Metabolic pathways underlying neuropsychiatric disorders and obesity

The prevalence of both obesity and neuropsychiatric disorders is growing worldwide. While sociocultural changes have been implicated in this phenomenon, biological factors might also play a role. This chapter will address the intricate relationship between obesity and neuropsychiatric disorders, focusing on mood disorders, schizophrenia and major neurocognitive disorder or dementia. Obese people have a higher risk of developing depression than non-obese subjects. Conversely, depression contributes to unhealthy lifestyle (e.g. sedentarism) and unhealthy eating habits, which favour weight gain. The prevalence of obesity and overweight is elevated among patients with schizophrenia. Unhealthy behaviours and, notably, the use of antipsychotics can contribute to weight gain in this population. High BMI and central obesity in midlife may increase the risk of dementia later in life. After midlife, however, lower BMI has been associated with faster progression of dementia. Therefore, specific mechanisms can be involved in the relationship between obesity and each neuropsychiatric disorder, including inflammation, alterations in neurotransmitter biosynthesis, endocrine pathways (e.g. insulin, leptin and cortisol production and/or sensitization) and changes in gut microbiota. The treatment of obesity must consider the potential comorbidity with neuropsychiatric disorders.