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International analyses identify brain abnormalities in patients with schizophrenia

Analyses of MRI scans at 15 centers across the world provide insight into how schizophrenia may develop and respond to treatment, based on brain abnormalities in patients.

“Individuals with schizophrenia show significant brain morphological abnormalities, but there is considerable heterogeneity in the effect sizes and patterns of brain differences across studies. The study of structural brain abnormalities in schizophrenia can help us understand its causes, progression and even treatment effects. Even so, brain differences are influenced by multiple factors — some with opposing effects,” study researcher Theo G.M. van Erp, PhD, of the University of California, Irvine, and colleagues wrote in Molecular Psychiatry.

To validate a prospective meta-analysis approach to analyzing neuroimaging data, researchers assessed MRI scans from 2,028 patients with schizophrenia (mean age, 34 years) and 2,540 healthy controls (mean age, 31 years) who were assessed with standard methods at 15 centers across the world. Mean age at illness onset was 23 years.

Jessica Turner

“This is the largest structural brain meta-analysis to date in schizophrenia, and specifically, it is not a meta-analysis pulled only from the literature,” study researcher Jessica Turner, PhD, of Georgia State University, said in a press release. “Investigators dug into their desk drawers, including unpublished data to participate in these analyses. Everyone performed the same analyses using the same statistical models, and we combined the results. We then identified brain regions that differentiated patients from controls and ranked them according to their effect sizes.”

Patients with schizophrenia had smaller hippocampus (Cohen’s d = –0.46), amygdala (d = –0.31), thalamus (d = –0.31), accumbens (d = –0.25) and intracranial volumes (d = –0.12) compared with controls.

Pallidum (d = 0.21) and lateral ventricle volumes (d = 0.37) were larger among patients with schizophrenia compared with controls.

Duration of illness and hippocampal deficits were positively associated with increases in putamen and pallidum volume when scaled for the proportion of unmedicated patients.

“This study shows a robust pattern of subcortical brain abnormalities, suggests that that larger putamen and pallidum volumes may be associated with duration of illness in schizophrenia and suggests that treatment with predominantly second-generation (atypical) antipsychotics may ameliorate hippocampal volume deficits,” van Erp and colleagues wrote. “The consistency between the reported prospective meta-analysis findings and those from traditional retrospective meta-analyses validate the prospective meta-analysis approach.”

Researchers plan to apply similar analysis methods to cortical thickness and surface and subcortical shape measures.

“There’s the increased possibility, not just because of the massive datasets, but also because of the collaborative brain power being applied here from around the world, that we will find something real and reliable that will change how we think about these disorders and what we can do about them,” Turner said in the release. – by Amanda Oldt

Disclosure: The researchers report no relevant financial disclosures.

For more information:

To learn more about the ENIGMA project, visit http://enigma.ini.usc.edu/.