Prefrontal neuronal integrity predicts symptoms and cognition in schizophrenia and is sensitive to genetic heterogeneity

SCHIZOPHRENIA RESEARCH

卷:172

Article

Malaspina, Dolores¹  Kranz, Thorsten M.^2,3,4  Heguy, Adriana⁵  Harroch, Sheila⁶  Mazgaj, Robert¹  Rothman, Karen¹  Berns, Adam¹  Hasan, Sumya¹  Antonius, Daniel⁷  Goetz, Raymond^8,10  Lazar, Mariana^9,11  Chao, Moses V.^2,3,4  Gonen, Oded^9,11 

[1] NYU, Sch Med, Dept Psychiat, Inst Social & Psychiat Initiat InSPIRES, New York, NY 10016 USA

[2] NYU, Dept Cell Biol, Skirball Inst Biomol Med, 550 1st Ave, New York, NY 10016 USA

[3] NYU, Dept Neurosci & Physiol, Skirball Inst Biomol Med, 550 1st Ave, New York, NY 10016 USA

[4] NYU, Dept Psychiat, Skirball Inst Biomol Med, 550 1st Ave, New York, NY 10016 USA

[5] NYU, Sch Med, Genome Technol Ctr, New York, NY 10016 USA

[6] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA

[7] SUNY Buffalo, Dept Psychiat, Buffalo, NY 14260 USA

[8] New York State Psychiat Inst & Hosp, Div Clin Phenomenol, 1051 Riverside Dr, New York, NY 10032 USA

[9] NYU, Sch Med, Dept Radiol, Ctr Adv Imaging Innovat & Res CAI2R, New York, NY 10016 USA

[10] Columbia Univ, Dept Psychiat, New York, NY USA

[11] NYU, Sch Med, Dept Radiol, Bernard & Irene Schwartz Ctr Biomed Imaging, New York, NY 10016 USA

关键词: Schizophrenia;    Rostralization;    Genotype;    N-acetylaspartate;    Anterior cingulate cortex;    Magnetic resonance spectroscopy imaging;   

DOI  :  10.1016/j.schres.2016.02.031

来源: Elsevier

【 摘 要 】

Schizophrenia is a genetically complex syndrome with substantial inter-subject variability in multiple domains. Person-specific measures to resolve its heterogeneity could focus on the variability in prefrontal integrity, which this study indexed as relative rostralization within the anterior cingulate cortex (ACC). Twenty-two schizophrenia cases and 11 controls underwent rigorous diagnostic procedures, symptom assessments (PANSS, Deficit Syndrome Scale) and intelligence testing. All underwent multivoxel MRSI at 3 T to measure concentrations of the neuronal-specific biomarker N-acetylaspartate (NAA) in all of the voxels of the ACC. The concentrations of NAA were separately calculated and then compared across the rostral and caudal subregions to generate a rostralization ratio, which was examined with respect to the study measures and to which cases carried a missense coding polymorphism in PTPRG, SCL39A13, TGM5, NTRK1 or ARMS/KIDINS220. Rostralization significantly differed between cases and controls (chi(2) = 18.40, p < .0001). In cases, it predicted verbal intelligence (r = .469, p = .043) and trait negative symptoms (diminished emotional range (r = -.624, p = .010); curbed interests, r = -.558, p = .025). Rostralization was similar to controls for missense coding variants in TGM5 and was significantly greater than controls for the PTPRG variant carrier. This is the first study examining the utility of MRS metrics in describing pathological features at both group and person-specific levels. Rostralization predicted core illness features and differed based on which signaling genes were disrupted. While future studies in larger populations are needed, ACC rostralization appears to be a promising measure to reduce the heterogeneity of schizophrenia for genetic research and selecting cases for treatment studies. (C) 2016 Published by Elsevier B.V.

【 授权许可】

Free