Dataset Information

Association of Prepubertal and Postpubertal Exposure to Childhood Maltreatment With Adult Amygdala Function.

ABSTRACT:

Importance

Abnormalities in amygdala response to threatening faces have been observed in anxiety disorders, autism, bipolar disorder, depression, posttraumatic stress disorder, and schizophrenia. Abnormally hyperactive and hypoactive responses have typically been associated with anxiety and inhibition vs risk taking and inappropriate social behaviors. Maltreatment is a major risk factor for most of these disorders and is associated with abnormal amygdala function.

Objective

To identify the type and age of exposure to childhood maltreatment that are associated with hyperactive and hypoactive amygdala responses in young adulthood.

Design, setting, and participants

Data collection for this retrospective cohort study took place from November 8, 2010, to August 23, 2012. Data analyses were conducted from September 20, 2012, to June 27, 2018. Participants were recruited from the urban and suburban Boston vicinity without diagnostic restrictions based on exposure history.

Exposures

The Maltreatment and Abuse Chronology of Exposure (MACE) scale was used to retrospectively assess type and age of exposure to childhood maltreatment.

Main outcomes and measures

Activation and pattern information functional magnetic resonance imaging were used to assess bilateral amygdala response to angry and fearful faces vs neutral faces or shapes, and sensitive exposure periods were identified using cross-validated artificial intelligence predictive analytics (50 averaged randomized iterations with training on 63.3% and testing on 36.7% of the sample).

Results

Of the 202 participants (mean [SD] age, 23.2 [1.7] years; 118 [58.4%] female), 52 (25.7%) reported no exposure to maltreatment and 150 (74.3%) reported exposure to 1 or more maltreatment types. Eight participants (15.1%) with a MACE score of 0 and 51 (34.2%) with a MACE score of 1 or higher had a history of major depression (odds ratio, 2.40; 95% CI, 1.05-6.06; P = .03); 8 unexposed participants (15.1%) and 46 with MACE scores of 1 or higher (30.9%) had a history of 1 or more anxiety disorders (odds ratio, 2.45; 95% CI, 1.03-6.50; P = .03). Retrospective self-report of physical maltreatment between 3 and 6 years of age and peer emotional abuse at 13 and 15 years were associated with amygdala activation to emotional faces vs shapes. Early exposure was associated with blunted response (β = -0.17, P < .001), whereas later exposure was associated with augmented response (β = 0.16, P < .001). Prepubertal vs postpubertal maltreatment was associated with an opposite response on the voxelwise response pattern in clustering stimuli of the same type (eg, mean [SD] emotional ellipse areas for physical maltreatment at age 4 years vs nonverbal emotional abuse at 13 years: 1.41 [1.05] vs 0.25 [0.10], P < .001) and in distinguishing between stimuli of different types (eg, mean [SD] emotional vs neutral faces distance for peer emotional abuse at age 6 years vs 13 years: 1.89 [0.75] vs 0.80 [0.39], P < .001).

Conclusions and relevance

The findings suggest that prepubertal vs postpubertal developmental differences in the association between maltreatment and amygdala response to threatening or salient stimuli exist. Understanding the role of adversity in different sensitive exposure periods and the potential adaptive significance of attenuated vs enhanced amygdala response may help explain why maltreatment may be a risk factor for many different disorders and foster creation of targeted interventions to preempt the emergence of psychopathology in at-risk youths.

SUBMITTER: Zhu J

PROVIDER: S-EPMC6596335 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Although a growing literature describes the effects of negative childhood experiences on biological outcomes, it is difficult to compare results across studies because of differences in measures of childhood experiences, biological markers, sample characteristics, and included covariates. To ensure comparability across its analyses, this study used a single national survey of adults in the United States-the Midlife in the United States (MIDUS) study-to examine comprehensively the association between adverse childhood experiences, operationalized as childhood maltreatment (CM), and biological markers of risk for poor health and to assess whether these associations differ by type of maltreatment, sex, or race. The sample included 1254, mostly White (78%), adults aged 34-86 years (mean age 57 years), 57% of whom were female. We present incidence rate ratios (IRR) from negative binomial and Poisson regressions to examine the relationships between exposure to CM (emotional, physical, and sexual abuse; emotional and physical neglect; and a CM-index reflecting frequency across all five types of maltreatment) and four biological risk summary scores (overall physiological dysregulation, cardiometabolic risk, inflammation, and hypothalamic pituitary axis/sympathetic nervous system (HPA/SNS) function). We also tested whether the effect of each type of CM varied by sex and by race. The CM-index was associated with higher overall physiological dysregulation and inflammation, but the associations were weaker and not statistically significant for cardiometabolic risk and HPA/SNS function. With the exception of a possible sex difference in the association between sexual abuse and overall physiological dysregulation, there was little evidence that the associations varied systematically by type of CM or by sex or race. We conclude that exposure to CM predicts adult biological risk, particularly inflammation. Inconsistency with previous research suggests that additional research is needed to confirm findings regarding sex and race differences.