Efficacy of noradrenergic-selective agents in the treatment of neuropsychiatric diseases.

In recent years, a number of antidepressants with varying degrees of selectivity for the noradrenergic neurotransmitter system have become available. However, these agents represent a pharmacologically heterogeneous group and differ in terms of their precise side-effect profile and, possibly, their clinical efficacy. Bupropion, which is thought to act on both the dopamine and norepinephrine (NE) systems, has not been widely used as an antidepressant and has more recently been licensed as adjunctive therapy for smoking cessation. The serotonin-NE reuptake inhibitors venlafaxine and nefazodone, the noradrenergic and specific serotonergic antidepressant mirtazapine, and the selective NE reuptake inhibitor reboxetine (the only truly NE-selective agent available) have all demonstrated efficacy in the treatment of depressive disorders. Evidence is now emerging for their use in the treatment of anxiety and panic disorders. There is some suggestion of a role for noradrenergic agents in other disorders, including attention-deficit/hyperactivity disorder and social phobia. The full range of disorders for which noradrenergic agents can be used remains to be seen and further research in this area is necessary.

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

There is some evidence that the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) may be involved in the pathogenesis of seasonal affective disorder (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 before and 24 h after TRP depletion. Some of the patients showed behavioral responses such as lowered mood, feelings of guilt, loss of interest, agitation, loss of energy, fatigue, social withdrawal, increased appetite, and carbohydrate craving. It was the aim of our study to investigate whether the genotypes of the serotonin transporter gene were associated with symptoms of transient depressive relapse after TRP depletion. In addition, we matched the SAD patients with healthy control subjects to see if alleles and genotypes of the serotonin transporter gene were associated with SAD. High molecular weight DNA was isolated from peripheral blood leukocytes using standard methods. For the 5-HTT receptor gene, a 17-bp repetitive element of intron 2 was genotyped (variable number tandem repeat, VNTR). Alterations in HDRS scores after TRP depletion showed no significant association with alleles or genotypes of the 5-HTT gene, although heterozygotes showed a trend toward increased HDRS scores. The serotonin transporter is known to play a critical role in the termination of serotonergic neurotransmission by sodium-dependent 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 plays a role in the pathogenesis of SAD or in short-term depressive relapse after TRP depletion.

Prevalence of seasonal affective disorder at four latitudes.

The Seasonal Pattern Assessment Questionnaire (SPAQ) was mailed to a sample population balanced for sex and randomly selected from local telephone directories in four areas: Nashua, NH, New York, NY, Montgomery County, MD, and Sarasota, FL. On the basis of responses to this questionnaire, prevalence rates of winter seasonal affective disorder (winter SAD), summer seasonal affective disorder (summer SAD), and subsyndromal winter SAD were estimated for the four areas. Rates of winter SAD and subsyndromal SAD were found to be significantly higher at the more northern latitudes, while no correlation was found between latitude and summer SAD. The positive correlation between latitude and prevalence of winter SAD applied predominantly to the age groups over 35.