The effect of ageing on grey and white matter reductions in schizophrenia

MRC-Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, UK.
Schizophrenia Research (Impact Factor: 3.92). 06/2009; 112(1-3):7-13. DOI: 10.1016/j.schres.2009.04.023
Source: PubMed


Total brain volume and, in particular gray matter (GM) volume is reduced in patients with schizophrenia and recent studies suggest there is greater progressive loss of brain volume in the patients with schizophrenia than in normal controls. However, as the longitudinal studies do not include life-long follow-up, it is not clear if this occurs across the lifespan or only in the early phase of the illness. In this study we investigated this by studying the effects of age on brain tissue volumes in schizophrenia (n=34, age range=27-65 years)to test the prediction that there is a progressive loss in grey matter volume with increasing age in patients compared to healthy controls (n=33, age range=18-73 years). The results showed there was diminished relative GM volume loss with age in patients with schizophrenia compared to controls--in contrast to our prediction. However, there was increased relative white matter (WM) loss with age in schizophrenia. The results also replicated previous findings that patients with schizophrenia have significantly lower total (1509 versus 1596 mm(3)) and regional GM volume (755 versus 822 mm(3)) and increased cerebrospinal fluid (CSF) volume when compared to matched healthy volunteers. Overall these findings indicate that the proportion of grey matter in schizophrenia is reduced compared to controls early in the illness, and this difference diminishes with age; the corresponding effect in the proportion of WM is an increase with age compared to controls. This suggests that illness related factors may differentially affect grey and white matter, with implications for understanding the pathophysiology of schizophrenia and related psychotic disorders.

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Available from: Sudhakar Selvaraj, Mar 20, 2015
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    • "Atrophy in these regions has been directly related to cognitive or other deficits of aging [Park and Reuter-Lorenz, 2009], but the patterns and degree of atrophy may differ between brain regions. Of note, age effects on the volume of specific subcortical brain structures with known function related to cognitive and emotional control might be even more important for understanding the effects of aging in the elderly , for example in Alzheimer's disease [Anderton, 1997; Driscoll et al., 2009] and psychiatric disorders [Bose et al., 2009; Kubota et al., 2011]. "
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    • "Many studies in the literature have investigated the effect of medication in brain structural age-related trajectories followed by SZ patients. Most authors focused particularly on DTI microstructural age-related changes in SZ and found no significant effects of medication [43], [77], [113]–[124]. "
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    • "Findings of reduced frontal blood flow,25-28 altered cortical structure29,30 and the different distribution of dopamine receptors (ie, high density of D1 in cortex and D2 in subcortex) led to the reconceptualization of the dopamine hypothesis in 1980s to include regional specificity, which was first discussed by Bannon and Roth in 198331 and later by Andreasen in 1988.32 Drawing on these and other findings, Davis et al33 hypothesized that positive symptoms resulted from subcortical hyperdopaminergia and negative symptoms resulted from frontal hypodopaminergia. "
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