Pathways linking obesity to neuropsychiatric disorders

Obesity has been associated with cognitive and behavioral syndromes. Individuals who are obese have higher risk for developing neuropsychiatric disorders such as depression and dementia than non-obese. Conversely, patients with neuropsychiatric conditions may exhibit some features that contribute to obesity development such as unhealthy behaviors and treatment with drugs that increase appetite. This review addresses the multiple pathways implicated in the relationship between obesity and neuropsychiatric disorders, mainly mood disorders, schizophrenia, and major neurocognitive disorder or dementia. Both obesity and neuropsychiatric disorders are characterized by a low-grade systemic inflammation and neuroinflammation. Obesity is frequently accompanied by neuroendocrine changes, particularly involving the hypothalamic–pituitary–adrenal (HPA) axis. Indeed, activation of the stress system is commonly seen as a trigger for mood episodes, psychosis exacerbation, and cognitive decline. Growing evidence suggests the role of gut microbiota in obesity and brain functioning through the modulation of the inflammatory response and HPA axis. Owing to the intricate relationship between obesity and neuropsychiatric disorders, tackling one of them may affect the other. Therefore, a better understanding of the pathways underlying the link between obesity and neuropsychiatric disorders can contribute to the development of therapeutic strategies for these conditions.