A neural biomarker of psychological vulnerability to future life stress.

We all experience a host of common life stressors such as the death of a family member, medical illness, and financial uncertainty. While most of us are resilient to such stressors, continuing to function normally, for a subset of individuals, experiencing these stressors increases the likelihood of developing treatment-resistant, chronic psychological problems, including depression and anxiety. It is thus paramount to identify predictive markers of risk, particularly those reflecting fundamental biological processes that can be targets for intervention and prevention. Using data from a longitudinal study of 340 healthy young adults, we demonstrate that individual differences in threat-related amygdala reactivity predict psychological vulnerability to life stress occurring as much as 1 to 4 years later. These results highlight a readily assayed biomarker, threat-related amygdala reactivity, which predicts psychological vulnerability to commonly experienced stressors and represents a discrete target for intervention and prevention

Association of subcortical gray-matter volumes with life-course-persistent antisocial behavior in a population-representative longitudinal birth cohort

Neuropsychological evidence supports the developmental taxonomy theory of antisocial behavior, suggesting that abnormal brain development distinguishes life-course-persistent from adolescence-limited antisocial behavior. Recent neuroimaging work confirmed that prospectively-measured life-course-persistent antisocial behavior is associated with differences in cortical brain structure. Whether this extends to subcortical brain structures remains uninvestigated. This study compared subcortical gray-matter volumes between 672 members of the Dunedin Study previously defined as exhibiting life-course-persistent, adolescence-limited or low-level antisocial behavior based on repeated assessments at ages 7-26 years. Gray-matter volumes of 10 subcortical structures were compared across groups. The life-course-persistent group had lower volumes of amygdala, brain stem, cerebellum, hippocampus, pallidum, thalamus, and ventral diencephalon compared to the low-antisocial group. Differences between life-course-persistent and adolescence-limited individuals were comparable in effect size to differences between life-course-persistent and low-antisocial individuals, but were not statistically significant due to less statistical power. Gray-matter volumes in adolescence-limited individuals were near the norm in this population-representative cohort and similar to volumes in low-antisocial individuals. Although this study could not establish causal links between brain volume and antisocial behavior, it constitutes new biological evidence that all people with antisocial behavior are not the same, supporting a need for greater developmental and diagnostic precision in clinical, forensic, and policy-based interventions

Investigating patterns of neural response associated with childhood abuse v. childhood neglect

BACKGROUND: Childhood maltreatment is robustly associated with increased risk of poor mental health outcome and changes in brain function. The authors investigated whether childhood experience of abuse (e.g. physical, emotional and sexual abuse) and neglect (physical and emotional deprivation) was differentially associated with neural reactivity to threat. METHODS: Participants were drawn from an existing study and allocated to one of four groups based on self-report of childhood maltreatment experience: individuals with childhood abuse experiences (n = 70); individuals with childhood neglect experiences (n = 87); individuals with combined experience of childhood abuse and neglect (n = 50); and non-maltreated individuals (n = 207) propensity score matched (PSM) on gender, age, IQ, psychopathology and SES. Neural reactivity to facial cues signalling threat was compared across groups, allowing the differential effects associated with particular forms of maltreatment experience to be isolated. RESULTS: Brain imaging analyses indicated that while childhood abuse was associated with heightened localised threat reactivity in ventral amygdala, experiences of neglect were associated with heightened reactivity in a distributed cortical fronto-parietal network supporting complex social and cognitive processing as well as in the dorsal amygdala. Unexpectedly, combined experiences of abuse and neglect were associated with hypo-activation in several higher-order cortical regions as well as the amygdala. CONCLUSIONS: Different forms of childhood maltreatment exert differential effects in neural threat reactivity: while the effects of abuse are more focal, the effects of neglect and combined experiences of abuse are more distributed. These findings are relevant for understanding the range of psychiatric outcomes following childhood maltreatment and have implications for intervention

Heightened amygdala reactivity and increased stress generation predict internalizing symptoms in adults following childhood maltreatment

Background: Childhood maltreatment is one of the most potent predictors of future psychopathology, including internalizing disorders. It remains unclear whether heightened amygdala reactivity to threat and elevated stress exposure may be implicated in the pathogenesis and maintenance of internalizing disorders among individuals with a history of childhood maltreatment. / Methods: Using data from a sample of 1,144 young adults, we investigated the contribution of baseline threat‐related amygdala reactivity and prospective major stressful life events to internalizing symptoms severity 1 year later (on average) in individuals with a history of maltreatment (n = 100) and propensity score matched nonmaltreated peers (n = 96). / Results: Even after stringently matching for several potentially confounding variables – including baseline internalizing symptoms, socioeconomic status and IQ – childhood maltreatment status predicted increased amygdala reactivity at baseline, elevated post‐baseline exposure to major stressful life events and internalizing symptoms at follow‐up. We also showed, for the first time, that amygdala reactivity at baseline and also post‐baseline exposure to major stressful life events mediated the association between a history of maltreatment and future internalizing symptoms. / Conclusions: These findings provide support for the view that maltreatment is a potent developmental insult leading to long‐lasting neurocognitive recalibrations of the threat processing system. It is possible that such alterations, over time, may impact mental health functioning by compromising the ability to effectively negotiate everyday challenges (stress susceptibility). These alterations were not, however, found to sensitize an individual to the impact of major stressful life events. The results of this study also lend compelling support to the view that increased psychiatric risk, in the context of childhood maltreatment, follows from an increased propensity to experience major stressful life events (stress generation)