Mood and neuropsychological function in depression: the role of corticosteroids and serotonin

Abstract

We argue that there is a neurobiological cause of impaired neuropsychological function in depression. The complex relationship between neuropsychological function and mood may be a result of interactions between the serotonergic system and the HPA axis, particularly in the hippocampus with involvement of serotonergic 5-HT1A and glucocorticoid receptors. A primary dysfunction in these receptors will produce a lowering of mood and neuropsychological impairment respectively. Either dysfunction will result in a secondary impairment of the alternate system. Thus, the effective and psychological changes of depressive illness are likely to have complex relationships in time and severity to one another and the illness as a whole may result from a range of primary aetio-pathologies.

Evidence of an early information processing speed deficit in unipolar major depression

“…Hypothalamicpituitary-adrenal (HPA) axis abnormalities have also been attributed a role (McAllister-Williams et al 1998 ;Holsboer, 2000). There is some suggestion that the mood-alleviating effects of antidepressants are in part mediated by effects on corticosteriodal systems (Barden et al 1995).…”

Dissociable Hormonal, Cognitive and Mood Responses to Neuroendocrine Challenge Evidence for Receptor-Specific Serotonergic Dysregulation in Depressed Mood

“…due to long-term repeated overstimulation with cortisol. The latter would also explain the decreased memory performance seen in patients with depressed mood (McAllister-Williams et al 1998). …”

Glucocorticoid modulation of tryptophan hydroxylase-2 protein in raphe nuclei and 5-hydroxytryptophan concentrations in frontal cortex of C57/Bl6 mice

“…There is considerable interplay between the serotonergic and HPA systems and evidence suggests that dysfunction in one of these systems could lead to impairment in the other. 44,45 Glucocorticoid regulation of TPH2 expression and the resulting changes in serotonin biosynthesis may contribute to the serotonergic response to stressful stimuli and may have relevance to the etiology of psychiatric disease accompanied by HPA axis dysregulation, 46,47 as well as psychiatric illness that can be triggered by glucocorticoid therapy.…”