The Mechanisms Underlying the Intergenerational Transmission of Substance Use and Misuse: An Integrated Research Approach.

Substance use and substance use disorders run in families. While it has long been recognized that the etiology of substance use behaviors and disorders involves a combination of genetic and environmental factors, two key questions remain largely unanswered: (1) the intergenerational transmission through which these genetic predispositions are passed from parents to children, and (2) the molecular mechanisms linking genetic variants to substance use behaviors and disorders. This article aims to provide a comprehensive conceptual framework and methodological approach for investigating the intergenerational transmission of substance use behaviors and disorders, by integrating genetic nurture analysis, gene expression imputation, and weighted gene co-expression network analysis.

Connecting the dots: Network structures of internalizing and functional symptoms in a population-based cohort.

Objective: Comorbidities between internalizing disorders (IDs) and functional disorders (FDs) are well-documented, indicating shared pathways. However, their symptom-level relationships have been largely unexplored. This exploratory study employs a network approach to investigate symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS) to identify bridge symptoms explaining comorbidity between the two domains.

Comorbidity and sex differences in functional disorders and internalizing disorders.

Objective: In the current exploratory study we estimate comorbidity rates between FDs [fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and irritable bowel syndrome (IBS)]-and IDs-[major depressive disorder (MDD) and generalized anxiety disorder (GAD)] by using self-reported diagnostic criteria.

Method: We analyzed data from 107,849 participants (mean age = 49.3 (SD = 13.

Genomics Research of Lifetime Depression in the Netherlands: The BIObanks Netherlands Internet Collaboration (BIONIC) Project.

In this cohort profile article we describe the lifetime major depressive disorder (MDD) database that has been established as part of the BIObanks Netherlands Internet Collaboration (BIONIC). Across the Netherlands we collected data on () lifetime MDD diagnosis in 132,850 Dutch individuals. Currently, = 66,684 of these also have genomewide single nucleotide polymorphism (SNP) data.

Using parent-offspring pairs and trios to estimate indirect genetic effects in education.

We investigated indirect genetic effects (IGEs), also known as genetic nurture, in education with a novel approach that uses phased data to include parent-offspring pairs in the transmitted/nontransmitted study design. This method increases the power to detect IGEs, enhances the generalizability of the findings, and allows for the study of effects by parent-of-origin. We validated and applied this method in a family-based subsample of adolescents and adults from the Lifelines Cohort Study in the Netherlands (N = 6147), using the latest genome-wide association study data on educational attainment to construct polygenic scores (PGS).

Clinical characteristics indexing genetic differences in bipolar disorder - a systematic review.

Bipolar disorder is a heterogenous condition with a varied clinical presentation. While progress has been made in identifying genetic variants associated with bipolar disorder, most common genetic variants have not yet been identified. More detailed phenotyping (beyond diagnosis) may increase the chance of finding genetic variants.

Testing the mood brightening hypothesis: Hedonic benefits of physical, outdoor, and social activities in people with anxiety, depression or both.

Background: The mood brightening hypothesis postulates that people with depressive symptoms report more positive affect (PA) and less negative affect (NA) than healthy controls after rewarding daily life activities. Whether mood brightening also occurs in people with anxiety symptoms remains unclear. This study examined effects of physical activity, being outdoors, and social activity on PA and NA across different levels of depression and anxiety symptoms in the general Dutch population.

Sociodemographic, lifestyle and clinical characteristics of energy-related depression symptoms: A pooled analysis of 13,965 depressed cases in 8 Dutch cohorts.

Background: In a substantial subgroup of depressed patients, atypical, energy-related depression symptoms (e.g. increased appetite/weight, hypersomnia, loss of energy) tend to cluster with immuno-metabolic dysregulations (e.

Loneliness associates strongly with anxiety and depression during the COVID pandemic, especially in men and younger adults.

Loneliness is associated with major depressive disorder (MDD), and likely also with generalized anxiety disorder (GAD). It is unclear if these associations are moderated by age, sex, or genetic susceptibility for MDD. We included 75,279 individuals from the Lifelines COVID-19 study, a longitudinal study of a Dutch population-based cohort.

The structure of the symptoms of major depression: Factor analysis of a lifetime worst episode of depressive symptoms in a large general population sample.

Background: A range of depressive symptoms may occur during an episode of major depression (MD). Do these symptoms describe a single disorder liability or different symptom dimensions? This study investigates the structure and clinical relevance of an expanded set of depressive symptoms in a large general population sample.

Methods: We studied 43,431 subjects from the Dutch Lifelines Cohort Study who participated in an online survey assessing the 9 symptom criteria of MD (DSM-IV-TR) and additional depressive symptoms during their worst lifetime episode of depressive symptoms lasting two weeks or more.

Intermediate stable states in substance use.

Many people across the world use potentially addictive legal and illegal substances, but evidence suggests that not all use leads to heavy use and dependence, as some substances are used moderately for long periods of time. Here, we empirically examine, the stability of and transitions between three substance use states: zero-use, moderate use, and heavy use. We investigate two large datasets from the US and the Netherlands on yearly usage and change of alcohol, nicotine, and cannabis.

Symptom networks in major depression do not diverge across sex, familial risk, and environmental risk.

Background: Major depression (MD) is a heterogeneous disorder in terms of its symptoms. Symptoms vary by presence of risk factors such as female sex, familial risk, and environmental adversity. However, it is unclear if these factors also influence interactions between symptoms.

Investigating data-driven biological subtypes of psychiatric disorders using specification-curve analysis.

Background: Cluster analyses have become popular tools for data-driven classification in biological psychiatric research. However, these analyses are known to be sensitive to the chosen methods and/or modelling options, which may hamper generalizability and replicability of findings. To gain more insight into this problem, we used Specification-Curve Analysis (SCA) to investigate the influence of methodological variation on biomarker-based cluster-analysis results.

Data mining algorithm predicts a range of adverse outcomes in major depression.

Background: Course of illness in major depression (MD) is highly varied, which might lead to both under- and overtreatment if clinicians adhere to a 'one-size-fits-all' approach. Novel opportunities in data mining could lead to prediction models that can assist clinicians in treatment decisions tailored to the individual patient. This study assesses the performance of a previously developed data mining algorithm to predict future episodes of MD based on clinical information in new data.

Measurement and genetic architecture of lifetime depression in the Netherlands as assessed by LIDAS (Lifetime Depression Assessment Self-report).

Background: Major depressive disorder (MDD) is a common mood disorder, with a heritability of around 34%. Molecular genetic studies made significant progress and identified genetic markers associated with the risk of MDD; however, progress is slowed down by substantial heterogeneity as MDD is assessed differently across international cohorts. Here, we used a standardized online approach to measure MDD in multiple cohorts in the Netherlands and evaluated whether this approach can be used in epidemiological and genetic association studies of depression.

Data-driven biological subtypes of depression: systematic review of biological approaches to depression subtyping.

Research into major depressive disorder (MDD) is complicated by population heterogeneity, which has motivated the search for more homogeneous subtypes through data-driven computational methods to identify patterns in data. In addition, data on biological differences could play an important role in identifying clinically useful subtypes. This systematic review aimed to summarize evidence for biological subtypes of MDD from data-driven studies.

Predicting antidepressant response by monitoring early improvement of individual symptoms of depression: individual patient data meta-analysis.

Background: Improvement in depression within the first 2 weeks of antidepressant treatment predicts good outcomes, but non-improvers can still respond or remit, whereas improvers often do not.AimsWe aimed to investigate whether early improvement of individual depressive symptoms better predicts response or remission.

Method: We obtained individual patient data of 30 trials comprising 2184 placebo-treated and 6058 antidepressant-treated participants.

Sex similarities and differences in risk factors for recurrence of major depression.

Background: Major depression (MD) occurs about twice as often in women as in men, but it is unclear whether sex differences subsist after disease onset. This study aims to elucidate potential sex differences in rates and risk factors for MD recurrence, in order to improve prediction of course of illness and understanding of its underlying mechanisms.

Methods: We used prospective data from a general population sample (n = 653) that experienced a recent episode of MD.

PSYCHIATRIC COMORBIDITY DOES NOT ONLY DEPEND ON DIAGNOSTIC THRESHOLDS: AN ILLUSTRATION WITH MAJOR DEPRESSIVE DISORDER AND GENERALIZED ANXIETY DISORDER.

Background: High rates of psychiatric comorbidity are subject of debate: To what extent do they depend on classification choices such as diagnostic thresholds? This paper investigates the influence of different thresholds on rates of comorbidity between major depressive disorder (MDD) and generalized anxiety disorder (GAD).

Methods: Point prevalence of comorbidity between MDD and GAD was measured in 74,092 subjects from the general population (LifeLines) according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria. Comorbidity rates were compared for different thresholds by varying the number of necessary criteria from ≥ 1 to all nine symptoms for MDD, and from ≥ 1 to all seven symptoms for GAD.