Multiple neuroendocrine axes are abnormally regulated during major depression. Possibly the most clinically relevant and the least investigated of these is the hypothalamic pituitary gonadal axis (HPG). Unlike other neuroendocrine axes studied, in which immediate clinical ramifications are obscure, manifestations of HPG dysregulation would include menstrual abnormalities and impaired fertility. Data suggesting abnormal regulation of the HPG derives from both neuroendocrine and epidemiologic investigation. In their classic study of the phenominology of depression Cassidy et al (1957) report that """"""""menstrual lapses"""""""" were 10 times more common in affective disorder patients than normal women. Similarly, there is a significant amount of epidemiologic data suggesting that women with chronic affective disorders have decreased rates of fertility (Barron et al, 1982), and women presenting to infertility clinics have high rates of major depression (Domar et al, 1992). Direct neuroendocrine investigation of the HPG in depressed women is sparse, in fact, most investigations have excluding women of child bearing years. The largest study completed suggests that depressed, menstruating women had decreased levels of FSH and attenuated LH response to GNRH (Brambilla et al, 1980). The most compelling neuroendocrine evidence comes from studies of functional hypothalamic amenorrhea. This syndrome is associated with many of the same neuroendocrine abnormalities as depression including hypercortisolemia and attenuated ACTH response to CRH. It is believed to be caused by CRH induced inhibition of the hypothalamic GNRH pulse generator with secondary abnormalities of LH pulsatility (Khoury et al 1986). In order to determine whether women with depression exhibit similar LH abnormalities, twenty-six women with major depression and twenty-six control subjects will be interviewed with a SADS and admitted to the GCRC where blood will drawn every 10 minutes for 8 hours. All subjects will be evaluated during the early follicular phase. Samples will be analyzed for serum LH using a specific and sensitive enzymatic assay. LH pulse characteristics will be analyzed and compared using the computerized cluster analysis algorithm of Veldhuis and Johnson (1989). The investigation of LH pulsatility should provide insight into a potential relationship of fertility, HPG regulation and depression.
| Grambsch, Patricia; Young, Elizabeth A; Meller, William H (2004) Pulsatile luteinizing hormone disruption in depression. Psychoneuroendocrinology 29:825-9 |
| Grambsch, Patricia; Meller, William H; Grambsch, P Victor (2002) Periodograms and pulse detection methods for pulsatile hormone data. Stat Med 21:2331-44 |
| Meller, William H; Grambsch, Patricia L (2002) Rhythmicity in the regulation of luteinizing hormone release. Arch Gen Psychiatry 59:566 |
| Meller, W H; Grambsch, P L; Bingham, C et al. (2001) Hypothalamic pituitary gonadal axis dysregulation in depressed women. Psychoneuroendocrinology 26:253-9 |
| Meller, W H; Zander, K M; Crosby, R D et al. (1997) Luteinizing hormone pulse characteristics in depressed women. Am J Psychiatry 154:1454-5 |
