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Association of White Matter With Core Cognitive Deficits in Patients With Schizophrenia.

ABSTRACT: Importance:Efforts to remediate the multiple cognitive function impairments in schizophrenia should consider white matter as one of the underlying neural mechanisms. Objective:To determine whether altered structural brain connectivity is responsible for 2 of the core cognitive deficits in schizophrenia- reduced information processing speed and impaired working memory. Design, Setting, and Participants:This cross-sectional study design took place in outpatient clinics from August 1, 2004, to August 31, 2015. Participants included 166 patients with schizophrenia and 213 healthy control individuals. These participants were from 3 independent cohorts, each of which had its own healthy control group. No participant had current or past neurological conditions or major medical conditions. Patients were diagnosed with either schizophrenia or schizoaffective disorder as defined by the DSM-IV. Controls had no Axis I psychiatric disorder. Main Outcomes and Measures:Mediation analyses and structural equation modeling were used to analyze the associations among processing speed, working memory, and white matter microstructures. Whole-brain and regional diffusion tensor imaging fractional anisotropy were used to measure white matter microstructures. Results:Of the study participants, the 166 patients with schizophrenia had a mean (SD) age of 38.2 (13.3) years and the 213 healthy controls had a mean (SD) age of 39.2 (14.0) years. There were significantly more male patients than controls in each of the 3 cohorts (117 [70%] vs 91 [43%]), but there were no significant differences in sex composition among the 3 cohorts. Patients had significantly reduced processing speed (Cohen d?=?1.24; P?=?6.91?×?10-30) and working memory deficits (Cohen d?=?0.83; P?=?1.10?×?10-14) as well as a significant whole-brain fractional anisotropy deficit (Cohen d?=?0.63; P?=?2.20?×?10-9). In schizophrenia, working memory deficit was mostly accounted for by processing speed deficit, but this deficit remained when accounting for working memory (Cohen d?=?0.89; P?=?2.21?×?10-17). Mediation analyses showed a significant association pathway from fractional anisotropy to processing speed to working memory (P?=?5.01?×?10-7). The strength of this brain-to-cognition pathway in different white matter tracts was strongly associated with the severity of schizophrenia-associated fractional anisotropy deficits in the corresponding white matter tracts as determined by a meta-analysis (r?=?0.85-0.94; all P?

SUBMITTER: Kochunov P

PROVIDER: S-EPMC5710230 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Association of White Matter With Core Cognitive Deficits in Patients With Schizophrenia.

Kochunov Peter P Coyle Thomas R TR Rowland Laura M LM Jahanshad Neda N Thompson Paul M PM Kelly Sinead S Du Xiaoming X Sampath Hemalatha H Bruce Heather H Chiappelli Joshua J Ryan Meghann M Fisseha Feven F Savransky Anya A Adhikari Bhim B Chen Shuo S Paciga Sara A SA Whelan Christopher D CD Xie Zhiyong Z Hyde Craig L CL Chen Xing X Schubert Christian R CR O'Donnell Patricio P Hong L Elliot LE

JAMA psychiatry 20170901 9

<h4>Importance</h4>Efforts to remediate the multiple cognitive function impairments in schizophrenia should consider white matter as one of the underlying neural mechanisms.<h4>Objective</h4>To determine whether altered structural brain connectivity is responsible for 2 of the core cognitive deficits in schizophrenia- reduced information processing speed and impaired working memory.<h4>Design, setting, and participants</h4>This cross-sectional study design took place in outpatient clinics from A ...[more]

PMID: 28768312

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Project description:Cognitive deficits contribute to functional disability in patients with schizophrenia and may be related to altered functional networks that serve cognition. We evaluated the integrity of major functional networks and assessed their role in supporting two cognitive functions affected in schizophrenia: processing speed (PS) and working memory (WM). Resting-state functional magnetic resonance imaging (rsfMRI) data, N = 261 patients and 327 controls, were aggregated from three independent cohorts and evaluated using Enhancing NeuroImaging Genetics through Meta Analysis rsfMRI analysis pipeline. Meta- and mega-analyses were used to evaluate patient-control differences in functional connectivity (FC) measures. Canonical correlation analysis was used to study the association between cognitive deficits and FC measures. Patients showed consistent patterns of cognitive and resting-state FC (rsFC) deficits across three cohorts. Patient-control differences in rsFC calculated using seed-based and dual-regression approaches were consistent (Cohen's d: 0.31?±?0.09 and 0.29?±?0.08, p?<?10-4 ). RsFC measures explained 12-17% of the individual variations in PS and WM in the full sample and in patients and controls separately, with the strongest correlations found in salience, auditory, somatosensory, and default-mode networks. The pattern of association between rsFC (within-network) and PS (r = .45, p = .07) and WM (r = .36, p = .16), and rsFC (between-network) and PS (r = .52, p = 8.4?×?10-3 ) and WM (r = .47, p = .02), derived from multiple networks was related to effect size of patient-control differences in the functional networks. No association was detected between rsFC and current medication dose or psychosis ratings. Patients demonstrated significant reduction in several FC networks that may partially underlie some of the core neurocognitive deficits in schizophrenia. The strength of connectivity-cognition relationships in different networks was strongly associated with network's vulnerability to schizophrenia.

Dataset Information

Association of White Matter With Core Cognitive Deficits in Patients With Schizophrenia.

Publications

Association of White Matter With Core Cognitive Deficits in Patients With Schizophrenia.

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