Introduction: Previous studies examining brain effects of duration of illness in schizophrenia have focused on either cortical or subcortical structures. Hence this study sought to elucidate the regional grey matter changes (both cortical and subcortical) and neurocognitive correlates with increased duration of illness in a large sample of patients with schizophrenia using voxel-based morphometry. Materials and Methods: Ninety patients (72 males and 18 females) with DSM-IV diagnosis of schizophrenia were recruited and assessed using magnetic resonance imaging and a battery of neuropsychological tests. Results: A longer duration of illness was associated with smaller grey matter volumes in the left superior frontal gyrus, bilateral putamen, right superior temporal gyrus, right superior occipital gyrus as well as the right thalamus. No region showed increased grey matter volume above threshold with longer duration of illness. Longer duration of illness was correlated with poorer attention. Conclusions: The grey matter reductions in different brain regions highlighted that a distributed network of cortical and subcortical regions was associated with duration of illness. This is consistent with neural models that implicate involvement of thalamo-cortical circuitry as the disruption in these neural pathways can result in specific deficits such as poorer attention. The results have implications for the understanding of brain changes in schizophrenia, and with further studies, may guide better tailored and targeted clinical management in terms of reducing the impact of duration of illness on neural substrates in schizophrenia in the future.
Schizophrenia is a potentially devastating illness with a tremendous impact on the lives of both patients as well as the caregivers. Conceptualised as a lifelong disorder,1 the specific effects of schizophrenia on the brain and cognition are still being actively studied using modern imaging techniques such as magnetic resonance imaging (MRI).2-4 Earlier studies have provided evidence for specific brain grey matter changes in patients compared to healthy controls, mostly implicating the frontal and temporal regions,5,6 as well as brain grey matter changes in these regions over the time course of the disease. Reductions in frontal grey matter volumes are found to be associated with longer duration of illness in stable outpatients,6 chronic7,8 as well as patients with first episode schizophrenia.5 Longitudinal studies reveal a decrease in prefrontal grey matter and that further progressive frontal grey matter losses can occur with greater number of psychotic episodes.9 Recent studies have used voxel-based morphometry (VBM) to investigate the relationship between prefrontal grey matter volumes and duration of illness.10,11 Looking at a younger adolescent population with a mean duration of illness of 14 months, Burke et al10 found that the duration of illness was inversely related to regional grey matter in the left inferior frontal gyrus. In a separate study of an adult patient population with a mean duration of illness of 13.7 years, Premkumar et al11 found inverse associations between duration of illness and grey matter volumes in the left dorsomedial prefrontal, and right middle frontal cortex. In addition, lower grey matter volume in the temporal lobe,12 occipital lobe,5 and thalamus13 are also observed with an increased duration of illness in schizophrenia. These diverse findings from extant studies seem to suggest that duration of illness is associated with grey matter volume changes in a distributed pattern involving both cortical (such as frontal and temporal regions) and subcortical structures (such as thalamus).
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