The chances of developing schizophrenia rise substantially for the small number of children who possess only one copy of a gene variant that regulates a crucial chemical messenger in the brain, according to a new finding of a long-term investigation.
A team led by psychiatrist Allan L. Reiss of Stanford University School of Medicine studied 24 children missing a small piece of DNA on chromosome 22. About 30 percent of youngsters with this deletion, which occurs in 1 in 4,000 births, eventually develop the severe mental disorder schizophrenia or related psychotic conditions. These children are also prone to other problems, including heart defects, cleft palate, and learning disorders.
Prior studies showed that people with this deletion lack one copy of the usual two copies of the COMT gene, which triggers production of a protein that breaks down the neurotransmitter dopamine. The protein comes mainly in two variants with contrasting dopamine-busting power, one weak and the other strong.
By young adulthood, seven of the study participants with the deletion had developed schizophrenia or another psychotic disorder, Reiss and his coworkers report in the November Nature Neuroscience. Of that number, the four individuals with the weak COMT variant—who presumably grew up with excessive amounts of dopamine in their brains—displayed larger drops in verbal intelligence and language skills, and harsher psychotic symptoms, than their three peers with the strong variant did. Also, the prefrontal brain area of the four participants with the weak variant shrank more than did that area in three participants with the strong variant. This brain region is linked to schizophrenia.
COMT-associated dopamine drenching of children’s growing brains creates a strong susceptibility to schizophrenia, Reiss proposes. He also hypothesizes that a dopamine drought in children who inherit a single copy of the strong COMT variant can also foster psychotic symptoms.