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: 10.26). 07/2011; 70(7):672-9. DOI: 10.1016/j.biopsych.2011.05.017
Source: PubMed


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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    • "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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    ABSTRACT: Altered spontaneous brain activity as measured by ALFF, fALFF, and ReHo has been reported in schizophrenia, but no consensus has been reached on alternations of these indexes in the disorder. We aimed to clarify the regional alterations in ALFF, fALFF, and ReHo in schizophrenia using a meta-analysis and a large-sample validation. A meta-analysis of activation likelihood estimation was conducted based on the abnormal foci of ten studies. A large sample of 86 schizophrenia patients and 89 healthy controls was compared to verify the results of the meta-analysis. Meta-analysis demonstrated that the alternations in ALFF and ReHo had similar distribution in schizophrenia patients. The foci with decreased ALFF/fALFF and ReHo in schizophrenia were mainly located in the somatosensory cortex, posterior parietal cortex, and occipital cortex; however, foci with increased ALFF/fALFF and ReHo were mainly located in the bilateral striatum, medial temporal cortex, and medial prefrontal cortex. The large-sample study showed consistent findings with the meta-analysis. These findings may expound the pathophysiological hypothesis and guide future research.
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    • "The change score of clinical assessments were calculated by subtracting the scores of clinical assessments at follow-up from the scores of clinical assessments at baseline. We also recorded time in hospital during the interscan interval as a measure of illness severity in patients with schizophrenia, reasoning that hospitalization time was a proxy measure of relapse duration, which has been associated with volume loss in schizophrenia (Andreasen et al., 2011). "
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    • "There is evidence of volume reduction compared with healthy subjects in both the gray matter (GM) and white matter (WM) of many brain regions, but in particular in the temporal and frontal lobes (Highley et al., 1999; Selemon et al., 2002; Honea et al., 2005; Vita et al., 2012; Haijma et al., 2013). Reduced brain volumes are seen in people with firstepisode schizophrenia, suggesting that the changes that lead to this observation may be neurodevelopmental in origin (Asami et al., 2012; Rais et al., 2012; Vita et al., 2012), but greater tissue loss over time has been observed in patients with established schizophrenia compared with healthy subjects, suggesting that there are also progressive brain changes throughout the disease (Andreasen et al., 2011; Olabi et al., 2011). These studies all demonstrate the structural heterogeneity between subjects and regions and over time, however, which may be related to some extent to the diversity of symptoms patients experience and their individual responses to antipsychotic medication. "
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