11Beta-HSD and 17beta-HSD as biological markers of depression: sex differences and correlation with symptom severity

There is growing interest in the hydroxysteroid dehydrogenases (HSDs) as local modulators of hormone action. We have studied urinary steroid profiles from nine men and nine women with Major Depression to determine whether 11beta-HSD and 17beta-HSD activity are altered. Urinary steroid profiles were determined by high resolution gas chromatography. The ratio of 11-oxo over 11beta-hydroxy metabolites of cortisol was used as the index of 11beta-HSD activity and the ratio of dehydroepiandrosterone (DHA) over androstenediol-17beta was used as the index of 17beta-HSD activity. Symptom severity was assessed using the Hamilton Depression Rating Scale (HDRS). None of the measures of cortisol production, 9 AM plasma cortisol, 24 hour urinary free cortisol or 24 hour total urinary cortisol metabolites, correlated with HDRS in either men or women. 11Beta-HSD activity was altered and correlated with symptom severity in depressed women (r=0.688, p<0.05) but not men (r=0.132). In both depressed men and women, 17beta-HSD activity was altered and correlated with HDRS scores (r=-0.796, p<0.05 and r=0.688, p<0.05 respectively). However, although the ratio was changed in the same direction in depressed men and women. the correlation with symptom severity was positive in women but negative in men. We conclude that markers of subtle change such as these may prove more useful and informative than gross changes in plasma cortisol in depression.