Abstract
Depression and insulin resistance are becoming increasingly prevalent in younger populations. The origin and consequence of insulin resistance in depressed youth may, in part, be rooted in exposure to environmental stressors, such as early life abuse, that may lead to aberrant brain motivational networks mediating maladaptive food-seeking behaviors and insipient insulin resistance. In this paper, we aimed to investigate the impact of early life abuse on the development of insulin resistance in depressed and overweight youth aged 9 to 17 years. We hypothesized that youth with the greatest burden of early life abuse would have the highest levels of insulin resistance and corresponding aberrant reward network connectivities. To test this hypothesis, we evaluated sixty-nine depressed and overweight youth aged 9 to 17, using multimodal assessments of early life abuse, food-seeking behavior, and insulin resistance. Based on results of the Childhood Trauma Questionnaire (CTQ), we separated our study participants into two groups: 35 youth who reported high levels of the sum of emotional, physical, or sexual abuse and 34 youth who reported insignificant or no levels of any abuse. Results of an oral glucose tolerance test (OGTT) and resting state functional connectivity (RSFC), using the amygdala, insula, and nucleus accumbens (NAcc) as seed-based reward network regions of interest, were analyzed for group differences between high abuse and low abuse groups. High abuse youth exhibited differences from low abuse youth in amygdala-precuneus, NAcc-paracingulate gyrus, and NAcc-prefrontal cortex connectivities, that correlated with levels of abuse experienced. The more different their connectivity from of that of low abuse youth, the higher were their fasting glucose and glucose at OGTT endpoint. Importantly, level of abuse moderated the relation between reward network connectivity and OGTT glucose response. In contrast, low abuse youth showed hyperinsulinemia and more insulin resistance than high abuse youth, and their higher OGTT insulin areas under the curve correlated with more negative insula-precuneus connectivity. Our findings suggest distinct neural and endocrine profiles of youth with depression and obesity based on their histories of early life abuse.
Highlights
Depression is a common psychiatric disorder that significantly impacts youth worldwide [1, 2]
We found significant group differences in connectivity between bilateral nucleus accumbens (NAcc) and two regions: a prefrontal cluster which included the left dorsolateral prefrontal cortex (DLPFC), precentral gyrus, and inferior frontal gyrus (IFG) (k = 597 voxels, peak x/y/z Montreal Neurological Institute (MNI) coordinates = −54/4/30, z = 3.46, P = 0.0013, Brodmann areas 6, 9, 45, 46) and a cluster encompassing the bilateral paracingulate gyri in the medial prefrontal cortex (k = 386 voxels, peak x/y/z MNI coordinates = −12/48/−4, z = 3.89, P = 0.023, Brodmann areas 10, 32) (Figures 2C,D)
Our findings suggest that depressed and overweight youth with high abuse exposure have different neural and endocrine characteristics compared to low abuse-exposed counterparts
Summary
Depression is a common psychiatric disorder that significantly impacts youth worldwide [1, 2]. Recent studies distinguish the effects of inadequate input (such as neglect and deprivation) from the effects of harmful input (such as abuse and trauma) on brain structure and function, as well as on psychopathology, cortisol metabolism, and epigenetic changes [12,13,14]. Among these various maltreatment inputs, childhood abuse has been shown to worsen depression course [15], and emotional abuse in particular has been shown to best predict psychiatric symptomatology in children compared to other maltreatment types [16]. Contributing to this literature, we here focus principally on exposure to childhood abuse and its specific neural and endocrine correlates
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