43,46,47 These altered subjective responses, which appear to resolve

after light therapy, are likely to be a state marker of winter depression. Interestingly, a study of m-CPP in nonseasonal depression demonstrated no differences in subjective click here responses in patients compared with controls, and only minor changes in neuroendrocine responses,48 suggesting that altered serotonin receptor function Inhibitors,research,lifescience,medical in SAD may be relatively specific. On the other hand, the eating disorder bulimia nervosa has also been associated with altered responses to serotonergic agonists such as m-CPP,49-51 suggesting that some serotonin receptor changes may be associated with increased appetitive behavior, independently of depression, across psychiatric disorders. It is well established that serotonin has a major role in suppressing various aspects of feeding behavior.52 Depletion of tryptophan, the amino-acid precursor of serotonin, has also been used to assess brain serotonergic functioning in various psychiatric populations. Inhibitors,research,lifescience,medical This uses a specialized diet which includes

various amino acids other than tryptophan. Imaging studies suggest that Inhibitors,research,lifescience,medical this procedure is capable of rapidly lowering brain tryptophan levels by over 80% within just a few hours.53 Tryptophan depletion does not worsen depressive symptoms in untreated SAD patients during the fall/winter period, suggesting a possible floor effect in terms of decreased serotonergic functioning and lowered mood.54 However, similar to patients with nonseasonal depression,55,56 SAD patients who are in short-term clinical remission do show a brief relapse of depressive symptoms in response to tryptophan Inhibitors,research,lifescience,medical depletion.57,58 This procedure may also produce a brief relapse of symptoms when patients are in their summer Inhibitors,research,lifescience,medical remitted state,59 although negative findings have also been reported.60 Tryptophan depletion may have particularly strong effects in triggering the appetitive symptoms of SAD.57 Subjective loss of control of eating

following tryptophan depletion has also been demonstrated in recovered patients with bulimia nervosa,61 adding further evidence for serotonergic involvement in the increased eating behavior manifest in these disorders. The fact that SAD patients report distinct subjective responses to high-carbohydrate meals,62 which can enhance serotonin turnover via increased tryptophan uptake into Bay 11-7085 the brain,63 adds further support to this hypothesis. There have been relatively few brain imaging studies looking at serotonin function in SAD; however, one study using single photon emission computed tomography (SPECT) showed reduced availability of brain serotonin transporters, the proteins responsible for reuptake of serotonin into presynaptic neurons, in drug-free patients with SAD during a winter depressive episode.64 These findings were clearest in the thalamus and hypothalamus, a finding that has also been reported in nonseasonal atypical depression.