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Cumulative adversity sensitizes neural response to acute stress: association with health symptoms.

ABSTRACT: Cumulative adversity (CA) increases stress sensitivity and risk of adverse health outcomes. However, neural mechanisms underlying these associations in humans remain unclear. To understand neural responses underlying the link between CA and adverse health symptoms, the current study assessed brain activity during stress and neutral-relaxing states in 75 demographically matched, healthy individuals with high, mid, and low CA (25 in each group), and their health symptoms using the Cornell Medical Index. CA was significantly associated with greater adverse health symptoms (P=0.01) in all participants. Functional magnetic resonance imaging results indicated significant associations between CA scores and increased stress-induced activity in the lateral prefrontal cortex, insula, striatum, right amygdala, hippocampus, and temporal regions in all 75 participants (p<0.05, whole-brain corrected). In addition to these regions, the high vs low CA group comparison revealed decreased stress-induced activity in the medial orbitofrontal cortex (OFC) in the high CA group (p<0.01, whole-brain corrected). Specifically, hypoactive medial OFC and hyperactive right hippocampus responses to stress were each significantly associated with greater adverse health symptoms (p<0.01). Furthermore, an inverse correlation was found between activity in the medial OFC and right hippocampus (p=0.01). These results indicate that high CA sensitizes limbic-striatal responses to acute stress and also identifies an important role for stress-related medial OFC and hippocampus responses in the effects of CA on increasing vulnerability to adverse health consequences.

SUBMITTER: Seo D

PROVIDER: S-EPMC3895244 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Cumulative adversity sensitizes neural response to acute stress: association with health symptoms.

Seo Dongju D Tsou Kristen A KA Ansell Emily B EB Potenza Marc N MN Sinha Rajita R

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20130920 3

Cumulative adversity (CA) increases stress sensitivity and risk of adverse health outcomes. However, neural mechanisms underlying these associations in humans remain unclear. To understand neural responses underlying the link between CA and adverse health symptoms, the current study assessed brain activity during stress and neutral-relaxing states in 75 demographically matched, healthy individuals with high, mid, and low CA (25 in each group), and their health symptoms using the Cornell Medical ...[more]

PMID: 24051900

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Project description:AIM:Psychotic-spectrum symptoms are linked to trauma, substance/alcohol use (SAU), criminality/violence and poor functional outcomes, supporting the need for early detection in vulnerable populations. To better understand high-risk girls' mental health, we assessed: (1) psychotic-spectrum symptoms; (2) cumulative trauma, adversity and loss exposures (C-TALE) and adversity-indicators (symptoms, maladaptive coping, stressor-reactivity); and SAU risk-factors; and (3) relationships among psychotic-spectrum symptoms, adversity-indicators and SAU risk-factors. METHODS:We administered the Structured Clinical Interviews for Psychotic Spectrum, and Trauma and Loss Spectrum to 158 adolescent delinquent girls. RESULTS:Girls' psychotic-spectrum profiles were similar to previously reported adult psychotic patients and characterized by typical symptoms (hallucinations/delusions, reported largely SAU-independent), interpersonal sensitivity, schizoid traits and paranoia (over-interpretation, anger over-reactivity, hypervigilance). Auditory/visual hallucinations (55.7%), delusions (92.4%), ideas of reference (96.8%) and adversity (90.0% ?10/24 C-TALE-types) were common. Mean loss (4) and trauma (8) onset-age occurred before SAU-onset (12). Significant positive correlations were found among psychotic-spectrum symptoms, stressor-reactivity, C-TALE, adversity-indicators; and number of SAU-types; and a negative correlation occurred between psychotic-spectrum symptoms and earlier alcohol use onset. After controlling for number of SAU-types, stressor-reactivity and adversity-related numbing individually had the largest associations with total psychotic-spectrum symptoms (b?=?2.6-4.3). Girls averaged more than 4 maladaptive coping strategies (e.g., 24.8% attempted suicide) in response to adversity, amplifying potential health-disparities. No racial/ethnic differences emerged on psychotic-spectrum symptoms. CONCLUSIONS:This symptom constellation during adolescence likely interferes with social and academic functioning. Whether representing a prodromal phase, trauma-response or cross-diagnostic psychopathology, accurate early detection and appropriate treatment of psychotic-spectrum symptoms are warranted to improve functional outcomes in vulnerable populations.

Project description:Importance:Childhood adversity (CA) is associated with an increased risk of suicide in young adulthood that might be explained by maladaptive trajectories during adolescence. Although adolescent violent offending is linked with suicide, little is known about its role in the association between CA and suicide. Objective:To examine whether adolescent violent offending mediates the association between CA and suicide in early adulthood. Design, Setting, and Participants:This population-based, longitudinal cohort study with a follow-up time spanning 5 to 9 years included 476?103 individuals born in Sweden between 1984 and 1988. The study population was prospectively followed up from 20 years of age until December 31, 2013, with respect to suicide. Data analysis was performed from January 1, 1984, to December 31, 2013. Exposures:Register-based CAs included parental death, parental substance abuse and psychiatric disorder, parental criminal offending, parental separation, public assistance recipiency, child welfare intervention, and residential instability. Adolescent violent offending was defined as being convicted of a violent crime between the ages of 15 and 19 years. Main Outcomes and Measures:Estimates of risk of suicide after 20 years of age (from 2004 if born in 1984 and from 2008 if born in 1988) until the end of 2013 were calculated as incidence rate ratios (IRRs) with 95% CIs using Poisson regression analysis. Adjustments were made for demographics and psychiatric disorder. In addition, binary mediation analysis with logistic regression was used. Results:A total of 476?103 individuals (231 699 [48.7%] female) were included in the study. Those with a conviction for violent offending had been exposed to all CAs to a greater extent than those with no violent offending. Cumulative CA was associated with risk of suicide in nonconvicted (adjusted IRR, 2.4; 95% CI, 1.5-3.9) and convicted youths, who had a higher risk of suicide (adjusted IRR, 8.5; 95% CI, 4.6-15.7). Adolescent violent offending partly mediated the association between CA and suicide. Conclusions and Relevance:Individuals with a history of CA who also engage in violent offending in adolescence have a high risk of suicide. Interventions to prevent externalizing behavior during childhood and increased support to youths with delinquent behavior may have the potential to prevent suicide related to CA.

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Cumulative adversity sensitizes neural response to acute stress: association with health symptoms.

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Cumulative adversity sensitizes neural response to acute stress: association with health symptoms.

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