It’s fair to say that the more our understanding of mental health grows, the more we realize how little we actually know about mental health. It’s an ironic statement, for sure, but no less true because of it. If we look back on how mental health disorders have been diagnosed and treated over past decades, though, it’s definitely clear that we take it very seriously — more so than in the past. That’s why a recent large-scale study should be both fascinating and uplifting, after scientists across 15 different institutions analyzed approximately 2,000 brains in 11 studies in an effort to learn more about mental health, specifically focusing on schizophrenia, bipolar disorder, and autism. The findings were published in a special edition of Science and two other journals, reportedly.
Much of the research focused on genetics and how they affect the brain as it develops as well as how those factors can lead to causes of certain mental disorders. This allowed them to examine the genetic risk of schizophrenia and bipolar disorder up to six times more accurately than previous genetic analyses could offer, according to studies led by Mark Gerstein, a professor of biomedical informatics, molecular biophysics and biochemistry, computer science, and of statistics and data science at Yale University. What they found is that genetic risk variants have a greater chance of bringing about symptoms during different stages of brain development based on the illness. For example, Gerstein and his team of researchers determined that the greatest differences in gene expression activity take place early in the womb, decrease later in pregnancy and early in childhood, and increase once again as a child moves into adolescence. This was a particularly significant find because these same patterns of brain development often match the time when genes associated with the risks of neuropsychiatric disorders are known to or tend to form in specific regions of the brain. For example, modules associated with autism typically take shape early in development while the modules associated with something like schizophrenia, for example, will form later in life. Similarly, the symptoms of each disorder will appear at the same times as well.
It’s been long believed that these particular conditions are prone to some kind of an inherited component but researchers haven’t been able to locate exactly how genes contribute to their development. While certain illnesses can be caused by a mutation of a single gene, neuropsychiatric disorders like the ones Gerstein and his team examined require hundreds of genes contributing to overall disease risk. In previous studies, the challenge seems to have been that the sequence of these gene changes is unclear, making it difficult to pinpoint how and when genetics play a role in determining or influencing mental health.
“Typically, when we do a genetic study, we might find 50 associated genetic variants all clustered in the same region of the genome, and maybe only one of them is directly influencing the risk of disease,” says Michael O’Donovan, a psychiatric geneticist at Cardiff University, UK.
According to Scientific American, this particular study was the most comprehensive genomic analysis of the human brain ever, giving scientists brand new insights into this realm.
“We’re not claiming in the remotest way to have figured out the underlying mechanism of these diseases, or how you would go about designing drugs, but we are highlighting genes, pathways and also cell types that are associated with these diseases,” Gerstein said. “We know that [common neuropsychiatric] diseases are extremely heritable, but people still don’t have a good idea of mechanism; the goal is to use functional genomics to try to figure out what’s going on.”
“These publications are important, but they do not provide the definitive answer to how genetic changes contribute to brain diseases,” O’Donovan says. “These are reasonably substantial steps, but they are just steps — although we do hope that a lot more work of this sort will help us link the genetics to the biology of these disorders.”
According to the National Institute of Mental Health (NIMH), many mental disorders stem from a combination of “biological, environmental, psychological, and genetic factors,” citing that family history is often one of your biggest clues as to risks. Although, it’s also important to point out that the NIMH maintains no one gene variant can or will predict with certainty that a person will develop a mental disorder. In most cases, they say, even the most significant genetic variant will only raise a person’s risk by a small amount.
And in 2013, the NIHM cited common genetic factors among five mental disorders: autism, attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depression, and schizophrenia — three of which were, of course, studied in the most recent research. At the time, the NIH pointed out a very obvious observation: the shared similar symptoms may also share similarities at the biological level. They searched through thousands of different genetic markers in an attempt to pinpoint anything that may appear more often in people with those conditions.
“These included variations in two genes that code for the cellular machinery that helps regulate the flow of calcium into neurons,” the National Institute of Health wrote at the time. “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.”
"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.
Even now, with all the growing bodies of research, there’s still not enough information to definitively pinpoint which genes and variations predict mental health disorders, however, understanding which of these hereditary factors contribute to the risks and development of them is still a massive leap in growing an understanding of mental health.