to metabolite ratio varied significantly in patients with co-medication of a CYP2D6 inhibitor. Patients with extrapyramidal symptoms (EPS) had on average higher RIS\(_{am}\) concentrations than patients without (p = 0.05). Considering EPS, the upper threshold of the therapeutic range of RIS\(_{am}\) was determined to be 33 ng/ml. A rough estimation method also indicated a possibly decreased lower limit of the preliminary therapeutic range in minors compared to adults. These preliminary data may contribute to the definition of a therapeutic window in children and adolescents with schizophrenic disorders treated with risperidone. TDM is recommended in this vulnerable population to prevent concentration-related adverse drug reactions. KW - risperidone KW - children KW - serum concentration KW - schizophrenia KW - therapeutic drug monitoring KW - pharmacovigilance Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324833 VL - 129 IS - 5-6 ER - TY - JOUR A1 - Schwarzmeier, Hanna A1 - Leehr, Elisabeth Johanna A1 - Böhnlein, Joscha A1 - Seeger, Fabian Reinhard A1 - Roesmann, Kati A1 - Gathmann, Bettina A1 - Herrmann, Martin J. A1 - Siminski, Niklas A1 - Junghöfer, Markus A1 - Straube, Thomas A1 - Grotegerd, Dominik A1 - Dannlowski, Udo T1 - Theranostic markers for personalized therapy of spider phobia: Methods of a bicentric external cross‐validation machine learning approach JF - International Journal of Methods in Psychiatric Research N2 - Objectives Embedded in the Collaborative Research Center “Fear, Anxiety, Anxiety Disorders” (CRC‐TRR58), this bicentric clinical study aims at identifying biobehavioral markers of treatment (non‐)response by applying machine learning methodology with an external cross‐validation protocol. We hypothesize that a priori prediction of treatment (non‐)response is possible in a second, independent sample based on multimodal markers. Methods One‐session virtual reality exposure treatment (VRET) with patients with spider phobia was conducted on two sites. Clinical, neuroimaging, and genetic data were assessed at baseline, post‐treatment and after 6 months. The primary and secondary outcomes defining treatment response are as follows: 30% reduction regarding the individual score in the Spider Phobia Questionnaire and 50% reduction regarding the individual distance in the behavioral avoidance test. Results N = 204 patients have been included (n = 100 in Würzburg, n = 104 in Münster). Sample characteristics for both sites are comparable. Discussion This study will offer cross‐validated theranostic markers for predicting the individual success of exposure‐based therapy. Findings will support clinical decision‐making on personalized therapy, bridge the gap between basic and clinical research, and bring stratified therapy into reach. The study is registered at ClinicalTrials.gov (ID: NCT03208400). KW - machine learning KW - spider phobia KW - theranostic markers Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-213430 VL - 29 IS - 2 ER - TY - JOUR A1 - Meyer, Neele A1 - Richter, S. Helene A1 - Schreiber, Rebecca S. A1 - Kloke, Vanessa A1 - Kaiser, Sylvia A1 - Lesch, Klaus-Peter A1 - Sachser, Norbert T1 - The Unexpected Effects of Beneficial and Adverse Social Experiences during Adolescence on Anxiety and Aggression and Their Modulation by Genotype JF - Frontiers in Behavioral Neuroscience N2 - Anxiety and aggression are part of the behavioral repertoire of humans and animals. However, in their exaggerated form both can become maladaptive and result in psychiatric disorders. On the one hand, genetic predisposition has been shown to play a crucial modulatory role in anxiety and aggression. On the other hand, social experiences have been implicated in the modulation of these traits. However, so far, mainly experiences in early life phases have been considered crucial for shaping anxiety-like and aggressive behavior, while the phase of adolescence has largely been neglected. Therefore, the aim of the present study was to elucidate how levels of anxiety-like and aggressive behavior are shaped by social experiences during adolescence and serotonin transporter (5-HTT) genotype. For this purpose, male mice of a 5-HTT knockout mouse model including all three genotypes (wildtype, heterozygous and homozygous 5-HTT knockout mice) were either exposed to an adverse social situation or a beneficial social environment during adolescence. This was accomplished in a custom-made cage system where mice experiencing the adverse environment were repeatedly introduced to the territory of a dominant opponent but had the possibility to escape to a refuge cage. Mice encountering beneficial social conditions had free access to a female mating partner. Afterwards, anxiety-like and aggressive behavior was assessed in a battery of tests. Surprisingly, unfavorable conditions during adolescence led to a decrease in anxiety-like behavior and an increase in exploratory locomotion. Additionally, aggressive behavior was augmented in animals that experienced social adversity. Concerning genotype, homozygous 5-HTT knockout mice were more anxious and less aggressive than heterozygous 5-HTT knockout and wildtype mice. In summary, adolescence is clearly an important phase in which anxiety-like and aggressive behavior can be shaped. Furthermore, it seems that having to cope with challenge during adolescence instead of experiencing throughout beneficial social conditions leads to reduced levels of anxiety-like behavior. KW - adolescence KW - aggressiveness KW - serotonin transporter KW - coping with challenge KW - adversity KW - anxiety-like behavior KW - social experience KW - 5-HTT knockout mice Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165090 VL - 10 IS - 97 ER - TY - THES A1 - Raab, Annette T1 - The role of Rgs2 in animal models of affective disorders T1 - Über die Bedeutung von Rgs2 in Tiermodellen affektiver Störungen N2 - Anxiety and depressive disorders result from a complex interplay of genetic and environmental factors and are common mutual comorbidities. On the level of cellular signaling, regulator of G protein signaling 2 (Rgs2) has been implicated in human and rodent anxiety as well as rodent depression. Rgs2 negatively regulates G protein-coupled receptor (GPCR) signaling by acting as a GTPase accelerating protein towards the Gα subunit. The present study investigates, whether mice with a homozygous Rgs2 deletion (Rgs2-/-) show behavioral alterations as well as an increased susceptibility to stressful life events related to human anxiety and depressive disorders and tries to elucidate molecular underlying’s of these changes. To this end, Rgs2-/- mice were characterized in an aversive-associative learning paradigm to evaluate learned fear as a model for the etiology of human anxiety disorders. Spatial learning and reward motivated spatial learning were evaluated to control for learning in non-aversive paradigms. Rgs2 deletion enhanced learning in all three paradigms, rendering increased learning upon deletion of Rgs2 not specific for aversive learning. These data support reports indicating increased long-term potentiation in Rgs2-/- mice and may predict treatment response to conditioning based behavior therapy in patients with polymorphisms associated with reduced RGS2 expression. Previous reports of increased innate anxiety were corroborated in three tests based on the approach-avoidance conflict. Interestingly, Rgs2-/- mice showed novelty-induced hypo-locomotion suggesting neophobia, which may translate to the clinical picture of agoraphobia in humans and reduced RGS2 expression in humans was associated with a higher incidence of panic disorder with agoraphobia. Depression-like behavior was more distinctive in female Rgs2-/- mice. Stress resilience, tested in an acute and a chronic stress paradigm, was also more distinctive in female Rgs2-/- mice, suggesting Rgs2 to contribute to sex specific effects of anxiety disorders and depression. Rgs2 deletion was associated with GPCR expression changes of the adrenergic, serotonergic, dopaminergic and neuropeptide Y systems in the brain and heart as well as reduced monoaminergic neurotransmitter levels. Furthermore, the expression of two stress-related microRNAs was increased upon Rgs2 deletion. The aversive-associative learning paradigm induced a dynamic Rgs2 expression change. The observed molecular changes may contribute to the anxious and depressed phenotype as well as promote altered stress reactivity, while reflecting an alter basal stress level and a disrupted sympathetic tone. Dynamic Rgs2 expression may mediate changes in GPCR signaling duration during memory formation. Taken together, Rgs2 deletion promotes increased anxiety-like and depression-like behavior, altered stress reactivity as well as increased cognitive function. N2 - Angststörungen sowie Depressionserkrankungen entstehen in der Regel aus der Interaktion genetischer Faktoren mit Umwelteinflüssen und sind häufig gegenseitige Begleiterkrankungen. Das Protein, Regulator of G protein signaling 2 (Rgs2), wurde mit dem vermehrten Auftreten von Angststörungen im Menschen, sowie mit angstähnlichem sowie depressionsähnlichem Verhalten im Mausmodell assoziiert. Rgs2 beeinflusst auf zellulärer Ebene G Protein gekoppelte Signalwege, indem es die GTPase Aktivität der Gα Untereinheit beschleunigt. In der vorliegenden Arbeit wurden die Folgen einer homozygoten Rgs2-Defizienz im Mausmodell untersucht. In Anlehnung an die humanen Krankheitsbilder wurde angst- und depressions-ähnliches Verhalten, Stress Reaktivität und den phänotypischen Veränderungen zugrundeliegende molekulare Ursachen evaluiert. Erlernte Furcht gilt als Model der Ätiologie humaner Angsterkrankungen. Aus diesem Grund, wurden Rgs2-/- Mäuse in einem aversiv-assoziativen Lernmodell, der sogenannten Furcht-Konditionierung, untersucht. Dabei zeigte sich erhöhtes Furchtlernen und Furchtgedächtnis in Rgs2-/- Mäusen. Um zu zeigen, dass die erhöhte kognitive Fähigkeit spezifisch für erlernte Furcht sei, wurde räumliches Lernen in zwei Modellen getestet. Rgs2-Defizienz verbesserte auch in diesen Modellen die Lernfähigkeit. Somit konnte gezeigt werden, dass verbesserte kognitive Fähigkeit nicht spezifisch für emotionales Lernen war. Diese Daten auf Verhaltensebene unterstützen bisherige Befunde von erhöhter Langzeit Potenzierung im Hippocampus von Rgs2-/- Mäusen. Im Menschen könnte eine durch Polymorphismen vermittelte reduzierte Rgs2 Expression das Therapieansprechen auf konditionierungsbasierte Verhaltenstherapien verbessern. Bisherige Befunde von erhöhter, angeborener Angst in Rgs2-/- Mäusen konnten in drei Tests, basierend auf dem Annäherungs-Vermeidungs-Konflikt, bestätigt werden. Interessanterweise, zeigten Rgs2-/- Mäuse in allen Tests verminderte Lokomotion in neuen, ungewohnten Umgebungen. Dies könnte auf Neophobie und somit auf das Krankheitsbild der Agoraphobie im Menschen hindeuten. Tatsächlich wurden RGS2 Polymorphismen bereits mit einer erhöhten Inzidenz von Panikstörung mit Agoraphobie assoziiert. Rgs2-/- Mäuse zeigten zudem depressionsähnliches Verhalten, welches in weiblichen Mäusen ausgeprägter war. Des Weiteren zeigten, insbesondere weibliche Rgs2-/- Mäuse, erhöhte Stress Resilienz nach akuter und chronischer Stressexposition. Rgs2 könnte somit ein Faktor der Geschlechtsspezifität von Angst und Depressionserkrankungen sein. Rgs2-Defizienz konnte mit Expressionsänderungen von G Protein gekoppelten Rezeptoren des adrenergen, serotonergen, dopaminergen und Neuropeptid Y Systems in Gehirn und Herz, sowie mit verminderten Spiegeln monoaminerger Neurotransmitter assoziiert werden. Diese Veränderungen könnten zu dem beobachteten ängstlichen sowie depressiven Phänotyp und der veränderten Stress Reaktivität beitragen. Des Weiteren war die Expression zweier, in der Stressreaktion involvierten, microRNAs erhöht. Dies könnte auf einen veränderten basalen Stress Level hindeuten. Furcht-Konditionierung löste dynamische Expressionsänderungen der Rgs2 mRNA aus. Somit könnte die GPCR Signaldauer während der Gedächtnisbildung durch Rgs2 moduliert werden. Zusammengefasst, führt Rgs2-Defizienz im Mausmodell zu erhöhtem angst- und depressions-ähnlichem Verhalten, veränderter Stress Reaktivität sowie erhöhter kognitiver Leistung. KW - Angst KW - Depression KW - Tiermodell KW - Rgs2 KW - Regulator of G protein signaling 2 KW - Animal model KW - Anxiety KW - Depression KW - Stress KW - Knockout Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-152550 ER - TY - JOUR A1 - Stöber, Gerald A1 - Franzek, E. A1 - Beckmann, H. T1 - The role of maternal infectious diseases during pregnancy in the etiology of schizophrenia in offspring N2 - In 55 chronic schizophrenics, the occurrence of infectious diseases during their mothers' pregnancies was investigated. Different psychiatrie diagnostic systems were compared. Infections were reported by the mothers of familial and sporadic DSM I1I-R schizophrenics in equal proportion. However, applying Leonhard's classification, the frequency of infections was found to be significantly increased in 'systematic' schizophrenia (mainly exogenously induced in the view of Leonhard) compared to 'unsystematic' schizophrenia (mainly genetically determined according to Leonhard's findings). Most of the infections occurred during the second trimester (nine out of 13). Thus, in the 'systematic' forms of schizophrenia (low genetic loading), maternal infections in this crucial period of neurodevelopment would appear to be important causative factors in the cytoarchitectural deviance detected in the central nervous system of schizophrenics. KW - Psychiatrie KW - maternal infection KW - pregnancy KW - schizophrenia KW - familial-sporadic concept KW - Leonhard classification Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-82216 ER - TY - JOUR A1 - Wulf, Maximilian A1 - Barkovits, Katalin A1 - Schork, Karin A1 - Eisenacher, Martin A1 - Riederer, Peter A1 - Gerlach, Manfred A1 - Eggers, Britta A1 - Marcus, Katrin T1 - The proteome of neuromelanin granules in dementia with Lewy bodies JF - Cells N2 - Neuromelanin granules (NMGs) are organelle-like structures present in the human substantia nigra pars compacta. In addition to neuromelanin, NMGs contain proteins, lipids and metals. As NMG-containing dopaminergic neurons are preferentially lost in Parkinson’s disease and dementia with Lewy bodies (DLB), it is assumed that NMGs may play a role in neurodegenerative processes. Until now, this role is not completely understood and needs further investigation. We therefore set up an exploratory proteomic study to identify differences in the proteomic profile of NMGs from DLB patients (n = 5) compared to healthy controls (CTRL, n = 5). We applied a laser microdissection and mass-spectrometry-based approach, in which we used targeted mass spectrometric experiments for validation. In NMG-surrounding (SN\(_{Surr.}\)) tissue of DLB patients, we found evidence for ongoing oxidative damage and an impairment of protein degradation. As a potentially disease-related mechanism, we found α-synuclein and protein S100A9 to be enriched in NMGs of DLB cases, while the abundance of several ribosomal proteins was significantly decreased. As S100A9 is known to be able to enhance the formation of toxic α-synuclein fibrils, this finding points towards an involvement of NMGs in pathogenesis, however the exact role of NMGs as either neuroprotective or neurotoxic needs to be further investigated. Nevertheless, our study provides evidence for an impairment of protein degradation, ongoing oxidative damage and accumulation of potentially neurotoxic protein aggregates to be central mechanisms of neurodegeneration in DLB. KW - neuromelanin granules KW - neurodegeneration KW - dementia with Lewy bodies KW - proteomics KW - stress granules KW - substantia nigra pars compacta Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297465 SN - 2073-4409 VL - 11 IS - 22 ER - TY - THES A1 - Wagener, Annika T1 - The NoGo-anteriorization and its relation to a central inhibitory mechanism T1 - Die NoGo-Anteriorisierung und ihr Bezug zu einem zentralen Hemmmechanismus N2 - The maximum of the brain electrical field after NoGo stimuli is located more anteriorly than that after stimuli that tells participants to respond. The difference in topography was called NoGo-Anteriorization (NGA). Recently, there was a debate, whether the NGA is related to a central inhibitory process or not. However, experiments showed that the NGA is not the result of motor potentials during Go trials, the NGA does not represent higher response conflict and or higher mental effort in NoGo trials, and the NGA is not based on less cognitive response selection in NoGo trials. Therefore, the experiments support the assumption that the NGA is connected to an inhibitory mechanism in NoGo conditions. N2 - In Go-NoGo-Aufgaben unterscheidet sich das ereignis-korrelierte Potential der P300 nach einem Go-Stimulus topographisch von dem der P300 nach einem NoGo-Stimulus. Dieser Unterschied wurde auch als NoGo-Anteriorisierung bezeichnet, da die Topographie der NoGo-P300 weiter anterior liegt. Es wurde diskutiert, ob diese NGA als Korrelat eines Hemmprozesses interpretiert werden darf. Es konnte gezeigt werden, dass die NGA weder auf motorische Potentiale während Go-Trials, noch auf Handlungskonflikt, oder auf fehlende Antwortprozesse während NoGo-Trials zurückzuführen war. Deshalb wird die Erklärung als Korrelat eines Hemmprozesses favorisiert. KW - Handlung KW - Hemmung KW - Neuropsychologie KW - NoGo-P300 KW - Hemmung KW - EEG KW - NoGo-P300 KW - inhibition KW - EEG Y1 - 2005 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-14799 ER - TY - JOUR A1 - Sian-Hulsmann, Jeswinder A1 - Riederer, Peter T1 - The nigral coup in Parkinson's Disease by α-synuclein and its associated rebels JF - Cells N2 - The risk of Parkinson's disease increases with age. However, the etiology of the illness remains obscure. It appears highly likely that the neurodegenerative processes involve an array of elements that influence each other. In addition, genetic, endogenous, or exogenous toxins need to be considered as viable partners to the cellular degeneration. There is compelling evidence that indicate the key involvement of modified α-synuclein (Lewy bodies) at the very core of the pathogenesis of the disease. The accumulation of misfolded α-synuclein may be a consequence of some genetic defect or/and a failure of the protein clearance system. Importantly, α-synuclein pathology appears to be a common denominator for many cellular deleterious events such as oxidative stress, mitochondrial dysfunction, dopamine synaptic dysregulation, iron dyshomeostasis, and neuroinflammation. These factors probably employ a common apoptotic/or autophagic route in the final stages to execute cell death. The misfolded α-synuclein inclusions skillfully trigger or navigate these processes and thus amplify the dopamine neuron fatalities. Although the process of neuroinflammation may represent a secondary event, nevertheless, it executes a fundamental role in neurodegeneration. Some viral infections produce parkinsonism and exhibit similar characteristic neuropathological changes such as a modest brain dopamine deficit and α-synuclein pathology. Thus, viral infections may heighten the risk of developing PD. Alternatively, α-synuclein pathology may induce a dysfunctional immune system. Thus, sporadic Parkinson's disease is caused by multifactorial trigger factors and metabolic disturbances, which need to be considered for the development of potential drugs in the disorder. KW - Parkinson's disease KW - substantia nigra KW - alpha-synuclein KW - genetics KW - iron KW - neuroinflammation KW - viruses KW - immunology KW - aging and cell death Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234073 SN - 2073-4409 VL - 10 IS - 3 ER - TY - JOUR A1 - Brem, Silvia A1 - Grünblatt, Edna A1 - Drechsler, Renate A1 - Riederer, Peter A1 - Walitza, Susanne T1 - The neurobiological link between OCD and ADHD JF - Attention Deficit and Hyperactivity Disorders N2 - Obsessive compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) are two of the most common neuropsychiatric diseases in paediatric populations. The high comorbidity of ADHD and OCD with each other, especially of ADHD in paediatric OCD, is well described. OCD and ADHD often follow a chronic course with persistent rates of at least 40–50 %. Family studies showed high heritability in ADHD and OCD, and some genetic findings showed similar variants for both disorders of the same pathogenetic mechanisms, whereas other genetic findings may differentiate between ADHD and OCD. Neuropsychological and neuroimaging studies suggest that partly similar executive functions are affected in both disorders. The deficits in the corresponding brain networks may be responsible for the perseverative, compulsive symptoms in OCD but also for the disinhibited and impulsive symptoms characterizing ADHD. This article reviews the current literature of neuroimaging, neurochemical circuitry, neuropsychological and genetic findings considering similarities as well as differences between OCD and ADHD. KW - OCD KW - ADHD KW - neuroimaging KW - genetics KW - neuropsychology KW - fMRI KW - MRI KW - EEG KW - neurobiology Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121312 VL - 6 IS - 3 ER - TY - JOUR A1 - Saulin, Anne A1 - Horn, Ulrike A1 - Lotze, Martin A1 - Kaiser, Jochen A1 - Hein, Grit T1 - The neural computation of human prosocial choices in complex motivational states JF - NeuroImage N2 - Motives motivate human behavior. Most behaviors are driven by more than one motive, yet it is unclear how different motives interact and how such motive combinations affect the neural computation of the behaviors they drive. To answer this question, we induced two prosocial motives simultaneously (multi-motive condition) and separately (single motive conditions). After the different motive inductions, participants performed the same choice task in which they allocated points in favor of the other person (prosocial choice) or in favor of themselves (egoistic choice). We used fMRI to assess prosocial choice-related brain responses and drift diffusion modeling to specify how motive combinations affect individual components of the choice process. Our results showed that the combination of the two motives in the multi-motive condition increased participants' choice biases prior to the behavior itself. On the neural level, these changes in initial prosocial bias were associated with neural responses in the bilateral dorsal striatum. In contrast, the efficiency of the prosocial decision process was comparable between the multi-motive and the single-motive conditions. These findings provide insights into the computation of prosocial choices in complex motivational states, the motivational setting that drives most human behaviors . KW - motivation KW - social decision-making KW - hierarchical drift-diffusion modeling KW - fMRI KW - social neuroscience Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265852 VL - 247 ER - TY - JOUR A1 - Deckert, Jürgen A1 - Ozawa, Hiroki T1 - The joint Nagasaki–Würzburg approach to challenges and perspectives in neuropsychiatric and regenerative research JF - Journal of Neural Transmission N2 - No abstract available. KW - neuropsychiatry KW - regenerative research Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235359 SN - 0300-9564 VL - 127 ER - TY - JOUR A1 - Biernacka, J. M. A1 - Sangkuhl, K. A1 - Jenkins, G. A1 - Whaley, R. M. A1 - Barman, P. A1 - Batzler, A. A1 - Altman, R. B. A1 - Arolt, V. A1 - Brockmöller, J. A1 - Chen, C. H. A1 - Domschke, K. A1 - Hall-Flavin, D. K. A1 - Hong, C. J. A1 - Illi, A. A1 - Ji, Y. A1 - Kampman, O. A1 - Kinoshita, T. A1 - Leinonen, E. A1 - Liou, Y. J. A1 - Mushiroda, T. A1 - Nonen, S. A1 - Skime, M. K. A1 - Wang, L. A1 - Baune, B. T. A1 - Kato, M. A1 - Liu, Y. L. A1 - Praphanphoj, V. A1 - Stingl, J. C. A1 - Tsai, S. J. A1 - Kubo, M. A1 - Klein, T. E. A1 - Weinshilboum, R. T1 - The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response JF - Translational Psychiatry N2 - Response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably between patients. The International SSRI Pharmacogenomics Consortium (ISPC) was formed with the primary goal of identifying genetic variation that may contribute to response to SSRI treatment of major depressive disorder. A genome-wide association study of 4-week treatment outcomes, measured using the 17-item Hamilton Rating Scale for Depression (HRSD-17), was performed using data from 865 subjects from seven sites. The primary outcomes were percent change in HRSD-17 score and response, defined as at least 50% reduction in HRSD-17. Data from two prior studies, the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study (PGRN-AMPS) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, were used for replication, and a meta-analysis of the three studies was performed (N = 2394). Although many top association signals in the ISPC analysis map to interesting candidate genes, none were significant at the genome-wide level and the associations were not replicated using PGRN-AMPS and STAR*D data. Top association results in the meta-analysis of response included single-nucleotide polymorphisms (SNPs) in the HPRTP4 (hypoxanthine phosphoribosyltransferase pseudogene 4)/VSTM5 (V-set and transmembrane domain containing 5) region, which approached genome-wide significance (P = 5.03E - 08) and SNPs 5' upstream of the neuregulin-1 gene, NRG1 (P = 1.20E - 06). NRG1 is involved in many aspects of brain development, including neuronal maturation and variations in this gene have been shown to be associated with increased risk for mental disorders, particularly schizophrenia. Replication and functional studies of these findings are warranted. KW - major depressive disorder KW - genetic variation KW - schizophrenia KW - neuregulin-1 KW - population KW - microcephalin 1 KW - susceptibility KW - metaanalysis KW - MCPH1 KW - loci Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143223 VL - 5 IS - e553 ER - TY - JOUR A1 - Hübner, Theresa A1 - Wolfgang, Tanja A1 - Theis, Ann-Catrin A1 - Steber, Magdalena A1 - Wiedenmann, Lea A1 - Wöckel, Achim A1 - Diessner, Joachim A1 - Hein, Grit A1 - Gründahl, Marthe A1 - Kämmerer, Ulrike A1 - Kittel-Schneider, Sarah A1 - Bartmann, Catharina T1 - The impact of the COVID-19 pandemic on stress and other psychological factors in pregnant women giving birth during the first wave of the pandemic JF - Reproductive Health N2 - Background The onset of mental illness such as depression and anxiety disorders in pregnancy and postpartum period is common. The coronavirus induced disease 2019 (COVID-19) pandemic and the resulting public policy responses represent an exceptional situation worldwide and there are hints for adverse psychosocial impact, hence, the study of psychological effects of the pandemic in women during hospitalization for delivery and in the postpartum period is highly relevant. Methods Patients who gave birth during the first wave of the COVID-19 pandemic in Germany (March to June 2020) at the Department of Obstetrics and Gynecology, University of Würzburg, Germany, were recruited at hospital admission for delivery. Biosamples were collected for analysis of SARS-CoV-2 infection and various stress hormones and interleukin-6 (IL-6). In addition to sociodemographic and medical obstetric data, survey questionnaires in relation to concerns about and fear of COVID-19, depression, stress, anxiety, loneliness, maternal self-efficacy and the mother–child bonding were administered at T1 (delivery stay) and T2 (3–6 months postpartum). Results In total, all 94 recruited patients had a moderate concern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at T1 with a significant rise at T2. This concern correlated with low to low-medium general psychosocial stress levels and stress symptoms, and the women showed a significant increase of active coping from T1 to T2. Anxiety levels were low and the Edinburgh Postnatal Depression Scale showed a medium score of 5 with a significant (T1), but only week correlation with the concerns about SARS-CoV-2. In contrast to the overall good maternal bonding without correlation to SARS-CoV-2 concern, the maternal self-efficiency correlated negatively with the obstetric impairment caused by the COVID-19 pandemic. Conclusion Obstetric patients` concerns regarding SARS-CoV-2 and the accompanying pandemic increased during the course of the pandemic correlating positively with stress and depression. Of note is the increase in active coping over time and the overall good mother–child-bonding. Maternal self-efficacy was affected in part by the restrictions of the pandemic. KW - Covid-19 KW - stress KW - pregnancy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300189 VL - 19 IS - 1 ER - TY - JOUR A1 - Biehl, Stefanie C. A1 - Ehlis, Ann-Christine A1 - Müller, Laura D. A1 - Niklaus, Andrea A1 - Pauli, Paul A1 - Herrmann, Martin J. T1 - The impact of task relevance and degree of distraction on stimulus processing JF - BMC Neuroscience N2 - Background The impact of task relevance on event-related potential amplitudes of early visual processing was previously demonstrated. Study designs, however, differ greatly, not allowing simultaneous investigation of how both degree of distraction and task relevance influence processing variations. In our study, we combined different features of previous tasks. We used a modified 1-back task in which task relevant and task irrelevant stimuli were alternately presented. The task irrelevant stimuli could be from the same or from a different category as the task relevant stimuli, thereby producing high and low distracting task irrelevant stimuli. In addition, the paradigm comprised a passive viewing condition. Thus, our paradigm enabled us to compare the processing of task relevant stimuli, task irrelevant stimuli with differing degrees of distraction, and passively viewed stimuli. EEG data from twenty participants was collected and mean P100 and N170 amplitudes were analyzed. Furthermore, a potential connection of stimulus processing and symptoms of attention deficit hyperactivity disorder (ADHD) was investigated. Results Our results show a modulation of peak N170 amplitudes by task relevance. N170 amplitudes to task relevant stimuli were significantly higher than to high distracting task irrelevant or passively viewed stimuli. In addition, amplitudes to low distracting task irrelevant stimuli were significantly higher than to high distracting stimuli. N170 amplitudes to passively viewed stimuli were not significantly different from either kind of task irrelevant stimuli. Participants with more symptoms of hyperactivity and impulsivity showed decreased N170 amplitudes across all task conditions. On a behavioral level, lower N170 enhancement efficiency was significantly correlated with false alarm responses. Conclusions Our results point to a processing enhancement of task relevant stimuli. Unlike P100 amplitudes, N170 amplitudes were strongly influenced by enhancement and enhancement efficiency seemed to have direct behavioral consequences. These findings have potential implications for models of clinical disorders affecting selective attention, especially ADHD. KW - Selective attention KW - Working memory KW - Cognitive control KW - P100 KW - N170 KW - ADHD Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97271 UR - http://www.biomedcentral.com/1471-2202/14/107 ER - TY - JOUR A1 - Franke, B. A1 - Faraone, S. V. A1 - Asherson, P. A1 - Buitelaar, J. A1 - Bau, C. H. D. A1 - Ramos-Quiroga, J. A. A1 - Mick, E. A1 - Grevet, E. H. A1 - Johansson, S. A1 - Haavik, J. A1 - Lesch, K.-P. A1 - Cormand, B. A1 - Reif, A. T1 - The genetics of attention deficit/hyperactivity disorder in adults, a review JF - Molecular Psychiatry N2 - The adult form of attention deficit/hyperactivity disorder (aADHD) has a prevalence of up to 5% and is the most severe long-term outcome of this common neurodevelopmental disorder. Family studies in clinical samples suggest an increased familial liability for aADHD compared with childhood ADHD (cADHD), whereas twin studies based on self-rated symptoms in adult population samples show moderate heritability estimates of 30–40%. However, using multiple sources of information, the heritability of clinically diagnosed aADHD and cADHD is very similar. Results of candidate gene as well as genome-wide molecular genetic studies in aADHD samples implicate some of the same genes involved in ADHD in children, although in some cases different alleles and different genes may be responsible for adult versus childhood ADHD. Linkage studies have been successful in identifying loci for aADHD and led to the identification of LPHN3 and CDH13 as novel genes associated with ADHD across the lifespan. In addition, studies of rare genetic variants have identified probable causative mutations for aADHD. Use of endophenotypes based on neuropsychology and neuroimaging, as well as next-generation genome analysis and improved statistical and bioinformatic analysis methods hold the promise of identifying additional genetic variants involved in disease etiology. Large, international collaborations have paved the way for well-powered studies. Progress in identifying aADHD risk genes may provide us with tools for the prediction of disease progression in the clinic and better treatment, and ultimately may help to prevent persistence of ADHD into adulthood. KW - IMpACT KW - persistent ADHD KW - molecular genetics KW - heritability KW - endophenotype Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124677 VL - 17 ER - TY - JOUR A1 - Straube, B. A1 - Reif, A. A1 - Richter, J. A1 - Lueken, U. A1 - Weber, H. A1 - Arolt, V. A1 - Jansen, A. A1 - Zwanzger, P. A1 - Domschke, K. A1 - Pauli, P. A1 - Konrad, C. A1 - Gerlach, A. L. A1 - Lang, T. A1 - Fydrich, T. A1 - Alpers, G. W. A1 - Stroehle, A. A1 - Wittmann, A. A1 - Pfleiderer, B. A1 - Wittchen, H.-U. A1 - Hamm, A. A1 - Deckert, J. A1 - Kircher, T. T1 - The functional - 1019C/G HTR1A polymorphism and mechanisms of fear JF - Translational Psychiatry N2 - Serotonin receptor 1A gene (HTR1A) knockout mice show pronounced defensive behaviour and increased fear conditioning to ambiguous conditioned stimuli. Such behaviour is a hallmark of pathological human anxiety, as observed in panic disorder with agoraphobia (PD/AG). Thus, variations in HTR1A might contribute to neurophysiological differences within subgroups of PD/AG patients. Here, we tested this hypothesis by combining genetic with behavioural techniques and neuroimaging. In a clinical multicentre trial, patients with PD/AG received 12 sessions of manualized cognitive-behavioural therapy (CBT) and were genotyped for HTR1A rs6295. In four subsamples of this multicentre trial, exposure behaviour (n = 185), defensive reactivity measured using a behavioural avoidance test (BAT; before CBT: n = 245; after CBT: n = 171) and functional magnetic resonance imaging (fMRI) data during fear conditioning were acquired before and after CBT (n = 39). HTR1A risk genotype (GG) carriers more often escaped during the BAT before treatment. Exploratory fMRI results suggest increased activation of the amygdala in response to threat as well as safety cues before and after treatment in GG carriers. Furthermore, GG carriers demonstrated reduced effects of CBT on differential conditioning in regions including the bilateral insulae and the anterior cingulate cortex. Finally, risk genotype carriers demonstrated reduced self-initiated exposure behaviour to aversive situations. This study demonstrates the effect of HTR1A variation on defensive behaviour, amygdala activity, CBT-induced neural plasticity and normalization of defence behaviour in PD/AG. Our results, therefore, translate evidence from animal studies to humans and suggest a central role for HTR1A in differentiating subgroups of patients with anxiety disorders. KW - randomized-controlled trial KW - panic disorder KW - 5-HT1A receptor KW - defensive reactivity KW - major depression KW - cognitive-behavioral therapy KW - receptor gene polymorphism KW - C(-1019)G polymorphism KW - anxiety disorders KW - serotonin(1A) receptor Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114369 SN - 2158-3188 VL - 4 ER - TY - JOUR A1 - Kingslake, Jonathan A1 - Dias, Rebecca A1 - Dawson, Gerard R. A1 - Simon, Judit A1 - Goodwin, Guy M. A1 - Harmer, Catherine J. A1 - Morriss, Richard A1 - Brown, Susan A1 - Guo, Boliang A1 - Dourish, Colin T. A1 - Ruhé, Henricus G. A1 - Lever, Anne G. A1 - Veltman, Dick J. A1 - van Schaik, Anneke A1 - Deckert, Jürgen A1 - Reif, Andreas A1 - Stäblein, Michael A1 - Menke, Andreas A1 - Gorwood, Philip A1 - Voegeli, Géraldine A1 - Perez, Victor A1 - Browning, Michael T1 - The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial JF - Trials N2 - Background Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4–6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen. Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual. Methods/design The study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient’s antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50% or greater decrease in baseline scores of depressionmeasured using the Quick Inventory of Depressive Symptoms – Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed. Discussion This trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients. Trial registration ClinicalTrials.gov, ID: NCT02790970. Registered on 30 March 2016. KW - psychiatry KW - depression KW - prediction KW - treatment KW - antidepressant KW - primary care Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173012 VL - 18 ER - TY - JOUR A1 - Bartmann, Catharina A1 - Fischer, Leah-Maria A1 - Hübner, Theresa A1 - Müller-Reiter, Max A1 - Wöckel, Achim A1 - McNeill, Rhiannon V. A1 - Schlaiss, Tanja A1 - Kittel-Schneider, Sarah A1 - Kämmerer, Ulrike A1 - Diessner, Joachim T1 - The effects of the COVID-19 pandemic on psychological stress in breast cancer patients JF - BMC Cancer N2 - Background: The majority of breast cancer patients are severely psychologically affected by breast cancer diagnosis and subsequent therapeutic procedures. The COVID-19 pandemic and associated restrictions on public life have additionally caused significant psychological distress for much of the population. It is therefore plausible that breast cancer patients might be particularly susceptible to the additional psychological stress caused by the pandemic, increasing suffering. In this study we therefore aimed to assess the level of psychological distress currently experienced by a defined group of breast cancer patients in our breast cancer centre, compared to distress levels preCOVID-19 pandemic. Methods: Female breast cancer patients of all ages receiving either adjuvant, neoadjuvant, or palliative therapies were recruited for the study. All patients were screened for current or previous COVID-19 infection. The participants completed a self-designed COVID-19 pandemic questionnaire, the Stress and Coping Inventory (SCI), the National Comprehensive Cancer Network (R) (NCCN (R)) Distress Thermometer (DT), the European Organization for Research and Treatment of Cancer (EORTC) QLQ C30, and the BR23. Results: Eighty-two breast cancer patients were included. Therapy status and social demographic factors did not have a significant effect on the distress caused by the COVID-19 pandemic. The results of the DT pre and during COVID-19 pandemic did not differ significantly. Using the self-designed COVID-19 pandemic questionnaire, we detected three distinct subgroups demonstrating different levels of concerns in relation to SARS-CoV-2. The subgroup with the highest levels of concern reported significantly decreased life quality, related parameters and symptoms. Conclusions: This monocentric study demonstrated that the COVID-19 pandemic significantly affected psychological health in a subpopulation of breast cancer patients. The application of a self-created "COVID-19 pandemic questionnaire"could potentially be used to help identify breast cancer patients who are susceptible to increased psychological distress due to the COVID-19 pandemic, and therefore may need additional intensive psychological support. KW - COVID-19 KW - breast cancer KW - psychological distress Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265802 VL - 21 ER - TY - THES A1 - Waider, Jonas T1 - The effects of serotonin deficiency in mice: Focus on the GABAergic system T1 - Die Effekte einer Serotonindefizienz in der Maus: Das GABAerge System im Blickpunkt N2 - Based on genetic association and functional imaging studies, reduced function of tryptophan hydroxylase-2 (TPH2) has been shown to be critically involved in the pathophysiology of anxiety-disorders and depression. In order to elucidate the impact of a complete neuronal 5-HT deficiency, mice with a targeted inactivation of the gene encoding Tph2 were generated. Interestingly, survival of Tph2-/- mice, the formation of serotonergic neurons and the pathfinding of their projections was not impaired. Within this thesis, I investigated the influence of 5-HT deficiency on the γ-amino butyric acid (GABA) system. The GABAergic system is implicated in the pathophysiology of anxiety disorders. Therefore, measurement of GABA concentrations in different limbic brain regions was carried out. These measurements were combined with immunohistochemical estimation of GABAergic cell subpopulations in the dorsal hippocampus and amygdala. In Tph2-/- mice GABA concentrations were increased exclusively in the dorsal hippocampus. In heterozygous Tph2+/- mice concentrations of GABA were increased in the amygdala compared to Tph2-/- and wt control mice, while the reverse was found in the prefrontal cortex. The changes in GABA concentrations were accompanied by altered cell density of GABAergic neurons within the basolateral complex of the amygdala and parvalbumin (PV) neurons of the dorsal hippocampus and by adaptational changes of 5-HT receptors. Thus, adaptive changes during the development on the GABA system may reflect altered anxiety-like and depressive-like behavior in adulthood. Moreover, chronic mild stress (CMS) rescues the depressive-like effects induced by 5-HT deficiency. In contrast, 5-HT is important in mediating an increased innate anxiety-like behavior under CMS conditions. This is in line with a proposed dual role of 5-HT acting through different mechanisms on anxiety and depressive-like behavior, which is influenced by gene-environment interaction effects. Further research is needed to disentangle these complex networks in the future. N2 - Genomweite Assoziationsstudien in Kombination mit bildgebenden Studien zeigten, dass eine verringerte Funktion der Tryptophanhydroxylase-2 (Tph2) eine zentrale Rolle in der Pathophysiologie von Angststörungen und Depression spielt. Jedoch sind die einer Angststörung oder Depression zugrundeliegenden genauen Mechanismen noch nicht verstanden. Um den Einfluss einer 5-HT Defizienz zu untersuchen, wurden Tph2 ablatierte (Tph2-/-) Mäuse mittels zielgerichteter Mutagenese generiert. Der Verlust des Tph2 Gens hatte interessanterweise keinen Einfluss auf die Entwicklung vormals serotonerger Neurone und das Überleben der Tiere. In vorherigen Untersuchungen konnte gezeigt werden, dass 5-HT das GABAerge System, welches in der Pathophysiologie von Angststörungen eine zentrale Rolle spielt, in seiner Entwicklung beeinflusst. Daher wurden im Rahmen dieser Arbeit in verschiedenen Gehirnregionen des limbischen Systems Konzentrationen von GABA gemessen. Außerdem wurden mittels immunhistologischer Untersuchungen die Auswirkungen einer 5-HT Defizienz auf GABAerge Neuronenpopulationen hin untersucht. In Tph2-/- Mäusen wurden erhöhte Konzentrationen im Vergleich zu Tph2+/- und wt Kontrollen von GABA im Hippocampus festgestellt. In der Amygdala zeigten die Tph2+/- Mäuse dagegen eine erhöhte Konzentration von GABA. Dieser Effekt auf Tph2+/- Mäuse war umgekehrt im PFC Kortex zu finden, der erniedrigte GABA Konzentrationen in Tph2+/- aufwies. Die Veränderungen auf der neurochemischen Ebene wurden begleitet von veränderten GABAergen Zelldichten im basolateralen Komplex der Amygdala und parvalbuminergen GABAergen Neuronen in der CA3 Region des dorsalen hippocampus. Zudem waren 5-HT1A Rezeptoren und ihre Signalwege hochreguliert. Es scheint, dass der Verlust von 5-HT adaptive Veränderungen in der Entwicklung auf das GABAerge System zur Folge hat und die Basis für verändertes angstähnliches und depressionsähnliches Verhalten im Erwachsenenalter darstellt. Zusätzlich scheint eine 5-HT Defizienz den depressiven Phänotyp im Porsolt Test auszugleichen. Demgegenüber scheint 5-HT wichtig für ein erhöhtes angstähnliches Verhalten unter CMS Bedingungen zu sein. Dies unterstützt die Hypothese einer Doppelrolle von 5-HT innerhalb von Signalwegen und Mechanismen des angst- und depressionsähnlichem Verhalten, die durch Umweltfaktoren wie Stress stark beeinflusst werden. Um den Patienten noch besser helfen zu können erfordert dies in der Zukunft weiterhin eine fundierte Entschlüsselung der dahinter verborgenen Mechanismen. KW - Knockout KW - Serotonin KW - Maus KW - Knockout-Maus KW - GABA KW - serotonin deficiency KW - GABA KW - knockout-mice Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-74565 ER - TY - JOUR A1 - Gründahl, Marthe A1 - Weiß, Martin A1 - Stenzel, Kilian A1 - Deckert, Jürgen A1 - Hein, Grit T1 - The effects of everyday-life social interactions on anxiety-related autonomic responses differ between men and women JF - Scientific Reports N2 - Social buffering, a phenomenon where social presence can reduce anxiety and fear-related autonomic responses, has been studied in numerous laboratory settings. The results suggest that the familiarity of the interaction partner influences social buffering while also providing some evidence for gender effects. In the laboratory, however, it is difficult to mimic the complexity of real-life social interactions. Consequently, the social modulation of anxiety and related autonomic responses in everyday life remains poorly understood. We used smartphone-based Ecological Momentary Assessment (EMA) combined with wearable electrocardiogram sensors to investigate how everyday-life social interactions affect state anxiety and related cardiac changes in women and men. On five consecutive days, 96 healthy young participants (53% women) answered up to six EMA surveys per day, indicating characteristics of their most recent social interaction and the respective interaction partner(s). In women, our results showed lower heart rate in the presence of a male interaction partner. Men showed the same effect with female interaction partners. Moreover, only women showed decreased heart rate and increased heart rate variability with increasing interaction partner familiarity. These findings specify the conditions under which social interactions reduce anxiety-related responses in women and men. KW - physiology KW - psychology Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357840 VL - 13 ER - TY - JOUR A1 - Kopf, Juliane A1 - Dresler, Thomas A1 - Reicherts, Philipp A1 - Herrmann, Martin J. A1 - Reif, Andreas T1 - The Effect of Emotional Content on Brain Activation and the Late Positive Potential in a Word n-back Task JF - PLoS ONE N2 - Introduction There is mounting evidence for the influence of emotional content on working memory performance. This is particularly important in light of the emotion processing that needs to take place when emotional content interferes with executive functions. In this study, we used emotional words of different valence but with similar arousal levels in an n-back task. Methods We examined the effects on activation in the prefrontal cortex by means of functional near-infrared spectroscopy (fNIRS) and on the late positive potential (LPP). FNIRS and LPP data were examined in 30 healthy subjects. Results Behavioral results show an influence of valence on the error rate depending on the difficulty of the task: more errors were made when the valence was negative and the task difficult. Brain activation was dependent both on the difficulty of the task and on the valence: negative valence of a word diminished the increase in activation, whereas positive valence did not influence the increase in activation, while difficulty levels increased. The LPP also differentiated between the different valences, and in addition was influenced by the task difficulty, the more difficult the task, the less differentiation could be observed. Conclusions Summarized, this study shows the influence of valence on a verbal working memory task. When a word contained a negative valence, the emotional content seemed to take precedence in contrast to words containing a positive valence. Working memory and emotion processing sites seemed to overlap and compete for resources even when words are carriers of the emotional content. KW - analysis of variance KW - electrode recording KW - electroencephalography KW - emotions KW - eyes KW - near-infrared spectroscopy KW - reaction time KW - working memory Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96687 ER - TY - JOUR A1 - Gawlik, Micha A1 - Wehner, Ingeborg A1 - Mende, Meinhard A1 - Jung, Sven A1 - Pfuhlmann, Bruno A1 - Knapp, Michael A1 - Stoeber, Gerald T1 - The DAOA/G30 locus and affective disorders: haplotype based association study in a polydiagnostic approach N2 - Background: The DAOA/G30 (D-amino acid oxidase activator) gene complex at chromosomal region 13q32-33 is one of the most intriguing susceptibility loci for the major psychiatric disorders, although there is no consensus about the specific risk alleles or haplotypes across studies. Methods: In a case-control sample of German descent (affective psychosis: n = 248; controls: n = 188) we examined seven single nucleotide polymorphisms (SNPs) around DAOA/G30 (rs3916966, rs1935058, rs2391191, rs1935062, rs947267, rs3918342, and rs9558575) for genetic association in a polydiagnostic approach (ICD 10; Leonhard’s classification). Results: No single marker showed evidence of overall association with affective disorder neither in ICD10 nor Leonhard’s classification. Haplotype analysis revealed no association with recurrent unipolar depression or bipolar disorder according to ICD10, within Leonhard’s classification manic-depression was associated with a 3-locus haplotype (rs2391191, rs1935062, and rs3916966; P = 0.022) and monopolar depression with a 5-locus combination at the DAOA/G30 core region (P = 0.036). Conclusion: Our data revealed potential evidence for partially overlapping risk haplotypes at the DAOA/G30 locus in Leonhard’s affective psychoses, but do not support a common genetic contribution of the DAOA/G30 gene complex to the pathogenesis of affective disorders. KW - Psychisch Kranker KW - D-amino acid oxidase activator Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67963 ER - TY - THES A1 - Schulz, Sandra T1 - The Contribution of Common and Rare Variants to the Complex Genetics of Psychiatric Disorders T1 - Der Beitrag von häufigen und seltenen Varianten zur komplexen Genetik von psychiatrischen Krankheiten N2 - Attention deficit/hyperactivity disorder (ADHD), one of the most frequent childhood-onset, chronic and lifelong neurodevelopmental diseases, affects 5 - 10% of school – aged children and adolescents, and 4% of adults. The classified basic symptoms are - according to the diagnostic system DSM-VI - inattentiveness, impulsivity and hyperactivity. Also daily life of patients is impaired by learning problems, relationship crises, conflicts with authority and unemployment, but also comorbidities like sleep - and eating problems, mood - and anxiety disorders, depression and substance abuse disorders are frequently observed. Although several twin and family studies have suggested heritability of ADHD, the likely involvement of multiple genes and environmental factors has hampered the elucidation of its etiology and pathogenesis. Due to the successful medication of ADHD with dopaminergic drugs like methylphenidate, up to now, the search for candidate genes has mainly focused on the dopaminergic and - because of strong interactions - the serotonergic system, including the already analyzed candidate genes DAT1, DRD4 and 5, DBH or 5-HTTLPR. Recently, DNA copy number changes have been implicated in the development of a number of neurodevelopmental diseases and the analysis of chromosomal gains and losses by Array Comparative Genomic Hybridization (Array CGH) has turned out a successful strategy to identify disease associated genes. Here we present the first systematic screen for chromosomal imbalances in ADHD using sub-megabase resolution Array CGH. To detect micro-deletions and -duplications which may play a role in the pathogenesis of ADHD, we carried out a genome-wide screen for copy number variations (CNVs) in a cohort of 99 children and adolescents with severe ADHD. Using high-resolution aCGH, a total of 17 potentially syndrome-associated CNVs were identified. The aberrations comprise four deletions and 13 duplications with approximate sizes ranging from 110 kb to 3 Mb. Two CNVs occurred de novo and nine were inherited from a parent with ADHD, whereas five are transmitted by an unaffected parent. Candidates include genes expressing acetylcholine-metabolising butyrylcholinesterase (BCHE), contained in a de novo chromosome 3q26.1 deletion, and a brain-specific pleckstrin homology domain-containing protein (PLEKHB1), with an established function in primary sensory neurons, in two siblings carrying a 11q13.4 duplication inherited from their affected mother. Other genes potentially influencing ADHD-related psychopathology and involved in aberrations inherited from affected parents are the genes for the mitochondrial NADH dehydrogenase 1 alpha subcomplex assembly factor 2 (NDUFAF2), the brain-specific phosphodiesterase 4D isoform 6 (PDE4D6), and the neuronal glucose transporter 3 (SLC2A3). The gene encoding neuropeptide Y (NPY) was included in a ~3 Mb duplication on chromosome 7p15.2-15.3, and investigation of additional family members showed a nominally significant association of this 7p15 duplication with increased NPY plasma concentrations (empirical FBAT, p = 0.023). Lower activation of the left ventral striatum and left posterior insula during anticipation of large rewards or losses elicited by fMRI links gene dose-dependent increases in NPY to reward and emotion processing in duplication carriers. Additionally, further candidate genes were examined via Matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). This method enables the analysis of SNPs directly from human genomic DNA without the need for initial target amplification by PCR. All these findings implicate CNVs of behavior-related genes in the pathogenesis of ADHD and are consistent with the notion that both frequent and rare variants influence the development of this common multifactorial syndrome. The second part of this work concentrates on MLC1, a gene associated with Megalencephalic leukoencephalopathy with subcortical cysts, located on chromosome 22q13.33. To get more insight in the disease itself, a targeting vector for a conditional knockout mouse was constructed using homologous recombination. Furthermore, MLC1 has been suggested as a risk gene for schizophrenia, especially the periodic catatonia subtype. An initially identified missense mutation was found to be extremely rare in other patient cohorts; however, a recent report again argued for an association of two intronic MLC1 SNPs with schizophrenia and bipolar disorder. A case-control study of these polymorphisms as well as SNPs in the transcriptional control region of MLC1 was conducted in 212 chronic schizophrenic patients, 56 of which suffered from periodic catatonia, 106 bipolar patients, and 284 controls. Both intronic and promoter polymorphisms were specifically and significantly associated with periodic catatonia but not schizophrenia or bipolar disorder in general. A haplotype constructed from all polymorphisms was also associated with periodic catatonia. The MLC1 variation is associated with periodic catatonia; whether it constitutes a susceptibility or a modifier gene has to be determined. N2 - Aufmerksamkeitsdefizit/Hyperaktivitätssyndrom (ADHS) ist eine bereits im Kindesalter beginnende, chronische und lebenslängliche psychische Krankheit, die zu 5 - 10% Kinder und Jugendliche sowie zu 4% Erwachsene betrifft. Die klassifizierten Grundsyndrome sind laut dem diagnostischen System DSM-IV Unaufmerksamkeit, Impulsivität und Hyperaktivität. Auch der Alltag der Patienten ist aufgrund von Lernschwierigkeiten, Konflikten in der Beziehung, Autoritätsproblemen und Arbeitslosigkeit beeinträchtigt. Zudem werden häufig Komorbiditäten wie Schlaf- und Essprobleme, Stimmungs- und Angsterkrankungen, Depressionen sowie Alkohol- und Drogenmissbrauch beobachtet. Obwohl Zwillings- und Familienstudien auf die Vererbbarkeit von ADHS hinweisen, erschweren mehrere Gene und Umweltfaktoren die Aufklärung der Ätiologie und Pathogenese. Aufgrund der erfolgreichen Behandlung von ADHS mit dopaminergen Medikamenten wie Methylphenidat liegt der Fokus bei der Suche nach neuen Kandidatengenen hauptsächlich beim dopaminergen und, aufgrund der starken Interaktionen, beim serotonergen System, einschließlich der bereits analysierten Gene DAT1, DRD4 und 5, DBH oder 5-HTTLPR. Copy Number Changes sind in die Entstehung einer Vielzahl von Krankheiten mit einer Störung der Entwicklung des zentralen Nervensystems impliziert. Die Analyse von chromosomalen Deletionen oder Duplikationen durch Array Comparative Genomic Hybridization (Array CGH) hat sich als eine erfolgreiche Strategie herausgestellt, um krankheitsassoziierte Gene zu identifizieren. Diese Arbeit ist der erste systematische Screen für den Nachweis von chromosomalem Ungleichgewicht bei ADHS mit Hilfe von Array CGH. Um Mikrodeletionen und -duplikationen zu entdecken, die in der Pathogenese von ADHS eine Rolle spielen könnten, haben wir einen genomweiten Screen für Copy Number Variations (CNVs) an einer Gruppe mit 99 an ADHS erkrankten Kindern und Jugendlichen durchgeführt. Durch Hochauflösungs-Array CGH wurden insgesamt 17 potentielle Syndrom assoziierte CNVs identifiziert. Diese Aberrationen beinhalten vier Deletionen und 13 Duplikationen mit einer Größe von etwa 100 kb bis zu 3 Mb. Zwei CNVs sind de novo, neun wurden von einem ebenfalls an ADHS erkrankten Elternteil vererbt und fünf von einem nicht betroffenen Elter übertragen. Kandidatengene sind u. a. die Acetylcholin metabolisierende Butyrylcholonesterase (BCHE), welche de novo in einer Deletion auf Chromosom 3q26.1 auftritt, und das Gehirn spezifische Pleckstrin homology domain-containing Protein (PLEKHB1) mit einer bekannten Funktion in den primären sensorische Neuronen, welches von der an ADHS erkrankten Mutter an zwei Geschwister in einer 11q13.4 Duplikation vererbt wurde. Weitere Gene, die möglicherweise die Psychopathologie von ADHS beeinflussen und von einem betroffenen Elternteil in einer Aberration vererbt wurden, sind die Gene für die mitrochondriale NADH Dehydrogenase 1 Alpha Subcomplex Assembly Factor 2 (NDUFAF2), die Gehirn spezifische Phosphodiesterase 4D Isoform 6 (PDE4D6) und der neuronale Glukosetransporter 2 (SLC2A3). Das Gen, welches Neuropeptid Y (NPY) codiert, wurde in einer ~3 Mb großen Duplikation auf Chromosom 7p15.2-15.3 gefunden. Eine Untersuchung zusätzlicher Familienmitglieder zeigte eine nominell signifikante Assoziation dieser 7q15 Duplikation mit einer gesteigerten NPY Plasmakonzentration (empirischer FBAT, p = 0.023). Zusätzlich wurden weitere Kandidatengene durch Matrix-unterstützte Laser-Desorption/Ionisation-Massenspektrometrie (MALDI-TOF MS) untersucht. Diese Methode ermöglicht die Analyse von SNPs direkt von der humanen genomischen DNS ohne vorherige Target Amplifikation durch PCR. All diese Ergebnisse schließen CNVs von verhaltensverbundenen Genen in die Pathogenese von ADHS mit ein und stimmen außerdem mit der These überein, dass sowohl häufige wie auch seltene Variationen die Entwicklung dieses häufig auftretenden, multifaktoriellen Syndroms beeinflussen. Der zweite Teil dieser Arbeit beschäftigt sich mit dem Gen MLC1, das mit „Megalenzephaler Leukoenzephalopathie mit subkortikalen Cysten“ assoziiert und auf Chromosom 22q13.33 lokalisiert ist. Um mehr Einblick in diese Krankheit zu erlangen wurde ein spezieller Zielvektor für eine konditionale Knockout Maus durch homologe Rekombination erstellt. Zusätzlich wird angenommen, dass MLC1 ein Risikogen für Schizophrenie sein könnte, v. a. für den periodisch katatonischen Subtyp. Eine früher identifizierte Missense Mutation wurde extrem selten in anderen Patientenkohorten gefunden. Ein kürzlich veröffentlichter Bericht hingegen plädiert für eine Assoziation von zwei intronischen MLC1 SNPs mit Schizophrenie und manisch-depressiver Erkrankung. Eine Fall-Kontroll-Studie über diese Polymorphismen sowie über die SNPs der transkriptionalen Kontroll-Region von MLC1 wurde an 212 chronischen Schizophrenie-Patienten durchgeführt, von denen 56 an periodischer Katatonie leiden und 106 manisch-depressiv waren, sowie an 284 Kontrollen. Sowohl die intronischen Polymorphismen als auch die der Promotorregion waren spezifisch und signifikant mit periodischer Katatonie assoziiert, allerdings nicht mit Schizophrenie oder manisch-depressiver Erkrankung im Allgemeinen. Ein Haplotyp aus allen Polymorphismen konnte ebenfalls mit periodischer Katatonie assoziiert werden. Diese MLC1 Variation scheint somit mit periodischer Katatonie verknüpft zu sein. Ob es ein Suszeptibilitäts- oder ein Modifikatorgen darstellt, muss allerdings noch genauer bestimmt werden. KW - Aufmerksamkeits-Defizit-Syndrom KW - Molekulargenetik KW - Neuropeptid Y KW - Kandidatengen KW - Deletion KW - Duplikation KW - Schizophrenie KW - Attention-deficit/hyperactivity disorder KW - Neuropeptide Y KW - genome-wide KW - candidate genes KW - deletion KW - duplication KW - Schizophrenie Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-50677 ER - TY - JOUR A1 - Weiß, Martin A1 - Iotzov, Vassil A1 - Zhou, Yuqing A1 - Hein, Grit T1 - The bright and dark sides of egoism JF - Frontiers in Psychiatry N2 - Despite its negative reputation, egoism – the excessive concern for one’s own welfare – can incite prosocial behavior. So far, however, egoism-based prosociality has received little attention. Here, we first provide an overview of the conditions under which egoism turns into a prosocial motive, review the benefits and limitations of egoism-based prosociality, and compare them with empathy-driven prosocial behavior. Second, we summarize studies investigating the neural processing of egoism-based prosocial decisions, studies investigating the neural processing of empathy-based prosocial decisions, and the small number of studies that compared the neural processing of prosocial decisions elicited by the different motives. We conclude that there is evidence for differential neural networks involved in egoism and empathy-based prosocial decisions. However, this evidence is not yet conclusive, because it is mainly based on the comparison of different experimental paradigms which may exaggerate or overshadow the effect of the different motivational states. Finally, we propose paradigms and research questions that should be tackled in future research that could help to specify how egoism can be used to enhance other prosocial behavior and motivation, and the how it could be tamed. KW - egoism KW - incentives KW - prosociality KW - social motives KW - fMRI Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297183 SN - 1664-0640 VL - 13 ER - TY - JOUR A1 - Bellinger, Daniel A1 - Wehrmann, Kristin A1 - Rohde, Anna A1 - Schuppert, Maria A1 - Störk, Stefan A1 - Flohr-Jost, Michael A1 - Gall, Dominik A1 - Pauli, Paul A1 - Deckert, Jürgen A1 - Herrmann, Martin J. A1 - Erhardt-Lehmann, Angelika T1 - The application of virtual reality exposure versus relaxation training in music performance anxiety: a randomized controlled study JF - BMC Psychiatry N2 - Background Performance anxiety is the most frequently reported anxiety disorder among professional musicians. Typical symptoms are - on a physical level - the consequences of an increase in sympathetic tone with cardiac stress, such as acceleration of heartbeat, increase in blood pressure, increased respiratory rate and tremor up to nausea or flush reactions. These symptoms can cause emotional distress, a reduced musical and artistical performance up to an impaired functioning. While anxiety disorders are preferably treated using cognitive-behavioral therapy with exposure, this approach is rather difficult for treating music performance anxiety since the presence of a public or professional jury is required and not easily available. The use of virtual reality (VR) could therefore display an alternative. So far, no therapy studies on music performance anxiety applying virtual reality exposure therapy have investigated the therapy outcome including cardiovascular changes as outcome parameters. Methods This mono-center, prospective, randomized and controlled clinical trial has a pre-post design with a follow-up period of 6 months. 46 professional and semi-professional musicians will be recruited and allocated randomly to an VR exposure group or a control group receiving progressive muscle relaxation training. Both groups will be treated over 4 single sessions. Music performance anxiety will be diagnosed based on a clinical interview using ICD-10 and DSM-5 criteria for specific phobia or social anxiety. A behavioral assessment test is conducted three times (pre, post, follow-up) in VR through an audition in a concert hall. Primary outcomes are the changes in music performance anxiety measured by the German Bühnenangstfragebogen and the cardiovascular reactivity reflected by heart rate variability (HRV). Secondary outcomes are changes in blood pressure, stress parameters such as cortisol in the blood and saliva, neuropeptides, and DNA-methylation. Discussion The trial investigates the effect of VR exposure in musicians with performance anxiety compared to a relaxation technique on anxiety symptoms and corresponding cardiovascular parameters. We expect a reduction of anxiety but also a consecutive improvement of HRV with cardiovascular protective effects. Trial registration This study was registered on clinicaltrials.gov. (ClinicalTrials.gov Number: NCT05735860) KW - music performance anxiety KW - virtual reality exposure therapy KW - progressive muscle relaxation KW - heart rate variability Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357833 VL - 23 ER - TY - THES A1 - Siminski, Niklas T1 - Temporal predictability of threat: Evaluation of differential involvement of amygdala and BNST, and relevance for therapy response prediction in spider phobia T1 - Zeitliche Vorhersagbarkeit von Bedrohung: Evaluation der unterschiedlichen Aktivierung von Amygdala und BNST sowie die Relevanz für die Vorhersagbarkeit von Therapieerfolg bei der Spinnenphobie N2 - Predictability of threat is one of the key modulators of neural activity in fear and anxiety-related threat processes and there is a considerable number of studies focusing on the exact contribution of centromedial amygdala and Bed nucleus of stria terminalis (BNST) in animals as well as in humans. In this research field, some studies already investigated the differential involvement of both areas during temporally predictable and unpredictable threat processes in humans. However, these studies showed several limitations e.g. small sample size, no predictable threat conditions, no separation of anticipation and confrontation processes, which should be addressed in future studies. Furthermore, evidence for group-based inter-individual differences of amygdala and BNST activity during predictable and unpredictable threat processes have not been studied extensively. Several studies suggest a relevant role of the amygdala and BNST activity in phobic processes in patients with specific phobia, but no study so far has investigated the exact contribution of centromedial amygdala (CM) and BNST during temporally predictable and unpredictable threat processes in specific phobia. This thesis consisted of three studies and aimed to evaluate the exact contribution of CM and BNST during temporally predictable and unpredictable threat anticipation and confrontation with the use of an optimized functional magnetic resonance imaging (fMRI) paradigm, which aimed to solve methodological limitations of recent studies. Study 1 used a large sample of healthy participants who were grouped based on NPSR1 genotype, and study 2 and study 3 used a sample of patients with spider phobia. In sum, the results of all three studies indicated, that BNST is more relevant for anticipation processes as compared to the CM. Contrary, during the confrontation phase the CM displays a greater relevance for threat confrontation processes. In recent years, various studies have investigated the extent to which treatment success can be predicted in patients with anxiety disorders based on pre-treatment fMRI activity. Therefore, this was investigated for the first time in study 3 in patients with spider phobia during temporally predictable and unpredictable threat processes. Results indicated that independent of temporal predictability lower anterior cingulate cortex (ACC) activity during threat anticipation and engaged BNST during threat confrontation might be benefitting factors for successful therapy response in spider phobia. N2 - Die Vorhersagbarkeit der Bedrohung ist einer der wichtigsten Modulatoren der neuronalen Aktivität bei angst- und furchtbezogenen Bedrohungsprozessen, und es gibt eine beträchtliche Anzahl von Studien, die sich mit der unterschiedlichen Beteiligung der zentromedialen Amygdala (CM) und des Bed nucleus of stria terminalis (BNST) während dieser Prozesse sowohl bei Tieren als auch beim Menschen beschäftigen. In diesem Forschungsfeld untersuchten bereits einige Studien die exakte Beteiligung beider Areale während zeitlich vorhersehbarer und unvorhersehbarer Bedrohungsprozesse beim Menschen. Diese Studien wiesen jedoch einige Limitationen auf (z.B. geringe Stichprobengröße, keine vorhersagbaren Bedrohungsbedingungen, gemeinsame Analyse der Aktivierung über Antizipations- und Konfrontationsphasen hinweg), die in zukünftigen Studien verbessert werden sollten. Zudem gibt es bisher wenige Studien, welche die unterschiedliche Beteiligung der Amygdala und des BNST während Bedrohungsprozessen auf Grundlage gruppenbasierter inter-individueller Unterschiede untersucht haben. Mehrere Studien deuten auf eine erhöhte Aktivierung sowohl der Amygdala als auch des BNST während phobischer Angstprozesse bei Patient*Innen mit einer spezifischen Phobie hin. Allerdings hat bisher jedoch noch keine Studie die Aktivierung der CM und des BNST während zeitlich vorhersagbarer und unvorhersagbarer phobischer Bedrohungsprozesse bei Patient*Innen direkt verglichen. Unter Verwendung eines optimierten funktionelle Magnetresonanztomographie (fMRT)-Paradigmas, das darauf abzielte, methodische Probleme der bisherigen Studien zu lösen, wurde in dieser Arbeit die unterschiedliche Aktivierung von CM und BNST während zeitlich vorhersehbarer und unvorhersehbarer Bedrohungsantizipation und -konfrontation in einer großen Stichprobe gesunder Teilnehmer, die anhand des NPSR1-Genotyps gruppiert wurden (Studie 1), und Patient*Innen mit einer Spinnenphobie untersucht (Studie 2 und Studie 3). In Summe zeigten die Ergebnisse aller drei Studien, dass im Vergleich zur CM der BNST für Antizipationsprozesse relevanter ist. Hingegen zeigte die CM in der Konfrontationsphase mit einer Bedrohung eine größere Aktivierung als der BNST. In den letzten Jahren haben verschiedene Studien untersucht, inwieweit der Behandlungserfolg bei Patient*Innen mit einer Angststörung anhand der fMRT-Aktivität vor der Behandlung vorhergesagt werden kann. Daher wurde in Studie 3 dies erstmals bei Patient*Innen mit einer Spinnenphobie während zeitlich vorhersehbarer und unvorhersehbarer Bedrohungsprozesse untersucht. Die Ergebnisse deuteten darauf hin, dass eine geringere Aktivität im anterioren cingulären Cortex (ACC) während phobischen Antizipationsprozessen und eine höhere Aktivierung im BNST während der Konfrontation mit phobischen Stimuli günstige Faktoren für den Therapieerfolg bei Spinnenphobie sein könnten. KW - Amygdala KW - fMRI KW - Angststörung KW - Temporal predictability KW - fmri activity KW - amygdala KW - Bed nucleus of stria terminalis KW - spider phobia KW - Corpus amygdaloideum KW - Funktionelle Kernspintomografie Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246643 ER - TY - JOUR A1 - Barkhuizen, Melinda A1 - van Mechelen, Ralph A1 - Vermeer, Marijne A1 - Chedraui, Peter A1 - Paes, Dean A1 - van den Hove, Daniel L. A. A1 - Vaes, Bart A1 - Mays, Robert W. A1 - Steinbusch, Harry W. M. A1 - Robertson, Nicola J. A1 - Kramer, Boris W. A1 - Gavilanes, Antonio W. D. T1 - Systemic multipotent adult progenitor cells improve long-term neurodevelopmental outcomes after preterm hypoxic-ischemic encephalopathy JF - Behavioural Brain Research N2 - There is an urgent need for therapies that could reduce the disease burden of preterm hypoxic-ischemic encephalopathy. Here, we evaluate the long-term effects of multipotent adult progenitor cells (MAPC) on long-term behavioral outcomes in a preterm rat model of perinatal asphyxia. Rats of both sexes were treated with two doses of MAPCs within 24 h after the insult. Locomotor, cognitive and psychiatric impairments were evaluated starting at 1.5 (juvenile) and 6 months (adult). Hypoxia-ischemia affected locomotion, cognition, and anxiety in a sex-dependent manner, with higher vulnerability observed in males. The MAPC therapy partially attenuated deficits in object recognition memory in females of all tested ages, and in the adult males. The hypoxic insult caused delayed hyperactivity in adult males, which was corrected by MAPC therapy. These results suggest that MAPCs may have long-term benefits for neurodevelopmental outcome after preterm birth and global hypoxia-ischemia, which warrants further preclinical exploration. KW - hypoxic-ischemic encephalopathy KW - preterm brain KW - stem cell therapy KW - neurodevelopment Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221506 VL - 362 ER - TY - THES A1 - Saulin, Anne Christin T1 - Sustainability of empathy as driver for prosocial behavior and social closeness: insights from computational modelling and functional magnetic resonance imaging T1 - Nachhaltigkeit von Empathie als Motiv für prosoziales Verhalten und soziale Nähe: Erkenntnisse auf Grundlage von computational modelling und funktioneller Magnetresonanztomographie N2 - Empathy, the act of sharing another person’s affective state, is a ubiquitous driver for helping others and feeling close to them. These experiences are integral parts of human behavior and society. The studies presented in this dissertation aimed to investigate the sustainability and stability of social closeness and prosocial decision-making driven by empathy and other social motives. In this vein, four studies were conducted in which behavioral and neural indicators of empathy sustainability were identified using model-based functional magnetic resonance imaging (fMRI). Applying reinforcement learning, drift-diffusion modelling (DDM), and fMRI, the first two studies were designed to investigate the formation and sustainability of empathy-related social closeness (study 1) and examined how sustainably empathy led to prosocial behavior (study 2). Using DDM and fMRI, the last two studies investigated how empathy combined with reciprocity, the social norm to return a favor, on the one hand and empathy combined with the motive of outcome maximization on the other hand altered the behavioral and neural social decision process. The results showed that empathy-related social closeness and prosocial decision tendencies persisted even if empathy was rarely reinforced. The sustainability of these empathy effects was related to recalibration of the empathy-related social closeness learning signal (study 1) and the maintenance of a prosocial decision bias (study 2). The findings of study 3 showed that empathy boosted the processing of reciprocity-based social decisions, but not vice versa. Study 4 revealed that empathy-related decisions were modulated by the motive of outcome maximization, depending on individual differences in state empathy. Together, the studies strongly support the concept of empathy as a sustainable driver of social closeness and prosocial behavior. N2 - Empathie, das Teilen des Affekts einer anderen Person, ist eine allgegenwärtige Motivation, anderen Menschen zu helfen und sich ihnen nahe zu fühlen. Diese Erfahrungen sind wesentliche Bestandteile menschlichen Verhaltens und zentral für unsere Gesellschaft. Die vorliegende Dissertation setzte sich zum Ziel, die Nachhaltigkeit und Stabilität sozialer Nähe sowie prosozialem Entscheidungsverhalten basierend auf Empathie und anderen sozialen Motiven zu beleuchten. In den vier Studien wurden das Verhalten und neuronale Indikatoren für die Nachhaltigkeit von Empathie mit modellbasierter funktioneller Magnetresonanztomographie (fMRT) untersucht. Unter Verwendung von Verstärkungslernmodellen, Drift-Diffusionsmodellen (DDM) und fMRT untersuchten die ersten zwei Studien den zeitlichen Verlauf von empathiebasierter sozialer Nähe und prosozialem Verhalten. Mit Hilfe von DDM und fMRT wurde in den abschließenden Studien untersucht, wie Empathie in Kombination mit Reziprozität, der sozialen Norm, Gefallen zurückzuzahlen, und Empathie in Kombination mit dem Motiv der Gewinnmaximierung den verhaltensbezogenen und neuronalen sozialen Entscheidungsprozess verändert. Die Ergebnisse zeigten, dass empathiebasierte soziale Nähe und prosoziale Entscheidungstendenzen selbst dann fortbestanden wenn Empathie nur noch selten verstärkt wurde. Die Nachhaltigkeit dieser Effekte hing mit der Rekalibrierung des empathiebasierten Lernsignals für soziale Nähe (Studie 1) und dem Aufrechterhalten eines prosozialen Entscheidungsbias zusammen (Studie 2). Die Ergebnisse von Studie 3 zeigten, dass Empathie reziprozitätsbasierte soziale Entscheidungen stärkt, aber nicht umgekehrt. Studie 4 zeigte, dass empathiebasierte soziale Entscheidungen durch das Motiv der Gewinnmaximierung vereinfacht werden können. Zusammengefasst unterstützen die Ergebnisse der vorliegenden Dissertation nachdrücklich das Konzept von Empathie als nachhaltige Triebkraft für soziale Nähe und prosoziales Verhalten. KW - Einfühlung KW - Bestärkendes Lernen KW - Modellierung KW - Funktionelle Kernspintomografie KW - Prosoziales Verhalten KW - drift-diffusion model KW - reciprocity KW - anterior insula KW - temporo-parietal junction KW - inferior frontal gyrus Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-305550 ER - TY - THES A1 - Logina, Agate T1 - Structural brain alterations in spider phobia : A voxel-based morphometry study T1 - Strukturelle Hirnveränderungen bei Spinnenphobie : Voxel-basierte Morphometrie Studie N2 - In this study, we examined the regional grey matter density in 35 spider phobic patients and 33 age, gender and education matched healthy controls. We used a method called Voxel-Based Morphometry, which allowed us to conduct a voxel- by-voxel analysis of the entire brain. We also tried to determine if there was any relationship between the severity of fear (expressed in BAT and SPQ score) and grey matter density. Based on previous findings, we expected to find structural changes in the following brain regions: - prefrontal cortex; - orbitofrontal cortex; - anterior cingulate cortex; - insula; - visual and associative cortices. Between-group comparison of spider phobic patients and healthy controls yielded no significant results. Additionally, and as expected, we did not find a between- group difference in TIV. Surprisingly, however, we found several brain regions whose GMD was significantly correlated with severity of spider phobia. The score that correlated with several regions GMD and yielded the largest cluster was the SPQ. SPQ was positively correlated with dorsal anterior cingulate, right insula and left inferior parietal lobule. Final distance in centimetres was correlated with left superior frontal gyrus and right paracentral lobule densities. All correlations were observed at a cluster level and no significant results at peak level were found. Interestingly, out of all BAT fear values, only BAT when the spider was taken away had a positive correlation with GMD (vermis). There were no indications of reduced GMD in spider phobic patients. Overall, our regions of significance were in line of those of other structural and functional neuroimaging studies in the field of specific phobia. As expected, we found GMD changes in the prefrontal cortex, ACC, insula and the associative 60 cortices. The functions of these regions such as processing of disgust, attention, autonomous responses, consolidation of memory and regulation of affect support the possible involvement of these structures in SP. We did, however, also yield some unexpected results (vermis, right paracentral lobule). Interestingly and in contrast to other studies, our results were only limited to the phobic group itself- we found no regions of significance in the SP-HC between-group analysis. In the future, more VBM studies with larger size of spider phobic subjects should be conducted, further investigating both the between-group differences and the correlation between spider phobia severity and GMD. Additionally, studies should investigate the relationship between structural changes and activation patterns observed in fMRI, find out whether brain changes precede the clinical symptoms or vice versa and see, if structural changes normalize in response to CBT the same way functional changes do. N2 - In dieser Studie wurde mittels auf MRT-Datensätzen basierender VBM der Frage nachgegangen, ob Patienten mit einer Spinnenphobie Veränderungen der grauen oder weißen Substanz des Gehirns aufweisen. Bei VBM werden regionale Volumenveränderungen der grauen und der weißen Substanz auf dem Boden struktureller MRT-Bilder bestimmt. Wir haben veränderungen in folgenden Regionen erwartet: - präfrontalem Kortex - orbitofrontalem Kortex - anteriorem cingulärem Kortex - Inselkortex - Sehrinde. Der Spinnenphobie-Fragebogen (SPQ) ergab eine positive Korrelation mit dorsalem cingulärem Kortex, rechtem Inselkortex und dem linkem Lobulus parietalis inferior. Auch Vermis, rechter Lobulus paracentralis und der linke Gyrus frontalis superior Dichte zeigte eine positive Korrelation mit Schwergrad der Spinnenphobie. Zusammenfassend sind unsere Ergebnisse übereinstimmend mit den Ergebnissen von anderen Studien. Wie erwartet, haben wir Veränderungen im präfrontalen Kortex, anteriorem cingulärem Kortex und Inselkortex gefunden. Diese Regionen sind für Ekel, Aufmerksamkeit, autonome Reaktionen und Gedächtnis verantwortlich, alle diese Funktionen spielen eine Rolle in spezifischen Phobien. In Zukunft, mehr und größeren VBM-Studien sind notwendig, um die Ergebnisse von unserer Studie zu überprüfen. KW - vbm Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211335 ER - TY - JOUR A1 - Sun, Ping A1 - Ortega, Gabriela A1 - Tan, Yan A1 - Hua, Qian A1 - Riederer, Peter F. A1 - Deckert, Jürgen A1 - Schmitt-Böhrer, Angelika G. T1 - Streptozotocin impairs proliferation and differentiation of adult hippocampal neural stem cells in vitro-correlation with alterations in the expression of proteins associated with the insulin system JF - Frontiers in Aging Neuroscience N2 - Rats intracerebroventricularily (icv) treated with streptozotocin (STZ), shown to generate an insulin resistant brain state, were used as an animal model for the sporadic form of Alzheimer's disease (sAD). Previously, we showed in an in vivo study that 3 months after STZ icv treatment hippocampal adult neurogenesis (AN) is impaired. In the present study, we examined the effects of STZ on isolated adult hippocampal neural stem cells (NSCs) using an in vitro approach. We revealed that 2.5 mM STZ inhibits the proliferation of NSCs as indicated by reduced number and size of neurospheres as well as by less BrdU-immunoreactive NSCs. Double immunofluorescence stainings of NSCs already being triggered to start with their differentiation showed that STZ primarily impairs the generation of new neurons, but not of astrocytes. For revealing mechanisms possibly involved in mediating STZ effects we analyzed expression levels of insulin/glucose system-related molecules such as the glucose transporter (GLUT) 1 and 3, the insulin receptor (IR) and the insulin-like growth factor (IGF) 1 receptor. Applying quantitative Real time-PCR (qRT-PCR) and immunofluorescence stainings we showed that STZ exerts its strongest effects on GLUT3 expression, as GLUT3 mRNA levels were found to be reduced in NSCs, and less GLUT3-immunoreactive NSCs as well as differentiating cells were detected after STZ treatment. These findings suggest that cultured NSCs are a good model for developing new strategies to treat nerve cell loss in AD and other degenerative disorders. KW - Alzheimer’s disease KW - streptozotocin KW - proliferation KW - neural stem cells KW - insulin-like growth factor 1 receptor KW - insulin receptor KW - glucose transporter KW - differentiation Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176741 VL - 10 IS - 145 ER - TY - JOUR A1 - Heinsen, Helmut A1 - Heinsen, YL T1 - Strain-specific differences in the vermian granular layer of albino rats N2 - Foliation of the cerebella of Sprague-Dawley rats (strain Han:SPRD) is more advanced than in Wistar rats (strain Chbb:THOM). The differences expressed as length of the granular layer in median sections were significant in lobules VIa, VIII, IX and X. The length of the other vermian lobules is generally higher in the former strain. With regard to the volume of the granular layer, the situation is reversed, indicating that the lateral extent and thickness of vermian lobules in Wistar rats (strain Chbb:THOM) is generally larger. These quantitative differences may express differences in cerebellar microcircuitry and fibre connections in the cortex of Wistar and Sprague-Dawley rats. KW - Albino rats KW - Cerebellum KW - Granular layer KW - Quantitative anatomy KW - Strain differences Y1 - 1984 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-45735 ER - TY - JOUR A1 - Brunkhorst-Kanaan, Nathalie A1 - Trautmann, Sandra A1 - Schreiber, Yannick A1 - Thomas, Dominique A1 - Kittel-Schneider, Sarah A1 - Gurke, Robert A1 - Geisslinger, Gerd A1 - Reif, Andreas A1 - Tegeder, Irmgard T1 - Sphingolipid and endocannabinoid profiles in adult attention deficit hyperactivity disorder JF - Biomedicines N2 - Genes encoding endocannabinoid and sphingolipid metabolism pathways were suggested to contribute to the genetic risk towards attention deficit hyperactivity disorder (ADHD). The present pilot study assessed plasma concentrations of candidate endocannabinoids, sphingolipids and ceramides in individuals with adult ADHD in comparison with healthy controls and patients with affective disorders. Targeted lipid analyses of 23 different lipid species were performed in 71 mental disorder patients and 98 healthy controls (HC). The patients were diagnosed with adult ADHD (n = 12), affective disorder (major depression, MD n = 16 or bipolar disorder, BD n = 6) or adult ADHD with comorbid affective disorders (n = 37). Canonical discriminant analysis and CHAID analyses were used to identify major components that predicted the diagnostic group. ADHD patients had increased plasma concentrations of sphingosine-1-phosphate (S1P d18:1) and sphinganine-1-phosphate (S1P d18:0). In addition, the endocannabinoids, anandamide (AEA) and arachidonoylglycerol were increased. MD/BD patients had increased long chain ceramides, most prominently Cer22:0, but low endocannabinoids in contrast to ADHD patients. Patients with ADHD and comorbid affective disorders displayed increased S1P d18:1 and increased Cer22:0, but the individual lipid levels were lower than in the non-comorbid disorders. Sphingolipid profiles differ between patients suffering from ADHD and affective disorders, with overlapping patterns in comorbid patients. The S1P d18:1 to Cer22:0 ratio may constitute a diagnostic or prognostic tool. KW - attention deficit hyperactivity disorder KW - endocannabinoids KW - ceramides KW - bipolar disorder KW - major depression KW - tandem mass spectrometry Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246080 SN - 2227-9059 VL - 9 IS - 9 ER - TY - JOUR A1 - Denk, Johannes A1 - Oberhauser, Felix A1 - Kornhuber, Johannes A1 - Wiltfang, Jens A1 - Fassbender, Klaus A1 - Schroeter, Matthias L. A1 - Volk, Alexander E. A1 - Diehl-Schmid, Janine A1 - Prudlo, Johannes A1 - Danek, Adrian A1 - Landwehrmeyer, Bernhard A1 - Lauer, Martin A1 - Otto, Markus A1 - Jahn, Holger T1 - Specific serum and CSF microRNA profiles distinguish sporadic behavioural variant of frontotemporal dementia compared with Alzheimer patients and cognitively healthy controls JF - PLoS ONE N2 - Information on circulating miRNAs in frontotemporal lobar degeneration is very limited and conflicting results have complicated an interpretation in Alzheimer’s disease thus far. In the present study we I) collected samples from multiple clinical centers across Germany, II) defined 3 homogenous patient groups with high sample sizes (bvFTD n = 48, AD n = 48 and cognitively healthy controls n = 44), III) compared expression levels in both CSF and serum samples and IV) detected a limited set of miRNAs by using a MIQE compliant protocol based on SYBR-green miRCURY assays that have proven reliable to generate reproducible results. We included several quality controls that identified and reduced technical variation to increase the reliability of our data. We showed that the expression levels of circulating miRNAs measured in CSF did not correlate with levels in serum. Using cluster analysis we found expression pattern in serum that, in part, reflects the genomic organization and affiliation to a specific miRNA family and that were specifically altered in bvFTD, AD, and control groups. Applying factor analysis we identified a 3-factor model characterized by a miRNA signature that explained 80% of the variance classifying healthy controls with 97%, bvFTD with 77% and AD with 72% accuracy. MANOVA confirmed signals like miR-320a and miR-26b-5p at BH corrected significance that contributed most to discriminate bvFTD cases with 96% sensitivity and 90% specificity and AD cases with 89% sensitivity and specificity compared to healthy controls, respectively. Correlation analysis revealed that miRNAs from the 3-factor model also correlated with levels of protein biomarker amyloid-beta1-42 and phosphorylated neurofilament heavy chain, indicating their potential role in the monitoring of progressive neuronal degeneration. Our data show that miRNAs can be reproducibly measured in serum and CSF without pre-amplification and that serum includes higher expressed signals that demonstrate an overall better ability to classify bvFTD, AD and healthy controls compared to signals detected in CSF. Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223695 VL - 13 ER - TY - THES A1 - Kriegebaum, Claudia T1 - Spatio-temporal Expression Patterns of the Serotonin Synthesis Enzymes TPH1 and TPH2 and Effects of Acute Stress T1 - Regional-zeitliche Expressionsmuster der beiden Serotoninsynthese-Enzyme TPH1 und TPH2 und Effekte durch akuten Stress N2 - Several lines of evidence implicate a dysregulation of tryptophan hydroxylase (TPH)-dependent serotonin (5-HT) synthesis in emotions and stress and point to their potential relevance to the etiology and pathogenesis of various neuropsychiatric disorders. However, the differential expression pattern of the two isoforms TPH1 and TPH2 which encode two forms of the rate-limiting enzyme of 5-HT synthesis is controversial. Here, a comprehensive spatio-temporal analysis clarifies TPH1 and TPH2 expression during pre- and postnatal development of the mouse brain and in adult human brain as well as in peripheral organs including the pineal gland. Four different methods (real time PCR, in situ hybridization, immunohistochemistry and Western blot analysis) were performed to systematically control for tissue-, species- and isoform-specific expression on both the pre- and posttranslational level. TPH2 expression was consistently detected in the raphe nuclei, as well as in fibres in the deep pineal gland and in the gastrointestinal tract. Although TPH1 expression was found in these peripheral tissues, no significant TPH1 expression was detected in the brain, neither during murine development, nor in mouse and human adult brain. Also under conditions like stress and clearing the tissue from blood cells, no changes in expression levels were detectable. Furthermore, the reuptake of 5-HT into the presynaptic neuron by the serotonin transporter (SERT) is the major mechanism terminating the neurotransmitter signal. Thus, mice with a deletion in the Sert gene (Sert KO mice) provide an adequate model for human affective disorders to study lifelong modified 5-HT homeostasis in interaction with stressful life events. To further explore the role of TPH isoforms, Tph1 and Tph2 expression was studied in the raphe nuclei of Sert deficient mice under normal conditions as well as following exposure to acute immobilization stress. Interestingly, no statistically significant changes in expression were detected. Moreover, in comparison to Tph2, no relevant Tph1 expression was detected in the brain independent from genotype, gender and treatment confirming expression in data from native animals. Raphe neurons of a brain-specific Tph2 conditional knockout (cKO) model were completely devoid of Tph2-positive neurons and consequently 5-HT in the brain, with no compensatory activation of Tph1 expression. In addition, a time-specific Tph2 inducible (i) KO mouse provides a brain-specific knockdown model during adult life, resulting in a highly reduced number of Tph2-positive cells and 5-HT in the brain. Intriguingly, expression studies detected no obvious alteration in expression of 5-HT system-associated genes in these brain-specific Tph2 knockout and knockdown models. The findings on the one hand confirm the specificity of Tph2 in brain 5-HT synthesis across the lifespan and on the other hand indicate that neither developmental nor adult Tph2-dependent 5-HT synthesis is required for normal formation of the serotonergic system, although Tph1 does not compensate for the lack of 5-HT in the brain of Tph2 KO models. A further aim of this thesis was to investigate the expression of the neuropeptide oxytocin, which is primarily produced in the hypothalamus and released for instance in response to stimulation of 5-HT and selective serotonin reuptake inhibitors (SSRIs). Oxytocin acts as a neuromodulator within the central nervous system (CNS) and is critically involved in mediating pain modulation, anxiolytic-like effects and decrease of stress response, thereby reducing the risk for emotional disorders. In this study, the expression levels of oxytocin in different brain regions of interest (cortex, hippocampus, amygdala, hypothalamus and raphe nuclei) from female and male wildtype (WT) and Sert KO mice with or without exposure to acute immobilization stress were investigated. Results showed significantly higher expression levels of oxytocin in brain regions which are involved in the regulation of emotional stimuli (amygdala and hippocampus) of stressed male WT mice, whereas male Sert KO as well as female WT and Sert KO mice lack these stress-induced changes. These findings are in accordance with the hypothesis of oxytocin being necessary for protection against stress, depressive mood and anxiety but suggest gender-dependent differences. The lack of altered oxytocin expression in Sert KO mice also indicates a modulation of the oxytocin response by the serotonergic system and provides novel research perspectives with respect to altered response of Sert KO mice to stress and anxiety inducing stimuli. N2 - Durch zahlreiche Untersuchungen ist belegt, dass eine gestörte Tryptophan-Hydroxylase (TPH)-abhängige Serotonin (5-HT)-Synthese an einer veränderten emotionalen Reaktion sowie einer veränderten Stress-Antwort beteiligt ist und damit auch in der Ätiologie und Pathogenese psychischer Erkrankungen eine Rolle spielt. Dennoch werden nach wie vor die unterschiedlichen Expressionsmuster der beiden Isoformen TPH1 und TPH2, die für zwei Formen des Schrittmacherenzyms der 5-HT-Synthese kodieren, kontrovers diskutiert. Zentrales Anliegen dieser Arbeit ist daher eine Klärung der TPH1- und TPH2-Expression während der prä- und postnatalen Entwicklung des murinen Gehirns, sowie im adulten humanen Gehirn und in einigen peripheren Organen und der Zirbeldrüse. Durch die Verwendung von vier verschiedenen Methoden (Real time-PCR, In situ-Hybridisierung, Immunhistochemie und Westernblot-Analysen) wurde systematisch die Gewebs- und Isoform-spezifische Expression in Maus und Mensch auf prä- und posttranslationaler Ebene nachgewiesen. TPH2-Expression wurde Spezies-übergreifend in den Raphe-Kernen des Hirnstamms wie auch in Fasern zur Zirbeldrüse und im Gastrointestinaltrakt detektiert. Auch TPH1 konnte in diesen peripheren Organen (die Zirbeldrüse eingeschlossen) nachgewiesen werden, jedoch fand sich keine signifikante TPH1-Expression im Gehirn, weder während der Entwicklung des Maus-Gehirns noch im humanen und murinen adulten Gehirn. Auch durch veränderte Bedingungen wie der Entfernung von Blutzellen aus dem Gewebe oder der Anwendung von akutem Immobilisierungsstress konnte keine Änderung der Expression gemessen werden. Sert Knockout-Mäuse, stellen ein geeignetes Tiermodell für affektive Erkrankungen dar, insbesondere um eine lebenslang veränderte 5-HT-Homöostase in Verbindung mit belastenden Lebensereignissen zu untersuchen. Um die Bedeutung der TPH-Isoformen und deren korrekte Expression weiter zu untersuchen, wurde die Tph1- und Tph2-Expression in den Raphe-Kernen von Sert Knockout (KO)-Mäusen unter normalen Bedingungen und nach akutem Stress getestet. Interessanterweise konnten keine statistisch signifikanten Expressionsänderungen entdeckt werden. Mehr noch, relativ zu Tph2 konnte unabhängig von Behandlung, Geschlecht oder Genotyp keine relevante Tph1-Expression im Gehirn gemessen werden, was wiederum die Expressionsdaten aus nativen Tieren unterstützt. Die Raphe-Neurone eines Gehirn-spezifischen konditionalen Tph2 KO-Modells zeigten weder Tph2-positive Zellen noch 5-HT, wiesen aber auch keine kompensatorische Aktivierung der Tph1-Expression im Gehirn auf. Zusätzlich repräsentiert eine zeit-spezifische, induzierbare KO-Maus ein Gehirn-spezifisches Tph2 Knockdown-Modell ab dem Erwachsenenalter, das eine stark reduzierte Anzahl an Tph2-positiven Zellen und 5-HT im Gehirn aufweist. Expressionsuntersuchungen zeigten interessanterweise, dass diese Gehirn-spezifischen Tph2 Knockout- und Knockdown-Modelle keine sichtliche Änderung in der Expression von 5-HT-System-assoziierten Genen aufweisen. Diese Ergebnisse bestätigen zum einen, dass die 5-HT-Synthese im murinen Gehirn während der kompletten Lebensspanne ausschließlich durch Tph2 katalysiert wird und weisen außerdem darauf hin, dass eine Tph2-abhängige 5-HT-Synthese weder während der Entwicklung noch im Erwachsenalter für die Ausbildung eines normalen serotonergen Systems benötigt wird, obwohl Tph1 den Verlust des 5-HT-Vorkommens im Gehirn der Tph2 KO-Mäuse nicht kompensiert. Weiterhin beschäftigt sich diese Arbeit mit der Expression von Oxytocin, das hauptsächlich im Hypothalamus produziert. Oxytocin ist maßgeblich bei Angst-lösenden Effekten sowie einer verringerten Stressantwort beteiligt. In dieser Studie wurde die Expression von Oxytocin in verschiedenen Gehirnregionen (Cortex, Hippocampus, Amygdala, Hypothalamus und Raphe Nuclei) von weiblichen und männlichen Wildtyp- (WT) und Sert KO-Mäusen getestet, die entweder unter normalen Bedingungen gehalten wurden oder eine Stunde lang akutem Immobilisierungsstress ausgesetzt waren. Die Ergebnisse zeigten eine signifikant höhere Oxytocin-Expression in Gehirnregionen, die für die emotionale Reizverarbeitung zuständig sind (Amygdala und Hippocampus) in gestressten männlichen WT-Mäusen, während männliche Sert KO-Mäuse sowie weibliche WT- und Sert KO-Mäuse diese Stress-bedingten Unterschiede nicht aufwiesen. Diese Befunde sind im Einklang mit der Hypothese, dass Oxytocin eine schützende Rolle bei Stress, depressiver Stimmung und Angst übernimmt, weisen jedoch auf einen Geschlechterunterschied hin. Ferner legt das Fehlen einer veränderten Oxytocin-Expression in Sert KO-Mäusen eine Modulation der Oxytocin-Expression durch das serotonerge System nahe, was neue Forschungsperspektiven über eine veränderte Reaktion auf Stress und Angst-auslösende Reize in Sert KO-Mäusen eröffnet. KW - Serotonin KW - Neurotransmitter KW - Chemische Synthese KW - Stress KW - Enzym KW - Genexpression KW - Maus KW - serotonin KW - mouse KW - acute stress KW - gene expression KW - enzymatic synthesis Y1 - 2009 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-40839 ER - TY - JOUR A1 - Hamann, Catharina S. A1 - Bankmann, Julian A1 - Mora Maza, Hanna A1 - Kornhuber, Johannes A1 - Zoicas, Iulia A1 - Schmitt-Böhrer, Angelika T1 - Social fear affects limbic system neuronal activity and gene expression JF - International Journal of Molecular Sciences N2 - Social anxiety disorder (SAD) is a highly prevalent and comorbid anxiety disorder with rather unclear underlying mechanisms. Here, we aimed to characterize neurobiological changes occurring in mice expressing symptoms of social fear and to identify possible therapeutic targets for SAD. Social fear was induced via social fear conditioning (SFC), a validated animal model of SAD. We assessed the expression levels of the immediate early genes (IEGs) cFos, Fosl2 and Arc as markers of neuronal activity and the expression levels of several genes of the GABAergic, serotoninergic, oxytocinergic, vasopressinergic and neuropeptide Y (NPY)-ergic systems in brain regions involved in social behavior or fear-related behavior in SFC+ and SFC− mice 2 h after exposure to a conspecific. SFC+ mice showed a decreased number and density of cFos-positive cells and decreased expression levels of IEGs in the dorsal hippocampus. SFC+ mice also showed alterations in the expression of NPY and serotonin system-related genes in the paraventricular nucleus of the hypothalamus, basolateral amygdala, septum and dorsal raphe nucleus, but not in the dorsal hippocampus. Our results describe neuronal alterations occurring during the expression of social fear and identify the NPY and serotonergic systems as possible targets in the treatment of SAD. KW - social anxiety KW - fear expression KW - social avoidance KW - gene expression KW - Npy KW - Npyr1 KW - Npyr2 KW - Htr1a KW - Htr2a KW - Htr2c Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284274 SN - 1422-0067 VL - 23 IS - 15 ER -