Forty to fifty years ago, a prevalent theory was; schizophrenia was caused by having a bad mother. Since then there have been hundreds of theories about this mental illness over the years, but one of the enduring mysteries has been how the following three prominent findings are related to each other: the apparent involvement of immune molecules in the disorder, the age of its typical onset in late adolescence and early adulthood, and the thinning of grey matter seen in autopsies of people with this disease.
Researchers, chiefly from the Broad Institute, Harvard geneticist Steven McCarroll from Harvard Medical School and Beth Stevens from the Children’s Hospital in Boston, found that a person’s risk of schizophrenia is dramatically increased if they inherit modifications of a gene important to “synaptic pruning” — the healthy reduction during adolescence of brain-cell connections that are no longer needed. (Synapses are connections between brain cells, or neurons and occasional pruning is needed to remove rarely-used synapses to increase efficiency of the entire network — a process that typically begins during adolescence. Excessive pruning, though, can cause problems.)
For the first time, scientists have pinned down a molecular process in the brain that helps trigger schizophrenia providing the first evidence of a physiological source for the debilitating disorder. In July 2014, Broad researchers published the results of the largest genomic study on the disorder and found more than 100 genetic locations linked to schizophrenia. The information was drawn from dozens of studies performed in 22 countries, all of which contribute to the worldwide database called the Psychiatric Genome Consortium.
In patients with schizophrenia, a variation in a single position in the DNA sequence marks synapses for removal and that process goes out of control. The result is an abnormal loss of grey matter. The highest peak was on chromosome 6, where McCarroll’s team discovered the gene variant. C4 was “a dark corner of the human genome,” he said, an area difficult to decipher because of its “astonishing level” of diversity. C4 and numerous other genes reside in a region of chromosome 6 involved in the immune system, which clears out pathogens and similar cellular debris from the brain. The study’s researchers found that one of C4’s variants, C4A, was most associated with a risk for schizophrenia.
Most psychiatric drugs seek to interrupt psychotic thinking, but experts agree that psychosis is just a single symptom — and a late-occurring one at that. These findings may allow future treatments to be directed at the root of the affliction rather than at its symptoms. This research indicates the strong potential for early detection and new treatments that were unthinkable just a year ago and proves that having a bad mother is not the root cause of schizophrenia.