Toward a Unified Theory of Serotonin Dysregulation in Eating and Related Disorders

Patients with eating disorders (EDs) exhibit several clinical features and biologic findings indicative of serotonin (5-hydroxytryptamine, 5-HT) dysregulation. These include feeding disturbances, depression and suicide, impulsivity and violence, anxiety and harm avoidance, obsessive-compulsive features, seasonal variation of symptoms, as well as disturbances in neuroendocrine and vascular tissues, as well as other neurochemical systems linked to 5-HT, such as temperature. This review attempts to integrate available results from controlled studies in humans, with particular focus on cerebrospinal fluid (CSF), platelet and plasma studies, as well as pharmacologic challenge strategies using a variety of serotonergic agents. Taken together, these findings support the concept of altered post-synaptic, hypothalamic 5-HT receptor sensitivity in bulimia nervosa (BN), regardless of the presence of anorexia nervosa (AN) or major depression (MD), although these conditions may be associated with other disturbances in 5-HT function, perhaps pre-synaptic ones. The observation that different response measures of 5-HT function in the same subjects may be simultaneously increased, decreased and no different in patients compared to controls is consistent with a 5-HT dysregulation hypothesis. It may be that a variety of psychobiological stressors, such as dieting, binge-eating, purging, drug abuse, photoperiodic changes, as well as psychosocial-interpersonal stressors, perturb and interact with an already vulnerable 5-HT system.