Manic depression: A multiple hormone disorder?

Abstract

The finding by Paschalis et al. (1977) that the sweat of manics has an abnormally high K +/Na + ratio, whereas that of depressives has an abnormally low one, is an important clue to the causes of manic depression, which seems to have been completely ignored. It strongly suggests that there is an adrenal component in this disorder and it implicates aldosterone. Hendler (1975) has shown that aldosterone levels are elevated in mania and that lithium will lower them and alleviate the manic symptoms, but only after natriuresis has occurred. It has been known for some time that doparnine has natriuretic properties because it inhibits the output of aldosterone (Noth et al. 1980). What has been difficult to understand is at what point dopamine acted. However, it has just been reported (Franco-Saenz et al. 1984) that there appears to be atrophic hormone for aldosterone secreted by the intermediate lobe of the pituitary. This hormone does not raise cortisol levels, nor will glucocorticoids suppress it; dopamine, however, will do so. Dopamine also inhibits the release of thyroid-stimulating hormone (TSH) (Kaptein et al. 1980) and gonadotrophin-releasing factor (GnRF) (Husemarm et al. 1980). Hence, low dopamine levels/activity should lead to high sweat K+/Na + ratios because of the high levels of aldosterone and also to hyperactive behavior and hypersexuality because of the high levels of thyroid hormone and gonadotropins, respectively. All of these are manic features. It may also be significant that hyperthyroid patients have, like manics, elevated potassium sweat levels (Gibinski 1972), suggesting that mania and hyperthyroidism have more than one feature in common. Depressives have low sweat K÷/Na + ratios (Paschalis et al. 1977), so perhaps their aldosterone levels are too low, suggesting that dopamine activity might be too high. This last hypothesis would explain why depressives have a blunted response of TSH to thyrotropin-releasing hormone (TRH) stimulation (Maeda et al. 1975), as dopamine inhibits the release of TSH. It is well known that depression and hypothyroidism have features in common, e.g., weight and appetite abnormalities, anergy, and constipation. Moreover, Prange et al. (1969) have shown that thyroid treatment will improve depression. Finally, high dopamine activity would also explain the lack of sexual interest shown by depressives, as dopamine lowers gonadotrophin-releasing factor levels (Husemann et al. 1980). It has long been known that depression is often associated with raised serum cortisol