Platelet serotonin function and personality traits in affective disorder

Sammanfattning: Serotonin (5-HT, 5-hydroxytryptamine) is a neurotransmitter in the central nervous system which has been implicated m the aetiology and pathogenesis of affective disorders like depression and anxiety disorders. The serotonergic system has been shown to be involved in the modulation of mood, sleep, appetite, libido, energy and cognition and memory functions. The aim of the present study was to investigate and compare hypothesized divergences in central serotonergic function in major depression and panic anxiety and moreover to investigate the relationship between serotonergic function and personality traits in panic anxiety and healthy individuals. The influence of the light and dark seasons on serotonin function in healthy individuals was also investigated. On the basis of similarities in serotonin uptake, storage and release, and morphological, biochemical and pharmacological properties, we used platelets as peripheral models of serotonergic nerve terminals. To assess the serotonin. function we investigated serotonin uptake kinetics, the serotonin transporter density and 5-HT2A receptor density. Using the Temperament and Character Inventory (TCI) and Karolinska Scales of Personality (KSP) we studied the personality traits in untreated panic patients, in comparison with healthy controls, and during 6 months of citalopram treatment. Platelet serotonin uptake was significantly lowered in depression, particularly in women and there was a significant increase in the density of serotonin transporters in both sexes. There was no difference in 5-HT2A receptor density between patients and controls. The lowered serotonin uptake in combination with increased density of serotonin transporters may be an indication of malfunctioning transporters and reflect a specific vulnerability in depression. In panic anxiety the serotonergic dysfunction was illustrated by a reduced density of serotonin transporters, while there was no difference in serotonin uptake kinetics or 5- HT2A receptor density between patients and controls. We observed 75 % reduction in anxiety and depression scales (BAI, BDI) after 6 months citalopram treatment and 12 % changes in the direction to normalization in all KSP anxiety related items, aggression and hostility related items and the item of Socialisation. Citalopram. treatment caused a significant inhibition of serotonin uptake and a reduction in 5-HT2A receptor density but did not influence the density of serotonin transporters. Thus a reduced density of serotonin transporters may constitute a trait marker in panic disorder. Modulation of serotonergic functions in term of a reduction in serotonin uptake and downregulation of 5HT2A receptors appears to have an anxiolytic as well as an antidepressive effect. We observed significant seasonal changes in serotonergic variables and what seems to be a compensating relationship between these changes. The seasonal pattern for the serotonin uptake with peaks during dark period and lowest values during light period of the year was the opposite to what was described by the density of serotonin transporters and 5-HT2A receptors. This dynamics of the serotonin transporter function may explain our findings of a stable platelet serotonin content over the year. Compensating relationships in seasonal changes between serotonergic variables in healthy controls may be essential for mental health. Conversely, it seems reasonable to assume that disturbances in the annual rhythm of one serotonergic function could unsettle the balance between interrelated serotonergic mechanism and contribute to mental illness. The work presented here indicates that the serotonergic dysfunction in major depression and panic disorder has distinctive and separate features. The serotonin transporter density correlated negatively with Harm Avoidance scores and positively with Self-Directedness scores. These correlations corroborate each other and give tentative evidence for that one link between serotonergic function and behaviour implicates the serotonin transporter. Furthermore, the findings indicate that both the temperament and character dimensions may be serotonergically modulated.