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Common Genetic Factors Found in 5 Mental Disorders

Major mental disorders traditionally thought to be distinct share certain genetic glitches, according to a new study. The finding may point to better ways to diagnose and treat these conditions.

Scientists have long recognized that many psychiatric disorders tend to run in families, suggesting potential genetic roots. Such disorders include autism, attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depression and schizophrenia. Symptoms can overlap and so distinguishing among these 5 major psychiatric syndromes can be difficult. Their shared symptoms suggest they may also share similarities at the biological level. In fact, recent studies have turned up limited evidence of shared genetic risk factors, such as for schizophrenia and bipolar disorder, autism and schizophrenia, and depression and bipolar disorder.

To take a broader look, an international research consortium conducted an analysis that incorporated data from genome-wide association studies (GWAS) of the 5 major disorders. This type of study involves scanning through thousands of genetic markers in search of tiny variations that appear more often in people who have a particular condition than in those who don't. The research received primary funding from NIH’s National Institute of Mental Health (NIMH), along with other NIH components.

As reported online in the Lancet on February 28, 2013, the scientists screened for evidence of illness-associated genetic variation among over 33,000 patients. All had been diagnosed with at least 1 of the 5 disorders. A comparison group included about 28,000 people who had no major psychiatric diagnosis.

The analysis revealed variations significantly associated with all 5 disorders. These included variations in 2 genes that code for the cellular machinery that helps regulate the flow of calcium into neurons. Variation in one of these, called CACNA1C, had previously been linked to bipolar disorder, schizophrenia and major depression. CACNA1C is known to affect brain circuitry involved in emotion, thinking, attention and memory — functions that can be disrupted in mental illnesses. Variation in another calcium channel gene, called CACNB2, was also linked to the 5 disorders.

In addition, the researchers discovered illness-linked variation for all 5 disorders in certain regions of chromosomes 3 and 10. Each of these sites spans several genes, and causal factors haven’t yet been pinpointed. The suspect region along chromosome 3 had the strongest links to the disorders. This region also harbors certain variations previously linked to bipolar disorder and schizophrenia.

“Although statistically significant, each of these genetic associations individually can account for only a small amount of risk for mental illness,” says study co-author Dr. Jordan Smoller of Massachusetts General Hospital. Because of this, the variations couldn’t yet be used to predict or diagnose specific conditions. But these results may help researchers move closer to making more accurate diagnoses. They may also help lead to a better understanding of the factors that cause these major mental disorders.