E. Fuller Torrey is a psychiatrist and researcher on schizophrenia and bipolar disorder who has spent more than $550 million on biological research on schizophrenia and bipolar disorder over the past few decades. He is also the author of an article published in Psychiatry Research, “Did the human genome project affect research on Schizophrenia?” The Human Genome Project was thought to have the potential to transform the diagnosis and treatment of mental illness. Schizophrenia was widely believed to be a genetic disorder. However, “three decades later NIMH’s genetics investment has yielded almost nothing clinically useful for individuals currently affected.”
In “Searching for the ‘Psychiatric Yeti’: Schizophrenia is Not Genetic,” Peter Simons examined and assessed the Torrey article and remarked it was surprising since Torrey has argued in the past that schizophrenia is a brain disease and should be treated medically. Yet, Torrey thought the decades-long attempt to locate the genetic basis for schizophrenia has failed. He said: “Over twenty years later not a single gene has been identified to cause schizophrenia, despite the expenditure of almost $8 billion in genetic research by NIMH. Nor have any new treatments become available from this research.”
The NIH’s MedlinePlus website continues to list schizophrenia as a “genetic condition,” and acknowledges the “genetic changes related to schizophrenia are not well understood.” Simons observed that the Human Genome Project was designed by “true believers”, in part, to discover the genetic basis of psychiatric disorders, particularly schizophrenia. The director of the NIMH during the Human Genome Project said at the time, “The search for the genes associated with most mental illnesses will now move forward at a greatly accelerated pace… Highly selective, safe, and effective new therapies will become available for the treatment of the common mental illnesses in the not-too distant future.”
But the promised gains never materialized. The Human Genome Project did help in our understanding of other conditions, especially cancer, as well as the single-gene disorders. But for psychiatric disorders, no genetic test was found; no biological test was found; no psychiatric drug was developed based on a genetic discovery. Not for depression, anxiety, psychosis, bipolar disorder, OCD, ADHD, or any other “mental illness.”
Current research suggests that genetic testing explains less than 1% of whether someone would receive a schizophrenia diagnosis. “This failure of genetic research has paralleled the failure of the rest of psychiatry. Despite a massive increase in the amount of people receiving a diagnosis and taking psychiatric drugs, outcomes have only worsened over the years.” Researchers have said there is no evidence that psychiatry has improved outcomes over time. After controlling for symptom severity, antidepressant use, antipsychotic use, and receiving a psychiatric diagnosis, these individuals have worse outcomes than those who don’t get diagnosed or treated.
Research to identify the possible roots of a disorder that runs in families are called linkage analysis. Torrey noted there have been at least 32 linkage studies of schizophrenia and 40 of bipolar disorder. “None of them were able to replicate the findings of the others.” Another type of research tried to predict candidate genes. Genes that researchers think may be responsible for a particular diagnosis are selected, and then checked to see if they were more common in individuals with the disorder than without. Over a thousand candidate gene studies on schizophrenia and hundreds more for bipolar disorder have failed as completely as the linkage analysis approach.
Then there were genome-wide association studies (GWAS). Torrey said that the genes identified by GWAS as increasing the risk for schizophrenia overlap with other psychiatric diagnoses, including depression, ADHD, and autism. “Thus, these genes are not specific, but rather seem associated with emotional distress in general and altered cognition of many kinds.” Torrey quoted researchers McClellan and King, who said in “Genetic Heterogeneity in Human Disease”:
The general failure to confirm common risk variants is not due to a failure to carry out GWAS properly. The problem is underlying biology, not the operationalization of study design. The common disease–common variant model has been the primary focus of human genomics over the last decade. Numerous international collaborative efforts representing hundreds of important human diseases and traits have been carried out with large well-characterized cohorts of cases and controls. If common alleles influenced common diseases, many would have been found by now. The issue is not how to develop still larger studies, or how to parse the data still further, but rather whether the common disease–common variant hypothesis has now been tested and found not to apply to most complex human diseases.
The next type of genetic study on the quest to find the genetic basis of schizophrenia was identifying copy number variants (CNVs). CNVs are either duplicates copies or missing copies of genetic code. Usually CNVs don’t cause any problems, however certain CNVs can cause genetic disorders. It is estimated that approximately 1% of people with schizophrenia have a CNV associated with an increased risk of schizophrenia. “But again, this does little to explain a cause for the other 99% of people with schizophrenia—or why most people with DiGeorge syndrome don’t develop schizophrenia.”
Ultimately, Torrey thought the search for schizophrenia genes was a wild goose chase. “It is even worse than that since a wild goose chase has, at least theoretically, a wild goose that might be caught. If indeed genes causing schizophrenia do not exist, then the thirty-year search has been more like a search for a psychiatric yeti.”
The Train Wreck of Schizophrenia Genetic Research
Jay Joseph wrote in “The 110-Year ‘Schizophrenia Genetic Research’ Train Wreck” that research into the genetics of schizophrenia is in disaster mode. The evidence supporting schizophrenia as a genetic disorder is “stunningly weak,” and has important implications for prevention and intervention strategies. Joseph then went on to review the historical origins of psychiatric genetics and noted how linkage studies and candidate gene association studies of this earlier era of research failed to identify any causal genes. He went on to discuss Peter Simon’s article about E. Fuller Torrey, schizophrenia adoption studies, and an article titled: “It’s Fair to Describe Schizophrenia as Mostly Genetic.” Joseph said:
Since we supposedly “know” from family, twin, and adoption studies that schizophrenia is 80% heritable, how do we make sense of gene-discovery failure? I argue that we can make sense of it only: (a) by recognizing that schizophrenia family and twin study results can be interpreted environmentally; (b) by recognizing that the schizophrenia adoption studies were massively flawed and in most cases p-hacked (including Leonard Heston’s often-cited 1966 U.S. [Oregon] study); and (c) by abandoning the long-controversial practice of calculating heritability estimates, which are based on unsupported assumptions and do not record the “strength” or “magnitude” of the supposed genetic influence on psychiatric conditions.
See “How to Lie About Research” for an explanation of p-hacking.
When psychiatry finally acknowledges that “schizophrenia” (psychosis) is not “genetic” or a “disease,” society will part ways with biological diversions and inappropriate medical approaches. The behavioral sciences and society will instead focus on environmental causes, non-medical interventions, and prevention, with a necessary political change component. People might still wish to take prescribed drugs, or others might encourage or pressure them to do so, but the process should be completely transparent, including informing people in writing of potential withdrawal problems and side effects. No one should be told they are being prescribed drugs to treat a genetically influenced or caused schizophrenia brain disease, because no such disease exists.
