Hormone-specific psychiatric disorders: do they exist?

Abstract

A stated goal of the DSM-V process is to try to use the biological pathophysiology of mental disorders to inform psychiatric diagnoses, including dimensional features which may cut across diagnostic categories (Charney et al. 2002; Regier et al. 2009). At this point in time, however, biological markers have not been identified which are robust enough to be incorporated in diagnostic criteria. Progress in developing biologically-based diagnoses will depend on more detailed examination of clinical phenomenology associated with particular genetic, physiological, and neural processing characteristics. It is reasonable to expect that such an effort could result in identification of syndromes that map more closely to biological abnormalities than current diagnostic categories. As part of this effort, hormone-related syndromes deserve close attention as potential diagnostic entities or potential supraordinate dimensions that would cross diagnostic boundaries. Because mood and behavior are emergent properties, it is difficult to focus on a level of physiology that would be most informative for diagnostic classification. It is now recognized that individual genetic polymorphisms are unlikely to contribute more than a very small degree of risk for psychiatric disorders. Moreover, the pathway from genes to behavior is now known to incorporate multiple opportunities for modulation of risk, including epigenetic modification of gene expression and plasticity of neurons, synapses and neural networks. Hormones can impact each of these biological processes. Hormonal abnormalities may arise at the synthesis, metabolism or receptor level, but still form organized, identifiable psychiatric syndromes. There are several challenges to identifying hormone-related syndromes. First, in naturalistic reproductive hormone fluxes, such as puberty, the menstrual cycle, pregnancy, lactation and menopause, multiple hormonal changes occur simultaneously. There is an unfortunate tendency to attribute psychiatric symptoms to fluctuations in estrogen, rather than considering a more complete set of hormonal changes. In some cases, such a postpartum OCD, the full syndrome may not be evident following exposure to pregnancy levels of estrogen or progesterone alone. Another major challenge in sorting out hormonal influences on psychiatric disorders is the complex metabolism of circulating steroid hormones. Circulating hormone levels can differ from levels in specific brain areas or within specific cells because local tissue and cellular enzymes can metabolize steroid hormones to other compounds with distinct activities, such as neurosteroids. Approaches to sort out the hormone metabolite most proximal to symptom generation are to study the effects of enzyme inhibitors, receptor antagonists and hormonal agents which are resistant to metabolism. Finally, examination of psychiatric effects of peptide hormones such as oxytocin and inflammatory cytokines is complicated by lack of agonists and antagonists which can access the brain, and separate pools of hormone at specific brain sites and in the periphery.