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: 4.43). 06/2009; 112(1-3):7-13. DOI: 10.1016/j.schres.2009.04.023
Source: PubMed

ABSTRACT 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.


Available from: Sudhakar Selvaraj, Mar 20, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: The glutamate and dopamine hypotheses are leading theories of the pathoaetiology of schizophrenia. Both were initially based on indirect evidence from pharmacological studies supported by post-mortem findings, but have since been substantially advanced by new lines of evidence from in vivo imaging studies. This review provides an update on the latest findings on dopamine and glutamate abnormalities in schizophrenia, focusing on in vivo neuroimaging studies in patients and clinical high-risk groups, and considers their implications for understanding the biology and treatment of schizophrenia. These findings have refined both the dopamine and glutamate hypotheses, enabling greater anatomical and functional specificity, and have been complemented by preclinical evidence showing how the risk factors for schizophrenia impact on the dopamine and glutamate systems. The implications of this new evidence for understanding the development and treatment of schizophrenia are considered, and the gaps in current knowledge highlighted. Finally, the evidence for an integrated model of the interactions between the glutamate and dopamine systems is reviewed, and future directions discussed. © The Author(s) 2015.
    Journal of Psychopharmacology 01/2015; 29(2). DOI:10.1177/0269881114563634 · 2.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The diagnosis of schizophrenia lacks a broadly accepted biological basis and its heterogeneity may well represent a group of disorders with different etiologies. Even so, brain imaging can map and quantify structural brain abnormalities in vivo as an intermediate (or endo-) phenotype of the disorder. Brain structural abnormalities occur in the prodromal phase and progress in the course of illness, and patterns of grey matter deficits appear to determine the clinical phenotype, thus addressing some of the diagnostic heterogeneity. Here we examined cerebral grey matter with cortical pattern matching in MRI scans from 18 previously untreated patients meeting DSM-IV diagnostic criteria for schizophrenia by employing a three-dimensional spoiled gradient recalled (SPGR) pulse sequence at 1.5 T. Data were compared to 18 pair-wise age and sex-matched healthy volunteers from the patient communities. We found widespread cerebral grey matter deficits in schizophrenia. Grey matter deficits in the right dorsolateral prefrontal cortex were the strongest predictor of diagnosis. Symptom severity and treatment response were associated with regional grey matter deficits in older patients with a longer history of untreated illness, while significant structure/function associations with cognitive impairment in prefrontal and temporal cortices were found across all ages. Quantitative brain maps are useful for assessing disease burden in schizophrenia, and for understanding its heterogeneity, including its changing clinical characteristics as the illness progresses.
    Neurology Psychiatry and Brain Research 06/2014; 20(2). DOI:10.1016/j.npbr.2014.01.001 · 0.10 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: Although recent studies have demonstrated that patients with schizophrenia and healthy controls did not differ in the speed of age-related decline in cortical thickness and performances on cognitive tests, hemodynamic changes assessed by functional neuroimaging remain unclear. This study investigated age effects on regional brain cortical activity to determine whether there is similar age-related decline in cortical activity as those observed in cortical thickness and cognitive test performance. Method: A total of 109 patients with schizophrenia (age range: 16–59 y) and 106 healthy controls (age range: 16–59 y) underwent near-infrared spectroscopy (NIRS) while performing a verbal fluency test (VFT). Group comparison of cortical activity was examined using 2-tailed t tests, adopting the false discovery rate method. The relationship between age and cortical activity was investigated using correlational and multiple regression analyses, adjusting for potential confounding variables. A 2-way ANOVA was conducted to investigate differences in the age effects between diagnostic groups. Results: The patient group exhibited significantly decreased cortical activity in several regions of the frontotemporal cortices. However, slopes of age-dependent decreases in cortical activity were similar between patients and healthy individuals at the bilateral frontotemporal regions. Conclusions: Our study showed no significant between-group differences in the age-related decline in cortical activity, as measured by NIRS, over the frontotemporal regions during a VFT. The results of our study may indicate a decrease in cortical activity in a relatively limited period around illness onset rather than continuously progressing over the course of the illness.
    Schizophrenia Bulletin 06/2014; DOI:10.1093/schbul/sbu086 · 8.61 Impact Factor