Multilevel sex-influenced neurobiological signatures of early life adversity.

History of childhood trauma enhances the detrimental effects of recent stressors on brain structure and function in major depressive disorder.

Early life experiences, the neural epigenome and affective disorder risk.

Adversity and brainAGE associations with age of first cannabis use in the Adolescent Brain Cognitive Development (ABCD) Study

Importance: Adolescent cannabis use is a growing concern due to its associations with long-term adverse mental health outcomes. However, the distinct, temporal associations of neurodevelopmental factors and childhood adverse life experiences (ALEs) with adolescent substance use in have not yet been fully elucidated. The Adolescent Brain Cognitive Development (ABCD) Study offers an unprecedented opportunity to prospectively examine neurobiological and socioenvironmental predictors of cannabis onset. Objective: To investigate magnetic resonance imaging-derived neurodevelopmental cortical brain Age Gap Estimate (brainAGE) and adverse life events as risk factors of early cannabis initiation. Design, Setting, and Participants: The ABCD Study is a longitudinal study across 22 sites in the United States. Data are collected starting at approximately 10 years old (currently at year-7 follow-up). Our analyses comprised 6688 (48% female) youth after exclusions. Main Outcomes and Measures: Cox proportional hazard models were computed to investigate brainAGE-sex interactions and 10 adversity dimensions at baseline as predictors of time to cannabis initiation up to age 18. Results: Mean age of initiation was 14.8 years (SD=1.43). Global brainAGE was modestly associated with cannabis initiation in females only (Hazard Ratio [HR]=1.05; 95% Confidence Interval [CI]=1.00-1.10, p = .049). Low socioeconomic status, caregiver substance use, family anger and arguments, and caregiver lack of supervision were associated with initiation (HRs = 1.11, 1.56, 1.09, 0.85, respectively; CIs = 1.04-1.19, 1.44-1.69, 1.09-1.19, 0.76-0.91, respectively; p's < .05). Other ALE dimensions and network-specific brainAGEs were not significantly associated with initiation. Conclusions and Relevance: Findings suggest that while cortical brainAGE may be somewhat increase vulnerability to adolescent cannabis use in females, its contributions are modest at best. In contrast, early childhood adversities such as socioeconomic factors and familial characteristics may present more substantive targets for prevention and intervention.

The Importance of Predictability in the Early-Life Environment for Neurodevelopment and Mental Health

Predictability, the degree to which environmental inputs are structured, patterned, and reliably signaled over time, has emerged as a central dimension of early experience with unique implications for brain development, stress physiology, and mental health. This review synthesizes convergent evidence from human and animal studies to argue that predictability is intrinsic to optimal brain development. Thus, unpredictable signals from the proximate environment—parents, family, and neighborhood—are a type of early-life adversity that is distinct from, for example, threat or deprivation. We first delineate what predictability means in developmental science, distinguishing it from valence and intensity. We then summarize multilevel mechanisms, from epigenomic regulation to circuit-level adaptions, by which predictable versus unpredictable signals shape developmental trajectories. We consider predictable structure against the backdrop of established types of early-life adversity, examining how resource scarcity, caregiver stress, and chaotic routines create unpredictable patterns that link to childhood and adult psychopathology. Building on conceptual and methodological work in human study cohorts and large populations as well as experimental animals, we discuss how to measure unpredictability (e.g., signal entropy, ecological assessments, questionnaires) and highlight sensitive windows when predictability is crucial for brain maturation. Finally, we propose paths for translational research and prevention of unpredictability-related sequelae on cognitive and mental health.

Childhood Maltreatment as a Predictor of Depression-Anxiety Coupling Strength

Major depressive disorder (MDD) and anxiety disorders are among the most common psychiatric conditions, with their co-occurrence associated with increased severity, functional impairment, and relapse risk. However, not all individuals with depressive symptoms experience co-occurring anxiety symptoms, highlighting the need to identify mechanisms that explain this variability. Childhood maltreatment, including emotional, physical, and sexual abuse and neglect, is a well-established transdiagnostic risk factor for internalizing psychopathology, yet its role in shaping dynamic co-occurrence of symptoms and disorders remains poorly understood. This study will examine childhood maltreatment as a predictor of Depression-Anxiety Coupling Strength (DACS), a construct reflecting the extent to which fluctuations in anxiety and depressive symptoms co-vary over time. Archival data (N=250) will be drawn from the LAUREL cohort in the Mood Research Laboratory at Queen’s University. Participants completed the Childhood Experience of Care and Abuse (CECA) interview at baseline and the Mood and Anxiety Symptom Questionnaire (MASQ-D30) at two follow-ups over eight months. Multilevel modeling (MLM) will estimate within-person DACS and test whether childhood maltreatment severity and subtype predict stronger coupling and more persistent symptom trajectories. I hypothesize that individuals with greater childhood maltreatment severity, particularly severity of emotional abuse and neglect, will exhibit stronger DACS, reflecting greater temporal coupling between depression and anxiety symptoms. Clarifying how early adversity shapes these dynamic processes may enhance prediction of illness trajectories and inform more precise interventions for individuals who experience comorbidity.

Adversity and adolescent brain development: differential associations with grey and white matter across two longitudinal cohorts

Globally, 60% of the population has experienced at least one type of adversity (e.g., emotional abuse, bullying) across infancy, childhood, and adolescence. Such experiences have been linked to an increased risk for mental health disorders. Changes in brain structure following experiences of childhood adversity have been hypothesised to be a mechanistic pathway explaining later mental health issues. However, to understand how changes in brain structure might mediate the effects of adversity, it is essential to identify which underlying neuronal processes may be affected by different types of adverse experiences. A key open question is whether grey or white matter is more vulnerable to adversity, as these two structures reflect distinct neurobiological mechanisms. This study investigated whether differences in trajectories of grey and white matter development during adolescence can be explained by exposure to different types of adversity. We applied the Adverse Adolescent Experiences Framework (Pollmann et al., 2025) categorising adversity into four levels: Intrapersonal (e.g., accidents), Caregiver (e.g., emotional neglect), Peer (e.g., bullying), and Community (e.g., neighbourhood safety). Exposure to each of the four factors was estimated through principal components analyses. We analysed two large longitudinal datasets: the Adolescent Brain Cognitive Development study (∼12,000 adolescents measured at ages 10, 12, and 14) and the IMAGEN study (∼1,400 adolescents measured at ages 14, 19, and 22). Using latent growth curve models, we captured individual differences in brain development by estimating baseline levels (intercepts) and rates of change (slopes) for total grey matter volume and mean white matter fractional anisotropy. In both cohorts, we found significant interindividual variability in baseline levels and rates of change for both grey matter volume and fractional anisotropy. Caregiver, Peer, and Community adversities were negatively associated only with the intercepts of grey matter volume and white matter fractional anisotropy. Importantly, associations differed between grey and white matter. In ABCD, Peer and Community adversities were more strongly associated with grey matter volume intercepts. In contrast, in IMAGEN, Caregiver, Peer and Community adversities were more strongly linked to white matter fractional anisotropy intercepts. This suggests that adversity has unique associations with grey and white matter, rather than exerting a uniform influence on brain structure. By demonstrating that different environments generate distinct biological associations with brain maturation, this work underscores the need to consider both grey and white matter when assessing the neurodevelopmental pathways to outcomes across the lifespan.