title: 5-HTTLPR polymorphism modulates neural mechanisms of negative self-reflection.
abstract: Cognitive distortion in depression is characterized by enhanced negative thoughts about both environment and oneself. Carriers of a risk allele for depression, that is, the short (s) allele of the serotonin transporter promoter polymorphism (5-HTTLPR), exhibit amygdala hyperresponsiveness to negative environmental stimuli relative to homozygous long variant (l/l). However, the neural correlates of negative self-schema in s allele carriers remain unknown. Using functional MRI, we scanned individuals with s/s or l/l genotype of the 5-HTTLPR during reflection on their own personality traits or a friend's personality traits. We found that relative to l/l carriers, s/s carriers showed stronger distressed feelings and greater activity in the dorsal anterior cingulate (dACC)/dorsal medial prefrontal cortex (dmPFC) and the right anterior insula (AI) during negative self-reflection. The 5-HTTLPR effect on the distressed feelings was mediated by the AI/inferior frontal (IF) activity during negative self-reflection. The dACC/dmPFC activity explained 20% of the variation in harm-avoidance tendency in s/s but not l/l carriers. The genotype effects on distress and brain activity were not observed during reflection on a friend's negative traits. Our findings reveal that 5-HTTLPR polymorphism modulates distressed feelings and brain activities associated with negative self-schema and suggest a potential neurogenetic susceptibility mechanism for depression.
authors.affiliation: Department of Psychology, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Yina
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Peking-Tsinghua Center for Life Sciences at School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Bingfeng
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Psychology, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Chenbo
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Psychology, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Zhenhao
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Peking-Tsinghua Center for Life Sciences at School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Psychology, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Sheng
authors.affiliation: Department of Psychology, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Peking-Tsinghua Center for Life Sciences at School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Peking-Tsinghua Center for Life Sciences at School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Rao
authors.affiliation: Department of Psychology, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Han
mesh_terms: D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D005260:Female; D033062:Friends; D060005:Genotyping Techniques; D006801:Humans; D007600:Judgment / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010551:Personality; D011110:Polymorphism, Genetic; D012649:Self Concept; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D010100:Oxygen
keywords: 5-HTTLPR; FMRI; anterior cingulate; anterior insula; negative self-schema