@article{UeceylerSchliesserEvdokimovetal.2022, author = {{\"U}{\c{c}}eyler, Nurcan and Schließer, Mira and Evdokimov, Dimitar and Radziwon, Jakub and Feulner, Betty and Unterecker, Stefan and Rimmele, Florian and Walter, Uwe}, title = {Reduced midbrain raphe echogenicity in patients with fibromyalgia syndrome}, series = {PloS One}, volume = {17}, journal = {PloS One}, number = {11}, doi = {10.1371/journal.pone.0277316}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300639}, year = {2022}, abstract = {Objectives The pathogenesis of fibromyalgia syndrome (FMS) is unclear. Transcranial ultrasonography revealed anechoic alteration of midbrain raphe in depression and anxiety disorders, suggesting affection of the central serotonergic system. Here, we assessed midbrain raphe echogenicity in FMS. Methods Sixty-six patients underwent transcranial sonography, of whom 53 were patients with FMS (27 women, 26 men), 13 patients with major depression and physical pain (all women), and 14 healthy controls (11 women, 3 men). Raphe echogenicity was graded visually as normal or hypoechogenic, and quantified by digitized image analysis, each by investigators blinded to the clinical diagnosis. Results Quantitative midbrain raphe echogenicity was lower in patients with FMS compared to healthy controls (p<0.05), but not different from that of patients with depression and accompanying physical pain. Pain and FMS symptom burden did not correlate with midbrain raphe echogenicity as well as the presence and severity of depressive symptoms. Conclusion We found reduced echogenicity of the midbrain raphe area in patients with FMS and in patients with depression and physical pain, independent of the presence or severity of pain, FMS, and depressive symptoms. Further exploration of this sonographic finding is necessary before this objective technique may enter diagnostic algorithms in FMS and depression.}, language = {en} } @article{UeceylerKewenigKittelSchneideretal.2015, author = {{\"U}{\c{c}}eyler, Nurcan and Kewenig, Susanne and Kittel-Schneider, Sarah and Fallgatter, Andreas J. and Sommer, Claudia}, title = {Increased cortical activation upon painful stimulation in fibromyalgia syndrome}, series = {BMC Neurology}, volume = {15}, journal = {BMC Neurology}, number = {210}, doi = {10.1186/s12883-015-0472-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125230}, year = {2015}, abstract = {Background Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread pain and associated symptoms. We investigated cerebral activation in FMS patients by functional near-infrared spectroscopy (fNIRS). Methods Two stimulation paradigms were applied: a) painful pressure stimulation at the dorsal forearm; b) verbal fluency test (VFT). We prospectively recruited 25 FMS patients, ten patients with unipolar major depression (MD) without pain, and 35 healthy controls. All patients underwent neurological examination and all subjects were investigated with questionnaires (pain, depression, FMS, empathy). Results FMS patients had lower pressure pain thresholds than patients with MD and controls (p < 0.001) and reported higher pain intensity (p < 0.001). Upon unilateral pressure pain stimulation fNIRS recordings revealed increased bilateral cortical activation in FMS patients compared to controls (p < 0.05). FMS patients also displayed a stronger contralateral activity over the dorsolateral prefrontal cortex in direct comparison to patients with MD (p < 0.05). While all three groups performed equally well in the VFT, a frontal deficit in cortical activation was only found in patients with depression (p < 0.05). Performance and cortical activation correlated negatively in FMS patients (p < 0.05) and positively in patients with MD (p < 0.05). Conclusion Our data give further evidence for altered central nervous processing in patients with FMS and the distinction between FMS and MD.}, language = {en} } @article{ZetzlRennerPittigetal.2021, author = {Zetzl, Teresa and Renner, Agnes and Pittig, Andre and Jentschke, Elisabeth and Roch, Carmen and van Oorschot, Birgitt}, title = {Yoga effectively reduces fatigue and symptoms of depression in patients with different types of cancer}, series = {Supportive Care in Cancer}, volume = {29}, journal = {Supportive Care in Cancer}, issn = {0941-4355}, doi = {10.1007/s00520-020-05794-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235415}, pages = {2973-2982}, year = {2021}, abstract = {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}, language = {en} } @article{ZechScherfClavelDanielsetal.2021, author = {Zech, Linda D. and Scherf-Clavel, Maike and Daniels, Christine and Schwab, Michael and Deckert, J{\"u}rgen and Unterecker, Stefan and Herr, Alexandra S.}, title = {Patients with higher vitamin D levels show stronger improvement of self-reported depressive symptoms in psychogeriatric day-care setting}, series = {Journal of Neural Transmission}, volume = {128}, journal = {Journal of Neural Transmission}, number = {8}, issn = {1435-1463}, doi = {10.1007/s00702-021-02385-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268525}, pages = {1233-1238}, year = {2021}, abstract = {Depression is a common psychiatric disorder among geriatric patients that decreases the quality of life and increases morbidity and mortality. Vitamin D as a neuro-steroid hormone might play a role in the onset and treatment of depression. In the present study, the association between depressive symptoms and vitamin D concentration in serum was evaluated. 140 patients of a psychogeriatric day-care unit were included. The geriatric depression scale (GDS) and the Hamilton depression rating scale (HDRS) were assessed at the beginning and end of treatment, GDS scores additionally 6 weeks after discharge from the day-care unit. Vitamin D levels were measured at the beginning of the treatment, routinely. Patients with levels below 30 µg/L were treated with 1000 IU vitamin D per day. There was no association between the severity of depressive symptoms and the concentration of vitamin D at the beginning of the treatment. Patients with higher vitamin D levels showed a stronger decline of depressive symptoms measured by the GDS during their stay in the day-care unit. We provide evidence that vitamin D serum levels might influence antidepressant therapy response in a geriatric population. Prospective studies are necessary to determine which patients may profit from add-on vitamin D therapy.}, language = {en} } @phdthesis{Zech2021, author = {Zech, Linda}, title = {Vitamin-D-Status und depressive Symptome bei gerontopsychiatrischen Patienten}, doi = {10.25972/OPUS-25074}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250745}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {In der vorliegenden Studie wurde der Zusammenhang des depressiven Syndroms mit dem Vitamin D-Spiegel an einer Stichprobe gerontopsychiatrischer Patienten (n = 140) der Neurogerontopsychiatrischen Tagesklinik W{\"u}rzburg untersucht. Die Depressivit{\"a}t der Patienten zu Beginn und im Verlauf der Behandlung wurde zum einen mittels der ICD-10-Klassifikation, zum anderen mittels des Scores auf der GDS- und Hamilton-Skala zu Beginn und Ende des Aufenthalts in der Tagesklinik sowie bei einer poststation{\"a}ren Kontrolle bestimmt. Der Vitamin D-Spiegel wurde bei Behandlungsbeginn bestimmt und im Falle eines Mangels 1000 IU Vitamin D am Tag oral substituiert. Hierbei zeigte sich kein Zusammenhang zwischen der Auspr{\"a}gung des depressiven Syndroms und dem Vitamin D-Spiegel zu Beginn der Behandlung. Dagegen stellte sich heraus, dass Patienten mit einem h{\"o}heren Spiegel eine deutlichere Verbesserung der depressiven Symptome auf der GDS im Verlauf der Behandlung erfuhren. Außerdem bestand eine signifikante negative Korrelation zwischen BMI und Vitamin D-Spiegel sowie eine Abh{\"a}ngigkeit der Spiegelh{\"o}he von der Jahreszeit. Vitamin D k{\"o}nnte nach den Ergebnissen dieser Studie m{\"o}glicherweise eine wirkungssteigernde und nebenwirkungsarme Komedikation in der antidepressiven Therapie von {\"a}lteren psychisch erkrankten Menschen darstellen. Es bedarf weiterer ausf{\"u}hrlicher Forschung {\"u}ber den neurophysiologischen Zusammenhang zwischen Vitamin D und der Schwere einer depressiven Erkrankung. Besonders hinsichtlich der Verwendung von Vitamin D als Komedikation gilt es, weitere intensive Forschung in Form von gut designten, randomisierten Fall-Kontroll-Studien und prospektiven Interventionsstudien zu betreiben, um die Therapie von depressiven Patienten im h{\"o}heren Lebensalter weiter zu verbessern.}, subject = {Altersdepression}, language = {de} } @article{WernerKobayashiJavadietal.2018, author = {Werner, Rudolf A. and Kobayashi, Ryohei and Javadi, Mehrbod Som and K{\"o}ck, Zoe and Wakabayashi, Hiroshi and Unterecker, Stefan and Nakajima, Kenichi and Lapa, Constantin and Menke, Andreas and Higuchi, Takahiro}, title = {Impact of Novel Antidepressants on Cardiac Metaiodobenzylguanidine (mIBG) Uptake: Experimental Studies in SK-N-SH Cells and Healthy Rabbits}, series = {Journal of Nuclear Medicine}, journal = {Journal of Nuclear Medicine}, issn = {0161-5505}, doi = {10.2967/jnumed.117.206045}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161280}, year = {2018}, abstract = {Background: \(^{123}\)I-metaiodobenzylguanidine (mIBG) provides independent prognostic value for risk stratification among heart failure patients, but the use of concomitant medication should not impact its quantitative information. We aimed to evaluate the four most-prescribed antidepressants currently used as a first‑line treatment for patients with major depressive disorder (MDD) and their potential on altering mIBG imaging results. Methods: The inhibition effect of four different types of antidepressants (desipramine, escitalopram, venlafaxine and bupropion) for MDD treatment on \(^{131}\)I-mIBG uptake was assessed by in-vitro cell uptake assays using human neuroblastoma SK-N-SH cells. The half maximal inhibitory concentration (IC50) of tracer uptake was determined from dose-response curves. To evaluate the effects of IV pretreatment with desipramine (1.5 mg/kg) and escitalopram (2.5, 15 mg/kg) on mIBG cardiac uptake, in-vivo planar 123I-mIBG scans in healthy New Zealand White Rabbits were conducted. Results: The IC50 values of desipramine, escitalopram, venlafaxine and bupropion on \(^{131}\)I-mIBG cellular uptake were 11.9 nM, 7.5 μM, 4.92 μM, and 12.9 μM, respectively. At the maximum serum concentration (Cmax, as derived by previous clinical trials), the inhibition rates of 131I-mIBG uptake were 90.6 \% for desipramine, 25.5 \% for venlafaxine, 11.7 \% for bupropion and 0.72 \% for escitalopram. A low inhibition rate for escitalopram in the cell uptake study triggered investigation of an in-vivo rabbit model: with dosage considerably higher than clinical practice, the non-inhibitory effect of escitalopram was confirmed. Furthermore, pretreatment with desipramine led to a marked reduction of cardiac 123I-mIBG uptake. Conclusions: In the present in-vitro binding assay and in-vivo rabbit study, the selective-serotonin reuptake inhibitor escitalopram had no major impact on neuronal cardiac mIBG uptake within therapeutic dose ranges, while other types of first-line antidepressants for MDD treatment led to a significant decrease. These preliminary results warrant further confirmatory clinical trials regarding the reliability of cardiac mIBG imaging, in particular, if the patient's neuropsychiatric status would not tolerate withdrawal of a potentially norepinephrine interfering antidepressant.}, subject = {Antidepressants}, language = {en} } @article{WeissGruendahlDeckertetal.2023, author = {Weiß, Martin and Gr{\"u}ndahl, Marthe and Deckert, J{\"u}rgen and Eichner, Felizitas A. and Kohls, Mirjam and St{\"o}rk, Stefan and Heuschmann, Peter U. and Hein, Grit}, title = {Differential network interactions between psychosocial factors, mental health, and health-related quality of life in women and men}, series = {Scientific Reports}, volume = {13}, journal = {Scientific Reports}, organization = {STAAB-COVID Study Group}, doi = {10.1038/s41598-023-38525-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357858}, year = {2023}, abstract = {Psychosocial factors affect mental health and health-related quality of life (HRQL) in a complex manner, yet gender differences in these interactions remain poorly understood. We investigated whether psychosocial factors such as social support and personal and work-related concerns impact mental health and HRQL differentially in women and men during the first year of the COVID-19 pandemic. Between June and October 2020, the first part of a COVID-19-specific program was conducted within the "Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB)" cohort study, a representative age- and gender-stratified sample of the general population of W{\"u}rzburg, Germany. Using psychometric networks, we first established the complex relations between personal social support, personal and work-related concerns, and their interactions with anxiety, depression, and HRQL. Second, we tested for gender differences by comparing expected influence, edge weight differences, and stability of the networks. The network comparison revealed a significant difference in the overall network structure. The male (N = 1370) but not the female network (N = 1520) showed a positive link between work-related concern and anxiety. In both networks, anxiety was the most central variable. These findings provide further evidence that the complex interplay of psychosocial factors with mental health and HRQL decisively depends on gender. Our results are relevant for the development of gender-specific interventions to increase resilience in times of pandemic crisis.}, language = {en} } @article{RiedererterMeulen2020, author = {Riederer, Peter and ter Meulen, Volker}, title = {Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses}, series = {Journal of Neural Transmission}, volume = {127}, journal = {Journal of Neural Transmission}, number = {9}, issn = {0300-9564}, doi = {10.1007/s00702-020-02230-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-314637}, pages = {1217-1228}, year = {2020}, abstract = {While there is abounding literature on virus-induced pathology in general and coronavirus in particular, recent evidence accumulates showing distinct and deleterious brain affection. As the respiratory tract connects to the brain without protection of the blood-brain barrier, SARS-CoV-2 might in the early invasive phase attack the cardiorespiratory centres located in the medulla/pons areas, giving rise to disturbances of respiration and cardiac problems. Furthermore, brainstem regions are at risk to lose their functional integrity. Therefore, long-term neurological as well as psychiatric symptomatology and eventual respective disorders cannot be excluded as evidenced from influenza-A triggered post-encephalitic Parkinsonism and HIV-1 triggered AIDS-dementia complex. From the available evidences for coronavirus-induced brain pathology, this review concludes a number of unmet needs for further research strategies like human postmortem brain analyses. SARS-CoV-2 mirroring experimental animal brain studies, characterization of time-dependent and region-dependent spreading behaviours of coronaviruses, enlightening of pathological mechanisms after coronavirus infection using long-term animal models and clinical observations of patients having had COVID-19 infection are calling to develop both protective strategies and drug discoveries to avoid early and late coronavirus-induced functional brain disturbances, symptoms and eventually disorders. To fight SARS-CoV-2, it is an urgent need to enforce clinical, molecular biological, neurochemical and genetic research including brain-related studies on a worldwide harmonized basis.}, language = {en} } @article{RiedererLaux2011, author = {Riederer, Peter and Laux, Gerd}, title = {MAO-inhibitors in Parkinson's Disease}, series = {Experimental Neurobiology}, volume = {20}, journal = {Experimental Neurobiology}, number = {1}, doi = {10.5607/en.2011.20.1.1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140930}, pages = {1-17}, year = {2011}, abstract = {Monoamine oxidase inhibitors (MAO-I) belong to the earliest drugs tried in Parkinson's disease (PD). They have been used with or without levodopa (L-DOPA). Non-selective MAO-I due to their side-effect/adverse reaction profile, like tranylcypromine have limited use in the treatment of depression in PD, while selective, reversible MAO-A inhibitors are recommended due to their easier clinical handling. For the treatment of akinesia and motor fluctuations selective irreversible MAO-B inhibitors selegiline and rasagiline are recommended. They are safe and well tolerated at the recommended daily doses. Their main differences are related to (1) metabolism, (2) interaction with CYP-enzymes and (3) quantitative properties at the molecular biological/genetic level. Rasagiline is more potent in clinical practise and has a hypothesis driven more favourable side effect/adverse reaction profile due to its metabolism to aminoindan. Both selegiline and rasagiline have a neuroprotective and neurorestaurative potential. A head-to head clinical trial would be of utmost interest from both the clinical outcome and a hypothesis-driven point of view. Selegiline is available as tablet and melting tablet for PD and as transdermal selegiline for depression, while rasagiline is marketed as tablet for PD. In general, the clinical use of MAO-I nowadays is underestimated. There should be more efforts to evaluate their clinical potency as antidepressants and antidementive drugs in addition to the final proof of their disease-modifying potential. In line with this are recent innovative developments of MAO-I plus inhibition of acetylcholine esterase for Alzheimer's disease as well as combined MAO-I and iron chelation for PD.}, language = {en} } @article{PoppSchmittBoehrerLangeretal.2021, author = {Popp, Sandy and Schmitt-B{\"o}hrer, Angelika and Langer, Simon and Hofmann, Ulrich and Hommers, Leif and Schuh, Kai and Frantz, Stefan and Lesch, Klaus-Peter and Frey, Anna}, title = {5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction}, series = {Journal of Clinical Medicine}, volume = {10}, journal = {Journal of Clinical Medicine}, number = {14}, issn = {2077-0383}, doi = {10.3390/jcm10143104}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242739}, year = {2021}, abstract = {Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation of experimentally na{\"i}ve male mice revealed a mild cardiac dysfunction in ≥4-month-old 5-HTT knockout (-/-) animals. Following induction of chronic cardiac dysfunction (CCD) by MI vs. sham operation 5-HTT-/- mice with infarct sizes >30\% experienced 100\% mortality, while 50\% of 5-HTT+/- and 37\% of 5-HTT+/+ animals with large MI survived the 8-week observation period. Surviving (sham and MI < 30\%) 5-HTT-/- mutants displayed reduced exploratory activity and increased anxiety-like behavior in different approach-avoidance tasks. However, CCD failed to provoke a depressive-like behavioral response in either 5-Htt genotype. Mechanistic analyses were performed on mice 3 days post-MI. Electrocardiography, histology and FACS of inflammatory cells revealed no abnormalities. However, gene expression of inflammation-related cytokines (TGF-β, TNF-α, IL-6) and MMP-2, a protein involved in the breakdown of extracellular matrix, was significantly increased in 5-HTT-/- mice after MI. This study shows that 5-HTT deficiency leads to age-dependent cardiac dysfunction and disrupted early healing after MI probably due to alterations of inflammatory processes in mice.}, language = {en} } @article{MerglKoburgerHeinrichsetal.2015, author = {Mergl, Roland and Koburger, Nicole and Heinrichs, Katherina and Sz{\´e}kely, Andr{\´a}s and T{\´o}th, M{\´o}nika Ditta and Coyne, James and Quint{\~a}o, S{\´o}nia and Arensman, Ella and Coffey, Claire and Maxwell, Margaret and V{\"a}rnik, Airi and van Audenhove, Chantal and McDaid, David and Sarchiapone, Marco and Schmidtke, Armin and Genz, Axel and Gusm{\~a}o, Ricardo and Hegerl, Ulrich}, title = {What Are Reasons for the Large Gender Differences in the Lethality of Suicidal Acts? An Epidemiological Analysis in Four European Countries}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {7}, doi = {10.1371/journal.pone.0129062}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151547}, pages = {e0129062}, year = {2015}, abstract = {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.}, language = {en} } @article{Menke2019, author = {Menke, Andreas}, title = {Is the HPA axis as target for depression outdated, or is there a new hope?}, series = {Frontiers in Psychiatry}, volume = {10}, journal = {Frontiers in Psychiatry}, number = {101}, issn = {1664-0640}, doi = {10.3389/fpsyt.2019.00101}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195780}, year = {2019}, abstract = {Major depressive disorder (MDD) is a very common stress-related mental disorder that carries a huge burden for affected patients and the society. It is associated with a high mortality that derives from suicidality and the development of serious medical conditions such as heart diseases, diabetes, and stroke. Although a range of effective antidepressants are available, more than 50\% of the patients do not respond to the first treatment they are prescribed and around 30\% fail to respond even after several treatment attempts. The heterogeneous condition of MDD, the lack of biomarkers matching patients with the right treatments and the situation that almost all available drugs are only targeting the serotonin, norepinephrine, or dopamine signaling, without regulating other potentially dysregulated systems may explain the insufficient treatment status. The hypothalamic-pituitary-adrenal (HPA) axis is one of these other systems, there is numerous and robust evidence that it is implicated in MDD and other stress-related conditions, but up to date there is no specific drug targeting HPA axis components that is approved and no test that is routinely used in the clinical setting identifying patients for such a specific treatment. Is there still hope after these many years for a breakthrough of agents targeting the HPA axis? This review will cover tests detecting altered HPA axis function and the specific treatment options such as glucocorticoid receptor (GR) antagonists, corticotropin-releasing hormone 1 (CRH1) receptor antagonists, tryptophan 2,3-dioxygenase (TDO) inhibitors and FK506 binding protein 5 (FKBP5) receptor antagonists.}, language = {en} } @phdthesis{Lamprecht2006, author = {Lamprecht, Thorsten}, title = {Die NoGo-Anteriorisierung (NGA) im Verlauf einer Depression und ihr Wert als eventueller Pr{\"a}diktor f{\"u}r einen Behandlungserfolg}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-16679}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2006}, abstract = {Depressionen sind Erkrankungen, die mit vielf{\"a}ltigen pathophysiologischen Ver{\"a}nderungen einhergehen. So konnte mit Hilfe der funktionellen Bildgebung unter anderem eine verringerte Aktivit{\"a}t im dorsolateralen und dorsomedialen Pr{\"a}frontalkortex und im anterioren Cingulum (ACC) festgestellt werden. Dabei zeigen depressive Patienten, die im rostralen ACC (Brodmann-Areal 24) hypermetabolisch waren, ein besseres Therapieansprechen als in diesem Areal hypometabolische Personen. Da der ACC maßgeblich f{\"u}r die Generierung des elektrophysiologischen Ph{\"a}nomens der NoGo-Anteriorisierung (NGA) verantwortlich ist, k{\"o}nnte diese ein Marker f{\"u}r ein eventuelles Therapieansprechen sein. Dies wurde an 28 depressiven Patienten getestet, indem bei ihnen bei station{\"a}rer Aufnahme und nach Teilremission der depressiven Symptomatik die NGA bestimmt wurde. Hierbei konnte keine positive Korrelation zwischen initialer NGA und Depressivit{\"a}tsverbesserung, gemessen mittels HamD und BDI, nachgewiesen werden. Insofern scheint die NGA als elektrophysiologischer Marker kein geeigneter Parameter f{\"u}r die Vorhersagbarkeit eines Therapieansprechens im Rahmen einer depressiven Erkrankung zu sein.}, language = {de} } @phdthesis{Kaese2011, author = {K{\"a}se, Mirjam}, title = {Transkranielle Theta Burst Behandlung depressiver Patienten: Untersuchung der Wirkung auf evozierte Potentiale in einem Oddball Paradigma}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69314}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {Ziel der vorliegenden Arbeit war es die Wirksamkeit einer Behandlung mit Transkranieller Magnetstimulation bei depressiven Patienten zu untersuchen. Der Behandlungserfolg wurde mit depressionsspezfischen Frageb{\"o}gen, der Testleistung in einer kognitiven Aufgabe und ereigniskorrelierten Potentialen im EEG objektiviert. Es konnte nicht abschließend gekl{\"a}rt werden, ob die Theta-Burst-Stimulation in der Therapie depressiver Patienten geeignet ist. Es fanden sich allerdings Hinweise darauf, dass die pr{\"a}frontal applizierte Behandlung Ver{\"a}nderungen in den frontal generierten ereigniskorrelierten Potentialen bewirkte.}, subject = {Chronische Depression}, language = {de} } @article{KittelSchneiderKenisScheketal.2012, author = {Kittel-Schneider, Sarah and Kenis, Gunter and Schek, Julia and van den Hove, Daniel and Prickaerts, Jos and Lesch, Klaus-Peter and Steinbusch, Harry and Reif, Andreas}, title = {Expression of monoamine transporters, nitric oxide synthase 3, and neurotrophin genes in antidepressant-stimulated astrocytes}, series = {Frontiers in Psychiatry}, volume = {3}, journal = {Frontiers in Psychiatry}, doi = {10.3389/fpsyt.2012.00033}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123627}, pages = {33}, year = {2012}, abstract = {Background: There is increasing evidence that glial cells play a role in the pathomechanisms of mood disorders and the mode of action of antidepressant drugs. Methods: To examine whether there is a direct effect on the expression of different genes encoding proteins that have been implicated in the pathophysiology of affective disorders, primary astrocyte cell cultures from rats were treated with two different antidepressant drugs, imipramine and escitalopram, and the RNA expression of brain-derived neurotrophic factor (Bdnf), serotonin transporter (5Htt), dopamine transporter (Dat), and endothelial nitric oxide synthase (Nos3) was examined. Results: Stimulation of astroglial cell culture with imipramine, a tricyclic antidepressant, led to a significant increase of the Bdnf RNA level whereas treatment with escitalopram did not. In contrast, 5Htt was not differentially expressed after antidepressant treatment. Finally, neither Dat nor Nos3 RNA expression was detected in cultured astrocytes. Conclusion: These data provide further evidence for a role of astroglial cells in the molecular mechanisms of action of antidepressants.}, language = {en} } @article{KittelSchneiderFeliceBuhagiaretal.2022, author = {Kittel-Schneider, Sarah and Felice, Ethel and Buhagiar, Rachel and Lambregtse-van den Berg, Mijke and Wilson, Claire A. and Banjac Baljak, Visnja and Vujovic, Katarina Savic and Medic, Branislava and Opankovic, Ana and Fonseca, Ana and Lupattelli, Angela}, title = {Treatment of peripartum depression with antidepressants and other psychotropic medications: a synthesis of clinical practice guidelines in Europe}, series = {International Journal of Environmental Research and Public Health}, volume = {19}, journal = {International Journal of Environmental Research and Public Health}, number = {4}, issn = {1660-4601}, doi = {10.3390/ijerph19041973}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262130}, year = {2022}, abstract = {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.}, language = {en} } @article{KingslakeDiasDawsonetal.2017, author = {Kingslake, Jonathan and Dias, Rebecca and Dawson, Gerard R. and Simon, Judit and Goodwin, Guy M. and Harmer, Catherine J. and Morriss, Richard and Brown, Susan and Guo, Boliang and Dourish, Colin T. and Ruh{\´e}, Henricus G. and Lever, Anne G. and Veltman, Dick J. and van Schaik, Anneke and Deckert, J{\"u}rgen and Reif, Andreas and St{\"a}blein, Michael and Menke, Andreas and Gorwood, Philip and Voegeli, G{\´e}raldine and Perez, Victor and Browning, Michael}, title = {The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial}, series = {Trials}, volume = {18}, journal = {Trials}, doi = {10.1186/s13063-017-2247-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173012}, year = {2017}, abstract = {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.}, language = {en} } @phdthesis{Jay2010, author = {Jay, Johanna Tharsilla}, title = {Pr{\"a}frontale Hirnoxygenierung w{\"a}hrend einer Aufgabe zum Arbeitsged{\"a}chtnis bei Patienten mit einer unipolaren Depression}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-51554}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2010}, abstract = {Patienten mit Depression zeigen typischerweise eine Beeintr{\"a}chtigung kognitiver Funktionen, vor allem im Bereich der exekutiven Funktionen. Als neuroanatomisches Korrelat konnte den exekutiven Funktionen der pr{\"a}frontale Kortex zugeordnet werden. In den bisherigen bildgebenden Untersuchungen bei depressiven Patienten konnte vor allem eine Hypofrontalit{\"a}t festgestellt werden. Durch verschiedene neuropsychologische Tests konnten kognitive Defizite vor allem im visuell-r{\"a}umlichen Arbeitsged{\"a}chtnis gezeigt werden. Als neuroanatomisches Korrelat konnte dem Arbeitsged{\"a}chtnis der DLPFC zugeordnet werden. Die bisher durchgef{\"u}hrten kombinierten Untersuchungen bei depressiven Patienten lieferten jedoch keine einheitlichen Ergebnisse. Mittelpunkt unserer Untersuchung war es deshalb mittels NIRS w{\"a}hrend der Durchf{\"u}hrung eines Tests f{\"u}r das visuell-r{\"a}umliche und das objektbezogene Arbeitsged{\"a}chtnis sowohl bei einer Patientengruppe mit unipolarer Depression als auch bei einer gesunden Kontrollgruppe die Aktivierungsmuster des pr{\"a}frontalen Kortex zu ermitteln. F{\"u}r den Zusammenhang zwischen der Hirnaktivierung und der Schwere der depressiven Erkrankung konnten keine signifikanten Korrelationen gezeigt werden. Dies spricht gegen den „state"-Charakter und f{\"u}r den „trait"-Charakter der Hypofrontalit{\"a}t bei einer depressiven Erkrankung. Die bez{\"u}glich der Verhaltensdaten gerechneten Varianzanalysen zeigten eine deutliche Schwierigkeitsabstufung zwischen den drei Bedingungen (OWM>VWM>KON). Der fehlende Interaktionseffekt Gruppe x Bedingung, also eine h{\"o}here Reaktionszeit der Patienten w{\"a}hrend allen Aufgaben und nicht nur w{\"a}hrend OWM und VWM deutet auf eine allgemeine Verlangsamung im Sinne einer psychomotorischen Verlangsamung hin und nicht wie erwartet auf ein besonderes Defizit im Bereich kognitiver Funktionen. Interaktionseffekte bei den bildgebenden Daten bei gleichzeitig fehlenden Interaktionsnachweisen bei den Verhaltensdaten deuten an, dass die funktionellen Daten unabh{\"a}ngig von den Verhaltensdaten interpretiert werden k{\"o}nnen. Ein kognitives Defizit f{\"u}r beide Komponenten des visuell-r{\"a}umlichen Arbeitsged{\"a}chtnisses bei Patienten mit einer depressiven Erkrankung zeigt sich in unserer Untersuchung also weniger {\"u}ber die Verhaltensdaten als vielmehr {\"u}ber die verminderte Hirnaktivierung w{\"a}hrend OWM und VWM. Im Gruppenvergleich konnte in den ROI-Analysen f{\"u}r OWM und VWM wie erwartet ein spezieller Arbeitsged{\"a}chtniseffekt gezeigt werden, also eine h{\"o}here Aktivierung der Kontrollgruppe speziell f{\"u}r die Arbeitsged{\"a}chtnisaufgaben. Es wurde also insgesamt in unserer Untersuchung eine pr{\"a}frontale Hypoaktivierung bei Patienten mit einer depressiven Erkrankung festgestellt.}, subject = {Depression}, language = {de} } @article{HarrisMaxwellO'Connoretal.2013, author = {Harris, Fiona M. and Maxwell, Margaret and O'Connor, Rory C. and Coyne, James and Arensman, Ella and Andr{\´a}s, Sz{\´e}kely and Gusm{\~a}o, Ricardo and Coffey, Claire and Costa, Susana and Zoltan, Cserh{\´a}ti and Koburger, Nicole and van Audenhove, Chantal and McDaid, David and Maloney, Julia and V{\"a}rnik, Peeter and Hegerl, Ulrich}, title = {Developing social capital in implementing a complex intervention: a process evaluation of the early implementation of a suicide prevention intervention in four European countries}, series = {BMC Public Health}, volume = {13}, journal = {BMC Public Health}, number = {158}, doi = {10.1186/1471-2458-13-158}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122117}, year = {2013}, abstract = {Background: Variation in the implementation of complex multilevel interventions can impact on their delivery and outcomes. Few suicide prevention interventions, especially multilevel interventions, have included evaluation of both the process of implementation as well as outcomes. Such evaluation is essential for the replication of interventions, for interpreting and understanding outcomes, and for improving implementation science. This paper reports on a process evaluation of the early implementation stage of an optimised suicide prevention programme (OSPI-Europe) implemented in four European countries. Methods: The process analysis was conducted within the framework of a realist evaluation methodology, and involved case studies of the process of implementation in four European countries. Datasets include: repeated questionnaires to track progress of implementation including delivery of individual activities and their intensity; serial interviews and focus groups with stakeholder groups; and detailed observations at OSPI implementation team meetings. Results: Analysis of local contexts in each of the four countries revealed that the advisory group was a key mechanism that had a substantial impact on the ease of implementation of OSPI interventions, particularly on their ability to recruit to training interventions. However, simply recruiting representatives of key organisations into an advisory group is not sufficient to achieve impact on the delivery of interventions. In order to maximise the potential of high level 'gatekeepers', it is necessary to first transform them into OSPI stakeholders. Motivations for OSPI participation as a stakeholder included: personal affinity with the shared goals and target groups within OSPI; the complementary and participatory nature of OSPI that adds value to pre-existing suicide prevention initiatives; and reciprocal reward for participants through access to the extended network capacity that organisations could accrue for themselves and their organisations from participation in OSPI. Conclusions: Exploring the role of advisory groups and the meaning of participation for these participants revealed some key areas for best practice in implementation: careful planning of the composition of the advisory group to access target groups; the importance of establishing common goals; the importance of acknowledging and complementing existing experience and activity; and facilitating an equivalence of benefit from network participation.}, language = {en} } @phdthesis{Goetzelmann2018, author = {G{\"o}tzelmann, Moritz}, title = {Einfluss der aurikul{\"a}ren Vagusnervstimulation auf affektive Parameter bei depressiven Patienten}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159081}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Hintergrund und Ziele: Das Krankheitsbild der Depression geh{\"o}rt zu den h{\"a}ufigsten psychischen Erkrankungen. Als Therapieoptionen stehen in erster Linie Antidepressiva der verschiedensten Klassen und unterschiedliche Formen der Psychotherapie zur Verf{\"u}gung (M{\"o}ller, Laux et al. 2015). Trotz allem gibt es jedoch immer wieder Patienten, die trotz intensiver Therapiebem{\"u}hungen keine Besserung zeigen. Neben der Elektrokonvulsions-therapie (EKT) als Gold-Standard bietet hier die Vagusnervstimulation (VNS) in vielen L{\"a}ndern bereits ein zugelassenes Verfahren zur Behandlung sogenannter therapie-refrakt{\"a}rer Depressionen. Das Problem besteht allerdings im Verlauf des N. vagus, da dieser im Halsbereich nur schwer in einem operativen Verfahren zug{\"a}nglich ist und er hier mit anderen lebenswichtigen Strukturen gemeinsam verl{\"a}uft (Benninghoff, Drenckhahn et al. 2008). Dies macht eine Therapie nicht ganz ungef{\"a}hrlich. Allerdings gibt der N. vagus einen Hautast ab, der Teile des {\"a}ußeren Geh{\"o}rganges (insbesondere den Tragus), sensibel versorgt. Im Jahr 2000 schlug Ventureyra erstmals die M{\"o}glichkeit vor, diesen Ramus auricularis n. vagi als alternativen Zugangsweg zum Hals zu nutzen (Ventureyra 2000). Wenig sp{\"a}ter gelang es Fallgatter und Kollegen erstmals, durch elektrische Stimulation in diesem Innervationsgebiet somatosensibel evozierte Potentiale des N. vagus (VSEP) an der Sch{\"a}delkalotte abzuleiten (Fallgatter, Neuhauser et al. 2003). Hierbei konnte in Einzelf{\"a}llen gezeigt werden, dass nur an dieser Stelle diese Potentiale evoziert werden k{\"o}nnen, nicht jedoch an anderen Stellen des Ohres, die gr{\"o}ßtenteils vom N. trigeminus innerviert werden (Benninghoff, Drenckhahn et al. 2008). Dieser Vorbefund sollte in dieser Studie in einer Subgruppenanalyse an 10 Probanden {\"u}berpr{\"u}ft werden. Dar{\"u}ber hinaus stellte sich die Frage, ob durch transkutane Stimulation des Hautastes eine {\"a}hnliche gute klinische Verbesserung bei Depressionen wie bei konventioneller VNS, m{\"o}glich ist. Ziel dieser Studie war es zu untersuchen, ob {\"u}ber diesen alternativen Zugangsweg der VNS am Ohr positive Effekte auf affektive Parameter {\"a}hnlich denen der konventionellen VNS bei depressiven Patienten zu erzielen sind. Die Hypothese dabei lautete, dass nach der VNS ein stimmungsaufhellender Effekt zu sehen ist, w{\"a}hrend man bei der ausschließlichen Stimulation des N. trigeminus an den {\"u}brigen Stellen des Ohres keinen antidepressiven Effekt sieht. F{\"u}r viele Patienten w{\"a}re es eine Erleichterung, wenn man k{\"u}nftig die M{\"o}glichkeit einer einfachen Therapieform zur unterst{\"u}tzenden Behandlung von therapierefrakt{\"a}ren Depressionen h{\"a}tte. Methoden: Hierzu wurden 50 Patienten aus der Universit{\"a}tsklinik f{\"u}r Psychiatrie, Psychosomatik und Psychotherapie des Universit{\"a}tsklinikums W{\"u}rzburg, die unter unipolarer oder bipolarer Depressionen leiden rekrutiert. Jeder Patient wurde jeweils 20 Minuten sowohl im Innervationsgebiet des Vagus als auch an einer Stelle, welche rein vom Trigeminus innerviert wird, stimuliert. Die Reihenfolge der Stimulation erfolgte randomisiert, so dass der Patient nicht wusste, welche Stimulation er als erstes erh{\"a}lt. Jeweils vor und nach jeder Stimulation wurde der Proband mittels visueller Analogskala bez{\"u}glich affektiver Parameter befragt. 30 Patienten wurden kontinuierlich {\"u}ber 20 Minuten stimuliert, w{\"a}hrend 20 Patienten pulsatil dergestalt stimuliert wurden, dass immer nach 5 Minuten eine Stimulationspause von 30 Sekunden folgte, damit wieder ein neuer Reiz gesetzt werden konnte. Bei 10 Patienten wurden zus{\"a}tzlich noch evozierte Potentiale sowohl bei transkutaner Vagusnervstimulation, als auch bei Kontrollstimulation im Innervationsgebiet des N. trigeminus, abgeleitet. Ergebnisse und Beobachtungen: Zusammenfassend kann man sagen, w{\"a}hrend sich unter kontinuierlichen Stimulationsbedingungen keine signifikanten Ergebnisse zeigten, f{\"u}hlten sich die Probanden unter pulsatilen Stimulationsbedingungen nach der Versuchsstimulation signifikant fr{\"o}hlicher (t(38)= 5,24; p< 0,001), optimistischer (t(38)= 3,28; p= 0,002) und sch{\"a}tzten ihr allgemeines Empfinden danach besser ein (t(38)= 3,50; p= 0,001). Daher ist in k{\"u}nftigen Studien die pulsatile Stimulationsart der kontinuierlichen vorzuziehen. Keinen Einfluss hingegen schienen die Stimulationen auf die Vigilanz zu nehmen. Bei der Auswertung der evozierten Potentiale zeigte sich, dass die Amplitude P1-N1 in Ableitung FzF3 bei Kontrollstimulation signifikant kleiner als bei Versuchsstimulation war (t(9)= 3,13; p= 0,012). Dar{\"u}ber hinaus war die Amplitude im Schnitt immer unter Kontrollstimulation kleiner, als bei Versuchsstimulation. F{\"u}r die Amplitude P1-N1 in Ableitung C3F3 war hierf{\"u}r ebenfalls ein Trend zu sehen (t(9)= 1,85; p= 0,097). Auffallend war auch, dass die Latenzen P1, N1 und P2 sehr oft im Schnitt bei Kontrollstimulation verl{\"a}ngert waren. Die Latenz an Punkt P1 in Ableitung C3F3 war hier sogar bei Kontrollstimulation signifikant l{\"a}nger, als bei Versuchsstimulation (t(9)= -2,37; p= 0,042). Praktische Schlussfolgerungen: In Ans{\"a}tzen konnte gezeigt werden, dass die Versuchsstimulation am Tragus ein anderes Potential auf Hirnstammebene generiert als die Kontrollstimulation am Ohrl{\"a}ppchen. W{\"a}hrend sich bei kontinuierlicher Stimulationsart keine signifikanten Ergebnisse zeigten, f{\"u}hlten sich die Probanden nach pulsatiler Vagusnervstimulation signifikant fr{\"o}hlicher, optimistischer und sch{\"a}tzten ihr allgemeines Empfinden besser ein. Nur auf die Vigilanz scheint die pulsatile VNS keinen Einfluss zu nehmen. Gerade die pulsatile VNS zeigt vielversprechende Ergebnisse und sollte in k{\"u}nftigen Studien n{\"a}her untersucht und der kontinuierlichen Stimulationsart vorgezogen werden. Nat{\"u}rlich sind noch intensivere Studien notwendig, trotzdem besteht aufgrund der Ergebnisse die Hoffnung, die transkutane VNS in Zukunft zur unterst{\"u}tzenden Therapie bei der Depressionsbehandlung einsetzen zu k{\"o}nnen.}, subject = {Depression}, language = {de} } @article{GutknechtPoppWaideretal.2015, author = {Gutknecht, Lise and Popp, Sandy and Waider, Jonas and Sommerlandt, Frank M. J. and G{\"o}ppner, Corinna and Post, Antonia and Reif, Andreas and van den Hove, Daniel and Strekalova, Tatyana and Schmitt, Angelika and Colaςo, Maria B. N. and Sommer, Claudia and Palme, Rupert and Lesch, Klaus-Peter}, title = {Interaction of brain 5-HT synthesis deficiency, chronic stress and sex differentially impact emotional behavior in Tph2 knockout mice}, series = {Psychopharmacology}, volume = {232}, journal = {Psychopharmacology}, doi = {10.1007/s00213-015-3879-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154586}, pages = {2429 -- 2441}, year = {2015}, abstract = {Rationale While brain serotonin (5-HT) function is implicated in gene-by-environment interaction (GxE) impacting the vulnerability-resilience continuum in neuropsychiatric disorders, it remains elusive how the interplay of altered 5-HT synthesis and environmental stressors is linked to failure in emotion regulation. Objective Here, we investigated the effect of constitutively impaired 5-HT synthesis on behavioral and neuroendocrine responses to unpredictable chronic mild stress (CMS) using a mouse model of brain 5-HT deficiency resulting from targeted inactivation of the tryptophan hydroxylase-2 (Tph2) gene. Results Locomotor activity and anxiety- and depression-like behavior as well as conditioned fear responses were differentially affected by Tph2 genotype, sex, and CMS. Tph2 null mutants (Tph2\(^{-/-}\)) displayed increased general metabolism, marginally reduced anxiety- and depression-like behavior but strikingly increased conditioned fear responses. Behavioral modifications were associated with sex-specific hypothalamic-pituitary-adrenocortical (HPA) system alterations as indicated by plasma corticosterone and fecal corticosterone metabolite concentrations. Tph2\(^{-/-}\) males displayed increased impulsivity and high aggressiveness. Tph2\(^{-/-}\) females displayed greater emotional reactivity to aversive conditions as reflected by changes in behaviors at baseline including increased freezing and decreased locomotion in novel environments. However, both Tph2\(^{-/-}\) male and female mice were resilient to CMS-induced hyperlocomotion, while CMS intensified conditioned fear responses in a GxE-dependent manner. Conclusions Our results indicate that 5-HT mediates behavioral responses to environmental adversity by facilitating the encoding of stress effects leading to increased vulnerability for negative emotionality.}, language = {en} } @article{GruendahlWeissMaieretal.2022, author = {Gr{\"u}ndahl, Marthe and Weiß, Martin and Maier, Lisa and Hewig, Johannes and Deckert, J{\"u}rgen and Hein, Grit}, title = {Construction and validation of a scale to measure loneliness and isolation during social distancing and its effect on mental health}, series = {Frontiers in Psychiatry}, volume = {13}, journal = {Frontiers in Psychiatry}, issn = {1664-0640}, doi = {10.3389/fpsyt.2022.798596}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269446}, year = {2022}, abstract = {A variety of factors contribute to the degree to which a person feels lonely and socially isolated. These factors may be particularly relevant in contexts requiring social distancing, e.g., during the COVID-19 pandemic or in states of immunodeficiency. We present the Loneliness and Isolation during Social Distancing (LISD) Scale. Extending existing measures, the LISD scale measures both state and trait aspects of loneliness and isolation, including indicators of social connectedness and support. In addition, it reliably predicts individual differences in anxiety and depression. Data were collected online from two independent samples in a social distancing context (the COVID-19 pandemic). Factorial validation was based on exploratory factor analysis (EFA; Sample 1, N = 244) and confirmatory factor analysis (CFA; Sample 2, N = 304). Multiple regression analyses were used to assess how the LISD scale predicts state anxiety and depression. The LISD scale showed satisfactory fit in both samples. Its two state factors indicate being lonely and isolated as well as connected and supported, while its three trait factors reflect general loneliness and isolation, sociability and sense of belonging, and social closeness and support. Our results imply strong predictive power of the LISD scale for state anxiety and depression, explaining 33 and 51\% of variance, respectively. Anxiety and depression scores were particularly predicted by low dispositional sociability and sense of belonging and by currently being more lonely and isolated. In turn, being lonely and isolated was related to being less connected and supported (state) as well as having lower social closeness and support in general (trait). We provide a novel scale which distinguishes between acute and general dimensions of loneliness and social isolation while also predicting mental health. The LISD scale could be a valuable and economic addition to the assessment of mental health factors impacted by social distancing.}, language = {en} } @phdthesis{Gawlik2007, author = {Gawlik, Micha}, title = {Assoziations- und Haplotypuntersuchung der Kandidatengene DAOA und FKBP5 bei Patienten mit manisch-depressiver Erkrankung, mit monopolarer Depression oder zykloider Psychose}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-23798}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2007}, abstract = {Im Rahmen dieser Studie sollte die Frage beantwortet werden, ob sich einzelne SNPs oder Haplotypen als biologische Marker affektiver Psychosen identifizieren lassen. Hierf{\"u}r sollten Assoziations- und Haplotypuntersuchung an zwei Kandidatengenen, FKBP5 und G72 DAOA/G30, mit unterschiedlichen pathophysiologischen Theorien, durchgef{\"u}hrt werden. Das auf der Kortisolhypothese basierende Kandidatengen FKBP5 liegt auf dem Chromosom 6 p21 und stellt ein wichtiges Regulatorprotein f{\"u}r den Glukokortikoid- Rezeptor (GR) dar. In FKBP5 wurden drei SNPs mit einem schnelleren Ansprechen auf Antidepressiva assoziiert gefunden: rs4713916 in der vermuteten Promoterregion, rs1360780 im 2. Intron und rs3800373 im nicht translatiertem 3Ende (Binder et al. 2004). Die vorbeschriebenen Polymorphismen sollten in einem unabh{\"a}ngigen Kollektiv auf Assoziation mit affektiven Psychosen untersucht werden, um eine Rolle von FKBP5 bei der {\"A}tiopathogenese affektiver Psychosen zu {\"u}berpr{\"u}fen oder einen Einfluss auf verschiedene Variable des Krankheitsverlaufs zu best{\"a}tigen. In unserer Studie mit 248 F{\"a}llen und 188 Kontrollen unterschieden sich die untersuchten SNPs in FKBP5, rs4713916, rs1360780 und rs3800373 in ihrer Verteilung nicht bei Erkrankten und Gesunden. Den einzigen signifikanten Hinweis f{\"u}r eine Assoziation mit affektiven Erkrankungen bot der Risikophaplotyp G-C-G mit einer Odds Ratio von 6,4, der jedoch nur bei 2,1\% der F{\"a}lle vorkam. Auch zeigte sich kein Zusammenhang mit den untersuchten klinischen Parametern. Die Untersuchungsergebnisse k{\"o}nnen somit einen wesentlichen Beitrag von FKBP5 f{\"u}r die depressive Erkrankung nicht belegen. Es erscheint daher fraglich, ob Polymorphismen in FKBP5 als biologische Marker affektiver Psychosen dienen k{\"o}nnen. Das zweite Kandidatengen G72 DAOA /G30 war durch positive Kopplungsbefunde des chromosomalen Locus f{\"u}r die bipolare St{\"o}rung und schizophrenen Psychosen identifiziert worden. Neuere Befunde lassen einen Einfluss auf das glutamaterge Transmittersystem vermuten (Chumakov et al. 2002). Das Genprodukt von G72, D-Amino-Oxidase (DAOA) f{\"o}rdert die Oxidation von D-Serine durch D-Amino-Oxidase (DAO), was zum Beinamen D-Amino-Oxidase-Aktivator (DAOA) f{\"u}hrte. Da D-Serin ein wichtiger Aktivator des NMDA Glutamatrezeptors ist, k{\"o}nnte G72/DAOA einen wichtigen Faktor f{\"u}r die glutamatergen Signaltransduktion darstellen. Mehrfach wurde eine Assoziation von 69 Markern im Locus G72/G30 mit der bipolaren Depression aber auch schizophrenen Psychosen beschrieben (Detera-Wadleigh et al. 2006). In der Studie sollte eine m{\"o}gliche Assoziation von SNPs in G72/G30 mit der Erkrankung {\"u}berpr{\"u}ft und die vorbeschriebenen LD-Bl{\"o}cke am 5Ende von G72 n{\"a}her untersucht werden. Daf{\"u}r wurden sieben SNPs, die sich {\"u}ber den chromosomalen Locus von G72/G30 verteilen, bei 429 F{\"a}llen mit affektiven und zykloiden Psychosen und 188 Kontrollen, untersucht. Durch die LD-Analyse der untersuchten SNPs konnte die Ausdehnung der vorbeschriebenen LD-Bl{\"o}cke in G72 genauer definiert und rs9558575 dem 1. Block zugeordnet werden, der somit bis zum 5-Ende vom G72 reicht. Der SNP rs9558575 am 5- Ende vom G72 wurde erstmalig in dieser Studie untersucht. Trotz ad{\"a}quater Power (80\% bei \&\#945; = 0,05) erreichte kein Einzelmarker Signifikanzniveau (Tabelle 17). Dennoch zeigten sich Hinweise f{\"u}r eine Beteiligung von G72/G30 am Erkrankungsrisiko, insbesondere f{\"u}r den SNP rs2391191 bei den zykloiden Psychosen. Dar{\"u}ber hinaus scheint der Risikohaplotyp rs2391191A / rs3916966C sowohl f{\"u}r die zykloiden Psychosen (p = 0,002), als auch f{\"u}r die Gesamtgruppe der Affektpsychosen (p = 0,017) ein geeigneter biologischer Marker zu sein. Die in der vorliegenden Studie gefundene Assoziation mit zykloiden Psychosen k{\"o}nnte dabei helfen, die Vorbefunde f{\"u}r G72/G30 als Risikogen sowohl f{\"u}r die bipolare Depression als auch schizophrenen Psychosen zu erkl{\"a}ren, da die zykloiden Psychosen nach IDC10 beiden Krankheitsentit{\"a}ten zugerechnet werden k{\"o}nnen.}, language = {de} } @article{FreyPoppPostetal.2014, author = {Frey, Anna and Popp, Sandy and Post, Antonia and Langer, Simon and Lehmann, Marc and Hofmann, Ulrich and Siren, Anna-Leena and Hommers, Leif and Schmitt, Angelika and Strekalova, Tatyana and Ertl, Georg and Lesch, Klaus-Peter and Frantz, Stefan}, title = {Experimental heart failure causes depression-like behavior together with differential regulation of inflammatory and structural genes in the brain}, series = {Frontiers in Behavioral Neuroscience}, volume = {8}, journal = {Frontiers in Behavioral Neuroscience}, issn = {1662-5153}, doi = {10.3389/fnbeh.2014.00376}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118234}, pages = {376}, year = {2014}, abstract = {Background: Depression and anxiety are common and independent outcome predictors in patients with chronic heart failure (CHF). However, it is unclear whether CHF causes depression. Thus, we investigated whether mice develop anxiety- and depression-like behavior after induction of ischemic CHF by myocardial infarction (MI). Methods and Results: In order to assess depression-like behavior, anhedonia was investigated by repeatedly testing sucrose preference for 8 weeks after coronary artery ligation or sham operation. Mice with large MI and increased left ventricular dimensions on echocardiography (termed CHF mice) showed reduced preference for sucrose, indicating depression-like behavior. 6 weeks after MI, mice were tested for exploratory activity, anxiety-like behavior and cognitive function using the elevated plus maze (EPM), light-dark box (LDB), open field (OF), and object recognition (OR) tests. In the EPM and OF, CHF mice exhibited diminished exploratory behavior and motivation despite similar movement capability. In the OR, CHF mice had reduced preference for novelty and impaired short-term memory. On histology, CHF mice had unaltered overall cerebral morphology. However, analysis of gene expression by RNA-sequencing in prefrontal cortical, hippocampal, and left ventricular tissue revealed changes in genes related to inflammation and cofactors of neuronal signal transduction in CHF mice, with Nr4a1 being dysregulated both in prefrontal cortex and myocardium after MI. Conclusions: After induction of ischemic CHF, mice exhibited anhedonic behavior, decreased exploratory activity and interest in novelty, and cognitive impairment. Thus, ischemic CHF leads to distinct behavioral changes in mice analogous to symptoms observed in humans with CHF and comorbid depression.}, language = {en} } @phdthesis{Finger2007, author = {Finger, Mathias Johannes}, title = {Adulte hippocampale Neurogenese bei psychischen Erkrankungen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-27351}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2007}, abstract = {Es existiert bereits eine Vielzahl von tierexperimentellen Studien bez{\"u}glich Einflussfaktoren auf die adulte Neurogenese. Nachdem die Teilungsf{\"a}higkeit von neuralen Stammzellen Ende der 1990er Jahre auch im adulten humanen Gehirn nachgewiesen wurde, war es das Ziel der vorliegenden Arbeit, adulte Neurogenese bei psychischen Erkrankungen zu quantifizieren bzw. den Ein-fluss medikament{\"o}ser Therapien auf die adulte Neurogenese zu untersuchen. Diese Studie stellt dabei die bislang einzige Arbeit dar, die sich mit der humanen adulten Neurogenese bei psychischen Erkrankungen besch{\"a}ftigt. Mittels Doppelf{\"a}rbungen von Ki67 und BrdU an Mausgewebe wurde zun{\"a}chst nachgewiesen, dass das Ki67-Antigen ein zuverl{\"a}ssiger Marker f{\"u}r sich teilende Zellen ist, woraufhin die F{\"a}rbeprozedur problemlos auf Humangewebe {\"u}bertragen werden konnte. Die Quantifizierung von Ki67 positiven Zellen erfolgte entlang der K{\"o}rnerzellschicht in einem definierten Abstand in der Einheit Zellen pro Millimeter. Die Ergebnisse der hier vorliegenden Studie widersprechen in mehrfacher Hinsicht den Hypothesen, die sich aus tierexperimentellen Studien ergeben. W{\"a}hrend die neurale Stammzellproli-feration bei schizophrenen Psychosen signifikant vermindert ist, findet sich kein Unterschied bei affektiven Erkrankungen im Vergleich zu Kontrollen. Weder wird die „Neurogenese-Hypothese" der Depression best{\"a}tigt, noch zeigte sich ein Effekt antidepressiv oder antipsychotisch wirksamer Pharmaka auf die Rate adulter Neurogenese, da eine pharmakologische Therapie jedweder Art keinen Einfluss auf die Zahl Ki67 positiver Zellen hatte. Deshalb scheint eine Steigerung der adulten Neurogenese kein Wirkmechanismus dieser Medikamente zu sein. Ein {\"u}berraschendes Ergebnis jedoch ist die signifikant reduzierte Rate adulter Neurogenese bei an Schizophrenie erkrankten Patienten. Aufgrund der sehr begrenzten Anzahl untersuchter Patienten ist die vorliegende Studie in ihrer Aussagekraft jedoch eingeschr{\"a}nkt und muss daher an einem gr{\"o}ßeren Patientenkollektiv wiederholt werden. Eine Vielzahl von Fragen bzgl. des Stellenwerts der adulten Neurogenese bei psychischen Erkrankungen bleibt dar{\"u}ber hinaus weiter ungekl{\"a}rt, was die Durchf{\"u}hrung weiterer Studien am adulten humanen Gehirn verlangt.}, subject = {Neurogenese}, language = {de} } @phdthesis{Doenitz2010, author = {Doenitz, Christian}, title = {Adulte Neurogenese in alten Serotonin-Transporter defizienten M{\"a}usen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-49745}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2010}, abstract = {Das serotonerge System des Gehirns mit seinen Projektionen ins limbische System ist an der Pathogenese der Depression und anderer neuropsychiatrischer Erkrankungen beteiligt. Bei der serotonergen Neurotransmission spielt der Serotonintransporter (5-HTT) eine wichtige Rolle und ist auch therapeutischer Angriffspunkt verschiedener Antidepressiva. Das Tiermodell der 5-HTT-Knockout(KO)-Maus dient der Untersuchung des serotonergen Systems. Diese Tiere besitzen neben einem verst{\"a}rkten Angst-{\"a}hnlichen Verhalten auch erh{\"o}hte 5-HT-Konzentrationen im synaptischen Spalt. Lange Zeit war man der Meinung, dass nahezu alle Nervenzellen w{\"a}hrend der Embryogenese bis kurz nach der Geburt gebildet werden. Neuere Untersuchungen konnten Neurogenese jedoch auch im Gehirn adulter Tiere und auch des Menschen nachweisen. Eine wichtige Gehirnregion mit adulter Neurogenese (aN) bis ins hohe Alter ist der Gyrus dentatus (GD) des Hippocampus. Der Hippocampus ist zentraler Teil des limbischen Systems und hat Schl{\"u}sselfunktionen bei Lernprozessen und der Ged{\"a}chtnisbildung und unterliegt durch seine serotonerge Innervation auch dem Einfluss von 5-HT. Die Zusammenfassung dieser Beobachtungen f{\"u}hrte zu folgender Arbeitshypothese: Eine erniedrigte Zahl von 5-HTT f{\"u}hrt zu chronisch erh{\"o}hten 5-HT-Spiegeln im synaptischen Spalt. Die damit verbundene Stimulation des serotonergen Systems f{\"u}hrt zu einer ver{\"a}nderten aN. Ziel der vorliegenden Arbeit war die quantitative Bestimmung von Proliferation, {\"U}berleben und Migration neu entstandener Zellen in der KZS des GD von heterozygoten (HET) und homozygoten 5-HTT-M{\"a}usen (KO), die mit Wildtyptieren (WT) verglichen wurden. Dabei wurden {\"a}ltere M{\"a}usen mit einem Durchschnittsalter von 13,8 Monaten verwendet. In der Gruppe zur Untersuchung der Proliferation wurden die Versuchstiere (n=18) 24 h nach Injektionen mit BrdU get{\"o}tet und histologische Schnitte des Hippocampus post mortem untersucht. In der Gruppe zur Untersuchung der {\"U}berlebensrate und Migration wurden die M{\"a}use (n=18) 4 Wochen nach den BrdU-Injektionen get{\"o}tet. Im Proliferationsversuch wurde ein signifikanter Unterschied bei der Konzentration BrdU-markierter Zellkerne in der SGZ zwischen KO-M{\"a}usen im Vergleich zu WT-Tieren gefunden, wobei HET-M{\"a}use ebenfalls eine signifikant h{\"o}here Konzentration BrdU-markierter Zellkerne in der SGZ gegen{\"u}ber WT-M{\"a}usen zeigten. In diesem Experiment ist somit ein positiver Einfluss des heterozygoten und homozygoten 5-HTT-KO auf die Entstehungsrate neuer Zellen im GD des Hippocampus im Vergleich zu den WT-Tieren feststellbar. Im Versuch zur Feststellung der {\"U}berlebensrate neu gebildeter Zellen im Hippocampus nach vier Wochen zeigten KO-M{\"a}use gegen{\"u}ber WT- und HET-M{\"a}usen keine signifikant h{\"o}here Zahl BrdU-markierter Zellkerne. Auch bei der Untersuchung der Migration war beinahe die H{\"a}lfte der BrdU-markierten Zellen von der SGZ in die KZS eingewandert. Ein signifikanter Unterschied zwischen den verschiedenen 5-HTT-Genotypen zeigte sich nicht. Offenbar hat der heterozygote oder homozygote 5-HTT-KO keinen Einfluss auf die {\"U}berlebensrate und das Migrationsverhalten neu entstandener Zellen. Bei den in dieser Arbeit durchgef{\"u}hrten Untersuchungen zur aN in 5-HTT-KO-M{\"a}usen konnte weder bei der Gruppe zur Untersuchung der Proliferation von neuronalen Vorl{\"a}uferzellen noch bei der Untersuchung der {\"U}berlebensrate oder Migration eine Abh{\"a}ngigkeit der ermittelten Konzentration BrdU-positiver Zellen vom Geschlecht oder Alter gefunden werden. Es zeigte sich jedoch eine signifikante negative Korrelation zwischen dem Gewicht der Tiere und dem Anteil gewanderter Zellen im Migrationsversuch, d.h. leichtere Tiere hatten tendenziell einen h{\"o}heren Anteil von in die KZS eingewanderten Zellen. Zusammengefasst zeigt die vorliegende Arbeit zum einen, dass {\"a}ltere KO- oder HET-M{\"a}use im Vergleich zu WT-Tieren eine erh{\"o}hte Proliferationsrate von neuronalen Vorl{\"a}uferzellen aufweisen. Zum anderen konnte ein indirekter Zusammenhang zwischen dem Gewicht der Versuchstiere und der Anzahl von in die KZS eingewanderten Zellen nachgewiesen werden. Bei einer Vergleichsuntersuchung in unserem Hause mit zwei Gruppen j{\"u}ngerer adulter 5-HTT-KO M{\"a}use mit einem Durchschnittalter von 7 Wochen und 3 Monaten konnte die Beobachtung einer erh{\"o}hten Proliferation nicht gemacht werden. Wir gehen deshalb davon aus, dass in diesem 5-HTT-KO Modell nur in h{\"o}herem Alter eine ver{\"a}nderte 5-HT-Hom{\"o}ostase zu einer verst{\"a}rkten Proliferation von neuronalen Vorl{\"a}uferzellen f{\"u}hrt.}, subject = {Neurogenese}, language = {de} } @article{BiereKranzMaturaetal.2020, author = {Biere, Silvia and Kranz, Thorsten M. and Matura, Silke and Petrova, Kristiyana and Streit, Fabian and Chiocchetti, Andreas G. and Grimm, Oliver and Brum, Murielle and Brunkhorst-Kanaan, Natalie and Oertel, Viola and Malyshau, Aliaksandr and Pfennig, Andrea and Bauer, Michael and Schulze, Thomas G. and Kittel-Schneider, Sarah and Reif, Andreas}, title = {Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults}, series = {Frontiers in Psychiatry}, volume = {11}, journal = {Frontiers in Psychiatry}, doi = {10.3389/fpsyt.2020.552532}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214976}, year = {2020}, abstract = {Objective: Identifying high-risk groups with an increased genetic liability for bipolar disorder (BD) will provide insights into the etiology of BD and contribute to early detection of BD. We used the BD polygenic risk score (PRS) derived from BD genome-wide association studies (GWAS) to explore how such genetic risk manifests in young, high-risk adults. We postulated that BD-PRS would be associated with risk factors for BD. Methods: A final sample of 185 young, high-risk German adults (aged 18-35 years) were grouped into three risk groups and compared to a healthy control group (n = 1,100). The risk groups comprised 117 cases with attention deficit hyperactivity disorder (ADHD), 45 with major depressive disorder (MDD), and 23 help-seeking adults with early recognition symptoms [ER: positive family history for BD, (sub)threshold affective symptomatology and/or mood swings, sleeping disorder]. BD-PRS was computed for each participant. Logistic regression models (controlling for sex, age, and the first five ancestry principal components) were used to assess associations of BD-PRS and the high-risk phenotypes. Results: We observed an association between BD-PRS and combined risk group status (OR = 1.48, p < 0.001), ADHD diagnosis (OR = 1.32, p = 0.009), MDD diagnosis (OR = 1.96, p < 0.001), and ER group status (OR = 1.7, p = 0.025; not significant after correction for multiple testing) compared to healthy controls. Conclusions: In the present study, increased genetic risk for BD was a significant predictor for MDD and ADHD status, but not for ER. These findings support an underlying shared risk for both MDD and BD as well as ADHD and BD. Improving our understanding of the underlying genetic architecture of these phenotypes may aid in early identification and risk stratification.}, language = {en} } @phdthesis{Altides2011, author = {Altides, Anastasia Elisabeth}, title = {BDNF Plasma Level als Marker f{\"u}r Alzheimer in der VITA Studie}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-57274}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {HINTERGRUND: Der brain-derived neurotrophic factor (BDNF) reguliert die synaptische Plastizit{\"a}t und spielt somit eine wichtige Rolle in der Ged{\"a}chtnisbildung und -erhaltung. Deswegen gibt es eingehende Untersuchungen dieses neurotrophischen Faktors in Bezug auf Demenzerkrankungen, vor allem der Alzheimer Demenz. In dieser Studie wurde nach einem Zusammenhang zwischen BDNF Blutplasmawerten und der Alzheimer Demenz in einer longitudinalen Kohortenstudie, der Vienna-Transdanube-Aging(VITA)-Studie gesucht. METHODEN: Die VITA-Studie ist eine kommunale Kohortenstudie aller 75j{\"a}hrigen Einwohner einer geographischen Region Wiens. Es wurden die BDNF Plasmawerte der Basisuntersuchung und der ersten Folgeuntersuchung 30 Monate sp{\"a}ter als m{\"o}gliche Biomarker f{\"u}r die Alzheimer Demenz untersucht. Assoziationen zwischen BDNF Plasmawerten und anderen epidemiologischen Eckdaten wurden ebenfalls analysiert. ERGEBNISSE: Wir konnten keine Assoziation zwischen BDNF Plasmawerten und der Entwicklung oder einer bereits bestehenden Alzheimer Demenz finden. Geschlecht, Body-Maß-Index und Depression stellten sich als Komorbidit{\"a}ts-Faktoren von Demenz-erkrankungen dar. SCHLUSSFOLGERUNG: BDNF Plasmawerte sind diesen Ergebnissen nach kein so viel versprechender molekularer Marker f{\"u}r Alzheimer Demenz wie erhofft. BDNF wird jedoch weiterhin in vielen interessanten Studienprotokollen untersucht, da es sowohl im Blutserum als auch im Hirngewebe nachgewiesen werden kann und somit viele diagnostische und therapeutische Ans{\"a}tze inspiriert.}, subject = {Alzheimer-Krankheit}, language = {de} }