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

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

PAKs inhibitors ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during late adolescence

“…In accordance with this hypothesis, dynamic changes in brain morphology and glutamate signaling have also been reported in recent onset schizophrenia cases and subjects in the prodromal stages of schizophrenia (35,36). In this study, by using two-photon spine imaging, we demonstrated that administration of a PAK inhibitor FRAX486 in late adolescence is sufficient to block deteriorating spine loss and effective in preventing an adult behavioral deficit associated with schizophrenia.…”

Abnormal synaptic pruning in schizophrenia: Urban myth or reality?

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Dynamic endophenotypes and longitudinal trajectories: capturing changing aspects of development in early psychosis

“…[15][16][17] In a more homogeneous sample of patients with firstepisode schizo phrenia, Andreasen and colleagues 18,19 found progressive grey and white matter loss in multiple regions over time related to the severity of psychotic symptoms, relapse duration and anti psychotic treatment intensity. The presence and persist ence of negative symptoms in patients with schizophrenia and related psychoses is also associated with abnormalities in cortical thickness 20 and white matter, 21,22 cognitive deficits, and poor functional and vocational outcomes.…”