Sex Differences in Bipolar Disorders: Impact on Psychopathological Features and Treatment Response

Abstract

IntroductionSex differences were demonstrated in bipolar disorders (BD) concerning epidemiological, clinical, and psychopathological characteristics, but consensus is lacking. Moreover, data concerning the influence of sex on treatment response in BD is contrasting. The present cross-sectional study aimed to analyze sex differences in a population of BD subjects, with specific focus on psychopathological features and treatment response.Materials and MethodsSubjects diagnosed with BD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th version (DSM-5) were recruited. Socio-demographic and clinical characteristics were collected. The Hamilton Rating Scale for Depression, the Mania Rating Scale (MRS), the brief version of the Temperament Evaluation of Memphis, Pisa and San Diego—Münster version (briefTEMPS-M), and the Barratt Impulsiveness Scale−11 items (BIS-11) were used for psychopathological assessment. Treatment response was appraised with the Alda Scale. We performed bivariate analyses to compare socio-demographic, clinical, and psychopathological characteristics between men and women (p < 0.05). A logistic regression was run to analyze features that were significantly associated with female sex.ResultsAmong the recruited 219 BD subjects, 119 (54.3%) were females. Women had a lower scholarity (p = 0.015) and were less frequently employed (p = 0.001). As for psychopathological features, a higher MRS total score (p < 0.001) was detected among women, as well as higher BIS-11 total score (p = 0.040), and briefTEMPS-M score for anxious temperament (p = 0.006). Men showed higher prevalence of DSM-5 mixed features (p = 0.025), particularly during a depressive episode (p = 0.014). Women reported longer duration of untreated illness (DUI) (p < 0.001). There were no sex differences in the Alda Scale total score when considering the whole sample, but this was significantly higher among men (p = 0.030) when evaluating subjects treated with anticonvulsants. At the logistic regression, female sex was positively associated with longer DUI (p < 0.001; OR 1.106, 95% CI 1.050–1.165) and higher MRS total score (p < 0.001; OR 1.085, 95% CI 1.044–1.128) and negatively associated with employment (p = 0.003; OR 0.359, 95% CI 0.185–0.698) and DSM-5 mixed features (p = 0.006; OR 0.391, 95% CI 0.200–0.762).ConclusionsThe clinical presentation of BD may differ depending on sex. The severity of BD should not be neglected among women, who may also display worse treatment response to anticonvulsants.

Altered sex differences in hippocampal subfield volumes in schizophrenia

“…To examine sex-by-diagnostic group differences in hippocampal volumes, we used analysis of covariance (ANCOVA, type III). Total hippocampal volume and each subfield volume were entered as dependent variables in separate models, which included diagnostic group-by-sex interaction as a fixed factor and age, age 2 , and ICV as covariates. Age 2 was added to more accurately model the effect of age, which may have a nonlinear relationship with volume 44 .…”

“…Total hippocampal volume and each subfield volume were entered as dependent variables in separate models, which included diagnostic group-by-sex interaction as a fixed factor and age, age 2 , and ICV as covariates. Age 2 was added to more accurately model the effect of age, which may have a nonlinear relationship with volume 44 . Levene’s tests (volume∼diagnostic group) were performed to test whether the key assumption of ANCOVAs – homogeneity of variance – was met.…”

“…Post hoc Tukey tests were performed to contrast volume differences between females vs. males, females vs. females and males vs. males for each diagnostic group. Effect sizes were calculated as partial eta-squared (partial η 2 ) based on the F-statistic. Based on diagnostic plots, one outlier was removed from the analysis (male with bipolar I disorder, Cook’s distance > 0.5).…”

“…Based on diagnostic plots, one outlier was removed from the analysis (male with bipolar I disorder, Cook’s distance > 0.5). Case-control differences in hippocampal volumes, corrected by sex, age, age 2 , and ICV, are reported in Table S2 in the supplemental material. To explore the absolute differences in hippocampal volumes by sex and diagnostic group, we re-ran the main analyses without adjustment for ICV.…”

“…To further evaluate hippocampal volume differences between diagnostic groups across age, we fitted multiple regression models with total hippocampal and subfield volumes as dependent variables and group-by-age interaction, group-by-age 2 interaction, sex and ICV as independent variables. Additional multiple regression models were fitted to further examine sex-by-diagnostic subgroup differences (i.e., bipolar I, bipolar II, SCZ-AF, SCZ, OPD) in total hippocampal and subfield volumes, adjusting for age, age 2 and ICV. Due to sample size limitations, individuals with schizophreniform disorder or bipolar not otherwise specified were excluded from the diagnostic subgroup analysis.…”