Neurotransmitters and neuropeptides in depression

There are no specific structural neuropathological hallmarks found in the brain of patients with mood disorders. The described alterations confirm, however, a neurodevelopmental underpinning, which is in agreement with the genetic and developmental risk factors. The effect of developmental sequelae and the genetic polymorphisms resulting in functional changes in a network of neurotransmitter and neuropeptide pathways can make the stress-related brain systems more vulnerable to stressful events in many different ways. Region- and type-of-depression-specific molecular neuropathological alterations are found in mood disorders in neurotransmitter systems such as monoamines and amino acids, and in centrally projecting neuropeptides such as corticotropin-releasing hormone (CRH), arginine vasopressin, oxytocin, and orexin. Sex hormones are also involved. The hypothalamo-pituitary-adrenal (HPA) axis, to which all these systems project, has a prominent position in this network. The HPA axis is activated in depressive disorders and in Alzheimer's disease with depression. High levels of CRH and corticosteroids are both able to induce signs and symptoms of depression. For most depressed people the monoamine hypothesis, which postulates dysfunctional noradrenergic and serotonergic systems as the underlying primary cause of depression, does not seem to hold. An increasing body of clinical and postmortem evidence is pointing to a role of γ-aminobutyric acid, glutamate, and neuropeptides in the etiology of depression in groups of patients. The genetic polymorphisms and the inordinate network of neurotransmitters and neuropeptides involved as risk factors in depression raise hope regarding better predictions of the most vulnerable neurobiological system in a particular depressed patient as well as their optimal tailor-made antidepressive therapy