Decreased mononuclear leukocyte TSH responsiveness in patients with major depression

A subgroup of individuals with major depressive disorder have an impaired thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH). The molecular relationship between the mechanism of this "blunted" TSH response and depression is unknown. Numerous recent studies have characterized similarities and interactions between the immune and neuroendocrine systems. As the immune system both produces and responds to TSH, we utilized a peripheral blood leukocyte system to compare immunoreactive (ir)-TSH responsiveness in 10 adult patients (1 man, 9 women) with Research Diagnostic Criteria for major depressive disorder to that of 9 control subjects. All subjects had normal baseline serum TSH and T4 concentrations. Isolated mononuclear leukocytes were treated in vitro with either 0.5 micrograms/ml staphylococcal enterotoxin A (SEA), 50 micrograms/ml TRH, or no stimulant. After incubation, the cells were monitored for ir-TSH production by indirect immunofluorescence and reverse hemolytic plaque assay using antisera to TSH-beta. The culture supernates were analyzed by TSH radioimmunoassay. SEA- and TRH-treated cell cultures from depressed individuals had significantly fewer immunofluorescent positive cells, as well as significantly fewer and smaller plaques, than did similarly treated leukocytes from control subjects. The increase in supernatant ir-TSH was significantly less in TRH-treated cultures from depressed patients as compared to normals (p less than 0.05). These results suggest that examination of mononuclear leukocyte TSH production may reflect an altered state of neuroendocrine function and may thus be a useful marker for major depressive disorder.