Causal complexity in human research: On the shared challenges of behavior genetics, medical genetics, and environmentally oriented social science.

We received 23 spirited commentaries on our target article from across the disciplines of philosophy, economics, evolutionary genetics, molecular biology, criminology, epidemiology, and law. We organize our reply around three overarching questions: (1) What is a cause? (2) How are randomized controlled trials (RCTs) and within-family genome-wide association studies (GWASs) alike and unalike? (3) Is behavior genetics a qualitatively different enterprise? Throughout our discussion of these questions, we advocate for the idea that behavior genetics shares many of the same pitfalls and promises as environmentally oriented research, medical genetics, and other arenas of the social and behavioral sciences.

Strong intercorrelations among global graph-theoretic indices of structural connectivity in the human brain.

Graph-theoretic metrics derived from neuroimaging data have been heralded as powerful tools for uncovering neural mechanisms of psychological traits, psychiatric disorders, and neurodegenerative diseases. In N = 8,185 human structural connectomes from UK Biobank, we examined the extent to which 11 commonly-used global graph-theoretic metrics index distinct versus overlapping information with respect to interindividual differences in brain organization. Using unthresholded, FA-weighted networks we found that all metrics other than Participation Coefficient were highly intercorrelated, both with each other (mean |r| = 0.

General dimensions of human brain morphometry inferred from genome-wide association data.

Understanding the neurodegenerative mechanisms underlying cognitive decline in the general population may facilitate early detection of adverse health outcomes in late life. This study investigates genetic links between brain morphometry, ageing and cognitive ability. We develop Genomic Principal Components Analysis (Genomic PCA) to model general dimensions of brain-wide morphometry at the level of their underlying genetic architecture.

An in-laboratory stressor reveals unique genetic variation in child cortisol output.

Dysregulation of biological stress response, as measured by cortisol output, has been a primary candidate mechanism for how social experiences become biologically embedded. Cortisol is the primary output of the hypothalamic pituitary adrenal (HPA) axis. Cortisol levels vary systematically across the day and change in response to both sudden, acute stress experiences as well as prolonged exposure to environmental stress.

Building causal knowledge in behavior genetics.

Behavior genetics is a controversial science. For decades, scholars have sought to understand the role of heredity in human behavior and life-course outcomes. Recently, technological advances and the rapid expansion of genomic databases have facilitated the discovery of genes associated with human phenotypes such as educational attainment and substance use disorders.

Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction.

Behaviors and disorders related to self-regulation, such as substance use, antisocial behavior and attention-deficit/hyperactivity disorder, are collectively referred to as externalizing and have shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association analyses. By pooling data from ~1.

The relationship between executive function, processing speed, and attention-deficit hyperactivity disorder in middle childhood.

Attention-Deficit Hyperactivity Disorder (ADHD) is a heterogeneous disorder that is highly impairing. Early, accurate diagnosis maximizes long-term positive outcomes for youth with ADHD. Tests of executive functioning (EF) are potential tools for screening and differential diagnosis of ADHD subtypes.

Rising to the Occasion of This COVID-19-Impacted Nation: Development, Implementation, and Feasibility of the Brief Assessment-Informed Skills Intervention for COVID-19 (BASIC).

The COVID-19 pandemic has had a profound impact on the global economy, physical health, and mental health. This pandemic, like previous viral outbreaks, has resulted in spikes in anxiety, depression, and stress. Even though millions of individuals face the physical health consequences of infection by COVID-19, even more individuals are confronted with the mental health consequences of this pandemic.

Aging-Sensitive Networks Within the Human Structural Connectome Are Implicated in Late-Life Cognitive Declines.

Background: Aging-related cognitive decline is a primary risk factor for Alzheimer's disease and related dementias. More precise identification of the neurobiological bases of cognitive decline in aging populations may provide critical insights into the precursors of late-life dementias.

Methods: Using structural and diffusion brain magnetic resonance imaging data from the UK Biobank (n = 8185; age range, 45-78 years), we examined aging of regional gray matter volumes (nodes) and white matter structural connectivity (edges) within 9 well-characterized networks of interest in the human brain connectome.

Weak and uneven associations of home, neighborhood, and school environments with stress hormone output across multiple timescales.

The progression of lifelong trajectories of socioeconomic inequalities in health and mortality begins in childhood. Dysregulation in cortisol, a stress hormone that is the primary output of the hypothalamus-pituitary-adrenal (HPA) axis, has been hypothesized to be a mechanism for how early environmental adversity compromises health. However, despite the popularity of cortisol as a biomarker for stress and adversity, little is known about whether cortisol output differs in children being raised in socioeconomically disadvantaged environments.

Testing Cold and Hot Cognitive Control as Moderators of a Network of Comorbid Psychopathology Symptoms in Adolescence.

Comorbidity is pervasive across psychopathological symptoms, diagnoses, and domains. Network analysis is a method for investigating symptom-level associations that underlie comorbidity, particularly through connecting diagnostic syndromes. We applied network analyses of comorbidity to data from a population-based sample of adolescents ( = 849).

The effect of network thresholding and weighting on structural brain networks in the UK Biobank.

Whole-brain structural networks can be constructed using diffusion MRI and probabilistic tractography. However, measurement noise and the probabilistic nature of the tracking procedure result in an unknown proportion of spurious white matter connections. Faithful disentanglement of spurious and genuine connections is hindered by a lack of comprehensive anatomical information at the network-level.

A Model of Aggressive Behavior: Early Adversity, Impulsivity, and Response Inhibition.

Exposure to adverse environments during childhood is robustly linked to future aggressive behavior. In this study we tested a model of emotional and neurocognitive mechanisms related to aggressive behavior in the context of childhood adversity. More specifically, we used path analysis to assess the distal contribution of childhood adversity and the more proximal contributions of emotion-related and non-emotion-related forms of impulsivity, and behavioral response inhibition to aggressive behavior.