Neural and Endocrine Correlates of Early Life Abuse in Youth With Depression and Obesity

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.

Associations of Different Types of Maternal Diabetes and Body Mass Index With Offspring Psychiatric Disorders

“…28 In fact, increased peripheral insulin results in insulin resistance, which itself has substantial outcomes on the brain 29 and has been associated with depression. [30][31][32] Furthermore, persons with, for example, ADHD and JAMA Network Open | Psychiatry mood disorders have been reported to have an increased risk of developing obesity. Whether this is genetically or solely environmentally underpinned is not clear.…”

Relationship of prenatal maternal obesity and diabetes to offspring neurodevelopmental and psychiatric disorders: a narrative review

“…Moreover, insulin is an important growth factor in brain development [88]. Increased peripheral insulin levels results in insulin resistance which itself has large effects on the brain and have been associated with depression [89][90][91][92].…”

Bibliometrics Analysis of the Research Status and Trends of the Association Between Depression and Insulin From 2010 to 2020

“…Changes in the endocrine system are also an important causes of depression pathophysiology. Research on changes of non-psychiatric symptoms link to affective disorders is increasing (4,5). For example, heart disease occurs more frequently in depressed patients (6), and among the factors associated with depression, diabetes have received widespread attention.…”