Elevated plasma thymopoietin associated with therapeutic nonresponsiveness in major depression

Stress predisposes to major depression, and hyperactivity of the stress-activated hypothalamic-pituitary-adrenal (HPA) axis occurs in this disease. Thymopentin, an active fragment of thymopoietin (TP), reduces endocrine and behavioral responses to experimental stress, possibly by lowering plasma TP (pTP) levels.

Plasma TP and the HPA hormones arginine vasopressin (pAVP), adrenocorticotropic hormone (pACTH), and plasma cortisol (pCORT) were measured in 21 untreated depressed patients and 21 matched control subjects. Clinical responses to antidepressants were evaluated in 17 depressed patients.

Plasma TP was elevated in depression (p < .002), with in 8 out of 21 (38%) depressed patients having significant elevations (p < .03). For 17 patients whose antidepressant responses were evaluated, nonresponsiveness occurred in 6 out of 7 (86%) with elevated pTP (>7.5 pg/mL) versus 3 out of 10 (30%) with normal pTP (p < .05).

The significant association of elevated pTP with nonresponsiveness to antidepressant drugs may signify a distinct pathogenesis for the depression of patients with elevated pTP.