Abstract:Imaging genetics offers the possibility of detecting associations between genotype and brain structure as well as function, with effect sizes potentially exceeding correlations between genotype and behavior. However, study results are often limited due to small sample sizes and methodological differences, thus reducing the reliability of findings. The IMAGEN cohort with 2000 young adolescents assessed from the age of 14 onwards tries to eliminate some of these limitations by offering a longitudinal approach an… Show more
“…This process involves disruption of the psychological and biological systems mediating responses to stressful events and may remain difficult to describe in precise mechanistic terms until the culmination of large-scale longitudinal studies, such as the UK Biobank, the Avon Longitudinal Study of Parents and Children (ALSPAC), the Adolescent Brain Cognitive Development (ABCD) study and the IMAGEN project. 173–176 These are well placed to address the interactions of CT with biological markers (eg, genetic, brain-derived, hormonal or inflammatory-based) to determine the contributions to the development of BD, its course and severity. Understanding the nature of and key players in this protracted course of causal events and the ensuing altered trajectories of individuals’ mental wellbeing and resilience will be vital to the potential progress of effective monitoring, management and intervention standards.…”
Childhood trauma (CT) has been repeatedly linked to earlier onset and greater severity of bipolar disorder (BD) in adulthood. However, such knowledge is mostly based on retrospective and cross-sectional studies in adults with BD. The first objective of this selective review is to characterize the short-term effects of CT in the development of BD by focusing on studies in young people. The second objective is to describe the longer-term consequences of CT by considering studies with adult participants. This review first outlines the most prominent hypotheses linking CT exposure and the onset of BD. Then, it summarizes the psychological and biological risk factors implicated in the development of BD, followed by a discussion of original studies that investigated the role of CT in young people with early-onset BD, youths at increased risk of developing BD, or young people with BD with a focus on subclinical and clinical outcome measures. The review considers additional biological and psychological factors associated with a negative impact of CT on the long-term course of BD in later adulthood. Finally, we discuss how the integration of information of CT can improve ongoing early identification of BD and mitigate severe clinical expression in later adulthood.
“…This process involves disruption of the psychological and biological systems mediating responses to stressful events and may remain difficult to describe in precise mechanistic terms until the culmination of large-scale longitudinal studies, such as the UK Biobank, the Avon Longitudinal Study of Parents and Children (ALSPAC), the Adolescent Brain Cognitive Development (ABCD) study and the IMAGEN project. 173–176 These are well placed to address the interactions of CT with biological markers (eg, genetic, brain-derived, hormonal or inflammatory-based) to determine the contributions to the development of BD, its course and severity. Understanding the nature of and key players in this protracted course of causal events and the ensuing altered trajectories of individuals’ mental wellbeing and resilience will be vital to the potential progress of effective monitoring, management and intervention standards.…”
Childhood trauma (CT) has been repeatedly linked to earlier onset and greater severity of bipolar disorder (BD) in adulthood. However, such knowledge is mostly based on retrospective and cross-sectional studies in adults with BD. The first objective of this selective review is to characterize the short-term effects of CT in the development of BD by focusing on studies in young people. The second objective is to describe the longer-term consequences of CT by considering studies with adult participants. This review first outlines the most prominent hypotheses linking CT exposure and the onset of BD. Then, it summarizes the psychological and biological risk factors implicated in the development of BD, followed by a discussion of original studies that investigated the role of CT in young people with early-onset BD, youths at increased risk of developing BD, or young people with BD with a focus on subclinical and clinical outcome measures. The review considers additional biological and psychological factors associated with a negative impact of CT on the long-term course of BD in later adulthood. Finally, we discuss how the integration of information of CT can improve ongoing early identification of BD and mitigate severe clinical expression in later adulthood.
“…This decision is practical as we were unable to identify discordant MZ male twins in the register and it is essential that we only study twins who have passed through the age of risk to ensure unaffected status. Lastly, similar to other complex studies [76], planned analyses represent a mixture of hypothesis-driven and exploratory research questions. The exploratory aims emerge from findings in the literature regarding where differences may lie in affected versus unaffected individuals.…”
Background
Anorexia nervosa (AN) is a severe disorder, for which genetic evidence suggests psychiatric as well as metabolic origins. AN has high somatic and psychiatric comorbidities, broad impact on quality of life, and elevated mortality. Risk factor studies of AN have focused on differences between acutely ill and recovered individuals. Such comparisons often yield ambiguous conclusions, as alterations could reflect different effects depending on the comparison. Whereas differences found in acutely ill patients could reflect state effects that are due to acute starvation or acute disease-specific factors, they could also reflect underlying traits. Observations in recovered individuals could reflect either an underlying trait or a “scar” due to lasting effects of sustained undernutrition and illness. The co-twin control design (i.e., monozygotic [MZ] twins who are discordant for AN and MZ concordant control twin pairs) affords at least partial disambiguation of these effects.
Methods
Comprehensive Risk Evaluation for Anorexia nervosa in Twins (CREAT) will be the largest and most comprehensive investigation of twins who are discordant for AN to date. CREAT utilizes a co-twin control design that includes endocrinological, neurocognitive, neuroimaging, genomic, and multi-omic approaches coupled with an experimental component that explores the impact of an overnight fast on most measured parameters.
Discussion
The multimodal longitudinal twin assessment of the CREAT study will help to disambiguate state, trait, and “scar” effects, and thereby enable a deeper understanding of the contribution of genetics, epigenetics, cognitive functions, brain structure and function, metabolism, endocrinology, microbiology, and immunology to the etiology and maintenance of AN.
“…The IMAGEN consortium comprises a longitudinal, sex-balanced cohort of ∼2000 nonclinically ascertained adolescents from eight European centers [ 21 ]. These data allowed Barker et al [ 22 ] to report an association between ADHD PRS (from the first ADHD genome-wide significant findings) [ 17 ] with impulsivity and body mass index phenotypes, mediated by grey matter volumes (in bilateral cerebellum, amygdala, hippocampus, parahippocampus, and orbital frontal cortex), and by function on a monetary incentive delay fMRI task (in fusiform gyrus and parahippocampus, postcentral and parietal inferior, calcarine and occipital superior, and frontal superior medial cortices).…”
Purpose of review
Neuroimaging research on attention-deficit/hyperactivity disorder (ADHD) continues growing in extent and complexity, although it has yet to become clinically meaningful. We review recent MRI research on ADHD, to identify robust findings, current trends and challenges.
Recent findings
We identified 40 publications between January 2019 and September 2020 reporting or reviewing MRI research on ADHD. Four meta-analyses have presented conflicting results regarding across-study convergence of functional and resting-state functional (fMRI and R-fMRI) studies on ADHD. On the other hand, the Enhancing NeuroImaging Genetics Through Meta-Analysis international consortium has identified statistically robust albeit small differences in structural brain cortical and subcortical indices in children with ADHD versus typically developing controls. Other international consortia are harnessing open-science efforts and multimodal data (imaging, genetics, phenotypic) to shed light on the complex interplay of genetics, environment, and development in the pathophysiology of ADHD. We note growing research in ‘prediction’ science, which applies machine-learning analysis to identify biomarkers of disease based on big data.
Summary
Neuroimaging in ADHD is still far from informing clinical practice. Current large-scale, multimodal, and open-science initiatives represent promising paths toward untangling the neurobiology of ADHD.
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