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Social cognition (SC), the mental operations underlying social functioning, are impaired in schizophrenia. Their direct link to functional outcome and illness status have made them an important therapeutic target. However, no effective treatment for these deficits is currently applied as a standard of care. To address this need, we have developed SocialVille—an online, plasticity-based training program that targets SC deficits in schizophrenia. Here we report the outcomes of a double-blind, controlled, randomized, multi-site clinical trial of SocialVille. Outpatients with schizophrenia were randomized to complete 40 sessions of either SocialVille (N = 55 completers) or active control (computer games; N = 53 completers) from home. The a priori co-primary outcome measures were a social cognitive composite and a functional capacity outcome (UCSD Performance-based Skills Assessment [UPSA-2]). Secondary outcomes included a virtual functional capacity measure (VRFCAT), social functioning, quality of life, and motivation. Linear mixed models revealed a group × time interaction favoring the treatment group for the social cognitive composite (b = 2.81; P &amp;lt; .001) but not for the UPSA-2 measure. Analysis of secondary outcome measures showed significant group × time effects favoring the treatment group on SC and social functioning, on the virtual functional capacity measure and a motivation subscale, although these latter findings were nonsignificant with FDR correction. These results provide support for the efficacy of a remote, plasticity-based social cognitive training program in improving SC and social functioning in schizophrenia. Such treatments may serve as a cost-effective adjunct to existing psychosocial treatments. Trial Registration: NCT02246426.

Online Social Cognition Training in Schizophrenia: A Double-Blind, Randomized, Controlled Multi-Site Clinical Trial