Serum thyroid-stimulating-hormone concentration as an index of severity of major depression

Alterations in thyroid axis are common in depression and subclinical hypothyroidism may predispose to recurrent depressive episodes and resistance to antidepressants. The same normal reference ranges are used in both depressive and non-psychiatric patients to detect hypothyroidism. We hypothesized that in depressive patients, serum TSH (thyrotropin) elevation within the normal reference range (greater than or equal to upper 25th percentile) may be related to patients' characteristics reflecting the severity of the depressive illness. We analysed in a cross-sectional study, the relationship between serum TSH and serum-free thyroxine (T4) concentrations and different demographic and psychiatric characteristics in 94 depressive in-patients with DSM-III-R criteria for major depression. The frequency of subclinical hypothyroidism (normal serum T4, higher than normal serum TSH) was 5.3%. In univariate analyses patients who had serum TSH concentrations greater than or equal to upper 25th percentile of the normal range were more likely to have recurrent depression, longer disease duration, higher number of episodes of major depression, higher number of previous suicide attempts and higher body mass index than those patients who had serum TSH concentrations < upper 25th percentile of the normal range (age-adjusted p < 0.05). Stepwise logistic regression analysis showed that serum TSH < upper 25th percentile of the normal range was positively associated with recurrent depression (p = 0.0001), presence of somatic disease condition (p = 0.04), marital status (p = 0.06) and number of suicide attempt (p = 0.1). On the other hand, significantly higher serum TSH concentrations were observed in patients with recurrent depression, melancholia and associated somatic disease conditions. Correspondence analysis showed that serum TSH in the higher 25th percentile of the normal reference range projected together with the presence of melancholia, psychiatric and somatic disease conditions, severe major depressive episodes, recurrence of depressive episodes, prescription of at least two antidepressants or non-response to two antidepressants, and previous suicide attempts. Our study suggests that serum TSH concentration in the upper 25th percentile of the normal reference range may be associated with characteristics of severe major depression. Further prospective studies are needed to establish whether serum TSH concentration in the upper 25th percentile of the normal reference range is a contributory causal factor or a consequence of the severity of major depression.