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S/S carriers of 5-HTTLPR have been found to be more risk seeking for losses compared to L/L carriers. This finding may be the result of reduced top-down control from the frontal cortex due to altered signal pathways involving the amygdala and ventral striatum. The serotonergic system is known to be involved in neurodevelopment and neuroplasticity. Therefore, the aim of this study was to investigate whether structural differences in white matter can explain the differences in risk-seeking behaviour. Lower structural connectivity in S/S compared to L/L carriers and a negative relationship between risk seeking for losses and connectivity were assumed. Diffusion-weighted imaging was used to compute diffusion parameters for the frontostriatal and uncinate tract in 175 genotyped individuals. The results showed no significant relationship between diffusion parameters and risk seeking for losses. Furthermore, we did not find significant differences in diffusion parameters of the S/S vs. L/L group. There were only group differences in the frontostriatal tract showing stronger structural connectivity in the S/L group, which is also reflected in the whole brain approach. Therefore, the data do not support the hypothesis that the association between 5-HTTLPR and risk seeking for losses is related to differences in white matter pathways implicated in decision-making. [ABSTRACT FROM AUTHOR]

Objectives: Bipolar disorder (BD) and major depressive disorder (MDD) are characterized by specific alterations of mood. In both disorders, alterations in cognitive domains such as impulsivity, decision‐making, and risk‐taking have been reported. Identification of similarities and differences of these domains in BD and MDD could give further insight into their etiology. The present study assessed impulsivity, decision‐making, and risk‐taking behavior in BD and MDD patients from bipolar multiplex families. Methods: Eighty‐two participants (BD type I, n = 25; MDD, n = 26; healthy relatives (HR), n = 17; and healthy controls (HC), n = 14) underwent diagnostic interviews and selected tests of a cognitive battery assessing neurocognitive performance across multiple subdomains including impulsivity (response inhibition and delay aversion), decision‐making, and risk behavior. Generalized estimating equations (GEEs) were used to analyze whether the groups differed in the respective cognitive domains. Results: Participants with BD and MDD showed higher impulsivity levels compared to HC; this difference was more pronounced in BD participants. BD participants also showed lower inhibitory control than MDD participants. Overall, suboptimal decision‐making was associated with both mood disorders (BD and MDD). In risk‐taking behavior, no significant impairment was found in any group. Limitations: As sample size was limited, it is possible that differences between BD and MDD may have escaped detection due to lack of statistical power. Conclusions: Our findings show that alterations of cognitive domains—while present in both disorders—are differently associated with BD and MDD. This underscores the importance of assessing such domains in addition to mere diagnosis of mood disorders. [ABSTRACT FROM AUTHOR]

Genetic factors contribute significantly to interindividual differences in the susceptibility to stress‐related disorders. As stress can also be conceptualized as environmental exposure, controlled gene–environment interaction (GxE) studies with an in‐depth phenotyping may help to unravel mechanisms underlying the interplay between genetic factors and stress. In a prospective‐longitudinal quasi‐experimental study, we investigated whether polygenic scores (PGS) for depression (DEP‐PGS) and neuroticism (NEU‐PGS), respectively, were associated with responses to chronic stress in daily life. We examined law students (n = 432) over 13 months. Participants in the stress group experienced a long‐lasting stress phase, namely the preparation for the first state examination for law students. The control group consisted of law students without particular stress exposure. In the present manuscript, we analyzed perceived stress levels assessed at high frequency and in an ecologically valid manner by ambulatory assessments as well as depression symptoms and two parameters of the cortisol awakening response. The latter was only assessed in a subsample (n = 196). No associations between the DEP‐PGS and stress‐related variables were found. However, for the NEU‐PGS we found a significant GxE effect. Only in individuals experiencing academic stress a higher PGS for neuroticism predicted stronger increases of perceived stress levels until the exam. At baseline, a higher NEU‐PGS was associated with higher perceived stress levels in both groups. Despite the small sample size, we provide preliminary evidence that the genetic disposition for neuroticism is associated with stress level increases in daily life during a long‐lasting stress period. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic severely affected the lives of families and the well-being of both parents and their children. Various factors, including prenatal stress, dysregulated stress response systems, and genetics may have influenced how the stress caused by the pandemic impacted the well-being of different family members. The present work investigated if emotional well-being during the COVID-19 pandemic could be predicted by developmental stress-related and genetic factors. Emotional well-being of 7–10 year-old children (n = 263) and mothers (n = 241) (participants in a longitudinal German birth cohort (POSEIDON)) was assessed during the COVID-19 pandemic using the CRISIS questionnaire at two time periods (July 2020–October 2020; November 2020–February 2021). Associations of the children's and mothers' well-being with maternal perceived stress, of the children's well-being with their salivary and morning urine cortisol at 45 months, and polygenic risk scores (PRSs) for depression, schizophrenia, loneliness were investigated. Lower emotional well-being was observed in both children and mothers during compared to before the pandemic, with the children's but not the mothers' emotional well-being improving over the course of the pandemic. A positive association between the child and maternal emotional well-being was found. Prenatally assessed maternal perceived stress was associated with a lower well-being in children, but not in mothers. Cortisol measures and PRSs were not significantly associated with the children's emotional well-being. The present study confirms that emotional well-being of children and mothers are linked, and were negatively affected by the COVID-19 pandemic, with differences in development over time. [ABSTRACT FROM AUTHOR]

Major Depression and Bipolar Disorder Type I (BIP-I) and Type II (BIP-II), are characterized by depressed, manic, and hypomanic episodes in which specific changes of physical activity, circadian rhythm, and sleep are observed. It is known that genetic factors contribute to variation in mood disorders and biological rhythms, but unclear to what extent there is an overlap between their underlying genetics. In the present study, data from genome-wide association studies were used to examine the genetic relationship between mood disorders and biological rhythms. We tested the genetic correlation of depression, BIP-I, and BIP-II with physical activity (overall physical activity, moderate activity, sedentary behaviour), circadian rhythm (relative amplitude), and sleep features (sleep duration, daytime sleepiness). Genetic correlations of depression, BIP-I, and BIP-II with biological rhythms were compared to discover commonalities and differences. A gene-based analysis tested for associations of single genes and common circadian genes with mood disorders. Depression was negatively correlated with overall physical activity and positively with sedentary behaviour, while BIP-I showed associations in the opposite direction. Depression and BIP-II had negative correlations with relative amplitude. All mood disorders were positively correlated with daytime sleepiness. Overall, we observed both genetic commonalities and differences across mood disorders in their relationships with biological rhythms: depression and BIP-I differed the most, while BIP-II was in an intermediate position. Gene-based analysis suggested potential targets for further investigation. The present results suggest shared genetic underpinnings for the clinically observed associations between mood disorders and biological rhythms. Research considering possible joint mechanisms may offer avenues for improving disease detection and treatment. [ABSTRACT FROM AUTHOR]

(1) Background: Epigenome-wide association studies (EWAS) in peripheral blood have repeatedly found associations between tobacco smoking and aberrant DNA methylation (DNAm), but little is known about DNAm signatures of smoking in the human brain, which may contribute to the pathophysiology of addictive behavior observed in chronic smokers. (2) Methods: We investigated the similarity of DNAm signatures in matched blood and postmortem brain samples (n = 10). In addition, we performed EWASs in five brain regions belonging to the neurocircuitry of addiction: anterior cingulate cortex (ACC), Brodmann Area 9, caudate nucleus, putamen, and ventral striatum (n = 38–72). (3) Results: cg15925993 within the LOC339975 gene was epigenome-wide significant in the ACC. Of 16 identified differentially methylated regions, two (PRSS50 and LINC00612/A2M-AS1) overlapped between multiple brain regions. Functional enrichment was detected for biological processes related to neuronal development, inflammatory signaling and immune cell migration. Additionally, our results indicate the association of the well-known AHRR CpG site cg05575921 with smoking in the brain. (4) Conclusion: The present study provides further evidence of the strong relationship between aberrant DNAm and smoking. [ABSTRACT FROM AUTHOR]

Anxiety and depression are common mental health disorders and have a higher prevalence in females. They are modestly heritable, share genetic liability with other psychiatric disorders, and are highly heterogeneous. There is evidence that genetic liability to neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) is associated with anxiety and depression, particularly in females. We investigated sex differences in family history for neurodevelopmental and psychiatric disorders and neurodevelopmental genetic risk burden (indexed by ADHD polygenic risk scores (PRS) and rare copy number variants; CNVs) in individuals with anxiety and depression, also taking into account age at onset. We used two complementary datasets: 1) participants with a self-reported diagnosis of anxiety or depression (N = 4,178, 65.5% female; mean age = 41.5 years; N = 1,315 with genetic data) from the National Centre for Mental Health (NCMH) cohort and 2) a clinical sample of 13,273 (67.6% female; mean age = 45.2 years) patients with major depressive disorder (MDD) from the Psychiatric Genomics Consortium (PGC). We tested for sex differences in family history of psychiatric problems and presence of rare CNVs (neurodevelopmental and >500kb loci) in NCMH only and for sex differences in ADHD PRS in both datasets. In the NCMH cohort, females were more likely to report family history of neurodevelopmental and psychiatric disorders, but there were no robust sex differences in ADHD PRS or presence of rare CNVs. There was weak evidence of higher ADHD PRS in females compared to males in the PGC MDD sample, particularly in those with an early onset of MDD. These results do not provide strong evidence of sex differences in neurodevelopmental genetic risk burden in adults with anxiety and depression. This indicates that sex may not be a major index of neurodevelopmental genetic heterogeneity, that is captured by ADHD PRS and rare CNV burden, in adults with anxiety and depression. [ABSTRACT FROM AUTHOR]

Genetic research has identified a large number of genetic variants, both rare and common, underlying neurodevelopmental disorders (NDD) and major psychiatric disorders. Currently, these findings are being translated into clinical practice. However, there is a lack of knowledge and guidelines for psychiatric genetic testing (PsychGT) and genetic counseling (PsychGC). The European Union-funded COST action EnGagE (CA17130) network was started to investigate the current implementation status of PsychGT and PsychGC across 35 participating European countries. Here, we present the results of a pan-European online survey in which we gathered the opinions, knowledge, and practices of a self-selected sample of professionals involved/interested in the field. We received answers from 181 respondents. The three main occupational categories were genetic counselor (21.0%), clinical geneticist (24.9%), and researcher (25.4%). Of all 181 respondents, 106 provide GC for any psychiatric disorder or NDD, corresponding to 58.6% of the whole group ranging from 43.2% in Central Eastern Europe to 66.1% in Western Europe. Overall, 65.2% of the respondents reported that genetic testing is offered to individuals with NDD, and 26.5% indicated the same for individuals with major psychiatric disorders. Only 22.1% of the respondents indicated that they have guidelines for PsychGT. Pharmacogenetic testing actionable for psychiatric disorders was offered by 15%. Interestingly, when genetic tests are fully covered by national health insurance, more genetic testing is provided for individuals with NDD but not those with major psychiatric disorders. Our qualitative analyses of responses highlight the lack of guidelines and knowledge on utilizing and using genetic tests and education and training as the major obstacles to implementation. Indeed, the existence of psychiatric genetic training courses was confirmed by only 11.6% of respondents. The question on the relevance of up-to-date education and training in psychiatric genetics on everyday related practice was highly relevant. We provide evidence that PsychGC and PsychGT are already in use across European countries, but there is a lack of guidelines and education. Harmonization of practice and development of guidelines for genetic counseling, testing, and training professionals would improve equality and access to quality care for individuals with psychiatric disorders within Europe. [ABSTRACT FROM AUTHOR]