Many individuals with eating disorders and their family members are well-informed about advances in science that could affect the treatment and outcome of these illnesses. They appropriately apply this knowledge to evaluate available treatments and advocate for the best possible evidence-based care. They ask hard questions that many clinicians are often ill-prepared to answer. Genetics has advanced our understanding of eating disorders and provides a novel lens through which to understand these pernicious illnesses. Clinicians can now update their understanding of the etiology of eating disorders and abandon outdated etiological theories, some of which have done harm to patients and their families. Without becoming expert in psychiatric genetics, psychiatrists and other mental health care professionals can develop a general overview of the science, understand what it can and cannot offer, incorporate genetic factors into their case conceptualizations, and boost their confidence in discussing these topics with patients and families.

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UNASSIGNED: Schizophrenia is a brain disorder that originates during neurodevelopment and has complex genetic and environmental etiologies. Despite decades of clinical evidence of altered striatal function in affected patients, studies examining its cellular and molecular mechanisms in humans are limited. To explore neurodevelopmental alterations in the striatum associated with schizophrenia, the authors established a method for the differentiation of induced pluripotent stem cells (iPSCs) into ventral forebrain organoids (VFOs).
UNASSIGNED: VFOs were generated from postmortem dural fibroblast-derived iPSCs of four individuals with schizophrenia and four neurotypical control individuals for whom postmortem caudate genotypes and transcriptomic data were profiled in the BrainSeq neurogenomics consortium. Individuals were selected such that the two groups had nonoverlapping schizophrenia polygenic risk scores (PRSs).
UNASSIGNED: Single-cell RNA sequencing analyses of VFOs revealed differences in developmental trajectory between schizophrenia and control individuals in which inhibitory neuronal cells from the patients exhibited accelerated maturation. Furthermore, upregulated genes in inhibitory neurons in schizophrenia VFOs showed a significant overlap with upregulated genes in postmortem caudate tissue of individuals with schizophrenia compared with control individuals, including the donors of the iPSC cohort.
UNASSIGNED: The findings suggest that striatal neurons derived from high-PRS individuals with schizophrenia carry abnormalities that originated during early brain development and that the VFO model can recapitulate disease-relevant cell type-specific neurodevelopmental phenotypes in a dish.

Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD.
Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system.
No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD.
While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).

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Copy number variants (CNVs) are well-known genetic pleiotropic risk factors for multiple neurodevelopmental and psychiatric disorders (NPDs), including autism (ASD) and schizophrenia. Little is known about how different CNVs conferring risk for the same condition may affect subcortical brain structures and how these alterations relate to the level of disease risk conferred by CNVs. To fill this gap, the authors investigated gross volume, vertex-level thickness, and surface maps of subcortical structures in 11 CNVs and six NPDs.
Subcortical structures were characterized using harmonized ENIGMA protocols in 675 CNV carriers (CNVs at 1q21.1, TAR, 13q12.12, 15q11.2, 16p11.2, 16p13.11, and 22q11.2; age range, 6-80 years; 340 males) and 782 control subjects (age range, 6-80 years; 387 males) as well as ENIGMA summary statistics for ASD, schizophrenia, attention deficit hyperactivity disorder, obsessive-compulsive disorder, bipolar disorder, and major depression.
All CNVs showed alterations in at least one subcortical measure. Each structure was affected by at least two CNVs, and the hippocampus and amygdala were affected by five. Shape analyses detected subregional alterations that were averaged out in volume analyses. A common latent dimension was identified, characterized by opposing effects on the hippocampus/amygdala and putamen/pallidum, across CNVs and across NPDs. Effect sizes of CNVs on subcortical volume, thickness, and local surface area were correlated with their previously reported effect sizes on cognition and risk for ASD and schizophrenia.
The findings demonstrate that subcortical alterations associated with CNVs show varying levels of similarities with those associated with neuropsychiatric conditions, as well distinct effects, with some CNVs clustering with adult-onset conditions and others with ASD. These findings provide insight into the long-standing questions of why CNVs at different genomic loci increase the risk for the same NPD and why a single CNV increases the risk for a diverse set of NPDs.

Recent genome-wide association studies (GWASs) of alcohol-related phenotypes have uncovered key differences in the underlying genetic architectures of alcohol consumption and alcohol use disorder (AUD), with the two traits having opposite genetic correlations with psychiatric disorders. Understanding the genetic factors that underlie the transition from heavy drinking to AUD has important theoretical and clinical implications.
The authors used longitudinal data from the cross-ancestry Million Veteran Program sample to identify 1) novel loci associated with AUD and alcohol consumption (measured by the score on the consumption subscale of the Alcohol Use Disorders Identification Test [AUDIT-C]), 2) the impact of phenotypic variation on genetic discovery, and 3) genetic variants with direct effects on AUD that are not mediated through alcohol consumption.
The authors identified 26 loci associated with AUD and 22 loci associated with AUDIT-C score, including ancestry-specific and novel loci. In secondary GWASs that excluded individuals who report abstinence, the authors identified seven additional loci for AUD and eight additional loci for AUDIT-C score. Although the heterogeneity of the abstinent group biases the GWAS findings, unique variance between alcohol consumption and disorder remained after the abstinent group was excluded. Finally, using mediation analysis, the authors identified a set of variants with effects on AUD that are not mediated through alcohol consumption.
Differences in genetic architecture between alcohol consumption and AUD are consistent with their having different biological contributions. Genetic variants with direct effects on AUD are potentially relevant to understanding the transition from heavy alcohol consumption to AUD and may be targets for translational prevention and treatment efforts.

Stock structure is of paramount importance for sustainable management of exploited resources. In that context, genetic markers have been used for more than two decades to resolve spatial structure of marine exploited resources and to fully fathom stock dynamics and interactions. While genetic markers such as allozymes and RFLP dominated the debate in the early era of genetics, technology advances have provided scientists with new tools every decade to better assess stock discrimination and interactions (i.e. gene flow). Here, we provide a review of genetic studies performed to understand stock structure of Atlantic cod in Icelandic waters, from the early allozyme approaches to the genomic work currently carried out. We further highlight the importance of the generation of a chromosome-anchored genome assembly together with whole-genome population data, which drastically changed our perception of the possible management units to consider. After nearly 60 years of genetic investigation of Atlantic cod structure in Icelandic waters, genetic (and later genomic) data combined with behavioural monitoring using Data Storage Tags shifted the attention from geographical population structures to behavioural ecotypes. This review also demonstrates the need for future research to further disentangle the impact of these ecotypes (and gene flow among them) on the population structure of Atlantic cod in Icelandic waters. It also highlights the importance of whole-genome data to unravel unexpected within-species diversity related to chromosomal inversions and associated supergenes, which are important to consider for future development of sustainable management programmes of the species within the North Atlantic.

Despite substantial progress in identifying genomic variation associated with major depression, the mechanisms by which genomic and environmental factors jointly influence depression risk remain unclear. Genomically conferred sensitivity to the social environment may be one mechanism linking genomic variation and depressive symptoms. The authors assessed whether social support affects the likelihood of depression development differently across the spectrum of genomic risk in two samples that experienced substantial life stress: 1,011 first-year training physicians (interns) in the Intern Health Study (IHS) and 435 recently widowed Health and Retirement Study (HRS) participants.
Participants\' depressive symptoms and social support were assessed with questionnaires that were administered before and after the life stressor. Polygenic risk scores (PRSs) for major depressive disorder were calculated for both samples.
Depressive symptom scores increased by 126% after the start of internship in the IHS sample and by 34% after widowing in the HRS sample. There was an interaction between depression PRS and change in social support in the prediction of depressive symptoms in both the IHS sample (incidence rate ratio [IRR]=0.96, 95% CI=0.93, 0.98) and the HRS sample (IRR=0.78, 95% CI=0.66, 0.92), with higher depression PRS associated with greater sensitivity to changes in social support. Johnson-Neyman intervals indicated a crossover effect, with losses and gains in social support moderating the effect of PRS on depressive symptoms. (Johnson-Neyman interval in the IHS sample, -0.02, 0.71; in the HRS sample, -0.49, 1.92).
The study findings suggest that individuals with high genomic risk for developing increased depressive symptoms under adverse social conditions also benefit more from nurturing social environments.

Childhood maltreatment is associated with mental health problems, but the extent to which this relationship is causal remains unclear. To strengthen causal inference, the authors conducted a systematic review and meta-analysis of quasi-experimental studies examining the relationship between childhood maltreatment and mental health problems.
A search of PubMed, PsycINFO, and Embase was conducted for peer-reviewed, English-language articles from database inception until January 1, 2022. Studies were included if they examined the association between childhood maltreatment and mental health problems using a quasi-experimental method (e.g., twin/sibling differences design, children of twins design, adoption design, fixed-effects design, random-intercept cross-lagged panel model, natural experiment, propensity score matching, or inverse probability weighting).
Thirty-four quasi-experimental studies were identified, comprising 54,646 independent participants. Before quasi-experimental adjustment for confounding, childhood maltreatment was moderately associated with mental health problems (Cohen\'s d=0.56, 95% CI=0.41, 0.71). After quasi-experimental adjustment, a small association between childhood maltreatment and mental health problems remained (Cohen\'s d=0.31, 95% CI=0.24, 0.37). This adjusted association between childhood maltreatment and mental health was consistent across different quasi-experimental methods, and generalized across different psychiatric disorders.
These findings are consistent with a small, causal contribution of childhood maltreatment to mental health problems. Furthermore, the findings suggest that part of the overall risk of mental health problems in individuals exposed to maltreatment is due to wider genetic and environmental risk factors. Therefore, preventing childhood maltreatment and addressing wider psychiatric risk factors in individuals exposed to maltreatment could help to prevent psychopathology.