SummaryBackground Psychotic disorders, such as schizophrenia, are associated with neuroanatomical abnormalities, but whether these predate the onset of symptoms or develop progressively over the course of illness is unclear. We investigated this issue with MRI to study people with prodromal symptoms who are at ultra high-risk for the development of psychosis.Methods We did two comparisons, cross-sectional and longitudinal. For the cross-sectional comparison, 75 people with prodromal signs of psychosis were scanned with MRI. After at least 12 months of follow-up, 23 (31%) had developed psychosis and 52 (69%) had not. Baseline MRI data from these two subgroups were compared. For the longitudinal comparison, 21 of the ultra high-risk individuals were scanned again with MRI after at least 12 months. Ten of these had developed psychosis and 11 had not. MRI data from baseline and follow-up were compared within each group of people.
FindingsIn the cross-sectional comparison, compared with people who did not develop psychosis, those who did develop the disorder had less grey matter in the right medial temporal, lateral temporal, and inferior frontal cortex, and in the cingulate cortex bilaterally. In the longitudinal comparison, when re-scanned, individuals who had developed psychosis showed a reduction in grey matter in the left parahippocampal, fusiform, orbitofrontal and cerebellar cortices, and the cingulate gyri. In those who had
The study of executive function within a developmental framework has proven integral to the advancement of knowledge concerning the acquisition and decline of higher skill processes. Still in its early stages, there exists a discontinuity in the literature between the exploration of executive capacity in young children and the elderly. Research of age-related differences utilising a lifespan approach has been restricted by the lack of assessment tools for the measurement of executive skills that are applicable across all age levels. This paper addresses these issues using the computer-based Cambridge Neuropsychological Test Automated Battery (CANTAB) to identify periods of development in executive capacities using a normative sample of 194 participants ranging in age from 8 to 64 years. Findings of executive function in children as young as 8 years of age were extended, with functional gains found in the efficiency of working memory capacity, planning and problem-solving abilities, between the ages of 15 and 19 years and again at 20-29 years of age. Cognitive flexibility was assessed at adult-levels in even the youngest children. Declines in performance on all tasks were revealed for the 50-64 year old sample, providing support for the vulnerability of executive skills to normal aging.
These findings suggest that schizophrenia is associated with progressive structural brain abnormalities, affecting both gray and white matter. We found no evidence to suggest progressive medial temporal lobe involvement but did find evidence that this may be partly explained by heterogeneity between studies in patient age and illness duration. The causes and clinical correlates of these progressive brain changes should now be the focus of investigation.
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