MOOD AND NEUROPSYCHOLOGICAL FUNCTION IN DEPRESSION - THE ROLE OF CORTICOSTEROIDS AND SEROTONIN

Background. Depressed patients show deficits on neuropsychological tes ts. However, the basis of these impairments and their relationship wit h mood disturbance remains unclear. Methods. This paper reviews the li terature regarding the relationship between mood disturbance and neuro psychological impairment in depression and the evidence for serotonerg ic and hypothalamic-pituitary-adrenal (HPA) axis involvement in these two domains. Results. Mood disturbance and neuropsychological impairme nt both occur in depression, but have no clear relationship in time or degree. Impairment of post-synaptic 5-MT1A receptor function may resu lt in the symptom of low mood in depression. Depressed patients demons trate abnormalities in the functional control of the HPA axis with a r esultant hypercortisolaemia, which may impair neuropsychological funct ion. These processes may be related given the extensive interactions b etween the serotonergic system and the HPA axis. Conclusions. We argue that there is a neurobiological cause of impaired neuropsychological function in depression. The complex relationship between neuropsycholo gical function and mood may be a result of interactions between the se rotonergic system and the HPA axis, particularly in the hippocampus wi th involvement of serotonergic 5-MT1A and glucocorticoid receptors. A primary dysfunction in these receptors will produce a lowering of mood and neuropsychological impairment respectively. Either dysfunction wi ll result in a secondary impairment of the alternate system. Thus, the affective 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-pathol ogies.