Neuroendocrine evidence for an association between hypothyroidism, reduced central 5-HT activity and depression

OBJECTIVE The incidence of depression in those with hypothyroidism is increased compared to healthy populations, though the mechanism for this is unclear. We tested the hypothesis that central 5-HT activity is reduced in hypothyroidism, and that this subsequently lowers the threshold for developing depression. PATIENTS Twenty subjects entered the study: 10 drug free hypothyroid patients and 10 age, sex, weight and menstrual cycle matched controls. MEASUREMENTS Patients were diagnosed as being depressed using DSM-IIIR criteria and rated using the Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI). Cortisol and prolactin responses to dexfenfluramine, a centrally acting 5-HT releasing agent, were used as an index of central 5-HT responsivity. RESULTS Both cortisol and PRL responses were reduced in the hypothyroid group relative to the controls. Peak cortisol responses were inversely correlated to TSH levels. Four of the 10 patients were clinically depressed. Depressed patients had higher TSH levels than their nondepressed counterparts, and TSH levels were positively correlated with HAM-D and BDI scores. CONCLUSIONS These findings support animal work suggesting that hypothyroidism reduces central 5-HT activity. They also suggest a threshold effect in that higher TSH levels predicted both lower 5-HT mediated endocrine responses and the presence of clinical depression.