The single strongest genetic risk factor for schizophrenia identified to date is called “22q11.2 deletion syndrome.” The name refers to a missing piece of DNA on chromosome 22 that causes cardiac, palate and other abnormalities, and also increases the risk of developing a number of neuropsychiatric disorders. For the 25 percent of people with 22q11.2 deletion syndrome who develop schizophrenia, symptoms such as hallucinations and delusions usually begin between the ages of 16 and 30. New research finds that these individuals are likely to experience a significant intellectual decline that can begin as early as age 11.

The findings were published online January 15th in the journal JAMA Psychiatry. The paper’s first author is Jacob Vorstman, M.D., Ph.D., a two-time NARSAD Young Investigator grantee (2006, 2010) at the University Medical Center Utrecht, the Netherlands. Eight other current and former NARSAD grant recipients were part of Dr. Vorstman’s team.*

People with schizophrenia are not identified as patients until they experience their first psychotic symptoms. But they usually experience social and cognitive decline years earlier, a fact that suggests the disease process begins much earlier than the onset of obvious psychotic symptoms. Understanding the earlier phases of the disease's development could help doctors better predict its course and manage its symptoms. For the current study, Dr. Vorstman and his colleagues analyzed clinical psychiatric assessments and IQ measurements for more than 400 people with 22q11.2 deletion syndrome. Each person in the study had his or her IQ measured at least twice between the ages of 8 and 24.   

On average, the people analyze showed a decline in IQ as they got older. For most, this decline was mild. While the study was under way, 13 percent of the participants were diagnosed with psychotic disorder. For these people, the trajectory differed. Their IQ dropped more significantly, mostly driven by a decline in verbal IQ, which was linked with a twofold increase in the risk to develop a psychotic disorder later in life.

The scientists say that this study can provide important insights about the early trajectory of schizophrenia in people with 22q11.2 deletion syndrome. Not only could monitoring changes in IQ be an effective way to predict which of these people are most likely to develop schizophrenia, it could also help in the management of their treatment.

* The Foundation-funded team members are:

Stephan Eliez, M.D., Ph.D. - 2002 Young Investigator (YI)

Marco Armando, M.D., Ph.D. - 2013 YI

Vandana Shashi, M.D., MBBS - 2004 YI, 2010 Independent Investigator

Therese van Amelsvoort, M.D., Ph.D., MRCPsych - 2004 YI

Doron Gothelf, M.D. - 2006 YI

Wendy R. Kates, Ph.D. - 1998 YI, 2005 II

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

Carrie E. Bearden, Ph.D. - 2003, 2005 YI

Read the abstract.