Depressive relapse following acute tryptophan depletion in patients with major depressive disorder

Acute tryptophan depletion (ATD) lowers serotonin synthesis and elicits dep ressive symptoms in some, though not all, remitted patients with major depr essive disorder (MDD). In the present study, eight medication-free remitted patients with MDD, seasonal pattern, were tested twice, once following the ingestion of a tryptophan-containing mixture, once following ATD, ATD sign ificantly increased Hamilton depression scores (p < 0.001). Four of the pat ients had a family history of psychiatric disorders: substance abuse (n = 4 ), mood disorders (n = 3) or Cluster B personality disorders (n = 3). The m ood-lowering response to ATD was significantly greater in those patients wi th, than without, affected relatives (p < 0.001). These preliminary finding s (1) support the hypothesis that depressed states are related to disturbed serotonin neurotransmission and (2) suggest that depressive symptoms follo wing ATD might identify a subgroup of patients at high genetic risk for dis orders associated with affective lability and dysregulated impulse-control, conditions thought to be related to low serotonin neurotransmission.