The TNF-α System: Functional Aspects in Depression, Narcolepsy and Psychopharmacology

Changes of the tumor necrosis factor-alpha (TNF-α) system have been shown to be involved in the development of psychiatric disorders and are additionally associated with changes in body weight as well as endocrine and metabolic changes in psychiatric patients. TNF-α might, for example, contribute to the pathogenesis of depression by an activation of the hypothalamo-pituitaryadrenocortical (HPA) axis, an activation of neuronal serotonin transporters and the stimulation of the indoleamine 2,3- dioxygenase which leads to tryptophan depletion. On the other hand, during an acute depressive episode, an elevated HPA axis activity may suppress TNF-α system activity, while after remission, when HPA axis activity has normalized the suppression of the TNF-α system has been shown not to be apparent any more. In narcoleptic patients, soluble TNF receptor (sTNF-R) p75 plasma levels have been shown to be elevated, suggesting a functional role of the TNF-α system in the development of this disorder. Additionally, psychotropic drugs influence the TNF-α system as well as the secretion and the effect of hormones which counteract or interact with the TNF-α system such as the intestinal hormone ghrelin. However, only preliminary studies with restricted sample sizes exist on these issues, and many open questions remain.