Structural covariance networks in schizophrenia: A systematic review Part I

Background: Schizophrenia is proposed as a disorder of dysconnectivity. However, examination of complexities of dysconnectivity has been challenging. Structural covariance networks (SCN) provide important insights into the nature of dysconnectivity. This systematic review examines the SCN studies that employed statistical approaches to elucidate covariation of regional morphometric variations.

Methods: A systematic search of literature was conducted for peer-reviewed publications using different keywords and keyword combinations for schizophrenia. Fifty-two studies met the criteria.

Results: Early SCN studies began using correlational structure of selected regions. Over the last 3 decades, methodological approaches have grown increasingly sophisticated from examining selected brain regions using correlation tests on small sample sizes to recent approaches that use advanced statistical methods to examine covariance structure of whole-brain parcellations on larger samples. Although the results are not fully consistent across all studies, a pattern of fronto-temporal, fronto-parietal and fronto-thalamic covariation is reported. Attempts to associate SCN alterations with functional connectivity, to differentiate between disease-related and neurodevelopment-related morphometric changes, and to develop "causality-based" models are being reported. Clinical correlation with outcome, psychotic symptoms, neurocognitive and social cognitive performance are also reported.

Conclusions: Application of advanced statistical methods are beginning to provide insights into interesting patterns of regional covariance including correlations with clinical and cognitive data. Although these findings appear similar to morphometric studies, SCNs have the advantage of highlighting topology of these regions and their relationship to the disease and associated variables. Further studies are needed to investigate neurobiological underpinnings of shared covariance, and causal links to clinical domains.