EFFECTS OF META-CHLOROPHENYLPIPERAZINE INFUSIONS IN PATIENTS WITH SEASONAL AFFECTIVE-DISORDER AND HEALTHY CONTROL SUBJECTS - DIURNAL RESPONSES AND NOCTURNAL REGULATORY MECHANISMS

Background: Multiple lines of evidence suggest that brain serotonergic systems may be disturbed in seasonal affective disorder (SAD). Previo usly, we found that the serotonergic agent meta-chlorophenylpiperazine (m-CPP) produced increases in activation and euphoria in depressed pa tients with SAD, but not in patients with SAD following light treatmen t or in the summer, nor in healthy control subjects in any condition. In the present study, we attempted to replicate and extend this findin g using better methods. Methods: Seventeen outpatients with SAD and 15 control subjects underwent successive 3-week periods of bright light treatment and light avoidance in a randomized order. During the third week of each condition, on 2 different occasions, subjects were admitt ed to the hospital for a night of sleep (core temperatures were record ed), followed by infusions of m-CPP (0.08 mg/kg) or placebo the next m orning. Dependent measures included the 24-item National Institute of Mental Health Self-Rating Scale, plasma corticotropin, cortisol, prola ctin, growth hormone, and norepinephrine concentrations, and core temp eratures. Results: Meta-chlorophenylpiperazine produced (1) significan t increases in ''activation-euphoria'' ratings only in depressed patie nts with SAD in the untreated condition and (2) blunted corticotropin and norepinephrine responses in patients with SAD compared with contro ls across both light treatment conditions. In both groups, light treat ment was associated with significant reductions in nocturnal core temp eratures, which were correlated with similarly significant reductions in mean diurnal growth hormone concentrations. In patients with SAD, ( 1) the reductions in nocturnal core temperatures also were correlated with the reductions in baseline depression ratings and (2) the reducti ons in mean growth hormone concentrations were significantly smaller c ompared with controls. Conclusions: The abnormal m-CPP-induced activat ion-euphoria responses represent a replicated state marker of winter d epression in patients with SAD. The blunted m-CPP-induced responsivene ss of the hypothalamic-pituitary-adrenal axis and the sympathetic nerv ous system may represent traitlike abnormalities. The improvements in mood following light treatment in patients with SAD seem to be associa ted with the lowering of nocturnal core temperatures. The findings, al though not easily explained based on a uniform abnormality of serotoni n receptors, are nonetheless compatible with the notion that selected regions of the central nervous system are deficient in serotonin trans mission during winter depression.