Abstract: Lack of insight is a core feature of non-affective psychosis and has been associated with poorer outcomes. Brain abnormalities underlying lack of insight have been suggested, mostly in the frontal lobe, although previous research showed mixed results. We used a voxel-based morphometry (VBM) analysis in 108 first-episode non-affective psychosis patients to investigate the pattern of brain structural abnormalities related to lack of insight. In addition, 77 healthy volunteers were compared with the patients classified as having poor and good insight. The shortened version of the Scale to Assess Unawareness of Mental Disorder was used to evaluate insight. Patients with poor insight (n = 68) compared with patients with good insight (n = 40) showed a single significant cluster (kc = 5834; PcFWE = 0.001) of reduced grey matter volume (GMV) in the right occipital lobe extending to its lateral and medial surfaces, the cuneus, and the middle temporal gyrus. In addition, GMV at this cluster showed a negative correlation with the score of the SUMD (r = -0.305; p = 0.001). When comparing patients with poor insight with healthy subjects overall reductions of GMV were found, mainly in frontal and occipital lobes. Hence, poor insight in non-affective psychosis seems to be associated with specific brain abnormalities in the right occipital and temporal cortical regions. Dysfunction in any combination of these areas may contribute to lack of insight in non-affective psychosis. Specifically, the `right' hemisphere dysfunction underlying impaired insight in our sample is consistent with previously reported similarities between lack of insight in psychosis and anosognosia in neurological disorders.

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