Functional network dysconnectivity as a biomarker of treatment resistance in schizophrenia

SCHIZOPHRENIA RESEARCH

卷:195

Article

McNabb, Carolyn B.¹  Tait, Roger J.^2,3  McIlwain, Meghan E.¹  Anderson, Valerie M.¹  Suckling, John^2,3  Kydd, Robert R.⁴  Russell, Bruce R.⁵ 

[1] Univ Auckland, Sch Pharm, 85 Pk Rd, Auckland 1023, New Zealand

[2] Univ Cambridge, Cambridge & Peterborough Fdn NHS Trust, Dept Psychiat, Herchel Smith Bldg Brain & Mind Sci,Forvie Site, Cambridge CB2 0SZ, England

[3] Univ Cambridge, Behav & Clin Neurosci Inst, Downing St, Cambridge CB2 3EB, England

[4] Univ Auckland, Auckland City Hosp, Dept Psychol Med, 2 Pk Rd, Auckland 1023, New Zealand

[5] Univ Otago, Sch Pharm, POB 56, Dunedin 9054, New Zealand

关键词: Schizophrenia;    Treatment resistance;    Treatment response;    Magnetic resonance imaging;    Network based statistics;    Clozapine;   

DOI  :  10.1016/j.schres.2017.10.015

来源: Elsevier

【 摘 要 】

Schizophrenia may develop from disruptions in functional connectivity regulated by neurotransmitters such as dopamine and acetylcholine. The modulatory effects of these neurotransmitters might explain how antipsychotics attenuate symptoms of schizophrenia and account for the variable response to antipsychotics observed in clinical practice. Based on the putative mechanisms of antipsychotics and evidence of disrupted connectivity in schizophrenia, we hypothesised that functional network connectivity, as assessed using network-based statistics, would exhibit differences between treatment response subtypes of schizophrenia and healthy controls. Resting-state functional MRI data were obtained from 17 healthy controls as well as individuals with schizophrenia who responded well to first-line atypical antipsychotics (first-line responders; FLR, n = 18), had failed at least two trials of antipsychotics but responded to clozapine (treatment-resistant schizophrenia; TRS, n = 18), or failed at least two trials of antipsychotics and a trial of clozapine (ultra-treatment-resistant schizophrenia; UTRS, n = 16). Data were pre-processed using the Advanced Normalization Toolkit and BrainWavelet Toolbox. Network connectivity was assessed using the Network-Based Statistics toolbox in Matlab. ANOVA revealed a significant difference in functional connectivity between groups that extended between cerebellar and parietal regions to the frontal cortex (p < 0.05). Post-hoc t-tests revealed weaker network connectivity in individuals with UTRS compared with healthy controls but no other differences between groups. Results demonstrated distinct differences in functional connectivity between individuals with UTRS and healthy controls. Future workmust determinewhether these changes occur prior to the onset of treatment and if they can be used to predict resistance to antipsychotics during first-episode psychosis. (C) 2017 Published by Elsevier B.V.

【 授权许可】

Free