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Brain structural signatures of negative symptoms in depression and schizophrenia.



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Chuang, Jie-Yu 
Murray, Graham K 
Metastasio, Antonio 
Segarra, Nuria 
Tait, Roger 


Negative symptoms occur in several major mental health disorders with undetermined mechanisms and unsatisfactory treatments; identification of their neural correlates might unveil the underlying pathophysiological basis and pinpoint the therapeutic targets. In this study, participants with major depressive disorder (n = 24), schizophrenia (n = 22), and healthy controls (n = 20) were assessed with 10 frequently used negative symptom scales followed by principal component analysis (PCA) of the scores. A linear model with the prominent components identified by PCA was then regressed on gray and white-matter volumes estimated from T1-weighted magnetic resonance imaging. In depressed patients, negative symptoms such as blunted affect, alogia, withdrawal, and cognitive impairment, assessed mostly via clinician-rated scales were inversely associated with gray matter volume in the bilateral cerebellum. In patients with schizophrenia, anhedonia, and avolition evaluated via self-rated scales inversely related to white-matter volume in the left anterior limb of internal capsule/anterior thalamic radiation and positively in the left superior longitudinal fasiculus. The pathophysiological mechanisms underlying negative symptoms might differ between depression and schizophrenia. These results also point to future negative symptom scale development primarily focused on detecting and monitoring the corresponding changes to brain structure or function.



cerebellum, depression, negative symptoms, schizophrenia, white matter

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Front Psychiatry

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Frontiers Media SA
Medical Research Council (G0701911)
Medical Research Council (G0802226)
Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) (unknown)
Medical Research Council (G0001354)
Medical Research Council (G1000183)
Wellcome Trust (093875/Z/10/Z)
Wellcome Trust (095692/Z/11/Z)
Medical Research Council (G0701911/1)
This work was supported by Brain and Behavior Research Foundation (NARSAD) and Medical Research Council (MRC) awards to GKM, and by the Wellcome Trust/MRC Behavioural and Clinical Neuroscience Institute, University of Cambridge. We thank Dr. Zheng Ye for her help with image analysis and technical support, Niels Reinders and staff at the Wolfson Brain Imaging Centre for help with data collection, and staff at IAPT, CAMEO and the Rehabilitation and Recovery Service in the Cambridgeshire and Peterborough NHS Foundation Trust for help with recruitment. The study was supported by infrastructure provided by the Wellcome Trust/MRC Behavioural and Clinical Neuroscience Institute at the University of Cambridge.