Communication problems in the brain that are associated with schizophrenia are present prior to diagnosis, according to a new study in which researchers examined neural connectivity in people with a high risk of developing the disorder. The study, published August 12 in the journal JAMA Psychiatry, found that the connectivity alterations were most severe in participants who went on to develop full psychosis within two years.

NARSAD 2015 Independent Investigator and 2012 Young Investigator Alan Anticevic, Ph.D., at Yale University, was the lead author of the study. NARSAD 2006 Distinguished Investigator and 1997 Independent Investigator Tyrone D. Cannon, Ph.D., also at Yale, was the senior author.

The team focused on connections between a relay center in the brain called the thalamus and other brain regions that are involved in both higher cognitive functions and primary sensory functions. There is good evidence that these “thalamo-cortical” networks, which are involved in a wide range of neural processing, are disrupted in people with schizophrenia. No one knew, however, if those disruptions might be detectable prior to full-blown illness and clinical diagnosis. Earlier diagnosis and evaluation of clinical risk has long been an objective of researchers and doctors, as it is thought that by treating patients early, the severity of the illness may be reduced, at least in some cases.

To test their ideas, the researchers used sophisticated emerging brain imaging methods to examine thalamo-cortical connections in 243 people who had experienced symptoms indicating they were at high risk of developing schizophrenia, as well as in 154 healthy subjects. They found that in high-risk individuals, the communication between the thalamus and the prefrontal cortex was weaker than observed in healthy study participants. Connections between the thalamus and sensory-processing regions of the brain, in contrast, were relatively stronger in high-risk individuals than they were in healthy controls. These patterns are similar to those that have been observed in people with more chronic schizophrenia.

After brain imaging, the study participants were followed for two years, during which time 21 individuals developed full psychosis and received a diagnosis of schizophrenia. (Dr. Anticevic cautions that the two diagnoses are distinct and that having psychosis does not necessarily imply that someone has schizophrenia.) Although the imaging studies had found abnormal thalamic connections in all at-risk individuals, the scientists' final analysis showed that the disruptions had been most severe in those who went on to develop full psychosis.

The study suggests that examining thalamo-cortical connectivity could help clinicians predict which individuals are most likely to progress to full psychosis, improving opportunities for early intervention.

The research was conducted by a large international team of scientists, including the following NARSAD grantees: 2014 Young Investigator Sarah Christine McEwen, PhD; 2003 and 2005 Young Investigator Carrie E. Bearden, PhD; 1992 and 1999 Young Investigator Kristin S. Cadenhead, MD; 2013 Young Investigator Heline Mirzakhanian, PhD; 2001 Young Investigator and 2007 Independent Investigator Daniel H. Mathalon, MD, PhD; 1997 Distinguished Investigator Thomas H. McGlashan, MD; 1996 and 1999 Young Investigator and 2004 Independent Investigator Aysenil Belger, PhD; 1998 and 2004 Independent Investigator Larry J. Seidman, PhD; 1998 Distinguished Investigator and BBRF Scientific Council Member Ming T. Tsuang, MD, PhD, Dsc; 1989 Distinguished Investigator Elaine F. Walker, PhD; and 1998 Independent Investigator and 2005 Distinguished Investigator Scott W. Woods, MD.

Read the paper.