Patrick Sullivan, MD, FRANZCP, Yeargan Distinguished Professor of Psychiatry and Genetics at the UNC School of Medicine, and researchers at the Karolinska Institute in Stockholm, Sweden, have developed a comprehensive outline of the genetics of schizophrenia. The review was published in Nature Reviews on Neuroscience.
Schizophrenia is a neuropsychiatric disorder characterized by recurrent episodes of psychosis (such as hallucinations, delusions, and disorganized thinking) and, as a result, many patients develop apathy, social isolation, and poor emotional control.
Because schizophrenia has been known to be passed down through families for centuries, researchers have turned to genetic testing and analysis to identify risk factors for the disorder. Recent genomic research on schizophrenia has identified nearly 300 common genetic variants and more than 20 rare variants as major risk factors for the disorder.
These discoveries have emerged from genome-wide association studies, whole-exome sequencing, and other analyses. Simultaneously, studies of the functional organization of the brain have shed light on the intricate cellular makeup and interconnections of the brain in both neurotypical individuals and those with schizophrenia.
These findings reveal a surprising complexity in the mechanisms underlying schizophrenia, highlighting the role of multiple genes rather than single-gene causality. This “polygenicity” highlights a mechanism that remains difficult to fully understand due to a lack of robust theoretical frameworks and experimental tools. Sullivan and colleagues explored these questions and provided ideas for a path forward in research. Nature Reviews Neuroscience Article.
However, Sullivan and colleagues point out that environmental factors (including lifestyle, drug use, poverty, stress, and birth complications) are also relevant, in addition to genomic risk. Although these factors are more difficult to study compared to the genome, it is important for researchers to consider this genetic information because some environmental factors are modifiable.
“The findings to date strongly indicate that complexity exists,” wrote Sullivan, who is also director of the UNC Center for Psychiatric Genomics and the UNC Suicide Prevention Institute. “Rather than being an impediment to future research, this knowledge underscores the importance of accepting schizophrenia as a genetic and environmental enigma and expanding our research accordingly in our efforts to improve the lives of people affected by schizophrenia.”