In the first study of its kind, researchers have found unique brain structure patterns among people with schizophrenia, providing insight into how the condition may develop and respond to treatment.

Differences in brain structure have been noted in people with schizophrenia for decades. Ideally, such information should help us understand causes, progression and even treatment effects. Yet brain differences are influenced by many factors, some with opposing effects. Moreover, studies performed by different teams with different methods and standards have made it hard to distill results.  

Reporting June 2nd in Molecular Psychiatry, an international team called the ENIGMA Schizophrenia Working Group––19 of whose members are current and past NARSAD grantees*––presented a profile of brain abnormalities based on 15 schizophrenia cohorts worldwide. It was a first test of a way to analyze imaging data across traditional diagnostic boundaries. The aim: to generate “robust and consistent anatomical fingerprints associated with brain disorders to help formulate improved diagnostic classifications based on both brain and behavioral evaluations,” the team said.

The ENIGMA group confirmed that people with schizophrenia had some smaller brain regions compared with healthy controls: the hippocampi, twin structures on either side of the brain that are associated with memory; the amygdalae, another paired structure found in both brain hemispheres that are important for emotional processing; and the thalami, twin structures associated with the relay of sensory and motor information. They also noted that intracranial volume, a general measure of brain size, was smaller than average in people with the illness.  

The team found two structures larger than normal in people with schizophrenia: the pallidum, involved in motivation and emotion; and the lateral ventricles, important cavities in the brain. These findings add to the evidence that schizophrenia is characterized by specific abnormalities of deep brain structures.

The structural differences linked with schizophrenia in this study varied depending on factors such as age and sex, highlighting the variability of the illness. The biggest difference among people with schizophrenia was their smaller hippocampi, most pronounced among people who had never received medicine (typically, antipsychotic medicine) for their schizophrenia symptoms. This finding supports previous evidence that untreated schizophrenia may involve abnormal development of the hippocampus and that this can be reduced or reversed by treatment with antipsychotic medication.

Future work will examine how these structural differences unfold across the lifespan in affected individuals who take antipsychotic medications and those who do not. The team calls for attention in future studies to environmental and lifestyle factors that can affect brain structure, including nutrition levels, water intake, exercise, drug use, social isolation, and stress. Future research by ENIGMA will include the study of brain characteristics among family members of people with schizophrenia, as well as different measures of brain structure, and possible relationships between the structural differences found in this study and individual patients’ experience of schizophrenia symptoms.

*NARSAD grant recipients who contributed to the study:

David C. Glahn, Ph.D. - 2003, 2005 Young Investigator (YI); 2014 Independent Investigator (II)

Godfrey D. Pearlson, M.D., Ph.D. - 2000 Distinguished Investigator (DI), Scientific Council Member

Gary J. Donohoe, Psy.D., Ph.D. - 2008 YI

Colm McDonald, M.D., Ph.D. - 2002 YI, 2009 II

Dara M. Cannon, Ph.D. - 2004, 2006 YI

Theodore D. Satterthwaite, M.D., M.A. - 2010 YI, 2014 Klerman Prizewinner

Daniel H. Wolf, M.D., Ph.D. - 2005 YI

Ruben C. Gur, Ph.D. - 2007 DI

Raquel E. Gur, M.D., Ph.D. - 1999 DI

Steven G. Potkin, M.D. - 2013 DI, Scientific Council Member

Daniel H. Mathalon, M.D., Ph.D. - 2001 YI, 2007 II

Adrian Preda, M.D. - 2001 YI

Fabio Macciardi, M.D., Ph.D. - 2000 II

Stefan Ehrlich, M.D. - 2010 YI

Vince D. Calhoun, Ph.D. - 2004 YI

Roel A. Ophoff, Ph.D. - 2002, 2005 YI; 2008 II

Andrew M. McIntosh, M.D. - 2010 II

Stephen M. Lawrie, M.D., Ph.D. - 2009 DI

Peter M. Thompson, M.D., M.S. - 1996, 2001 YI

Read the study.