Objective To study the association between the epidermal growth factor(EGF) gene and intelligence in patients with major depression.Methods Intelligence measurement using Wechsler Adult Intelligence Scale(WAIS) was pe...Objective To study the association between the epidermal growth factor(EGF) gene and intelligence in patients with major depression.Methods Intelligence measurement using Wechsler Adult Intelligence Scale(WAIS) was perfor-med on 120 unrelated patients with major depression and 46 control subjects.Blood was collected from all subjects for extraction of genomic DNA.Four single nucleotide polymorphisms(SNPs) in the EGF gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS).Results Mean scores of both score lang and score task,two subtests in WAIS,differed significantly between major depression patients and controls(P<0.0001).Quantitative trait analysis showed that the genetype of rs2250724 was closely associated with score lang and score task in major depression patients.The associations were still significant after 10 000 permutations.Conclusions Although preliminary,our results provide evidence for association between the EGF gene and intelligence in patients with major depression.Genetic variation in the EGF gene may increase the susceptibility of major depression.展开更多
The subgenual anterior cingulate cortex(sgACC)plays a central role in the pathophysiology of major depressive disorder(MDD).Its functional interactive profile with the left dorsal lateral prefrontal cortex(DLPFC)is as...The subgenual anterior cingulate cortex(sgACC)plays a central role in the pathophysiology of major depressive disorder(MDD).Its functional interactive profile with the left dorsal lateral prefrontal cortex(DLPFC)is associated with transcranial magnetic stimulation(TMS)treatment outcomes.Previous research on sgACC functional connectivity(FC)in MDD has yielded inconsistent results,partly due to small sample sizes and limited statistical power.Furthermore,calculating sgACC-FC to target TMS individually is challenging.We used a large multi-site cross-sectional sample(1660 patients with MDD vs.1341 healthy controls)from Phase Ⅱ of the Depression Imaging REsearch ConsorTium(DIRECT)to systematically delineate case-control difference maps of sgACC-FC.We explored the potential impact of group-level abnormality profiles on TMS target localization and clinical efficacy.Next,we developed an MDD big data-guided,individualized TMS targeting algorithm to integrate group-level statistical maps with individual-level brain activity to individually localize TMS targets.We found enhanced sgACCDLPFC FC in patients with MDD compared with healthy controls(HC).These group differences altered the position of the sgACC anti-correlation peak in the left DLPFC.We showed that the magnitude of case-control differences in the sgACC-FC was related to clinical improvement in two independent clinical samples.This targeting algorithm may generate targets demonstrating stronger associations with clinical efficiency than group-level targets.We reliably delineated MDD-related abnormalities of sgACC-FC profiles in a large,independently ascertained sample and demonstrated the potential impact of such casecontrol differences on FC-guided localization of TMS targets.展开更多
Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder(MDD),repro-ducible findings are lacking,probably reflecting mostly small sample sizes and heterogeneity in analytic approac...Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder(MDD),repro-ducible findings are lacking,probably reflecting mostly small sample sizes and heterogeneity in analytic approaches.To address these issues,the Depression Imaging REsearch ConsorTium(DIRECT)was launched.The REST-meta-MDD project,pooling 2428 functional brain images processed with a standardized pipeline across all participating sites,has been the first effort from DIRECT.In this review,we present an overview of the moti-vations,rationale,and principal findings of the studies so far from the REST-meta-MDD project.Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network,in whole-brain topological properties,in dynamic features,and in functional lat-eralization.These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research.Following these fruitful explorations,DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations.A state-of-the-art,surface-based preprocessing pipeline has also been introduced to improve sensitivity.Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diag-nosis boundaries.In addition,large-scale longitudinal studies targeting brain network alterations following antidepressant treatment,aggregation of diffusion tensor images,and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway.Through these endeavours,we hope to accelerate the translation of functional neuroimaging findings to clinical use,such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets,while building an open repository for the scientific community.展开更多
基金Supported by National High Technology Research and Development Program of China (863 Program) (2006AA02A407)National Basic Research Program of China (973 Program) (2010CB529603)Beijing Natural Science Foundation (7102109)
文摘Objective To study the association between the epidermal growth factor(EGF) gene and intelligence in patients with major depression.Methods Intelligence measurement using Wechsler Adult Intelligence Scale(WAIS) was perfor-med on 120 unrelated patients with major depression and 46 control subjects.Blood was collected from all subjects for extraction of genomic DNA.Four single nucleotide polymorphisms(SNPs) in the EGF gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS).Results Mean scores of both score lang and score task,two subtests in WAIS,differed significantly between major depression patients and controls(P<0.0001).Quantitative trait analysis showed that the genetype of rs2250724 was closely associated with score lang and score task in major depression patients.The associations were still significant after 10 000 permutations.Conclusions Although preliminary,our results provide evidence for association between the EGF gene and intelligence in patients with major depression.Genetic variation in the EGF gene may increase the susceptibility of major depression.
基金the Beijing Nova Program of Science and Technology(20230484465)the Beijing Natural Science Foundation(J230040)+12 种基金the National Natural Science Foundation of China(82122035,81671774,81630031,and 32300933)the Sci-Tech Innovation 2030–Major Project of Brain Science and Braininspired Intelligence Technology(2021ZD0200600)the National Key R&D Program of China(2017YFC1309902)the Key Research Program of the Chinese Academy of Sciences(ZDBS-SSW-JSC006)the Scientific Foundation of Institute of Psychology,Chinese Academy of Sciences(E2CX4425YZ,E3CX1315,and Y9CX422005)the China Postdoctoral Science Foundation(2019M660847)the China National Postdoctoral Program for Innovative Talents(BX20200360)the Special Research Assistant Program of the Chinese Academy of Sciences(E2CX0624)the Key R&D Program of Sichuan Province(2023YFS0076)the Canadian Institutes of Health Research(CIHR),the National Institutes of Health–US(NIH)the Brain Canada Foundationthe Temerty Family through the Centre for Addiction and Mental Health(CAMH)Foundation and the Campbell Family Research Institutethe China Scholarship Council(202104910248)during a visit of Xiao Chen to the Centre for Addiction and Mental Health is acknowledged.
文摘The subgenual anterior cingulate cortex(sgACC)plays a central role in the pathophysiology of major depressive disorder(MDD).Its functional interactive profile with the left dorsal lateral prefrontal cortex(DLPFC)is associated with transcranial magnetic stimulation(TMS)treatment outcomes.Previous research on sgACC functional connectivity(FC)in MDD has yielded inconsistent results,partly due to small sample sizes and limited statistical power.Furthermore,calculating sgACC-FC to target TMS individually is challenging.We used a large multi-site cross-sectional sample(1660 patients with MDD vs.1341 healthy controls)from Phase Ⅱ of the Depression Imaging REsearch ConsorTium(DIRECT)to systematically delineate case-control difference maps of sgACC-FC.We explored the potential impact of group-level abnormality profiles on TMS target localization and clinical efficacy.Next,we developed an MDD big data-guided,individualized TMS targeting algorithm to integrate group-level statistical maps with individual-level brain activity to individually localize TMS targets.We found enhanced sgACCDLPFC FC in patients with MDD compared with healthy controls(HC).These group differences altered the position of the sgACC anti-correlation peak in the left DLPFC.We showed that the magnitude of case-control differences in the sgACC-FC was related to clinical improvement in two independent clinical samples.This targeting algorithm may generate targets demonstrating stronger associations with clinical efficiency than group-level targets.We reliably delineated MDD-related abnormalities of sgACC-FC profiles in a large,independently ascertained sample and demonstrated the potential impact of such casecontrol differences on FC-guided localization of TMS targets.
基金funded by the National Key R&D Program of China no.2017YFC1309902the National Natural Science Foundation of China grant numbers 82122035,81671774,and 81630031+3 种基金the 13th Five-year Informatization Plan of Chinese Academy of Sciences grant no.XXH13505the Key Research Program of the Chinese Academy of Sciences no.ZDBS-SSW-JSC006Beijing Nova Program of Science and Technology no.Z191100001119104the China National Postdoctoral Program for Innovative Talents no.BX20200360.
文摘Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder(MDD),repro-ducible findings are lacking,probably reflecting mostly small sample sizes and heterogeneity in analytic approaches.To address these issues,the Depression Imaging REsearch ConsorTium(DIRECT)was launched.The REST-meta-MDD project,pooling 2428 functional brain images processed with a standardized pipeline across all participating sites,has been the first effort from DIRECT.In this review,we present an overview of the moti-vations,rationale,and principal findings of the studies so far from the REST-meta-MDD project.Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network,in whole-brain topological properties,in dynamic features,and in functional lat-eralization.These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research.Following these fruitful explorations,DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations.A state-of-the-art,surface-based preprocessing pipeline has also been introduced to improve sensitivity.Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diag-nosis boundaries.In addition,large-scale longitudinal studies targeting brain network alterations following antidepressant treatment,aggregation of diffusion tensor images,and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway.Through these endeavours,we hope to accelerate the translation of functional neuroimaging findings to clinical use,such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets,while building an open repository for the scientific community.
