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Objectives: Cognitive rehabilitation can improve cognition in schizophrenia and prevent disability. It is unknown, however, whether a greater neurobiologic reserve, as measured by cortical volumes, will predict a favorable response to rehabilitation. We investigated this question in early course schizophrenia patients treated with Cognitive Enhancement Therapy (CET)., Methods: Outpatients in the early course of schizophrenia or schizoaffective disorder were randomly assigned to CET (n=29) or an Enriched Supportive Therapy control (n=21) and treated for two years. Cortical surface area and gray matter volume data were collected before treatment using structural magnetic resonance imaging. Neurocognition and social cognition were assessed before, and after one and two years of treatment. Moderator analyses examined the impact of pre-treatment cortical surface area and gray matter volume on differential neurocognitive and social-cognitive response to CET., Results: Pre-treatment, whole brain cortical surface area and gray matter volume significantly moderated the effects of CET on social cognition, but not neurocognition. Greater neurobiologic reserve predicted a rapid social-cognitive response to CET in the first year of treatment; patients with less neurobiologic reserve achieved a comparable social-cognitive response by the second year. While nearly every regional measurement significantly contributed to this accelerated social-cognitive treatment response, effects were the strongest in the temporal cortex., Conclusions: A broad cortical surface area and gray matter reserve is associated with an accelerated social-cognitive response to CET in early schizophrenia, yet the benefits of cognitive rehabilitation are achieved in those with less initial cognitive resources after a longer duration of treatment., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Grey-matter volumetric and cognitive deficits in young, high-risk relatives of schizophrenia patients may be vulnerability markers of the illness. Although these markers may be correlated, it is unclear if their distributions in relatives overlap. We examined convergence of these markers in 94 young first and second-degree relatives (HR) and 81 healthy controls. Subjects were assessed using WCST, CPT-IP and Benton-Hamscher tests and on grey-matter volumes of brain regions related to language, attention and executive function using FreeSurfer to process T1-MR-images. K-means clustering using cognitive performance scores split relatives into sub-samples with better (HR+C, n=35) and worse (HR-C, n=59) cognition after controlling for age and gender. All regional volumes and language related regional laterality-indices were compared between HR-C, HR+C and control subjects, controlling for age, gender and intra-cranial volume. Volumes of caudate nuclei, thalami, hippocampi, inferior frontal gyri, Heschl's gyri, superior parietal cortices, supramarginal gyri, right angular gyrus, right middle frontal gyrus and right superior frontal gyrus, leftward laterality of supramarginal and inferior frontal gyri and rightward laterality of the angular gyrus were reduced in HR-C compared to controls. Volumes of Heschl's gyri, left supramarginal gyrus, inferior frontal gyri, hippocampi and caudate nuclei HR-C were smaller in HR-C compared to HR+C. HR+C showed deficits compared to controls only for the superior parietal and right angular volumes. Premorbid neuroanatomical and laterality alterations in schizophrenia may selectively manifest in cognitively compromised relatives. Overlapping structural and cognitive deficits may define a hyper vulnerable sub-sample among individuals at familial predisposition to schizophrenia., (Copyright © 2010 Elsevier Inc. All rights reserved.)