Menstrual Cycle Effects on Hypothalamic Dopamine Receptor Function in Women with a History of Puerperal Bipolar Disorder

Abstract

Neuroendocrine challenge tests of hypothalamic dopamine receptor function in the early postpartum period suggest that the sensitivity of these receptors is increased in women with a history of bipolar disorder after childbirth. We tested the hypothesis that, in women predisposed to bipolar disorder in the puerperium, hypothalamic dopamine receptor function is more sensitive to changes in circulating ovarian hormone concentrations than in women without such histories. Eight fully recovered and drug-free women who had had at least one episode of bipolar illness following childbirth were compared with nine normal controls. Growth hormone (GH) responses to apomorphine (APO 0.005 mg s.c.) were measured in the early follicular phase, when plasma concentrations of ovarian hormones are low, and in the mid-luteal phase, when they are relatively high. The recovered bipolar subjects and the controls did not differ from each other in their follicular and midluteal oestrogen and progesterone concentrations. In the midluteal phase, both groups had increased oestrogen and progesterone levels. The recovered bipolar subjects did not differ from controls in baseline concentrations of GH in either of the menstrual phases. The APO-GH responses of the two groups did not differ in the follicular phase, but in the midluteal phase, when female sex steroids are relatively increased, the recovered group had significantly enhanced APO-GH responses [MANOVA for repeated measures: (i) area under the curve, group by phase effect: p < 0.04; (ii) GH peak rise after APO, group by phase effect: p < 0.056] and the responses were not related to concurrent measures of mood. The results of this small study of women predisposed to bipolar disorder in the puerperium shows an increased dopaminergic receptor sensitivity in the luteal phase of the menstrual cycle. It suggests that their dopaminergic systems have increased sensitivity to changes in circulating female sex steroids. This may be aetiologically relevant to the pathogenesis of puerperal bipolar disorder.

Effect of Menstrual Cycle Phase on Dopamine D2 Receptor Availability in Female Cynomolgus Monkeys

“…Sex differences have been demonstrated in the incidence and progression of, as well as medication effectiveness in, several neuropsychiatric disorders, including Parkinson's disease, schizophrenia, obsessive-compulsive disorder, and drug abuse (eg Seeman, 1996;Bogetto et al, 1999;Cyr et al, 2002;Wieck et al, 2003;Lynch et al, 2002;Lynch, 2006). Dysfunction of brain dopamine (DA) systems, particularly the D2-like superfamily of DA receptors, has been associated with these conditions (Cross et al, 1981;Guttman and Seeman, 1985;Volkow et al, 1993;Hesse et al, 2005).…”

Positron emission tomography imaging studies of dopamine receptors in primate models of addiction

“…Importantly, these reported sex differences extend beyond drug abuse to include most psychiatric disorders including schizophrenia, Parkinson's disease and obsessive-compulsive disorder (e.g. Seeman 1996;Wieck et al 2003). In female subjects, there is evidence that menstrual cycle phase can alter sensitivity to drugs of abuse (see Terner & de Wit 2006).…”

A Case of Menstruation Related Psychosis-A Rare Entity

“…Tyrosine hydroxylase which is the enzyme responsible for producing Dopamine is heavily modulated by estrogen [8]. Also estrogen treatment has been implicated in reducing the post synaptic activity of dopamine in ovarectomized rats [9].…”