Deep Phenotyping at Scale: Study Protocol for the Korean Mood Disorder Genetic Study-Depression (KOMOGEN-D).

A core challenge in the genetic analysis of major depressive disorder (MDD) is how to recruit large numbers of stringently diagnosed cases with sufficient information to explore the interplay between genetic and environmental risk factors and evaluate genetic influences on putative MD subtypes and key clinical features. Currently, most genome-wide association studies of MDD rely on self-administered questionnaires or electronic health records, both of which are limited in diagnostic accuracy and introduce systematic, heritable biases that confound the interpretation of genetic analyses. Here, we describe how to address this problem through a combination of targeted ascertainment and in-depth phenotyping by clinical interview.

Phenome-wide association study of male and female sex chromosome trisomies in 1.5 million participants of MVP, FinnGen, and UK Biobank.

Sex chromosome trisomies (SCTs) are the most common whole-chromosome aneuploidy in humans. Yet, our understanding of the prevalence and associated health outcomes is largely driven by observational studies of clinically diagnosed individuals, resulting in a disproportionate focus on 47,XXY and associated hypogonadism. We analyzed microarray intensity data of sex chromosomes for 1.

Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits.

Background: Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.

Methods: We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.

Results: We replicated the well-known association at the locus (lead single-nucleotide polymorphism [SNP]: rs147144681,  = 1.

The Impact of the Parental Patterns of Morbidity and Comorbidity in the Cross-Generational Transmission of Risk for Major Depression and Alcohol Use Disorder.

To further understand the inter-relationship of the familial transmission of major depression (MD) and alcohol use disorder (AUD), we examine, via a multivariable Cox proportional hazards model, risks for AUD and MD in 1,244,516 individuals born in Sweden from 1970 to 1990 to intact mother-father pairs as a function of parental diagnoses of MD and/or AUD. Across the nine possible mating types, we see both direct transmission (MD → MD, AUD → AUD) and also, less strongly, indirect transmission: MD → AUD and AUD → MD. Risks in offspring accumulate with multiple affected parents, which reveals the impact of interactive effects in risk prediction.

The outcome of major psychiatric and substance use disorders as an index of genetic risk and genetic heterogeneity.

Background: We investigate whether, in Swedish national registers, social and psychiatric outcomes for six major psychiatric and substance disorders - drug use disorder (DUD), alcohol use disorder (AUD), major depression (MD), bipolar disorder (BD), anxiety disorder (AD), and schizophrenia (SZ) - reflect the primary genetic risk for each disorder and the level of genetic heterogeneity.

Methods: We utilize Genetic Risk Ratios - defined as the ratio of the genetic risk for secondary disorders to the genetic risk for the primary disorder - derived from Family Genetic Risk Scores. Poor social outcome was defined by a common factor of four variables: receipt of social welfare, sick leave, early retirement pension, and residence in a socially deprived area.

Functional and internalizing disorders co-aggregate with cardiometabolic and immune-related diseases within families: a population-based cohort study.

Background: Functional disorders share familial risk with internalizing disorders such as generalized anxiety disorder and depression, and are comorbid with cardiometabolic and immune-related diseases. We investigated whether functional and internalizing disorders co-aggregate with these diseases in families to gain insight into the aetiology of functional and internalizing disorders.  METHODS: We included 166,774 subjects (aged 3-94), from the population-based Lifelines Cohort Study, a Dutch general population cohort.

Genetic risk effects on psychiatric disorders act in sets.

Genetic studies of psychiatric disorders have typically assumed that all genetic effects contribute additively to disease liability. However, it is likely that psychiatric disorders have unrecognized subtypes, where synergistic sets of risk variants co-occur within certain cases more than expected under additivity. The existence of synergistic sets induces a structured form of statistical interactions called coordinated epistasis.

The Genetics of Cerebellar Structure and Associations With Cognitive Performance: A Twin Magnetic Resonance Imaging Study.

The cerebellum, traditionally associated with motor control, is increasingly recognized for its involvement in higher-order cognitive functions. However, the role of cerebellar subregions in cognition remains underexplored, as are the roles of genetic factors on cerebellar structure and brain-behavioral associations. The primary goal of this study was to investigate the relationship between cerebellar subregion volumes and cognitive performance.

Longitudinal predictors of alcohol use and problems during the COVID-19 pandemic in an at-risk veteran sample.

Individuals with pre-existing heavy alcohol use, prior traumatic exposures, and psychiatric disorders were considered an at-risk group for increased alcohol use and problems in the context of the COVID-19 pandemic. This study recruited from a multi-centre longitudinal cohort study of US military service members/veterans with combat exposure to examine the trajectories of alcohol use and problems in the context of a prolonged stressor. Individuals who endorsed heavy drinking and completed a measure of PTSD symptoms prior to the pandemic were invited to participate in a longitudinal survey study at three time points, three months apart, during the second year of the pandemic.

Measuring the Associations Between Brain Morphometry and Polygenic Risk Scores for Substance use Disorders in Drug-Naive Adolescents.

Substance use has been associated with differences in adult brain morphology; however, it is unclear whether these differences precede or are a result of substance use substance use. We investigated the impact of polygenic risk scores (PRSs) for cannabis use disorder (CUD) and general substance use and substance use disorder liability (SU/SUD) on brain morphology in drug-naïve adolescents. Baseline data were used from 1874 European-descent participants (ages 9-11) comprising 222, 328 and 387 pairs of MZ twins, DZ twins, and Non-Twin Siblings, respectively, in the Adolescent Brain Cognitive Development Study.

Repeated Clozapine Administration Causes Extensive Changes to the Expression of Coding and Non-coding RNAs, Including miR-124, in the Mouse Frontal Cortex.

Clozapine is arguably the most effective antipsychotic drug for the treatment of schizophrenia, but the mechanisms underlying its efficacy are poorly understood. Therefore, we perform deep RNA sequencing to test for differential transcription and exon use resulting from clozapine's effects in the mouse frontal cortex, and integrate our findings with known schizophrenia risk genes. We used a dose (4 mg/kg/day, i.

Profiles of Genetic Risks for Psychotic Disorders.

Importance: The etiologic interrelationship of 4 rare/controversial psychotic disorders (delusional disorder [DD], acute psychoses [AP], psychosis not otherwise specified [PNOS], and schizoaffective disorder [SAD]) is poorly understood.

Objective: To assess levels of the family genetic risk score (FGRS) for schizophrenia (SZ), bipolar disorder (BD), and major depression (MD) in individuals with DD, AP, PNOS, and SAD, thereby clarifying their genetic relationships.

Design, Setting, And Participants: This cohort study included all individuals born in Sweden between 1950 and 2000 to Swedish-born parents followed up until 2018 with diagnoses of MD, BD, SZ, SAD, AP, PNOS, and DD, based on diagnosis codes from national registries.

Manifestation of emotion regulation difficulties in intraindividual emotion dynamics.

Emotion dynamics, which describe affective patterns over time, may illustrate how specific emotion regulation difficulties manifest in daily life. However, limited research links emotion regulation with emotion dynamics assessed naturalistically. In two samples, 62 and 304 university students completed the Difficulties in Emotion Regulation Scale then completed ecological momentary assessments of positive and negative affect thrice daily for seven and 14 days, respectively, to examine mean positive and negative affect, affective variability, affective instability, and emotional inertia.

Evaluation of a 20-Item Version of the Trauma-Related Drinking to Cope Questionnaire.

Objectives: This study sought to develop and psychometrically evaluate an expanded version of the Trauma-Related Drinking to Cope (TRD) scale, a four-item self-report tool, which was developed to address a crucial gap in self-medication research. Before the development of the TRD, no measures existed which assessed alcohol use for coping with symptoms of posttraumatic stress disorder (PTSD) specifically. Previous work showed that the TRD has strong psychometric properties and clinical utility in its ability to identify individuals with PTSD who may be at risk for developing comorbid alcohol use disorder (AUD).

The Landscape of Shared and Divergent Genetic Influences across 14 Psychiatric Disorders.

Psychiatric disorders display high levels of comorbidity and genetic overlap. Genomic methods have shown that even for schizophrenia and bipolar disorder, two disorders long-thought to be etiologically distinct, the majority of genetic signal is shared. Furthermore, recent cross-disorder analyses have uncovered over a hundred pleiotropic loci shared across eight disorders.

You've got mail: comparing individuals who do and do not provide DNA saliva samples by mail in a study of severe alcohol use disorder.

Objective: Many genetic studies of psychiatric disorders rely on participants to mail in DNA samples. Differences in who returns a sample may affect the generalizability of these studies, but little attention has focused on possible differences between participants who do and do not provide samples. The present study compared participants with severe lifetime alcohol use disorder (AUD) who did and did not return saliva DNA samples.

Missing data approaches for longitudinal neuroimaging research: Examples from the Adolescent Brain and Cognitive Development (ABCD) Study®.

This paper addresses the challenges of managing missing values within expansive longitudinal neuroimaging datasets, using the specific example of data derived from the Adolescent Brain and Cognitive Development (ABCD) Study. The conventional listwise deletion method, while widely used, is not recommended due to the risk that substantial bias can potentially be introduced with this method. Unfortunately, recommended alternative practices can be challenging to implement with large datasets.

Childhood Trauma and are Associated with Adolescent Brain Function, Posttraumatic Stress, and Alcohol-related Outcomes.

Childhood trauma affects neurodevelopment and lifelong risk for posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD). Changes in brain structures and function are observed in young carriers of , the genetic factor most associated with Alzheimer's disease. Longitudinal studies of , childhood trauma, and neural connectivity in adolescence have not been explored.

A history of metaphorical brain talk in psychiatry.

From the very beginnings of our field in the late 18th century, psychiatrists have engaged, often extensively, in "metaphorical brain talk" - rephrasing descriptions of mental processes in unconfirmed brain metaphors (e.g., "diseased working of the brain convolutions").

The Impact of a Registry-Based Environmental Risk Score on Episodes of Alcohol Use Disorder and Drug Use Disorder in Swedish National Samples.

Objective: Psychosocial stress increases the risk for subsequent episodes of alcohol use disorder (AUD) and drug use disorder (DUD), with most studies assessing stress exposure by questionnaire or interview methods. We developed an environmental risk score (ERS) using multiple classes of stressful life events (SLEs) obtained from national Swedish registries.

Method: We assessed, in the entire adult population of Sweden ( = 7,105,712), the occurrence of 51 categories of SLEs derived from registry information for the six months prior to 9/1/2010 and the risk for AUD and DUD registration over the subsequent 18 months.

Familial coaggregation and shared familiality of functional and internalizing disorders in the Lifelines cohort.

Background: Functional disorders (FDs) are characterized by persistent somatic symptoms and are highly comorbid with internalizing disorders (IDs). To provide much-needed insight into FD etiology, we evaluated FD and ID familial coaggregation and shared familiality.

Methods: Lifelines is a three-generation cohort study, which assessed three FDs (myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS], irritable bowel syndrome [IBS], and fibromyalgia [FM]) and six IDs (major depressive disorder [MDD], dysthymia [DYS], generalized anxiety disorder [GAD], agoraphobia [AGPH], social phobia [SPH], and panic disorder [PD]) according to diagnostic criteria.

Combining family history and alcohol screening measures to identify emerging adults at risk of not being in education, employment, or training (NEET).

Purpose: Being outside of the labor and education system during young adulthood, a status termed not in education, employment, or training (NEET), is a risk factor for later social and health outcomes. This study examined whether parental substance use (PSU) moderates the relationship between personal alcohol consumption and NEET. Such information may inform screening practices.