Article

Progressive Brain Change in Schizophrenia: A Prospective Longitudinal Study of First-Episode Schizophrenia

Psychiatric Iowa Neuroimaging Consortium, The University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
Biological psychiatry (Impact Factor: 9.47). 07/2011; 70(7):672-9. DOI: 10.1016/j.biopsych.2011.05.017
Source: PubMed

ABSTRACT Schizophrenia has a characteristic onset during adolescence or young adulthood but also tends to persist throughout life. Structural magnetic resonance studies indicate that brain abnormalities are present at onset, but longitudinal studies to assess neuroprogression have been limited by small samples and short or infrequent follow-up intervals.
The Iowa Longitudinal Study is a prospective study of 542 first-episode patients who have been followed up to 18 years. In this report, we focus on those patients (n = 202) and control subjects (n = 125) for whom we have adequate structural magnetic resonance data (n = 952 scans) to provide a relatively definitive determination of whether progressive brain change occurs over a time interval of up to 15 years after intake.
A repeated-measures analysis showed significant age-by-group interaction main effects that represent a significant decrease in multiple gray matter regions (total cerebral, frontal, thalamus), multiple white matter regions (total cerebral, frontal, temporal, parietal), and a corresponding increase in cerebrospinal fluid (lateral ventricles and frontal, temporal, and parietal sulci). These changes were most severe during the early years after onset. They occur at severe levels only in a subset of patients. They are correlated with cognitive impairment but only weakly with other clinical measures.
Progressive brain change occurs in schizophrenia, affects both gray matter and white matter, is most severe during the early stages of the illness, and occurs only in a subset of patients. Measuring severity of progressive brain change offers a promising new avenue for phenotype definition in genetic studies of schizophrenia.

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    • "The significance of neuroprogressive changes in the risk and progression of schizophrenia are being appreciated widely in recent times (Andreasen et al. 2011; Davis et al. 2014; Stein and Broome 2015). Several underlying mechanisms including neurotransmitter abnormality, immuno-inflammatory, oxidative and nitrosative stress (IO&NS) pathway, mitochondrial dysfunction, tryptophan catabolite (TRYCAT) pathway etc. contribute to neuroprogressive changes in schizophrenia (Anderson and Maes 2013; Venkatasubramanian and Debnath 2013; Debnath and Berk 2014; Rajasekaran et al. "
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    • "This suggests that these structures have a critical role in the initial stages of the disease. The percentage of white matter volume loss has been shown to be higher during the first year of the disease, with a slope attenuation during later stages, indicating that a significant decrease in the white matter is likely to occur in the early preclinical phase of SZ [88]. In chronically treated patients, DTI studies have shown decreased fractional anisotropy in the long association and interhemispheric fibers [89] [90] [91], anterior and posterior thalamic radiations [92], uncinate fasciculus [91], inferior frontal and middle temporal white matter [90]. "
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    • "Schizophrenia is a devastating and disabling neuropsychiatric disorder. The neural mechanisms of this disorder have been attributed to structural and functional abnormalities of the brain [1] [2] [3] [4] [5]. Schizophrenia patients have exhibited functional changes in both task-evoked activation and spontaneous brain activity [6] [7]. "
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