A variant in a gene that escalates synaptic pruning—a process that removes neurons from the brain that are no longer useful—could be linked to schizophrenia, according to a large study published in Nature.
The Link Between C4 and Schizophrenia
Researchers from the Broad Institute and Harvard University studied the genomes of 64,785 people to explore genetic links to schizophrenia. They found a clear connection between symptoms of schizophrenia and possession of a mutation in the complement component 4 (C4) gene, which has previously been known to help a person’s immune system to identify and target infections.
C4 is one of at least 100 genes that have been linked to schizophrenia, meaning it is not the sole cause of the condition. However, it may be the most significant. When researchers plotted the gene alongside other schizophrenia-related genes, mutant forms of C4 towered above all other genes associated with the condition.
Synaptic Pruning and Schizophrenia
Synaptic pruning is key to understanding the connection between C4 and schizophrenia. Schizophrenia typically appears during adolescence, which is also a time of rapid growth in the brain. Brain growth is usually followed by synaptic pruning, removing unnecessary or redundant connections.
Could This Change Schizophrenia Treatment?
Jeffrey Lieberman, MD, a renowned schizophrenia researcher, was the president of the American Psychiatric Association (APA) from May 2013 to May 2014. He explained the potential implications of the study.
“The schizophrenia phenotype has long been associated with loss of gray matter in the brain,” Lieberman said. “Now that we have more information about what underpins this phenomenon, we are closer to understanding schizophrenia.”
The research will not change schizophrenia treatment today, Lieberman explained, but could open new avenues for future treatment. Slowing down the pruning process in people who are genetically vulnerable to schizophrenia might one day be possible, potentially reducing the incidence or severity of the condition.
Tips for People with Schizophrenia
Lieberman’s 2015 book, Shrinks: The Untold Story of Psychiatry, tells the tale of the discipline’s transformation from a speculative endeavor to an experimental, evidence-based science. The book highlights many of psychiatry’s missteps: lobotomies, hydrotherapy, and primal scream therapy, to name a few.
“People with schizophrenia and other severe mental illnesses have long suffered from a kind of benign neglect,” he said. “Doctors often settle.”
Good schizophrenia treatment is typically a mix of several strategies, Lieberman said, including medication, supportive psychotherapy, psychoeducation, supportive educational and employment settings, and effective case management. Because schizophrenia has no cure, people with schizophrenia sometimes encounter economic, institutional, and other barriers to treatment.
“The patient should be the barometer for what is working,” Lieberman said.
He suggests the following strategies for people with schizophrenia who want highly effective treatment:
- Push your doctor. Each medication used should have a clear and rational justification. According to Lieberman, doctors sometimes continue prescribing a medication even when its benefits are unclear or minimal. Instead, providers should partner with the people they are treating to assess the value of each drug while working to limit side effects.
- Read reliable online information. Lieberman cautions that online information may not be credible and suggests people rely on sites such as the National Institutes of Health, hospital sites, and universities—not message boards or anonymous blogs. Information on these sites can better equip mental health consumers to ask intelligent questions and pursue effective treatments.
- Seek a second opinion. “No good doctor should be threatened by a second opinion. If you are not sure where to seek a second opinion, contact your local medical school’s department of psychology and ask for a referral,” Lieberman said.
- Courage, K. H. (2016, February 1). Variations in a gene provide clues about schizophrenia. Retrieved from http://www.npr.org/sections/health-shots/2016/01/29/464703705/variations-in-a-gene-provide-clues-about-schizophrenia
- Sekar, A., Bialas, A. R., Rivera, H. D., Davis, A., Hammond, T. R., Kamitaki, N. . . . Mccarroll, S. A. (2016). Schizophrenia risk from complex variation of complement component 4. Nature, 000. doi:10.1038/nature16549
- Schizophrenia’s strongest known genetic risk deconstructed | National Institutes of Health (NIH). (2016, January 27). Retrieved from http://www.nih.gov/news-events/news-releases/schizophrenias-strongest-known-genetic-risk-deconstructed
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