Comorbid Appetite and Mood Dysregulation

Shared hormone and brain substrates guide our appetitive and emotional drives, and deficits along the gut-brain axis can lead to disordered eating and mood dysregulation. Our studies in this area, led by Laura Holsen, Ph.D., are focused on investigating the hormone and brain anatomy substrates that underlie sex differences in the presentation of abnormally decreased and increased food motivation and mood dysregulation, given the higher risk of developing these conditions in women.

With a focus on the role of hedonic capacity, emotional eating, and functioning along the gut-brain axis, we hypothesize that individuals who demonstrate disordered eating and mood disturbances have abnormalities (structural and functional) in several regions involved in food reward and motivation, such as the hypothalamus, nucleus accumbens, amygdala, hippocampus, orbitofrontal cortex, medial prefrontal cortex, anterior cingulate cortex, and insula. In our research, we include measurement of appetite-regulatory peptides, HPA-axis hormones, and inflammatory cytokines in concert with brain activity using fMRI to assess food reward circuitry. We are examining relationships between these potential gut-brain biomarkers in women with anorexia nervosa, healthy-weight and obese women with depression, and women undergoing bariatric surgery.

We are also interested in understanding the influence of prenatal exposure to stress on the development of these conditions. Our aim is to characterize sex differences in the pathophysiology of mood and appetite dysregulation and provide a basis for the development of studies on genes, hormones, and sex-specific approaches to prevention, prediction, and treatment.

Examples of findings:

  1. Individuals with an extreme form of obesity (Prader-Willi syndrome), compared to those with simple obesity or healthy-weight individuals, demonstrate dysfunction (hyperactivity) in food reward regions associated with inhibitory control.

  2. Women with active anorexia nervosa exhibit widespread deficits (hypoactivity) in food reward circuitry, which are more pronounced than in weight-restored women and are related to abnormalities in self-reported homeostatic and hedonic aspects of appetite.

  3. Compared to healthy women, women with major depressive disorder exhibit hyperactivity in stress response circuitry regions, which is significantly related to HPA-axis functioning.