Brain Structure and Function in Women with Comorbid Bipolar and Premenstrual Dysphoric Disorder

Abstract

IntroductionHormonal 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.MethodologyEighty-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.ResultsWomen 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).ConclusionWomen with BD and comorbid PMDD display a distinct clinical and neurobiological phenotype of BD, which suggests differential sensitivity to endogenous hormones.

From anatomy to function: the role of the somatosensory cortex in emotional regulation

“…Increases in functional connectivity between the somatosensory cortex and thalamus have also been observed in schizophrenia, as well as between the somatosensory cortex and insular cortex in patients with bipolar disorder 49,51. Women with comorbid bipolar and premenstrual dysphoric disorder displayed decreased functional connectivity between the left somatosensory cortex and left hippocampus compared to women with premenstrual dysphoric disorder alone 53. Lower functional connectivity was also observed between the left SI and areas such as the left superior frontal gyrus, the right middle frontal gyrus, and the left mid cingulum in individuals with MDD 54…”

Resting-state functional connectivity in individuals with bipolar disorder during clinical remission: a systematic review

“…[70][71][72][73] Further, these differences also extend to brain structure and function: a recently published study found differences in cortical thickness, rsFC and the volume of the caudate nucleus in women with bipolar disorder and comorbid PMDD compared with women who have bipolar disorder without a comorbid diagnosis of PMDD. 74 We encourage researchers to explore these themes, because it would help to create a more diverse body of literature on rsFC in patients with bipolar disorder. Moreover, we encourage researchers to control for or at least include the presence of PMDD in women with bipolar disorder in their analysis models.…”

“…This is especially important given the high prevalence of PMDD in women with bipolar disorder, as well as differences in brain structure and function observed in euthymic women with bipolar disorder and comorbid PMDD relative to those without PMDD. 74 This study provided a concise review of the rsFC literature in bipolar euthymia, but it is not without limitations. A major limitation was the considerable heterogeneity in analytical approaches used in the included studies.…”

Effects of Estradiol Therapy on Resting-State Functional Connectivity of Transgender Women After Gender-Affirming Related Gonadectomy

“…Comparatively, in non-transgender individuals, shifts in estradiol and testosterone levels were demonstrated to negatively impact mood (Gordon et al, 2018; Ng et al, 2018), anxiety (Hwang et al, 2015), emotional regulation (Syan et al, 2017; Dan et al, 2018), and cognitive processes (Maki et al, 2001; Berent-Spillson et al, 2010). In this sense, there is growing evidence supporting the existence of a relationship between behavioral, affective and cognitive measures, and changes in brain anatomy and/or functionality (Berent-Spillson et al, 2010; Albert et al, 2015; Syan et al, 2017, 2018; Weis et al, 2017; Dan et al, 2018).…”