| ObjectivesGender differences in post-traumatic stress disorder(PTSD)have been widely reported by domestic and foreign research.However,due to the different types of traumas and the unbalanced gender ratio of the samples,the gender differences in PTSD need to be further explored.Because there is a lack of relevant studies and inconsistent reports on gender differences in PTSD in the context of the Coronavirus Disease 2019(COVID-19)pandemic,and the brain morphometry mechanism of gender differences in PTSD is still unclear.Therefore,this study focuses on gender differences in PTSD,firstly exploring the manifestation and influencing factors of gender differences in PTSD under COVID-19 epidemic conditions,and then exploring the brain morphological mechanism of gender differences in PTSD by starting with chronic stress.MethodsThe current study consists of three parts.First,a cross-sectional investigation of the gender differences in post-traumatic stress symptoms(PTSS)was conducted by convenient sampling among the general public from China’s hardest-hit areas in the early stages of the COVID-19 outbreak.Second,a propensity score matching(PSM)analysis was used for strictly 1:1 gender stratification among COVID-19 hospitalized patients from two designated hospitals in China to further explore the impact of delayed medical treatment on gender differences in PTSS based on the first part of the study.Finally,structural magnetic resonance imaging(s MRI)analysis was used to preliminarily explore gender differences in brain gray matter volume(GMV)under chronic stress among participants from MPILeipzig_Mind-Brain-Body project(ds000221)dataset in Open Neuro,an open-source website,to provide evidence for the brain mechanism of gender differences in PTSD.Results1.A total of 285 general publics from hardest-hit areas were enrolled in study I,including 124 females(54.4%)with an average age of 36.83±12.15.The results showed that women had a higher prevalence of PTSS and more severe overall symptoms one month after the outbreak of COVID-19 in China.The prevalence of PTSS was 9.7% in women and 3.8% in men,with an overall prevalence of 7%.Both the Mann-Whitney U test and the Wilcoxon W test showed that women were more severe than men in the three of four symptom clusters in PTSD,including re-experiencing(Criterion B),negative alterations in cognitions and mood(Criterion D),and hyper-arousal(Criterion E).Hierarchical regression analysis also showed that women(β=0.102,P<0.05)had more severe PTSS.In addition,poor subject sleep quality(β=0.312,P<0.001),and difficulty falling asleep(β=0.172,P<0.01)were also influential factors for PTSS.2.The whole sample of study II included 258 hospitalized COVID-19 patients,of whom 122(57.64%)were males.The age of the subjects ranged from 19 to 91 years old(M=56.63,SD=13.83).After PSM matching,the matching sample(n=164)included 82 males and 82 females,ranging in age from 19 to 91 years(M=55.67,SD=13.55).The results showed that the overall PTSS level among hospitalized COVID-19 patients was more severe in women(t=-3.26,P<0.01),and 12 of the 20 PTSD symptoms were worse in women.The prevalence of PTSS also higher in women(22.1%),and 14.8% in men,and the overall prevalence was 18.6%.After strict gender matching in PSM analysis,the first medical treatment time course(days from COVID-19 symptoms onset to first medical visit,D1,β=0.247,P<0.01)and difficulty falling asleep(β=0.209,P<0.05)were influencing factors for PTSS in men(R2=0.389,p<0.001),but not in women.The univariate analysis of variance(ANOVA)results showed an interaction between gender and time course(D1)in the prevalence of PTSS(F = 5.710,P< 0.05).Gender differences in PTSS were moderated by delayed treatment.When D1 was less than 7 days,the incidence of PTSS was higher in women than in men(HR=2.539,95%CI=1.14,5.66,P<0.05),while no such difference was observed when D1 was 7 days or more.3.A total of 32 subjects were included in study III,including 16 of the chronic stress group(8 males and 8 females)and 16 controls(8 males and 8 females).There were gender differences in changes in brain morphometry under chronic stress.Two-Way ANOVA showed an interaction between chronic stress and gender in the changes in GMV(GRF correction,voxel P<0.005,cluster P<0.05),and significant brain regions included cerebellum,thalamus,midbrain,limbic system,cingulate gyrus,precuneus,anterior central gyrus/motor cortex,posterior central gyrus/somatosensory cortex,angular gyrus/somatosensory cortex.According to the simple effect analysis,the GMV in the left cerebellum and brainstem decreased in males(Voxel size=1070,t=-3.8352,GRF correction,voxel P<0.005,cluster P<0.05),while the GMV in the left precentral gyrus/primary motor cortex and postcentral gyrus/somatosensory cortex increased in females(Voxel size=1719,t=4.2374,GRF correction,voxel P<0.005,cluster P<0.05)under chronic stress.Compared with females,males had larger GMV in two brain regions in the control group(GRF correction,voxel P<0.005,cluster P<0.05),including the right cerebellum(Voxel size=1567,t=3.3719),and the left anterior central gyrus/primary motor cortex and the posterior central gyrus/somatosensory cortex(Voxel size=1235,t=3.6445),while males had one larger MGV region under chronic stress,which is the left and right occipital lobes/cerebellum/visual cortex/lingual gyrus/fusiform gyrus(Voxel size=1812,t=4.5268,GRF correction,voxel P<0.01,cluster P<0.05).Conclusions1.There were gender differences in post-traumatic stress symptoms(PTSS)among the general public in the hardest-hit areas of China in the early stages of the COVID-19 pandemic,with females having more severe symptoms than males.Poor subjective sleep quality and disturbed sleep patterns(frequent nocturnal or early morning awakening)were also influencing factors for the development of PTSS.2.The overall prevalence of PTSS was higher in female hospitalized COVID-19 patients.However,males showed delayed PTSS effect,that is,the effect of delayed medical treatment on PTSS only occurred in males,which was manifested as low PTSS level in the early stage of COVID-19 infection,and an even women-exceeded sharp increase in PTSS level one week later if no timely medical anti-viral treatment was provided.3.The occipital lobe,cerebellum,and frontal-parietal lobe may be important brain regions for gender differences in PTSD,which is manifested as gender differences in gray matter volume(GMV)changes in these brain regions under chronic stress.Specifically,GMV was decreased in the cerebellum and increased in the occipital lobe(visual association cortex,lingual gyrus,fusiform gyrus,etc.)in males,and was increased in the frontal-parietal lobe(precentral gyrus/primary motor cortex,postcentral gyrus/somatosensory cortex,etc.)in females.In conclusion,the gender differences in PTSD were proved significant in the study,with higher overall prevalence and more severe symptoms in females,and delayed effects of PTSD symptoms in males.The occipital lobe,cerebellum,and frontal-parietal lobe regions may be important brain regions of gender differences in chronic stress and PTSD.These findings provide a guide for national and local health authorities to formulate COVID-19 related policies and highlight the importance of monitoring,early recognition,and timely treatment of sleep and psychological problems among the general public and COVID-19 patients during the pandemic.For example,timely relief of psychological stress is most important for women,while timely medical attention for physical symptoms should be the focus for men.In addition,the preliminary exploration of the brain morphometric mechanism of gender differences under chronic stress in the study provides significant evidence for the further study of the brain mechanism of gender differences in PTSD,which is expected to fill the critical research gap. |
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