***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BDNF plays a critical role in activity-dependent neuroplasticity underlying learning and memory in the hippocampus . A frequent single nucleotide polymorphism in the targeting region of the human BDNF gene ( val66met ) has been associated with abnormal intracellular trafficking and regulated secretion of BDNF in cultured hippocampal neurons transfected with the met allele . In addition , the met allele has been associated with abnormal hippocampal neuronal function as well as impaired episodic memory in human subjects , but a direct effect of BDNF alleles on hippocampal processing of memory has not been demonstrated . We studied the relationship of the  BDNF val66met genotype and hippocampal activity during episodic memory processing using blood oxygenation level-dependent functional magnetic resonance imaging and a declarative memory task in healthy individuals . Met carriers exhibited relatively diminished hippocampal engagement in comparison with val homozygotes during both encoding and retrieval processes . Remarkably , the interaction between the BDNF val66met genotype and the hippocampal response during encoding accounted for 25 % of the total variation in recognition memory performance . These data implicate a specific genetic mechanism for substantial normal variation in human declarative memory and suggest that the basic effects of BDNF signaling on hippocampal function in experimental animals are important in humans In a prospect ive-longitudinal study of a representative birth cohort , we tested why stressful experiences lead to  depression  in some people but not in others . A functional polymorphism in the promoter region of the serotonin transporter ( 5-HT T ) gene was found to moderate the influence of stressful life events on depression . Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms , diagnosable depression , and suicidality in relation to stressful life events than individuals homozygous for the long allele . This epidemiological study thus provides evidence of a gene-by-environment interaction , in which an individual 's response to environmental insults is moderated by his or her genetic makeup BACKGROUND Neurotrophic factors are known to play an important role in the survival and differentiation of many types of neurons during development . Both brain-derived neurotrophic factor ( BDNF ) and ciliary neurotrophic factor ( CNTF ) may act cooperatively in modulating the development and functioning of synapses . Both these neurotrophic factors were intensely investigated with regard to depression without conclusive results . METHODS We have investigated the possible use of both CNTF null-mutation and BDNF polymorphism C270 T as biomarkers for depression in the Vienna Transdanube Aging ( VITA ) study . The VITA is a prospect i ve community-based cohort study of all 75 years old inhabitants of a geographical region of Vienna . RESULTS We found no association between CNTF null-mutation and BDNF C270 T polymorphism to any depressive symptoms after exclusion of demented subjects . CONCLUSION These results call in question the hypothesis that either BDNF or CNTF can be used as molecular markers for depression or late onset depression in the elderly OBJECTIVE To compare differences in gray matter volumes , white matter and subcortical gray matter hyperintensities , neuropsychological factors , and treatment outcome between early- and late-onset late-life depressed ( LLD ) subjects . METHODS We conducted a prospect i ve , nonr and omized , controlled trial at the outpatient clinics at Washington University and Duke University on 126 subjects , aged 60 years or older , who met Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria for major depression , scored 20 or more on the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and received neuropsychological testing and magnetic resonance imaging . Subjects were excluded for cognitive impairment or severe medical disorders . After 12 weeks of sertraline treatment , subjects ' MADRS scores over time and neuropsychological factors were studied . RESULTS Left anterior cingulate thickness was significantly smaller in the late-onset depressed group than in the early-onset LLD subjects . The late-onset group also had more hyperintensities than the early-onset LLD subjects . No differences were found in neuropsychological factor scores or treatment outcome between early-onset and late-onset LLD subjects . CONCLUSION Age at onset of depressive symptoms in LLD subjects are associated with differences in cortical thickness and white matter and subcortical gray matter hyperintensities , but age at onset did not affect neuropsychological factors or treatment outcome We have developed an online catalog of SNP-trait associations from published genome-wide association studies for use in investigating genomic characteristics of trait/disease-associated SNPs ( TASs ) . Reported TASs were common [ median risk allele frequency 36 % , interquartile range ( IQR ) 21%−53 % ] and were associated with modest effect sizes [ median odds ratio ( OR ) 1.33 , IQR 1.20–1.61 ] . Among 20 genomic annotation sets , reported TASs were significantly overrepresented only in nonsynonymous sites [ OR = 3.9 ( 2.2−7.0 ) , p = 3.5 × 10−7 ] and 5kb-promoter regions [ OR = 2.3 ( 1.5−3.6 ) , p = 3 × 10−4 ] compared to SNPs r and omly selected from genotyping arrays . Although 88 % of TASs were intronic ( 45 % ) or intergenic ( 43 % ) , TASs were not overrepresented in introns and were significantly depleted in intergenic regions [ OR = 0.44 ( 0.34−0.58 ) , p = 2.0 × 10−9 ] . Only slightly more TASs than expected by chance were predicted to be in regions under positive selection [ OR = 1.3 ( 0.8−2.1 ) , p = 0.2 ] . This new online re source , together with bioinformatic predictions of the underlying functionality at trait/disease-associated loci , is well-suited to guide future investigations of the role of common variants in complex disease etiology OBJECTIVE This study compared microstructural abnormalities in depressed elders and controls and studied the association of the serotonin transporter gene status to white matter abnormalities and to remission of depression . METHODS The subjects were Caucasians with non-psychotic major depression and normal elders . Depressed subjects received escitalopram 10 mg daily for 12 weeks . Remission was defined as a HDRS score of 7 or below for 2 consecutive weeks . Diffusion tensor imaging was performed and voxel-based analysis of fractional anisotropy ( FA ) was conducted using age and mean diffusivity as covariates . RESULTS Depressed elders ( N=27 ) had lower FA than controls ( N=27 ) in several frontolimbic areas . Depressed elderly S-allele carriers also had lower FA than L homozygotes in frontolimbic brain areas , including the dorsal and rostral anterior cingulate , posterior cingulate , dorsolateral prefrontal and medial prefrontal regions , thalamus , and in other regions . S-allele carriers had a lower remission rate than L homozygotes . LIMITATIONS Small number of subjects , lack of r and om sampling , fixed antidepressant dose , short follow-up . CONCLUSIONS Lower FA was observed in several frontolimbic and other regions in depressed elders compared to controls . Depressed S-allele carriers had both microstructural white matter abnormalities in frontolimbic networks and a low remission rate . It remains unclear whether the risk for chronicity of geriatric depression in S-allele carriers is mediated by frontolimbic compromise . However , these observations set the stage for studies aim ing to identify the relationship of S allele to impairment in specific frontolimbic functions interfering with response of geriatric depression to antidepressants The recently shown association between apolipoprotein E ( APOE ) genotype and depressive illness has been challenged by subsequent studies . However , controversial results may derive from the different diagnostic criteria used for depression and from the small numbers of depressed patients included in the studies . We examined the association between depression and the genetic polymorphism of APOE in a large sample of depressed patients , Alzheimer ’s disease ( AD ) patients , and healthy controls following clear definitions for late-life depression . The cumulative incidence of depression depending on the age at onset of the first episode was examined by survival analysis . Our data do not disconfirm the hypothesis of depression sharing some common pathophysiologic features with AD , however , it seems very unlikely that the APOE genotype will eluci date the assumed common mechanisms BACKGROUND Alcoholism is a complex , genetically influenced disorder the cause of which may be better understood through the study of genetically influenced phenotypes that mediate the risk . One such intermediate phenotype is the low level of response ( LR ) to alcohol . This project used a case-control approach to search for genes that may contribute to LR . METHODS Data were available from alcohol challenges at approximately age 20 and regarding the development of alcohol use disorders over the subsequent 20 years for 85 men , including 40 reported in a previous genetic analysis .  LR was evaluated using oral  consumption  of 0.75 ml/kg of alcohol , after which changes in subjective feelings of intoxication and body sway were measured . Alcohol abuse and dependence were diagnosed by DSM-III-R criteria through structured interviews administered to both the participant and an informant ( usually the spouse ) 10 , 15 , and 20 years after initial testing . Four polymorphisms were evaluated , including the serotonin transporter HTTLPR promoter ins/del , GABAAalpha6 Pro385Ser , NPY Leu7Pro , and catalase 262C > T. Two of these , HTTLPR and GABAAalpha6 Pro385Ser , had been previously associated with LR and alcoholism in a preliminary study . RESULTS The HTTLPR L allele was significantly related to both the LR and alcoholism in an allele-dosage ( stepwise ) manner . Furthermore , the association remained when L alleles were subdivided into recently reported functional subtypes : the lowest LR was associated with genotypes correlated with the highest serotonin transporter expression . The GABAAalpha6 Ser385 allele showed a nonsignificant trend for association to a low LR , as had been previously observed , although the Ser385 allele is uncommon , and only 18 heterozygotes were in the current group . However , the six men with both LL and Pro385/Ser385 genotypes had the lowest LR , and each had developed alcoholism during follow-up . Neither NPY nor catalase was associated with either LR or alcoholic outcomes , although the sample did not have sufficient power for definitive conclusions . CONCLUSIONS This report strengthens the support for a relationship between the HTTLPR L and GABAAalpha6 Ser385 alleles to low alcohol LR and to alcoholism in a prospect ively studied cohort evaluated for LR in young adulthood and before the onset of alcohol dependence 
    Output:
    
These genes are implicated in hippocampal plasticity and stress reactivity , suggesting that dysregulation of these pathways may contribute to LLD .