A recent study reports to have broken new ground in the study of schizophrenia, discovering a potentially powerful genetic contributor to the mental disorder and illuminating why it normally takes hold in early adulthood. Genes associated with the immune system have long been suspected in schizophrenia, but understanding the nature of this relationship has eluded scientific research. A recent study, featuring researchers from MIT and Harvard, revealed that immune-related genetic variations linked to schizophrenia play a key role in prompting the “pruning” of brain connections in late adolescence.
The pruning of synapses—the connections among brain cells that proliferate during our early development—appears to play a significant role in our cognitive transition into adulthood. Scientists surmise that if this process is altered by a gene variation, the transition may be disrupted. This study offers one of the first clear evidence of a neurobiological basis to schizophrenia—a disease that places a lifelong burden on patients and their families. Schizophrenia is characterized by periodic episodes of delusional thinking, as well as difficulties with working memory, planning and executive functioning.
Schizophrenia has long been known to be a heritable disorder, and advances in genetic research have turned up 108 regions along the genome where variations appeared to increase the risk of schizophrenia. For the longest time, scientists have been unable to link schizophrenia to specific genes or genetic variations. This study proves to be a significant step in schizophrenia’s research because it has discovered specific genes related to schizophrenia’s development.
The genetic region called the major histocompatibility complex contains both genes that partly govern the immune system and DNA variants that appear with regularity in people with schizophrenia. After conducting genetic tests on nearly 65,00 people, researchers discovered a group of genes in that area called C4 genes. They found that people with certain variants of C4 genes had high odds of developing schizophrenia, even in the absence of other genetic risks.
After genetically engineering mice with the C4 gene deficiencies that in humans is linked to schizophrenia, researchers found that the pruning process that was activated during late adolescence was markedly overactive. It pruned synapses so ruthlessly that connections were likely to be missing throughout the brain. By showing a link between C4 genes and synaptic pruning, this new data builds on previous theories that maintain the over-editing of brain connections in late adolescence might be a contributing cause of schizophrenia. It could also establish a molecular explanation for the peculiar age-of-onset associated with schizophrenia.
Thanks to the human genome, we are able to look into schizophrenia in a powerful new way. The team’s finding may refine the search for better treatments for schizophrenia. Until now the disorder is treated with a lifelong regimen of antipsychotic medications that blunt the delusions, but do not remedy the subtler cognitive impairments associated with schizophrenia. With a better understanding of the molecular processes set in motion by errant genes, scientist can hope to develop more precise ways to treat, and perhaps prevent, the brain changes seen in schizophrenia. Clearly the C4 does not fully explain schizophrenia risk, however it is a massive first step in understanding a potential biological basis behind the disease.
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