Brain Dysfunctions In Lifelong Premature Ejaculation Patients And Brain Mechanism Of Dapoxetine Hydrochloride

Lifelong premature ejaculation(LPE)is one of the most common male sexual dysfunction.It is characterized as short intravaginal ejaculatory latency time(less than 1 minute)since the first sexual experience.The patients are often accompanied by anxiety and depression.Up to now,the biological mechanism of LPE remains unclear.Dapoxetine hydrochloride which belongs to a class of drugs called selective serotonin reuptake inhibitors,can be used to treat LPE.Dapoxetine hydrochloride can effectively prolongs intravaginal ejaculatory latency time of LPE patients.However,the mechanism of dapoxetine hydrochloride treatment for LPE is still unclear.Recently,several neuroimaging studies have shown that LPE patients may have abnormal brain function.And selective serotonin reuptake inhibitors are also considered to have influence on the central nervous system.Therefore,in the present study,based on resting state functional magnetic resonance imaging,we aim to explore the brain dysfunctions of LPE patients and the modulation of dapoxetine hydrochloride on brain function by using independent component analysis.Firstly,we detected the differences of brain functional network between 57 LPE patients and36 healthy controls based on resting state functional magnetic resonance imaging.Compared with the healthy controls,LPE patients showed abnormal functional connections of sensory_-motor network and executive control network with the whole brain,in which the functional connection between the right inferior frontal gyrus and sensory-motor network were significantly enhanced,while the functional connections between the right median cingulate and paracingulate gyri,the left inferior frontal gyrus and executive control network were significantly decreased.In addition,the abnormality of functional connection between the right median cingulate and paracingulate gyri and executive control network were significantly correlated with premature ejaculation diagnostic tool score and intravaginal ejaculatory latency time.This study suggests that LPE patients have abnormal brain functional network,mainly in the sensory-motor network and the executive control network.Secondly,the abnormal functional connections of brainstem subregions in LPE patients was studied by using mask independent component analysis.Compared with the healthy controls,LPE patients showed abnormal functional connections of the upper medulla oblongata and the ventral side of pons with the whole brain.In patients,the functional connections between the upper medulla oblongata and cerebellum were enhanced.And the increased functional connections between the ventral side of pons and the bilateral orbital middle frontal gyrus,the left insula,the left medial superior frontal gyrus were also observed in LPE patients.This study indicates that there is abnormal brainstem function in LPE patients,and the upper medulla oblongata and the ventral side of pons may be important targets for LPE neural intervention.Finally,we explored the modulation of dapoxetine hydrochloride on abnormal brain function network and brainstem subregions function connection in LPE patients.It showed that dapoxetine hydrochloride had a long-term regulatory effect on the functional connection between the right median cingulate and paracingulate gyri and executive control network in LPE patients.Moreover,the regulatory effect was significantly correlated with the change of intravaginal ejaculatory latency time in LPE patients after the fifth administration.These results suggest that dapoxetine hydrochloride can regulate some brain dysfunctions in LPE,thereby prolonging the intravaginal ejaculatory latency time of LPE patients.This study reveals the brain dysfunctions in LPE patients and the central modulation of dapoxetine hydrochloride in LPE patients from the perspective of brain function network and functional connectivity of brainstem subregions.These findings provide new insights into the study of LPE neural mechanisms,and may provide new evidence and potential intervention targets for future treatment of LPE.