Assessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research.

Psychiatric disorders are highly comorbid, heritable, and genetically correlated [1-4]. The primary objective of cross-disorder psychiatric genetics research is to identify and characterize both the shared genetic factors that contribute to convergent disease etiologies and the unique genetic factors that distinguish between disorders [4, 5]. This information can illuminate the biological mechanisms underlying comorbid presentations of psychopathology, improve nosology and prediction of illness risk and trajectories, and aid the development of more effective and targeted interventions.

Using Alternative Definitions of Controls to Increase Statistical Power in GWAS.

Genome-wide association studies (GWAS) are often underpowered due to small effect sizes of common single nucleotide polymorphisms (SNPs) on phenotypes and extreme multiple testing thresholds. The most common approach for increasing statistical power is to increase sample size. We propose an alternative strategy of redefining case-control outcomes into ordinal case-subthreshold-asymptomatic variables.

Using Alternative Definitions of Controls to Increase Statistical Power in GWAS.

Genome-wide association studies (GWAS) are underpowered due to small effect sizes of single nucleotide polymorphisms (SNPs) on phenotypes and extreme multiple testing thresholds. The most common approach for increasing statistical power is to increase sample size. We propose an alternative strategy of redefining case-control outcomes into ordinal case-subthreshold-asymptomatic variables.

The clinical presentation of major depressive disorder in youth with co-occurring obsessive-compulsive disorder.

Background: Major depressive disorder (MDD) is common in youth and among the most frequent comorbid disorders in pediatric obsessive-compulsive disorder (OCD), but it is unclear whether the presence of OCD affects the symptom presentation of MDD in youth.

Methods: A sample of youth with OCD and MDD (n = 124) and a sample of youth with MDD but no OCD (n = 673) completed the Patient Health Questionnaire for Adolescents (PHQ-A). The overall and symptom-level presentation of MDD were examined using group comparisons and network analysis.

Genetic and environmental influences on alpha amylase stress reactivity and shared genetic covariation with cortisol.

Salivary alpha amylase (sAA) is a common measure of stress reactivity, primarily reflecting sympathetic nervous system activity. Salivary cortisol is also a reliable, frequently used biomarker of stress and reflects the hypothalamic-pituitary-adrenal (HPA) axis response. This study examined heritability across varying metrics of sAA in response to a social evaluative stressor, the Trier Social Stress Test (TSST).

Methylome-wide association study of anxiety disorders.

Anxiety Disorders (ANX) such as panic disorder, generalized anxiety disorder, and phobias, are highly prevalent conditions that are moderately heritable. Evidence suggests that DNA methylation may play a role, as it is involved in critical adaptations to changing environments. Applying an enrichment-based sequencing approach covering nearly 28 million autosomal CpG sites, we conducted a methylome-wide association study (MWAS) of lifetime ANX in 1132 participants (618 cases/514 controls) from the Netherlands Study of Depression and Anxiety.

Dimensional and transdiagnostic phenotypes in psychiatric genome-wide association studies.

Genome-wide association studies (GWAS) provide biological insights into disease onset and progression and have potential to produce clinically useful biomarkers. A growing body of GWAS focuses on quantitative and transdiagnostic phenotypic targets, such as symptom severity or biological markers, to enhance gene discovery and the translational utility of genetic findings. The current review discusses such phenotypic approaches in GWAS across major psychiatric disorders.

Intergenerational transmission of parental neuroticism to emotional problems in 8-year-old children: Genetic and environmental influences.

Background: Children of parents with high levels of neuroticism tend to have high neuroticism themselves as well as increased risk of experiencing symptoms of anxiety and depression. It is not yet clear how much of this link is attributable to a potential effect of parent on child (e.g.

Pediatric anxiety associated with altered facial emotion recognition.

Multiple psychiatric disorders are associated with difficulties in facial emotion recognition. However, generalized anxiety disorder may be associated with more accurate recognition of others' emotional expressions, particularly expressions of happiness and fear, which index safety and threat. Children aged 9-14 from a community sample (N = 601) completed a facial emotion labeling task.

Rates of Incidental Findings in Brain Magnetic Resonance Imaging in Children.

Importance: Incidental findings (IFs) are unexpected abnormalities discovered during imaging and can range from normal anatomic variants to findings requiring urgent medical intervention. In the case of brain magnetic resonance imaging (MRI), reliable data about the prevalence and significance of IFs in the general population are limited, making it difficult to anticipate, communicate, and manage these findings.

Objectives: To determine the overall prevalence of IFs in brain MRI in the nonclinical pediatric population as well as the rates of specific findings and findings for which clinical referral is recommended.

Genetic and environmental influences on cortisol reactivity to a psychosocial stressor in adolescents and young adults.

Individuals vary in their response to psychological and physiological stressors, and this reactivity can be captured using measures of cortisol. Previous research suggests cortisol reactivity is under some degree of genetic control; however, the measures used have varied widely. This study (N = 524) examined potential differences in heritability across varying cortisol metrics of stress reactivity following the Trier Social Stress Test (TSST) and whether these measures are genetically or environmentally interrelated.

Resting-State Directional Connectivity and Anxiety and Depression Symptoms in Adult Cannabis Users.

Background: Anxiety and depression symptoms are common among cannabis users and could be a risk factor for cannabis use (CU) disorder. Thus, it is critical to understand the neuronal circuits underlying the associations between CU and these symptoms. Alterations in resting-state functional connectivity within and/or between the default mode network and salience network have been reported in CU, anxiety, and depressive disorders and thus could be a mechanism underlying the associations between CU disorder and anxiety/depression symptoms.

An epigenome-wide association study of early-onset major depression in monozygotic twins.

Major depression (MD) is a debilitating mental health condition with peak prevalence occurring early in life. Genome-wide examination of DNA methylation (DNAm) offers an attractive complement to studies of allelic risk given it can reflect the combined influence of genes and environment. The current study used monozygotic twins to identify differentially and variably methylated regions of the genome that distinguish twins with and without a lifetime history of early-onset MD.

Assessing Stakeholder Perceptions of the Utility of Genetic Information for the Clinical Care of Mental Health Disorders: We Have a Will but Need to See the Way.

Academic stakeholders' (primarily mental health researchers and clinicians) practices and attitudes related to the translation of genetic information into mental health care were assessed. A three-part survey was administered at two large, urban universities. Response frequencies were calculated.

Genetic and environmental risk structure of internalizing psychopathology in youth.

Background: Internalizing disorders (IDs), consisting of syndromes of anxiety and depression, are common, debilitating conditions often beginning early in life. Various trait-like psychological constructs are associated with IDs. Our prior analysis identified a tripartite model of Fear/Anxiety, Dysphoria, and Positive Affect among symptoms of anxiety and depression and the following constructs in youth: anxiety sensitivity, fearfulness, behavioral activation and inhibition, irritability, neuroticism, and extraversion.

Genome-wide association study of shared liability to anxiety disorders in Army STARRS.

Anxiety disorders (ANX), namely generalized anxiety, panic disorder, and phobias, are common, etiologically complex syndromes that show increasing prevalence and comorbidity throughout adolescence and beyond. Few genome-wide association studies (GWAS) examining ANX risk have been published and almost exclusively in individuals of European ancestry. In this study, we phenotyped participants from the Army Study To Assess Risk and Resilience in Servicemembers (STARRS) to approximate DSM-based ANX diagnoses.

A major role for common genetic variation in anxiety disorders.

Anxiety disorders are common, complex psychiatric disorders with twin heritabilities of 30-60%. We conducted a genome-wide association study of Lifetime Anxiety Disorder (n = 25 453, n = 58 113) and an additional analysis of Current Anxiety Symptoms (n = 19 012, n = 58 113). The liability scale common variant heritability estimate for Lifetime Anxiety Disorder was 26%, and for Current Anxiety Symptoms was 31%.

Image processing and analysis methods for the Adolescent Brain Cognitive Development Study.

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning.

Differential Associations of Distress Tolerance and Anxiety Sensitivity With Adolescent Internalizing Psychopathology.

Distress tolerance and anxiety sensitivity may differentiate among internalizing disorders, though few studies have examined differential associations of distress tolerance and anxiety sensitivity with depression and anxiety symptoms while adjusting for their intercorrelation. In an adolescent genetic epidemiological sample (ages 15-21), the present study ( = 848, 56.97% female) examined concurrent associations of distress tolerance and anxiety sensitivity with internalizing psychopathology (i.

Heritability, stability, and prevalence of tonic and phasic irritability as indicators of disruptive mood dysregulation disorder.

Background: Little is known about genetic and environmental influences on the components of disruptive mood dysregulation disorder (DMDD), tonic irritability (i.e., irritable mood) and phasic irritability (i.

Quantifying Dispositional Fear as Threat Sensitivity: Development and Initial Validation of a Model-Based Scale Measure.

The Research Domain Criteria initiative aims to reorient the focus of psychopathology research toward biobehavioral constructs that cut across different modalities of measurement, including self-report and neurophysiology. Constructs within the Research Domain Criteria framework are intentionally transdiagnostic, with the construct of "acute threat," for example, broadly relevant to clinical problems and associated traits involving fearfulness and stress reactivity. A potentially valuable referent for research on the construct of acute threat is a structural model of fear/fearlessness questionnaires known to predict variations in physiological threat reactivity as indexed by startle potentiation.