Brain and behavioral correlates of insulin resistance in youth with depression and obesity

Horm Behav. 2019 Feb:108:73-83. doi: 10.1016/j.yhbeh.2018.03.009. Epub 2018 Apr 23.


Depression, together with insulin resistance, is increasingly prevalent among youth. These conditions have traditionally been compartmentalized, but recent evidence suggests that a shared brain motivational network underlies their co-occurrence. We posit that, in the context of depressive symptoms, insulin resistance is associated with aberrant structure and functional connectivity in the Anterior Cingulate Cortex (ACC) and hippocampus. This motivational neural circuit underlies dysfunctional behavioral responses and increased sensitivity to rewarding aspects of ingesting high calorie food that lead to disinhibition of eating even when satiated. To investigate this shared mechanism, we evaluated a sample of forty-two depressed and overweight (BMI > 85th%) youth aged 9 to 17. Using ACC and hippocampus structural and seed-based regions of interest, we investigated associations between insulin resistance, depression, structure (ACC thickness, and ACC and hippocampal area), and resting-state functional connectivity (RSFC). We predicted that aberrant associations among these neural and behavioral characteristics would be stronger in insulin resistant compared to insulin sensitive youth. We found that youth with greater insulin resistance had higher levels of anhedonia and more food seeking behaviors, reduced hippocampal and ACC volumes, and greater levels of ACC and hippocampal dysconnectivity to fronto-limbic reward networks at rest. For youth with high levels of insulin resistance, thinner ACC and smaller hippocampal volumes were associated with more severe depressive symptoms, whereas the opposite was true for youth with low levels of insulin resistance. The ACC-hippocampal motivational network that subserves depression and insulin resistance separately, may represent a critical neural interaction that link these syndromes together.

Keywords: Insulin resistance; Neural structure; Obesity; Pediatric depression; Resting state functional connectivity.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adolescent Behavior / physiology
  • Age of Onset
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain / physiopathology*
  • Brain Mapping
  • Child
  • Child Behavior / physiology*
  • Depression / complications
  • Depression / epidemiology
  • Depression / metabolism*
  • Depression / physiopathology*
  • Female
  • Glucose Tolerance Test
  • Gyrus Cinguli / diagnostic imaging
  • Gyrus Cinguli / metabolism
  • Gyrus Cinguli / physiopathology
  • Humans
  • Insulin Resistance / physiology*
  • Magnetic Resonance Imaging
  • Male
  • Motivation / physiology
  • Overweight / complications
  • Overweight / epidemiology
  • Overweight / metabolism
  • Overweight / physiopathology
  • Pediatric Obesity / complications
  • Pediatric Obesity / epidemiology
  • Pediatric Obesity / metabolism*
  • Pediatric Obesity / physiopathology*
  • Reward