An older methodology, the study of twins, continues to provide important insight into this muddy genetic picture. Twin studies generally compare the concordance for a disease or other trait within monozygotic twin pairs, who share 100% of their DNA, versus concordance within dizygotic twin pairs, who share on average 50% of their DNA. In a recent article in the American Journal of Psychiatry, a Swedish team of researchers led by Paul Lichtenstein studied 7,982 twin pairs. They found a heritability of 80% for autism spectrum disorders, but also found substantial sharing of genetic risk factors among autism, attention deficit hyperactivity disorder, developmental coordination disorder, tic disorders, and learning disorders.
In another recent article in the American Journal of Psychiatry, Marina Bornovalova and her University of Minnesota colleagues studied 1,069 pairs of 11-year-old twins and their biological parents. They found that parent-child resemblance was accounted for by shared genetic risk factors: in parents, they gave rise to conduct disorder, adult antisocial behavior, alcohol dependence, and drug dependence; in the 11-year-olds these shared factors were manifest as attention deficit hyperactivity disorder, conduct disorder, and oppositional-defiant disorder. (Strikingly, attention deficit disorder co-occurs in both the autism spectrum cluster and disruptive disorder cluster.)
These and many other studies call into question two of the key validators of descriptive psychiatry championed by Robins and Guze. First, DSM disorders do not breed true. What is transmitted across generations is not discrete DSM categories but, perhaps, complex patterns of risk that may manifest as one or more DSM disorders within a related cluster. Second, instead of long-term stability, symptom patterns often change over the life course, producing not only multiple co-occurring diagnoses but also different diagnoses at different times of life.
How can these assertions be explained? In fairness to Robins and Guze, they could not have imagined the extraordinary genetic complexity that produces the risk of many common human ills, including mental disorders. What this means is that common mental disorders appear to be due to different combinations of genes in different families, acting in combination with epigenetics -- gene expression varies even if the underlying DNA sequence is the same -- and non-genetic factors.
In some families, genetic risk for mental disorders seems to be due to many, perhaps hundreds, of small variations in DNA sequence -- often single “letters” in the DNA code. Each may cause a very small increment in risk, but, in infelicitous combinations, can lead to illness. In other families, there may be background genetic risk, but the coup de grace arrives in the form of a relatively large DNA deletion, duplication, or rearrangement. Such “copy number variants” may occur de novo in apparently sporadic cases of schizophrenia or autism.
In sum, it appears that no gene is either necessary or sufficient for risk of a common mental disorder. Finally, a given set of genetic risks may produce different symptoms depending on broad genetic background, early developmental influences, life stage, or diverse environmental factors.
The complex nature of genetic risk offers a possible explanation for comorbidity: what the DSM treats as discrete disorders, categorically separate from health and from each other, are not, in fact, discrete. Instead, schizophrenia, autism-spectrum disorders, certain anxiety disorders, obsessive-compulsive disorder, attention deficit hyperactivity disorder, mood disorders, and others represent families of related disorders with heterogeneous genetic risk factors underlying them. I would hypothesize that what is shared within disorder families, such as the autism spectrum or the obsessive-compulsive disorder spectrum, are abnormalities in neural circuits that underlie different aspects of brain function, from cognition to emotion to behavioral control, and that these circuit abnormalities do not respect the narrow symptoms checklists within the DSM.