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Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder.

ABSTRACT: Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N?=?171) and a face-matching paradigm (N?=?181) and anatomical scans (N?=?181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2-19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years).CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors.

SUBMITTER: Holz NE

PROVIDER: S-EPMC5390727 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder.

Holz Nathalie E NE Boecker-Schlier Regina R Buchmann Arlette F AF Blomeyer Dorothea D Jennen-Steinmetz Christine C Baumeister Sarah S Plichta Michael M MM Cattrell Anna A Schumann Gunter G Esser Günter G Schmidt Martin M Buitelaar Jan J Meyer-Lindenberg Andreas A Banaschewski Tobias T Brandeis Daniel D Laucht Manfred M

Social cognitive and affective neuroscience 20170201 2

Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently heal ...[more]

PMID: 27694318

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Project description:BackgroundIrritability is a common symptom that may affect children's brain development. This study aims to (1) characterize age-dependent and age-independent neural correlates of irritability in a sample of 4-8 year old children, and (2) examine early irritability as a predictor of change in brain connectivity over time.MethodsTypically developing children, ages 4-8 years, with varying levels of irritability were included. Resting state fMRI and parent-rated irritability (via Child Behavior Checklist; CBCL) were collected at up to three time points, resulting in a cross-sectional sample at baseline (N = 176, M = 6.27, SD = 1.49), and two subsamples consisting of children who were either 4 or 6 years old at baseline that were followed longitudinally for two additional timepoints, one- and two-years post-baseline. That is, a "younger" cohort (age 4 at baseline, n = 34, M age = 4.44, SD = 0.25) and an "older" cohort (age 6 at baseline, n = 29, M age = 6.50, SD = 0.30). Across our exploratory analyses, we examined how irritability related to seed-based intrinsic connectivity via whole-brain connectivity ANCOVAs using the left and right amygdala, and left and right ventral striatum as seed regions.ResultsCross-sectionally, higher levels of irritability were associated with greater amygdala connectivity with the posterior cingulate, controlling for child age. No age-dependent effects were observed in the cross-sectional analyses. Longitudinal analyses in the younger cohort revealed that early higher vs. lower levels of irritability, controlling for later irritability, were associated with decreases in amygdala and ventral striatum connectivity with multiple frontal and parietal regions over time. There were no significant findings in the older cohort.ConclusionsFindings suggest that irritability is related to altered neural connectivity during rest regardless of age in early to middle childhood and that early childhood irritability may be linked to altered changes in neural connectivity over time. Understanding how childhood irritability interacts with neural processes can inform pathophysiological models of pediatric irritability and the development of targeted mechanistic interventions.

Project description:BackgroundHuman laboratory paradigms are a pillar in medication development for alcohol use disorders (AUD). Neuroimaging paradigms, in which individuals are exposed to cues that elicit neural correlates of alcohol craving (e.g., mesocorticolimbic activation), are increasingly utilized to test the effects of AUD medications. Elucidation of the translational effects of these neuroimaging paradigms on human laboratory paradigms, such as self-administration, is warranted. The current study is a secondary analysis examining whether alcohol cue-induced activation in the ventral striatum is predictive of subsequent alcohol self-administration in the laboratory.MethodsNon-treatment-seeking heavy drinkers of East Asian descent (n = 41) completed a randomized, placebo-controlled, double-blind, crossover experiment on the effects of naltrexone on neuroimaging and human laboratory paradigms. Participants completed 5 days of study medication (or placebo); on day 4, they completed a neuroimaging alcohol taste cue-reactivity task. On the following day (day 5), participants completed a 60-minute alcohol self-administration paradigm.ResultsMultilevel Cox regressions indicated a significant effect of taste cue-elicited ventral striatum activation on latency to first drink, Wald χ2 = 2.88, p = 0.05, such that those with higher ventral striatum activation exhibited shorter latencies to consume their first drink. Similarly, ventral striatum activation was positively associated with total number of drinks consumed, F(1, 38) = 5.90, p = 0.02. These effects were significant after controlling for alcohol use severity, OPRM1 genotype, and medication. Other potential regions of interest (anterior cingulate, thalamus) were not predictive of self-administration outcomes.ConclusionsNeuroimaging alcohol taste cue paradigms may be predictive of laboratory paradigms such as self-administration. Elucidation of the relationships among different paradigms will inform how these paradigms may be used synergistically in experimental medicine and medication development.

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Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder.

Publications

Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder.

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