Behavioral effects of tryptophan depletion in seasonal affective disorder associated with the serotonin transporter gene?

There is some evidence that the neurotransmitter serotonin (5-hydroxytrypta mine; 5-HT) may be involved in the pathogenesis of seasonal affective disor der (SAD). Short-term tryptophan (TRP) depletion was carried out in 18 drug -free remitted patients who met DSM-IV criteria for SAD. Behavioral effects were measured with the Hamilton Depression Rating Scale (HDRS) both 24 h b efore and 24 h after TRP depletion. Some of the patients showed behavioral responses such as lowered mood, feelings of guilt, loss of interest, agitat ion, loss of energy, fatigue, social withdrawal, increased appetite, and ca rbohydrate craving. It was the aim of our study to investigate whether the genotypes of the serotonin transporter gene were associated with symptoms o f transient depressive relapse after TRP depletion. In addition, we matched the SAD patients with healthy control subjects to see if alleles and genot ypes of the serotonin transporter gene were associated with SAD. High molec ular weight DNA was isolated from peripheral blood leukocytes using standar d methods. For the 5-HTT receptor gene, a 17-bp repetitive element of intro n 2 was genotyped (variable number tandem repeat, VNTR). Alterations in HDR S scores after TRP depletion showed no significant association with alleles or genotypes of the 5-HTT gene, although heterozygotes showed a trend towa rd increased HDRS scores. The serotonin transporter is known to play a crit ical role in the termination of serotonergic neurotransmission by sodium-de pendent uptake of 5-HT into the presynaptic neuron. The present study in a small group of SAD patients was unable to demonstrate that the 5-HTT gene p lays a role in the pathogenesis of SAD or in short-term depressive relapse after TRP depletion. (C) 1999 Elsevier Science Ireland Ltd. All rights rese rved.