Abstract
Hormonal fluctuations associated with female reproductive life events may precipitate or worsen affective episodes in women with bipolar disorder (BD). Previous studies have shown that women with BD report higher rates of premenstrual dysphoric disorder (PMDD) than controls. Further, bipolar women who report premenstrual worsening of mood display a worse course of their bipolar illness. Despite this, the neural correlates of comorbid BD and PMDD have not been investigated. Eighty-five [CTRL, n = 25; PMDD, n = 20; BD, n = 21; BD with comorbid PMDD (BDPMDD), n = 19], regularly cycling women, not on hormonal contraception, underwent two MRI scans: during their mid-follicular and late luteal menstrual phases. We investigated resting-state functional connectivity (Rs-FC), cortical thickness, and subcortical volumes of brain regions associated with the pathophysiology of BD and PMDD between groups, in the mid-follicular and late luteal phases of the menstrual cycle. All BD subjects were euthymic for at least 2 months prior to study entry. Women in the BDPMDD group displayed greater disruption in biological rhythms and more subthreshold depressive and anxious symptoms through the menstrual cycle compared to other groups. Rs-FC was increased between the L-hippocampus and R-frontal cortex and decreased between the R-hippocampus and R-premotor cortex in BDPMDD vs. BD (FDR-corrected, p < 0.05). Cortical thickness analysis revealed decreased cortical thickness of the L-pericalcarine, L-superior parietal, R-middle temporal, R-rostral middle frontal, and L-superior frontal, as well as increased cortical thickness of the L-superior temporal gyri in BDPMDD compared to BD. We also found increased left-caudate volume in BDPMDD vs. BD (pCORR < 0.05). Women with BD and comorbid PMDD display a distinct clinical and neurobiological phenotype of BD, which suggests differential sensitivity to endogenous hormones.
Highlights
Hormonal fluctuations associated with female reproductive life events may precipitate or worsen affective episodes in women with bipolar disorder (BD)
We investigated resting-state functional connectivity (Rs-FC), cortical thickness, and subcortical volumes of brain regions associated with the pathophysiology of BD and premenstrual dysphoric disorder (PMDD) between groups, in the mid-follicular and late luteal phases of the menstrual cycle
Women in the BD with comorbid PMDD (BDPMDD) group displayed greater disruption in biological rhythms and more subthreshold depressive and anxious symptoms through the menstrual cycle compared to other groups
Summary
Hormonal fluctuations associated with female reproductive life events may precipitate or worsen affective episodes in women with bipolar disorder (BD). Women with BD display high rates of premenstrual syndrome (PMS); with studies estimating that approximately 51–68% of women with BD report mood symptoms during the premenstrual period [7,8,9,10]. Fornaro and Perugi investigated the impact of premenstrual dysphoric disorder (PMDD) in a sample of 92 women with BD [11] In their sample, 27.2% of women met criteria for PMDD according to a semi-structured clinical interview. In a recent study of a large sample of women with BD (N = 1,099), our group found that women with comorbid PMDD had an earlier onset of bipolar illness, higher rates of rapid cycling, increased number of mood episodes, and higher rates psychiatric comorbidities [18]. Sex hormones have been implicated in the establishment and regulation of the HPA axis [19]; literature supports dysregulation of this axis in BD [20], suggesting that sex hormones may play a role in mediated an already dysregulated HPA axis in the case of BD
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