Gender Differences Of Amplitude Of Low-frequency Fluctuations In Bipolar Disorder: A Resting State FMRI Study

Objective: Bipolar disorder(BD)is a group of recurrent severe mental disorders.There are many differences in the clinical features and brain structure between females and males in BD.However,the association between brain function and gender in BD is unclear and studying the relationship between them can help us to find out the pathophysiological mechanism of females and males in BD.Therefore,this research was to investigate the association between brain function and gender in BD in order to further discover the pathophysiological mechanism of BD and provide evidences for early detection and different treatment of diseases.Methods: In this study,ninety-eight patients(49 females,49 males)with BD and One hundred and seventy-one matched healthy controls(HC)(89 females,82 males)were recruited to scan resting state functional magnetic resonance imaging(f MRI).Pre-process the image data and calculate the voxel-based whole-brain amplitude of low-frequency fluctuations(ALFF).Using analysis of variance and two-sample t test to analysis demographic information of four groups of participants.Using factor design of analysis of variance to acquire the main effect of diagnosis and gender and their interaction with diagnosis(BD,HC)and gender(female,male)as factors and age as covariates.GRF correction was used to correct the results(voxel P<0.005,P<0.05 after correction).Twosample t-test were performed on ALFF values to compare BD male with HC male,BD female with HC female and BD male with BD female.(voxel P<0.005,P<0.05 after correction).Results: 1.No significant differences in age and education among the four groups,and no significant differences in course of disease,HAMD-17 scores,YMRS scores and HAMA scores between the BD-Female group and the BD-Male group.Significant differences in HAMD-17 scores,YMRS scores and HAMA scores was found among the four groups.2.Significant main effect of diagnosis was observed in several brain regions,including the bilateral dorsal lateral prefrontal cortex(DLPFC),bilateral ventral prefrontal cortex(VPFC),bilateral caudate and occipital lobe.There were significant increased ALFF in the bilateral DLPFC,bilateral VPFC and bilateral caudate in BD compared to HC,while with significantly decreased ALFF in the occipital lobe in BD compared to HC.3.Significant main effect of gender was observed in several brain regions,including the bilateral DLPFC,right VPFC,thalamus,and occipital lobe.There were significant increased ALFF in the right VPFC,thalamus and occipital lobe in female participants compared to male participants,while with significantly decreased ALFF in the bilateral DLPFC in female participants compared to male participants.4.significant diagnosis by gender interaction was observed in the left DLPFC(corrected P<0.05).5.Two-sample t-tests indicated that there were significant increased ALFF in the right hippocampus,right amygdala,left caudate and left DLPFC in BD males compared to HC males,while with significantly decreased ALFF in the occipital lobe in BD males compared to HC males.Post-hoc analyzes indicated that there were significant increased ALFF in the right VPFC and right DLPFC in BD females compared to HC females.Post-hoc analyzes also indicated that there were significant increased ALFF in the right VPFC and left DLPFC in BD males compared to BD females,while with significantly decreased ALFF in the occipital lobe in BD males compared to BD females(corrected P<0.05).Conclusions: 1.BD patients showed dysfunctions in the DLPFC,VPFC,bilateral caudate and occipital lobe,implying the pathophysiological mechanism of BD.2.The differences of functional activities in the right VPFC,bilateral DLPFC,thalamus and occipital lobe between female participants and male participants,may indicate that these different brain regions are the biological markers to distinguish the them.3.Prefrontal cortex dysfunctions were discovered in both BD females and BD males,there were more severe dysfunctions of prefrontal cortex in BD males,while limbic system dysfunctions were found in BD males,which may provide a basis for the difference of pathophysiological mechanism between the them.