Sex effects on differentiating patients with major depressive disorder from bipolar disorder in depressive state: A fMRI study with follow-up

Background: Bipolar disorder (BD) is difficult to discriminate from major depressive disorder (MDD) before the appearance of mania or hypomania. This study was designed to identify whether patients with MDD and those who converted to BD are distinguishable using dynamic amplitude low-frequency fluctuations (dALFF) and describe the sex effects on the identification of the two disorders.Methods: We compared the dALFF values of 35 BD patients who converted from MDD during the 2-year followup, 99 MDD patients, and 130 healthy controls (HCs) using two-way ANOVA. Pearson's correlation was used to compare dALFF in dysfunctional brain regions and clinical characteristics.Results: A main effect of diagnosis was discovered in the frontal and occipital gyrus. For the main effect of sex, both the left middle occipital gyrus and the medial part of the superior frontal gyrus had higher dALFF values in males compared to females. An interaction of sex and diagnosis effect was observed in the right precentral gyrus. Male MDD patients exhibited a higher dALFF value than male BD patients. Additionally, we discovered a higher dALFF value in females than in males in BD patients. WCST scores were positively associated with dALFF values in the frontal and occipital gyrus in MDD patients. Meanwhile, dALFF values in the occipital gyrus positively correlated with WCST in female MDD patients only.Limitation: Most of the participants were on medication and the sample size was small.Conclusions: Our study is the first to find the non-neglectable role of sex effects in differentiating BD and MDD at an early stage.