General and specific effects of early-life psychosocial adversities on adolescent grey matter volume

AbstractExposure to childhood adversities (CA) is associated with subsequent alterations in regional brain grey matter volume (GMV). Prior studies have focused mainly on severe neglect and maltreatment. The aim of this study was to determine in currently healthy adolescents if exposure to more common forms of CA results in reduced GMV. Effects on brain structure were investigated using voxel-based morphometry in a cross-sectional study of youth recruited from a population-based longitudinal cohort. 58 participants (mean age=18.4) with (n=27) or without (n=31) CA exposure measured retrospectively from maternal interview were included in the study. Measures of recent negative life events (RNLE) recorded at 14 and 17years, current depressive symptoms, gender, participant/parental psychiatric history, current family functioning perception and 5-HTTLPR genotype were covariates in analyses. A multivariate analysis of adversities demonstrated a general association with a widespread distributed neural network consisting of cortical midline, lateral frontal, temporal, limbic, and cerebellar regions. Univariate analyses showed more specific associations between adversity measures and regional GMV: CA specifically demonstrated reduced vermis GMV and past psychiatric history with reduced medial temporal lobe volume. In contrast RNLE aged 14 was associated with increased lateral cerebellar and anterior cingulate GMV. We conclude that exposure to moderate levels of childhood adversities occurring during childhood and early adolescence exerts effects on the developing adolescent brain. Reducing exposure to adverse social environments during early life may optimize typical brain development and reduce subsequent mental health risks in adult life

The impact of psychological stress and trauma on later-life cognitive function and dementia

Dementia is an increasing global issue, currently affecting an estimated 50 million people worldwide. This number is predicted to increase to 82 million by the year 2030, due to the ageing global population. Theoretically, preventing late-onset dementia may seem extremely difficult as the greatest risk factor, age, is unmodifiable. However, it is estimated that a third of dementia cases could potentially be prevented or delayed by removing or reducing modifiable risk factors. Increasing evidence suggests that chronic stress, which may ari

Perigenual anterior cingulate morphology covaries with perceived social standing

Low socioeconomic status (SES) increases the risk for developing psychiatric and chronic medical disorders. A stress-related pathway by which low SES may affect mental and physical health is through the perception of holding a low social standing, termed low subjective social status. This proposal implicates overlapping brain regions mediating stress reactivity and socioemotional behaviors as neuroanatomical substrates that could plausibly link subjective social status to health-related outcomes. In a test of this proposal, we used a computational structural neuroimaging method (voxel-based morphometry) in a healthy community sample to examine the relationships between reports of subjective social status and regional gray matter volume. Results showed that after accounting for potential demographic confounds, subclinical depressive symptoms, dispositional forms of negative emotionality and conventional indicators of SES, self-reports of low subjective social status uniquely covaried with reduced gray matter volume in the perigenual area of the anterior cingulate cortex (pACC)—a brain region involved in experiencing emotions and regulating behavioral and physiological reactivity to psychosocial stress. The pACC may represent a neuroanatomical substrate by which perceived social standing relates to mental and physical health

The enduring impact of childhood maltreatment on grey matter development

Childhood maltreatment doubles an individual’s risk of developing a psychiatric disorder, yet the neurobiological nature of the enduring impact of childhood maltreatment remains elusive. This thesis explores the long-term effect of childhood maltreatment on grey matter. The primary aims of this thesis are to discern the spatial extent, temporal profile and physiological breadth of the developmental impact of childhood maltreatment amongst young people with emerging mental disorder. Chapter II comprises of a meta-analysis of thirty-eight published articles and demonstrates that adults with a history of childhood maltreatment most commonly exhibit reduced grey matter in the hippocampus, amygdala and right dorsolateral prefrontal cortex, compared to non-maltreated adults. Chapters III-V contain three original studies, involving a cohort of 123 young people, aged 14-26, with emerging mental illness. Chapter III bridges a gap between cross-sectional child and adult studies by longitudinally mapping the developmental trajectory of the hippocampus and amygdala following childhood maltreatment. This study provided the first direct evidence that childhood maltreatment stunts hippocampal development into young adulthood. Chapter IV assesses the utility of the cumulative stress and mismatch hypotheses in understanding the contribution of childhood abuse and recent stress to the structure and function of the limbic system. Chapter V extends on recent advances in connectome research to examine the effect of childhood maltreatment on structural covariance networks. Investigation of the correspondence of structural covariance with structural connectivity and functional connectivity revealed that reduced grey matter across the network is likely related to deceased functional coactivation following childhood maltreatment. Chapter VI discusses the significance of these studies in understanding how maltreatment shapes brain development and increases the risk of psychiatric illness

Neuroprogression in post-traumatic stress disorder : a systematic review

Introduction: Neuroprogression has been proposed as the pathological rewiring of the brain that takes place in parallel with clinical and neurocognitive deterioration in the course of psychiatric disorders. This study aims to review the biological underpinnings and clinical outcomes related to neuroprogression in post-traumatic stress disorder (PTSD). Methods: We performed a systematic review by searching PubMed, Embase, and Web of Science for articles published between January 1, 1960, and January 6, 2020. Inclusion criteria were met when articles assessed brain changes, neurocognition, functioning, inflammation, oxidative stress, and neurotrophins in patients with PTSD. Narrative review articles, case reports, and preclinical studies were excluded. Results: A total of 965 abstracts were identified and 15 articles were included in our systematic review. It seems that for a subset of patients whose symptoms worsen or are maintained at a high intensity there is a progressive change in the frontal lobe, especially the prefrontal cortex, and worsening of both neurocognition (verbal memory and facial recognition) and functioning (physical, psychological, social and environmental). Conclusion: Although current findings associate progressive reduction in frontal lobe size with neurocognitive impairment, further research is needed to characterize PTSD as a neuroprogressive disorder

More than a feeling: A unified view of stress measurement for population science.

Stress can influence health throughout the lifespan, yet there is little agreement about what types and aspects of stress matter most for human health and disease. This is in part because "stress" is not a monolithic concept but rather, an emergent process that involves interactions between individual and environmental factors, historical and current events, allostatic states, and psychological and physiological reactivity. Many of these processes alone have been labeled as "stress." Stress science would be further advanced if researchers adopted a common conceptual model that incorporates epidemiological, affective, and psychophysiological perspectives, with more precise language for describing stress measures. We articulate an integrative working model, highlighting how stressor exposures across the life course influence habitual responding and stress reactivity, and how health behaviors interact with stress. We offer a Stress Typology articulating timescales for stress measurement - acute, event-based, daily, and chronic - and more precise language for dimensions of stress measurement

Childhood socioeconomic status and childhood maltreatment: Distinct associations with brain structure

The present study examined the relationship between childhood socioeconomic status (SES), childhood maltreatment, and the volumes of the hippocampus and amygdala between the ages of 25 and 36 years. Previous work has linked both low SES and maltreatment with reduced hippocampal volume in childhood, an effect attributed to childhood stress. In 46 adult subjects, only childhood maltreatment, and not childhood SES, predicted hippocampal volume in regression analyses, with greater maltreatment associated with lower volume. Neither factor was related to amygdala volume. When current SES and recent interpersonal stressful events were also considered, recent interpersonal stressful events predicted smaller hippocampal volumes over and above childhood maltreatment. Finally, exploratory analyses revealed a significant sex by childhood SES interaction, with women’s childhood SES showing a significantly more positive relation (less negative) with hippocampus volume than men’s. The overall effect of childhood maltreatment but not SES, and the sex-specific effect of childhood SES, indicate that different forms of stressful childhood adversity affect brain development differently