The neurobiology of comorbidities

Psychiatric disorders are complex disorders with multifactorial etiopathogenesis. Some of the suggested underlying causes are associated with the disruption of various physiological systems and impaired brain function, resulting in the development of multiple comorbidities. There is still uncertainty surrounding the precise pathophysiological mechanism underlying these comorbidities due to their intricacy and the difficulty to study complex brain pathology. This chapter reviews biological elements and mechanisms underlying the comorbidities of mental and physical disorders, including the immune system, inflammatory processes, the hypothalamic-pituitary-adrenal axis, the autonomous nervous system, the gastrointestinal system (gut microbiota), mitochondria (energy metabolism), and brain structure and circuits. We explain to the reader how these biological components play a role in comorbidities and illustrate how impairment in these elements may lead to the emergence and development of co-occurring mental and physical disorders. Both intrinsic and extrinsic variables, such as genetics, stress, infections, and malnutrition, which can upset the balance and affect normal functioning in any of the systems, appear to be responsible for the disruption of homeostasis in the body and the development of comorbidities. This chapter outlines how comorbidities may be shaped by the interaction of several pathways that impact both physical and mental functioning. Research on comorbidities is still ongoing. This chapter shows how exploring pertinent molecular pathways and functional mechanisms can enhance knowledge of the pathophysiology of mental and physical comorbidities and help identify suitable targets for medication repurposing to achieve highly efficient binary treatment.