Comorbid Premenstrual Dysphoric Disorder and Bipolar Disorder: A Review

Abstract

Bipolar disorder (BD) differs in its clinical presentation in females compared to males. A number of clinical characteristics have been associated with BD in females: more rapid cycling and mixed features; higher number of depressive episodes; and a higher prevalence of BD type II. There is a strong link between BD and risk for postpartum mood episodes, and a substantial percentage of females with BD experience premenstrual mood worsening of varying degrees of severity. Females with premenstrual dysphoric disorder (PMDD)-the most severe form of premenstrual disturbances-comorbid with BD appear to have a more complex course of illness, including increased psychiatric comorbidities, earlier onset of BD, and greater number of mood episodes. Importantly, there may be a link between puberty and the onset of BD in females with comorbid PMDD and BD, marked by a shortened gap between the onset of BD and menarche. In terms of neurobiology, comorbid BD and PMDD may have unique structural and functional neural correlates. Treatment of BD comorbid with PMDD poses challenges, as the first line treatment of PMDD in the general population is selective serotonin reuptake inhibitors, which produce risk of treatment-emergent manic symptoms. Here, we review current literature concerning the clinical presentation, illness burden, and unique neurobiology of BD comorbid with PMDD. We additionally discuss obstacles faced in symptom tracking, and management of these comorbid disorders.

Keywords: bipolar disorder; comorbidities; premenstrual dysphoric disorder; premenstrual syndrome; women's mental health.

Figure 1

Psychiatric comorbidities in women with bipolar disorder with and without comorbid premenstrual dysphoric disorder. ^***p < 0.001; ^**p < 0.01, ^*p < 0.05. PMDD, Premenstrual Dysphoric Disorder; OCD, Obsessive Compulsive Disorder. Reproduced with permission from Slyepchenko et al. (26).

Figure 2

Resting state functional connectivity differences between females with bipolar disorder and females with bipolar disorder and comorbid premenstrual dysphoric disorder. (A) Shows that left hippocampus seed is more connected with the right frontal cortex in females with the comorbid disorders. (B) Shows that right hippocampus is less functionally connected with left premotor cortex in females with the comorbid disorders. Results corrected for multiple comparisons using false discovery rate procedure. Reproduced with permission from Syan et al. (27).

Figure 3

Cortical thickness differences in females with both bipolar disorder and premenstrual dysphoric disorder to a control population, females with premenstrual dysphoric disorder only and females with bipolar disorder only. Red regions indicate higher cortical thickness in the first group compared to females with bipolar disorder and premenstrual dysphoric disorder, while blue regions indicate lower cortical thickness in the first group compared to females with bipolar disorder and premenstrual dysphoric disorder. BD, bipolar disorder; BDPMDD, bipolar disorder with comorbid premenstrual dysphoric disorder; CTRL, healthy controls; PMDD, premenstrual dysphoric disorder. Reproduced with permission from Syan et al. (27).