Shared Dysregulation of Homeostatic Brain-Body Pathways in Depression and Type 2 Diabetes

Abstract

Purpose of review: The purpose of this review is to provide an overview of shared dysregulation of the hypothalamic-pituitary-adrenal (HPA) and brain-gut-microbiome (BGM) axes associated with depression and type 2 diabetes (T2D). Clinical implications and future research are also discussed.

Recent findings: Both depression and T2D are associated with dysregulation of the HPA and BGM axes. These pathways regulate immune function, glucose metabolism, and sleep, which are altered in both illnesses. Dysregulation of homeostatic brain-body pathways may be positively influenced through different therapeutic actions, including psychotherapy, healthy eating, physical activity, sleep promotion, and certain anti-inflammatory or antidepressant medications. While the causal nature of the relationship between depression and T2D remains unclear, these conditions share dysregulation of homeostatic brain-body pathways that are central to mental and physical health. Better understanding of this dysregulation may provide opportunities for interventions that could benefit both conditions. Future research should examine the additive burden of depression and T2D on HPA and BGM dysregulation and better differentiate depression from emotional distress.

Keywords: Biological pathways; Brain-gut-microbiome axis; Depression; Hypothalamic-pituitary-adrenal axis; Type 2 diabetes.

Conflict of interest statement

Conflict of Interest

Claire J. Hoogendoorn, Juan F. Roy, and Jeffrey S. Gonzalez declare that they have no conflict of interest.

Figures

Figure 1

Homeostatic Dysregulation of Brain-Body Pathways. Figure shows inter-regulation between physiological systems, which allows for maximum flexibility in maintaining homeostasis. The introduction of chronic disruptors to this homeostatic system at every level can contribute to dysregulation. Dysregulation of core homeostatic brain-body pathways, namely the hypothalamic-pituitary-adrenal (HPA) and brain-gut-microbiome (BGM) axes, are associated with mental and physical illness, including depression and type 2 diabetes.

Figure 2

Overview of the HPA axis. Activation of the HPA axis is initiated by the paraventricular nucleus of the hypothalamus in the brain, and this nucleus can be activated by perceptions of threat as well as internal physiological processes. This leads to the release of corticotropin-releasing factor/hormone (CRF/CRH), which stimulates the release of adrenocorticotrophic hormone (ACTH) into the vascular system from the pituitary gland. This in turn activates the adrenal glands situated atop the kidneys, which secrete the glucocorticoid hormone cortisol. (Figure reproduced from: Hiller-Sturmhöfel and Bartke. Alcohol Research and Health 1998;22(3):153) [101].

Figure 3

Brain–gut–microbe communication in health and disease. A stable gut microbiota is essential for normal gut physiology and contributes to appropriate signaling along the brain–gut axis and to the healthy status of the individual as shown on the left hand side of the diagram. Conversely, as shown on the right hand side of the diagram, intestinal dysbiosis can adversely influence gut physiology leading to inappropriate brain–gut axis signaling and associated consequences for CNS functions and disease states. Stress at the level of the CNS can also impact on gut function and lead to perturbations of the microbiota. (Legend and figure reproduced from: Grenham S, et al. Frontiers in Physiology 2011;2:94) [17].