Biological “markers” in dysthymia

There is increasing evidence that serotonergic dysfunction is important in the etiology of depression. Research on drug therapies indicate that several Selective Serotonin Reuptake Inhibitors (SSRIs) have equivalent efficacy, compared to tricyclic antidepressants in alleviating symptoms of depression but with fewer side effects. As part of a larger study on the effectiveness of Sertraline in the treatment of dysthymia we are investigating the interactions of the serotonergic system and the extent to which this system is influenced by gonadal and adrenal steroid hormones. Consenting adults with dysthymia or dysthymia with major depressive disorder are randomly assigned to one of three groups; Sertraline alone, Sertraline with interpersonal psychotherapy (IPT), or IPT alone. Refusers to randomization are also followed (Group 4) along with a control group of adults without disorder (Group 5). Baseline and follow up measures include both psychosocial and biological investigations in order to further establish the role of serotonergic dysregulation in the pathophysiology of dysthymia. Blood samples are taken at baseline, at 3 months and at 2 years following Sertraline therapy. Platelets isolated from these samples provide a model for the study of central serotonergic neurons since they share a number of biochemical and pharmacological similarities. The number of binding sites present in the platelet membranes (Bmax) and affinity (Kd) are derived from Scatchard analysis of the binding data using 3H-paroxetine and 3H-LSD as ligands. Preliminary results suggest that subjects with dysthymia have a lower number of binding sites for3 H-paroxetine and a higher number of binding sites to 3H-LSD relative to a matched group of controls. These results are similar to those observed for patients with a major depressive disorder in which 5HT2 type receptors, as measured by 3H-LSD binding, are increased and 5HT1 type receptors, as measured by 3H-paroxetine binding, are decreased. Preliminary results also suggest that subjects with dysthymia have elevated levels of cortisol at baseline relative to matched controls. These observations indicate that dysthymia may share common biological abnormalities generally associated with other mood disorders