Schizophrenia Genetic Research—Running on Empty: By Jay Joseph, Psy.D.
[This is a slightly revised and updated version of a 2017 article that first appeared at the Mad in America website.]
The May 2017 edition of Scientific American featured an article on schizophrenia research by freelance journalist Michael Balter, entitled “Schizophrenia’s Unyielding Mysteries.” Despite the decades-old failure to discover genes that cause schizophrenia, Balter believed that continuing the search for genes is necessary to help unravel the “mysteries” of the condition, for the development of new “antipsychotic drugs” and other interventions, and to develop prevention programs. As I concluded in my 2017 e-book Schizophrenia and Genetics: The End of an Illusion, however, decades of failed gene finding attempts have produced a scientific finding that “genes for schizophrenia” most likely do not exist.
Balter also discussed recent evidence pointing to the role of childhood trauma, poverty, and other environmental factors, and quoted Norwegian neuroscientist Roar Fosse’s call for “a stronger focus on changing the environment so we can prevent schizophrenia.” Balter’s general conclusion was that environmental data should be added to or incorporated into molecular genetic research, so that researchers can produce statistical models in support of their position that genes and environment interact to produce schizophrenia.
Although “schizophrenia” is usually presented as a valid disorder that can be reliably identified (diagnosed) by psychiatrists and others, there is plenty of evidence that it isn’t. And yet, establishing the reliability and validity of a psychiatric disorder is a prerequisite for any attempt to search for genetic influences or genes that cause it. Many critics of psychiatry have argued that psychiatric disorders are not reliable or valid discrete illnesses, but instead describe people’s varying psychological responses to having experienced adverse events and environments, or are socially disapproved behaviors or responses to oppression that psychiatry labels as mental disorders. Some reject the word “schizophrenia” entirely, and as critical psychiatrists Joanna Moncrieff and Hugh Middleton wrote, some prefer terms “such as ‘psychosis’ or just ‘madness,’ [which] would be preferable because they are less strongly associated with the disease model, and enable the uniqueness of each individual’s situation to be recognized.”
The Schizophrenia “Gene Pond” Is Empty
Schizophrenia gene finding attempts appear to date back to a 1958 French study. Countless gene discovery claims have been published since then, especially since the late 1980s, only to be relegated to the rapidly expanding psychiatric genetics “graveyard” of false positive results. In 2008 schizophrenia researcher Timothy Crow wrote—50 years after the French study was published—that molecular genetic researchers investigating disorders such as schizophrenia had previously thought that “success was inevitable—one would ‘drain the pond dry’ and there would be the genes!” He concluded, however, that “the pond is empty.”
Numerous gene discovery claims have appeared since 2008, including one published in the prestigious journal Nature in 2014 in which researchers believed that they identified 108 regions of the genome associated with schizophrenia. There have been other highly publicized claims, such as the Sekar et al. 2016 C4 “synaptic pruning” study, also appearing in Nature, which Balter discussed in some detail. Another group claimed that thousands of genes are “associated with” schizophrenia, and more claims will surely appear in the future.
Despite having obtained “samples from more than 900,000 subjects” worldwide, coupled with the development of newer techniques such as the polygenic score (PGS) method, there have been no confirmed discoveries of genetic variants shown to play a role in causing schizophrenia or psychosis. (Problems with the PGS method are discussed HERE, HERE, HERE, and HERE.) Balter quoted a leading genetic researcher who admitted that “people working in the schizophrenia genetics field have greatly overinterpreted their results.” Researchers, laboratories, and universities are no doubt aware that public statements of discovery, optimism, and excitement attract more research funding, publications in leading journals, and prestige than do public statements of failure, disappointment, and frustration.
The schizophrenia “gene pond” therefore remains empty of causative genes, or contains only false-positive “fool’s gold,” as psychiatry continues to suffer from its decades-long “nonreplication curse” of false-positive results. “At best,” Balter wrote, “the tangled genetic landscape of schizophrenia is…a series of faint hints of what causes the illness.” Yet elsewhere in the article he suggested that some genes have already been “identified,” and he quoted without comment a leading researcher who claimed that genetics has provided “the first hard biological leads in understanding schizophrenia.”
News Media “Hype”
Balter wrote that despite the news media’s tendency towards “overzealous enthusiasm,” given the historic “trail of disappointment” left by schizophrenia genetic research, media “hype” surrounding recent claims is “somewhat understandable.” On the contrary, because previous claims did not hold up, a healthy media response to new claims would not be enthusiasm or hype, but extreme skepticism and caution—similar to the “oh no, not again” skepticism and caution Peanuts comic strip character Charlie Brown responded with whenever Lucy van Pelt asked him to kick the football she was holding. The five corporations that control much of the U.S. media have an obvious agenda of promoting medical and genetic approaches, and dubious behavioral gene discovery claims, and of downplaying or ignoring the half-century history of claims that fell by the wayside. A parallel process occurs when the corporate media “hypes” wars, and other policies that favor corporate interests at the expense of people’s health, emotional well-being, and lives.
Genetic Theories of Schizophrenia Are Based on Faulty Research and False Assumptions
This brings us to the question of why, despite these failures, researchers continue to claim that schizophrenia is a “highly heritable disorder.” The answer lies in their belief that previous family, twin, and adoption studies have provided definitive proof of schizophrenia’s strong genetic foundation. Echoing the mainstream position, Balter wrote, “Decades of family and twin research suggest a strong genetic component to schizophrenia risk.” However, genetic interpretations of family studies are invalid because the members of the experimental group experience much more similar environments than do the members of the comparison (control) group, and the same holds true for twin studies.
Twin researchers originally assumed that reared-together MZ twins (monozygotic, identical) and DZ twins (dizygotic, fraternal) grow up experiencing similar environments (the MZ-DZ “equal environment assumption,” or EEA). The evidence, however, overwhelmingly shows that MZ pairs grow up experiencing much more similar environments and much higher levels of identity confusion, attachment, and emotional closeness, than experienced by DZ pairs. Most leading twin researchers long ago conceded the point that MZ environments are more similar than DZ environments. But instead of abandoning the twin method because its key theoretical assumption is false, as they should have, they devised illogical arguments in support of the EEA, and genetic theories and approaches remained intact. Authoritative psychiatric textbook authors, schizophrenia experts, science writers, and the media then endorse the original twin researchers’ conclusions, and rarely challenge the illogical arguments they put forward in support of these conclusions.
Furthermore, as I describe in detail in Schizophrenia and Genetics, the famous 1960s-1990s Danish-American schizophrenia adoption studies by American psychiatric genetic researchers Seymour Kety, David Rosenthal, Paul Wender and their Danish colleagues were flawed and biased to an extreme degree. It is only necessary to carefully read their publications with a critical eye, as several largely ignored critics have done over the past 50 years, to see that these researchers manipulated diagnoses, data, and group comparisons in order to obtain the desired genetic findings. The broad term now used to describe this practice is p-hacking, which includes various forms of scientific manipulation, misconduct, or fraud (see Chris Chambers’ 2017 book The Seven Deadly Sins of Psychology).
In addition, psychiatric adoption studies are subject to several major environmental confounds and biases. These include (1) the selective placement of adoptees on the basis of a child’s socioeconomic status and perceived genetic background; (2) the shared birthmother–child prenatal environment; (3) late separation from the birthparent(s); (4) late placement with the adoptive family; and (5) that birthparents who give up a child for adoption, and the adoptive parents who reared them, are not representative of birthparents and rearing parents in general. It therefore is not true, as adoption study supporters usually claim, that these studies are able to make a clean separation between (“disentangle”) the potential influences of genes and environments. Surprisingly, Balter did not mention adoption studies in his article.
It is telling that the American Psychiatric Association (APA), which since 1970 has created nearly 30 “task forces” to examine various issues, has never created one charged with performing an in-depth critical evaluation of the methods and assumptions of psychiatric family, twin, and adoption studies. As the schizophrenia gene-discovery bubble continues to burst, the creation of such a task force would be the order of the day in a vibrant scientific field in a healthy society, but would be off-limits in a stagnant field corrupted by a cozy relationship with Big Pharma, in a similarly corrupted corporate-controlled government and society.
Not a Setback, But a Cause for Celebration
Although Balter discussed the importance of environmental factors, and highlighted the controversies surrounding the EEA and the heritability concept, he left the leading role to molecular genetic approaches. The large graphic accompanying his article was about genes and molecular genetic research, not about environments. This suggests to the average reader that schizophrenia is a genetically based condition, in need of medical approaches to its treatment and prevention. Pictures and diagrams send powerful messages. Balter supported medical approaches while adding that environmental factors should supplement and be incorporated into these approaches. The genetic researchers whose work he highlighted believe that the failure to discover causative genes is a scientific setback. I argue that it is a cause for celebration, as society can now part ways with costly and diversionary genetic and medical approaches, and can instead focus on environmental causes, social interventions, non-medical treatment approaches, and prevention. (I strongly recommend the 2013 book Models of Madness: Psychological, Social, and Biological Approaches to Psychosis, second ed., edited by John Read and Jacqui Dillon.)
The time has come to halt the massive failure that has characterized schizophrenia molecular genetic research, and to thoroughly reassess what critics have always said are the severely flawed family, twin, and adoption studies that inspired and helped justify this research. The evidence in favor of environmental causes, coupled with the lack of evidence in favor of biological and genetic causes, supports a psychological/sociological/environmental understanding of “schizophrenia” and psychosis. Although Balter wrote that the “biological basis” of schizophrenia “has long been an enigma,” it is better characterized as a century-old unsupported hypothesis that helps form the bedrock of psychiatric dogma. Balter did give more weight to environmental factors than most other journalists and commentators, but he is in favor of continuing with attempts to identify predisposing genes. While these attempts are based on some researchers’ misguided belief that “social problems are biology problems,” the causes of the behaviors falling into the “schizophrenia” and psychosis categories are located outside of the body, not inside.
Jay Joseph, Psy.D. is a clinical psychologist practicing in the San Francisco Bay Area. He is the author of four books, most recently The Trouble with Twin Studies: A Reassessment of Twin Research in the Social and Behavioral Sciences (2015), and Schizophrenia and Genetics: The End of an Illusion (2017). His online articles can be found at the Mad in America website, and at https://thegeneillusion.blogspot.com/.
Notes:  Balter, M., (2017, May), Schizophrenia’s Unyielding Mysteries, Scientific American, 56-61.  Kirk, S. A., & Kutchins, H., (1992), The Selling of DSM: The Rhetoric of Science in Psychiatry New York: Aldine De Gruyter.  Kirk, S. A., Gomory, T., & Cohen, D., (2013), Mad Science: Psychiatric Coercion, Diagnosis, and Drugs, New Brunswick, NJ: Transaction; Hill, D., (1983).  Moncrieff, J., & Middleton, H., (2015), Schizophrenia: A Critical Psychiatry Perspective, Current Opinion in Psychiatry, 28, 264-268.  A 1958 French schizophrenia molecular genetic study by J. K. Constantinidis was cited in McGuffin, P., & Sturt, E., (1986), Genetic Markers in Schizophrenia, Human Heredity, 36, 65-88, p. 80.  Crow, T. J., (2008), The Emperors of the Schizophrenia Polygene Have No Clothes, Psychological Medicine, 38, 1681-1685, p. 1682.  Schizophrenia Working Group of the Psychiatric Genomics Consortium, (2014), Biological Insights from 108 Schizophrenia-Associated Genetic Loci, Nature, 511, 421-427.  Sekar et al., (2016), Schizophrenia Risk from Complex Variation of Complement Component 4, Nature, 530, 177-183.  Former American Psychiatric Association (APA) President Jeffrey Lieberman fittingly called past false-positive gene discovery claims “fool’s gold.” See Lieberman, J., & Ogas, O., (2016, March 3rd), Genetics and Mental Illness—Let’s Not Get Carried Away, Wall Street Journal.  The term “replication curse” was used in Faraone, S. V., (2013), Real Progress in Molecular Psychiatric Genetics, Journal of the American Academy of Child and Adolescent Psychiatry, 52, 1006-1008.  Joseph, J., (2015), The Trouble with Twin Studies: A Reassessment of Twin Research in the Social and Behavioral Sciences, New York: Routledge.  Twin researchers have also failed to assess the impact of identified environmental factors related specifically to schizophrenia and psychosis, which are more similarly experienced by MZ as opposed to DZ twin pairs. See Fosse R., Joseph J., & Richardson, K., (2015), A Critical Assessment of the Equal Environment Assumption of the Twin Method for Schizophrenia, Frontiers in Psychiatry, 6:62, DOI: 10.3389/fpsyt.2015.00062  See also Joseph, J., (2004), The Gene Illusion: Genetic Research in Psychiatry and Psychology Under the Microscope, New York: Algora, Chapter 7, for a critical analysis of schizophrenia adoption research.  Joseph, J., (2017), Schizophrenia and Genetics: The End of an Illusion, e-book.