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Association of decreased prefrontal hemodynamic response during a verbal fluency task with EGR3 gene polymorphism in patients with schizophrenia and in healthy individuals.
Neuroimage 2014; 85 Pt 1:527-34N

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+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23962955

Citation

Nishimura, Yukika, et al. "Association of Decreased Prefrontal Hemodynamic Response During a Verbal Fluency Task With EGR3 Gene Polymorphism in Patients With Schizophrenia and in Healthy Individuals." NeuroImage, vol. 85 Pt 1, 2014, pp. 527-34.
Nishimura Y, Takizawa R, Koike S, et al. Association of decreased prefrontal hemodynamic response during a verbal fluency task with EGR3 gene polymorphism in patients with schizophrenia and in healthy individuals. Neuroimage. 2014;85 Pt 1:527-34.
Nishimura, Y., Takizawa, R., Koike, S., Kinoshita, A., Satomura, Y., Kawasaki, S., ... Kasai, K. (2014). Association of decreased prefrontal hemodynamic response during a verbal fluency task with EGR3 gene polymorphism in patients with schizophrenia and in healthy individuals. NeuroImage, 85 Pt 1, pp. 527-34. doi:10.1016/j.neuroimage.2013.08.021.
Nishimura Y, et al. Association of Decreased Prefrontal Hemodynamic Response During a Verbal Fluency Task With EGR3 Gene Polymorphism in Patients With Schizophrenia and in Healthy Individuals. Neuroimage. 2014 Jan 15;85 Pt 1:527-34. PubMed PMID: 23962955.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of decreased prefrontal hemodynamic response during a verbal fluency task with EGR3 gene polymorphism in patients with schizophrenia and in healthy individuals. AU - Nishimura,Yukika, AU - Takizawa,Ryu, AU - Koike,Shinsuke, AU - Kinoshita,Akihide, AU - Satomura,Yoshihiro, AU - Kawasaki,Shingo, AU - Yamasue,Hidenori, AU - Tochigi,Mamoru, AU - Kakiuchi,Chihiro, AU - Sasaki,Tsukasa, AU - Iwayama,Yoshimi, AU - Yamada,Kazuo, AU - Yoshikawa,Takeo, AU - Kasai,Kiyoto, Y1 - 2013/08/17/ PY - 2013/01/17/received PY - 2013/08/08/revised PY - 2013/08/10/accepted PY - 2013/8/22/entrez PY - 2013/8/22/pubmed PY - 2014/7/30/medline KW - DLPFC KW - DSM-IV-TR KW - DTI KW - DUP KW - DeoxyHb KW - Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision KW - EGR KW - Early growth response 3 (EGR3) KW - GAF KW - Global Assessment of Functioning KW - HC KW - Hb KW - Imaging genetics KW - JART KW - Japanese version of the National Adult Reading Test KW - NIRS KW - Near-infrared spectroscopy (NIRS) KW - OxyHb KW - PANSS KW - Positive and Negative Symptom Scale KW - Prefrontal function KW - SNP KW - SZ KW - Schizophrenia KW - VFT KW - Verbal fluency task (VFT) KW - deoxygenated hemoglobin concentration KW - diffusion tensor imaging KW - dorsolateral prefrontal cortex KW - duration of untreated psychosis KW - early growth response KW - healthy control KW - hemoglobin KW - near-infrared spectroscopy KW - oxygenated hemoglobin concentration KW - schizophrenia KW - single nucleotide polymorphism KW - verbal fluency task SP - 527 EP - 34 JF - NeuroImage JO - Neuroimage VL - 85 Pt 1 N2 - 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. SN - 1095-9572 UR - https://www.unboundmedicine.com/medline/citation/23962955/Association_of_decreased_prefrontal_hemodynamic_response_during_a_verbal_fluency_task_with_EGR3_gene_polymorphism_in_patients_with_schizophrenia_and_in_healthy_individuals_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1053-8119(13)00875-6 DB - PRIME DP - Unbound Medicine ER -