Relations of sex, steroid hormones and menstrual cycle phase on cognitive functions in bipolar disorder

Introduction: Cognitive dysfunctions are seen in bipolar disorder during mania and depression, but also during remission, and it is thought that it may be an endophenotype for the disease. In addition to gender differences in the onset and clinical course of bipolar disorder, neurocognitive functions may also be affected by the gender factor. The aim of this study was to investigate whether there is a relationship between gender and sex-related hormones and neurocognitive functions in bipolar disorder. Methods: Forty-one patients with bipolar disorder (15 women) and 26 healthy controls (13 women) were included in the study. Blood samples were taken from female participants for the measurement of sex hormones in the early follicular (2-4 days) and midluteal (20-22 days) phases and neuropsychological tests were performed. Male participants also underwent two neuropsychological tests at a 45-55 day time interval. Verbal memory and mental rotation tests were applied to all participants as a neuropsychological test for the second time. Data were analyzed using chi-square, independent groups t test, Kruskal Wallis and Mann Whitney U tests. Results: Patients with bipolar disorder performed worse on Rey auditory verbal learning trial 7 and recognition, Wisconsin card sorting test category number, visual reproduction immediate recall tests, mean probability of responding on stop signal trials, mean stop signal reaction time, mean reaction time on signal respond trials parameters of stop signal task than healthy volunteers. Healthy men showed better performance on Trail making test (part A) and digit span test than healthy women; male patients showed better performance on mental rotation and auditory consonant trigrams than female patients, and the mean probability of responding on stop signal trials, mean stop signal delay and mean reaction time on signal respond trials parameters of stop signal task were significantly longer than female patients. Healthy women performed better in verbal learning and mental rotation test than women patients in the midluteal phase. Healthy men performed better in verbal learning than men patients. It was found that female patients had lower mental rotation test scores in follicular phase than male patients. Estradiol and progesterone levels were significantly higher in female patients diagnosed with bipolar disorder in midluteal phase compared to early follicular phase. It was found that high estradiol level in female healthy volunteers was associated with Rey auditory verbal learning test total score and female progesterone level was associated with Rey auditory verbal learning test trial 1. Conclusion: Male patients with bipolar disorder outperformed female patients in terms of spatial ability. The fact that healthy women performed better in patients with verbal learning and mental rotation tests in the midluteal period, and the absence of such a finding in male patients and healthy controls indicates that female and male patients are affected differently from bipolar disorder. Mental rotation test scores were not expected to differ between male and female participants in the follicular phase, whereas there was a difference in male and female patients diagnosed with bipolar disorder. Mental rotation performance of female patients in the follicular phase were not consistent with the literature. Gender differences are thought to be important when developing treatment related to the disease.