title: Association of decreased prefrontal hemodynamic response during a verbal fluency task with EGR3 gene polymorphism in patients with schizophrenia and in healthy individuals.
abstract: The early growth response 3 (EGR3) gene is an immediate early gene that is expressed throughout the brain and has been suggested as a potential susceptibility gene for schizophrenia (SZ). EGR3 impairment is associated with various neurodevelopmental dysfunctions, and some animal studies have reported a role for EGR3 function in the prefrontal cortex. Therefore, EGR3 genotype variation may be reflected in prefrontal function. By using multi-channel near-infrared spectroscopy (NIRS) in an imaging genetics approach, we tested for an association between the EGR3 gene polymorphism and prefrontal hemodynamic response during a cognitive task in patients with SZ. We assessed 73 chronic patients with SZ and 73 age-, gender-, and genotype-matched healthy controls (HC) who provided written informed consent. We used NIRS to measure changes in prefrontal oxygenated hemoglobin concentration (oxyHb) during the letter version of a verbal fluency task (VFT). Statistical comparisons were performed among EGR3 genotype subgroups (rs35201266, GG/GA/AA). The AA genotype group showed significantly smaller oxyHb increases in the left dorsolateral prefrontal cortex (DLPFC) during the VFT than the GG and GA genotype groups; this was true for both patients with SZ and HC. Our findings provide in vivo human evidence of a significant influence of EGR3 polymorphisms on prefrontal hemodynamic activation level in healthy adults and in patients with SZ. Genetic variation in EGR3 may affect prefrontal function through neurodevelopment. This study illustrates the usefulness of NIRS in imaging genetics investigations on psychiatric disorders.
authors: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; Department of Youth Mental Health, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: ynishimu-mie@umin.ac.jp.
authors: Yukika
authors: Y
authors: Nishimura
authors: Ryu
authors: R
authors: Takizawa
authors: Shinsuke
authors: S
authors: Koike
authors: Akihide
authors: A
authors: Kinoshita
authors: Yoshihiro
authors: Y
authors: Satomura
authors: Shingo
authors: S
authors: Kawasaki
authors: Hidenori
authors: H
authors: Yamasue
authors: Mamoru
authors: M
authors: Tochigi
authors: Chihiro
authors: C
authors: Kakiuchi
authors: Tsukasa
authors: T
authors: Sasaki
authors: Yoshimi
authors: Y
authors: Iwayama
authors: Kazuo
authors: K
authors: Yamada
authors: Takeo
authors: T
authors: Yoshikawa
authors: Kiyoto
authors: K
authors: Kasai
mesh_terms: D000328:Adult; D044466:Asian People; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004247:DNA / Q000235:genetics; D051776:Early Growth Response Protein 3 / Q000235:genetics*; D005189:False Positive Reactions; D005260:Female; D059907:Functional Neuroimaging; D006439:Hemodynamics / Q000502:physiology*; D006454:Hemoglobins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics; D017397:Prefrontal Cortex / Q000098:blood supply*; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000502:physiology; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology; D019265:Spectroscopy, Near-Infrared; D014705:Verbal Behavior / Q000502:physiology*
chemical_list: C079945:EGR3 protein, human; D006454:Hemoglobins; D051776:Early Growth Response Protein 3; D004247:DNA
keywords: DLPFC; DSM-IV-TR; DTI; DUP; DeoxyHb; Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision; EGR; Early growth response 3 (EGR3); GAF; Global Assessment of Functioning; HC; Hb; Imaging genetics; JART; Japanese version of the National Adult Reading Test; NIRS; Near-infrared spectroscopy (NIRS); OxyHb; PANSS; Positive and Negative Symptom Scale; Prefrontal function; SNP; SZ; Schizophrenia; VFT; Verbal fluency task (VFT); deoxygenated hemoglobin concentration; diffusion tensor imaging; dorsolateral prefrontal cortex; duration of untreated psychosis; early growth response; healthy control; hemoglobin; near-infrared spectroscopy; oxygenated hemoglobin concentration; schizophrenia; single nucleotide polymorphism; verbal fluency task