TY - JOUR A1 - Biere, Silvia A1 - Kranz, Thorsten M. A1 - Matura, Silke A1 - Petrova, Kristiyana A1 - Streit, Fabian A1 - Chiocchetti, Andreas G. A1 - Grimm, Oliver A1 - Brum, Murielle A1 - Brunkhorst-Kanaan, Natalie A1 - Oertel, Viola A1 - Malyshau, Aliaksandr A1 - Pfennig, Andrea A1 - Bauer, Michael A1 - Schulze, Thomas G. A1 - Kittel-Schneider, Sarah A1 - Reif, Andreas T1 - Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults JF - Frontiers in Psychiatry N2 - 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. KW - polygenic risk score KW - bipolar disorder KW - genetic phenotypes KW - depression KW - ADHD KW - early recognition Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214976 VL - 11 ER - TY - JOUR A1 - Gehrmann, Andrea A1 - Fiedler, Katrin A1 - Leutritz, Anna Linda A1 - Koreny, Carolin A1 - Kittel-Schneider, Sarah T1 - Lithium medication in pregnancy and breastfeeding — a case series JF - Medicina N2 - Lithium salts are the first-line prophylaxis treatment for bipolar disorder in most guidelines. The majority of bipolar women are treated with mood stabilizers at the time they wish to get pregnant. One reason for this is the rising average age at first childbirth, at least in the high-income countries, which increases in general the likelihood of a medication with psychotropic drugs. Previously, lithium exposition during pregnancy was thought to strongly increase the risk of severe cardiac malformation. However, recent studies only point to a low teratogenic risk, so nowadays an increasing number of women are getting pregnant with ongoing lithium treatment. Regarding lithium medication during breastfeeding, there is evidence that lithium transfers to the breastmilk and can also be detected in the infants' serum. The influence on the infant is still a largely understudied topic. Regular monitoring of the infants' renal clearance, thyroid function, and lithium levels is warranted when breastfeeding under lithium exposure. In this case series, we present three case reports of bipolar mothers who were treated with lithium during pregnancy and breastfeeding to add to the scarce literature on this important topic. In short, we strengthen the importance of therapeutic drug monitoring due to fluctuating plasma levels during pregnancy and after birth, and we can report the birth and development of three healthy infants despite lithium medication during pregnancy and breastfeeding. KW - lithium KW - pregnancy KW - lactation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285640 SN - 1648-9144 VL - 57 IS - 6 ER - TY - JOUR A1 - Brevik, Erlend J A1 - van Donkelaar, Marjolein M. J. A1 - Weber, Heike A1 - Sánchez-Mora, Cristina A1 - Jacob, Christian A1 - Rivero, Olga A1 - Kittel-Schneider, Sarah A1 - Garcia-martinez, Iris A1 - Aebi, Marcel A1 - van Hulzen, Kimm A1 - Cormand, Bru A1 - Ramos-Quiroga, Josep A A1 - Lesch, Klaus-Peter A1 - Reif, Andreas A1 - Ribases, Marta A1 - Franke, Barbara A1 - Posserud, Maj-Britt A1 - Johansson, Stefan A1 - Lundervold, Astri J. A1 - Haavik, Jan A1 - Zayats, Tetyana T1 - Genome-wide analyses of aggressiveness in attention-deficit hyperactivity disorder JF - American Journal of Medical Genetics Part B-Neuropsychiatric Genetics N2 - Aggressiveness is a behavioral trait that has the potential to be harmful to individuals and society. With an estimated heritability of about 40%, genetics is important in its development. We performed an exploratory genome-wide association (GWA) analysis of childhood aggressiveness in attention deficit hyperactivity disorder (ADHD) to gain insight into the underlying biological processes associated with this trait. Our primary sample consisted of 1,060 adult ADHD patients (aADHD). To further explore the genetic architecture of childhood aggressiveness, we performed enrichment analyses of suggestive genome-wide associations observed in aADHD among GWA signals of dimensions of oppositionality (defiant/vindictive and irritable dimensions) in childhood ADHD (cADHD). No single polymorphism reached genome-wide significance (P<5.00E-08). The strongest signal in aADHD was observed at rs10826548, within a long noncoding RNA gene (beta = -1.66, standard error (SE) = 0.34, P = 1.07E-06), closely followed by rs35974940 in the neurotrimin gene (beta = 3.23, SE = 0.67, P = 1.26E-06). The top GWA SNPs observed in aADHD showed significant enrichment of signals from both the defiant/vindictive dimension (Fisher's P-value = 2.28E-06) and the irritable dimension in cADHD (Fisher's P-value = 0.0061). In sum, our results identify a number of biologically interesting markers possibly underlying childhood aggressiveness and provide targets for further genetic exploration of aggressiveness across psychiatric disorders. KW - Large multicenter ADHD KW - Antisocial behavior KW - Diagnostic approach KW - Rating scale KW - Gene KW - Deficit/hyperactivity disorder KW - Susceptibility loci KW - Conduct disorder KW - Association KW - Adult KW - ADHD KW - Aggression KW - GWAS Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188116 VL - 171B IS - 5 ER - TY - JOUR A1 - Janson, Patrick A1 - Willeke, Kristina A1 - Zaibert, Lisa A1 - Budnick, Andrea A1 - Berghöfer, Anne A1 - Kittel-Schneider, Sarah A1 - Heuschmann, Peter U. A1 - Zapf, Andreas A1 - Wildner, Manfred A1 - Stupp, Carolin A1 - Keil, Thomas T1 - Mortality, morbidity and health-related outcomes in informal caregivers compared to non-caregivers: a systematic review JF - International Journal of Environmental Research and Public Health N2 - A systematic overview of mental and physical disorders of informal caregivers based on population-based studies with good methodological quality is lacking. Therefore, our aim was to systematically summarize mortality, incidence, and prevalence estimates of chronic diseases in informal caregivers compared to non-caregivers. Following PRISMA recommendations, we searched major healthcare databases (CINAHL, MEDLINE and Web of Science) systematically for relevant studies published in the last 10 years (without language restrictions) (PROSPERO registration number: CRD42020200314). We included only observational cross-sectional and cohort studies with low risk of bias (risk scores 0–2 out of max 8) that reported the prevalence, incidence, odds ratio (OR), hazard ratio (HR), mean- or sum-scores for health-related outcomes in informal caregivers and non-caregivers. For a thorough methodological quality assessment, we used a validated checklist. The synthesis of the results was conducted by grouping outcomes. We included 22 studies, which came predominately from the USA and Europe. Informal caregivers had a significantly lower mortality than non-caregivers. Regarding chronic morbidity outcomes, the results from a large longitudinal German health-insurance evaluation showed increased and statistically significant incidences of severe stress, adjustment disorders, depression, diseases of the spine and pain conditions among informal caregivers compared to non-caregivers. In cross-sectional evaluations, informal caregiving seemed to be associated with a higher occurrence of depression and of anxiety (ranging from 4 to 51% and 2 to 38%, respectively), pain, hypertension, diabetes and reduced quality of life. Results from our systematic review suggest that informal caregiving may be associated with several mental and physical disorders. However, these results need to be interpreted with caution, as the cross-sectional studies cannot determine temporal relationships. The lower mortality rates compared to non-caregivers may be due to a healthy-carer bias in longitudinal observational studies; however, these and other potential benefits of informal caregiving deserve further attention by researchers. KW - cohort studies KW - longitudinal studies KW - cross-sectional studies KW - family caregivers KW - informal caregiving KW - mental health KW - physical health KW - population-based studies KW - systematic review Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275219 SN - 1660-4601 VL - 19 IS - 10 ER - TY - JOUR A1 - McNeill, Rhiannon V. A1 - Ziegler, Georg C. A1 - Radtke, Franziska A1 - Nieberler, Matthias A1 - Lesch, Klaus‑Peter A1 - Kittel‑Schneider, Sarah T1 - Mental health dished up — the use of iPSC models in neuropsychiatric research JF - Journal of Neural Transmission N2 - Genetic and molecular mechanisms that play a causal role in mental illnesses are challenging to elucidate, particularly as there is a lack of relevant in vitro and in vivo models. However, the advent of induced pluripotent stem cell (iPSC) technology has provided researchers with a novel toolbox. We conducted a systematic review using the PRISMA statement. A PubMed and Web of Science online search was performed (studies published between 2006–2020) using the following search strategy: hiPSC OR iPSC OR iPS OR stem cells AND schizophrenia disorder OR personality disorder OR antisocial personality disorder OR psychopathy OR bipolar disorder OR major depressive disorder OR obsessive compulsive disorder OR anxiety disorder OR substance use disorder OR alcohol use disorder OR nicotine use disorder OR opioid use disorder OR eating disorder OR anorexia nervosa OR attention-deficit/hyperactivity disorder OR gaming disorder. Using the above search criteria, a total of 3515 studies were found. After screening, a final total of 56 studies were deemed eligible for inclusion in our study. Using iPSC technology, psychiatric disease can be studied in the context of a patient’s own unique genetic background. This has allowed great strides to be made into uncovering the etiology of psychiatric disease, as well as providing a unique paradigm for drug testing. However, there is a lack of data for certain psychiatric disorders and several limitations to present iPSC-based studies, leading us to discuss how this field may progress in the next years to increase its utility in the battle to understand psychiatric disease. KW - hiPSC KW - iPSC KW - stem cells KW - mental disorders KW - affective disorders KW - ADHD Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235666 SN - 0300-9564 VL - 127 ER - TY - JOUR A1 - Leutritz, Anna Linda A1 - van Braam, Lara A1 - Preis, Katharina A1 - Gehrmann, Andrea A1 - Scherf-Clavel, Maike A1 - Fiedler, Katrin A1 - Unterecker, Stefan A1 - Kittel-Schneider, Sarah T1 - Psychotropic medication in pregnancy and lactation and early development of exposed children JF - British Journal of Clinical Pharmacology N2 - There is still limited knowledge about alterations of blood concentrations of psychotropic drugs during pregnancy, the transfer of psychotropic drugs into breastmilk and the effects on exposed children. We investigated changes in concentrations of psychopharmacological medication during pregnancy and lactation in serum and breastmilk at different time points in a naturalistic sample of 60 mothers and observed the development of the exposed children in the first 12 months. We found a decrease in serum concentrations from the first to the second trimester of amitriptyline, duloxetine, escitalopram, quetiapine and sertraline. Citalopram stayed rather stable during pregnancy, sertraline levels interestingly increased again from the second to the third trimester. High concentration-by-dose ratios in breastmilk were found for venlafaxine as well as lamotrigine, low for quetiapine and clomipramine. Similarly, clomipramine and quetiapine showed low milk/serum–penetration ratios. Regarding the birth outcome measures in children, we found no significant differences between in utero exposed compared to nonexposed newborns. There were no significant differences in the development in the first 12 months. Psychotropic medication in the peripartum needs a balancing of risks and benefits and a continuous therapeutic drug monitoring can be a guidance for clinicians to monitor drug alteration patterns, which are likely to occur due to physiological pregnancy-associated changes in pharmacokinetics. Accordingly, therapeutic drug monitoring can optimize a medication in pregnancy and lactation with the lowest effective dose. KW - antidepressants KW - psychotropic medication KW - pregnancy KW - peripartum KW - mental disorders KW - lactation KW - child development Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318954 VL - 89 IS - 2 SP - 737 EP - 750 ER - TY - JOUR A1 - Kopf, Juliane A1 - Glöckner, Stefan A1 - Althen, Heike A1 - Cevada, Thais A1 - Schecklmann, Martin A1 - Dresler, Thomas A1 - Kittel-Schneider, Sarah A1 - Reif, Andreas T1 - Neural responses to a working memory task in acute depressed and remitted phases in bipolar patients JF - Brain Sciences N2 - (1) Cognitive impairments such as working memory (WM) deficits are amongst the most common dysfunctions characterizing bipolar disorder (BD) patients, severely contributing to functional impairment. We aimed to investigate WM performance and associated brain activation during the acute phase of BD and to observe changes in the same patients during remission. (2) Frontal brain activation was recorded using functional near-infrared spectroscopy (fNIRS) during n-back task conditions (one-back, two-back and three-back) in BD patients in their acute depressive (n = 32) and remitted (n = 15) phases as well as in healthy controls (n = 30). (3) Comparison of BD patients during their acute phase with controls showed a trend (p = 0.08) towards lower dorsolateral prefrontal cortex (dlPFC) activation. In the remitted phase, BD patients showed lower dlPFC and ventrolateral prefrontal cortex (vlPFC) activation (p = 0.02) compared to controls. No difference in dlPFC and vlPFC activation between BD patients’ phases was found. (4) Our results showed decreased working memory performance in BD patients during the working memory task in the acute phase of disease. Working memory performance improved in the remitted phase of the disease but was still particularly attenuated for the more demanding conditions. KW - verbal n-back KW - fNIRS KW - prefrontal cortex KW - cognitive deficits KW - bipolar disorder KW - remitted/acute phase Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313509 SN - 2076-3425 VL - 13 IS - 5 ER - TY - JOUR A1 - Hampf, Chantal A1 - Scherf-Clavel, Maike A1 - Weiß, Carolin A1 - Klüpfel, Catherina A1 - Stonawski, Saskia A1 - Hommers, Leif A1 - Lichter, Katharina A1 - Erhardt-Lehmann, Angelika A1 - Unterecker, Stefan A1 - Domschke, Katharina A1 - Kittel-Schneider, Sarah A1 - Menke, Andreas A1 - Deckert, Jürgen A1 - Weber, Heike T1 - Effects of anxious depression on antidepressant treatment response JF - International Journal of Molecular Sciences N2 - Anxious depression represents a subtype of major depressive disorder and is associated with increased suicidality, severity, chronicity and lower treatment response. Only a few studies have investigated the differences between anxious depressed (aMDD) and non-anxious depressed (naMDD) patients regarding treatment dosage, serum-concentration and drug-specific treatment response. In our naturalistic and prospective study, we investigated whether the effectiveness of therapy including antidepressants (SSRI, SNRI, NaSSA, tricyclics and combinations) in aMDD patients differs significantly from that in naMDD patients. In a sample of 346 patients, we calculated the anxiety somatization factor (ASF) and defined treatment response as a reduction (≥50%) in the Hamilton Depression Rating Scale (HDRS)-21 score after 7 weeks of pharmacological treatment. We did not observe an association between therapy response and the baseline ASF-scores, or differences in therapy outcomes between aMDD and naMDD patients. However, non-responders had higher ASF-scores, and at week 7 aMDD patients displayed a worse therapy outcome than naMDD patients. In subgroup analyses for different antidepressant drugs, venlafaxine-treated aMDD patients showed a significantly worse outcome at week 7. Future prospective, randomized-controlled studies should address the question of a worse therapy outcome in aMDD patients for different psychopharmaceuticals individually. KW - pharmacotherapy KW - depressive disorder KW - anxious depression KW - anxiety KW - therapy response Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-355801 SN - 1422-0067 VL - 24 IS - 24 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 - McNeill, Rhiannon V. A1 - Radtke, Franziska A1 - Nieberler, Matthias A1 - Koreny, Carolin A1 - Chiocchetti, Andreas G. A1 - Kittel-Schneider, Sarah T1 - Generation of four human induced pluripotent stem cells derived from ADHD patients carrying different genotypes for the risk SNP rs1397547 in the ADHD-associated gene ADGRL3 JF - Stem Cell Research N2 - Single nucleotide polymorphisms (SNPs) in the ADGRL3 gene have been significantly associated with the development of ADHD, the aetiology of which remains poorly understood. The rs1397547 SNP has additionally been associated with significantly altered ADGRL3 transcription. We therefore generated iPSCs from two wild type ADHD patients, and two ADHD patients heterozygous for the risk SNP. With this resource we aim to facilitate further investigation into the complex and heterogenous pathology of ADHD. Furthermore, we demonstrate the feasibility of using magnetic activated cell sorting to allow the unbiased selection of fully reprogrammed iPSCs. KW - induced pluripotent stem cells KW - ADHD patients KW - risk SNP rs1397547 KW - gene ADGRL3 KW - iPSCs Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350099 VL - 67 ER -