Friday, March 15, 2013

Psychiatric Genetics: The Trouble With Twin Studies

Mad In America has;
The Trouble With Twin Studies

March 13, 2013

As most readers are aware, it is widely believed that both within and without of psychiatry genetic factors play an important role in causing major psychiatric disorders such as schizophrenia, bipolar disorder, major depression, ADHD, autism, anxiety, and even post-traumatic stress disorder (PTSD). Twin studies provide the main pillar of support for this belief which is often, though mistakenly, presented as a scientific fact.
The mainstay of twin research is the “classical twin method,” developed in the 1920s, in which researchers compare the trait resemblance of reared together identical twin pairs (MZ, monozygotic) versus reared together same-sex fraternal (DZ, dizygotic) twin pairs. If identical pairs (who share a 100% genetic similarity) resemble each other more than fraternal pairs (who share an average 50% genetic similarity) for the disorder or trait in question, twin researchers conclude that the disorder or trait has an underlying genetic component. They arrive at this conclusion on the basis of several theoretical assumptions about twins, the most important and controversial of which is the assumption that identical and same-sex fraternal twin pairs grow up experiencing roughly equal environments. This is known as the “equal-environment assumption” (EEA) of the twin method. Psychiatric twin studies are based on twin pairs reared together in the same home, and in most cases identical pairs resemble each other more for psychiatric disorders and behavioral traits than do fraternal pairs.
Although the authors of psychiatry and psychology textbooks and other mainstream publications usually endorse genetic interpretations of psychiatric twin studies uncritically, there is a fatal flaw underlying these studies: identical twin pairs grow up experiencing much more similar environments than experienced by same-sex fraternal pairs, meaning that the equal environment assumption — upon which all conclusions in favor of genetics are based — is false. Therefore, many critics have argued that it is likely that identical-fraternal comparisons capture nothing more than identical pairs’ more similar treatment, greater environmental similarity, stronger attachment and emotional bond, and greater levels of identity confusion (feeling like they are two halves of the same whole).
Remarkably, since the 1960s most leading twin researchers have conceded the point that identicals experience more similar environments than fraternals. However, instead of relegating the twin method to a place alongside other discarded pseudosciences, twin researchers have attempted to validate the twin method by subtly redefining the equal environment assumption (EEA). The main way they have done this has been to argue that although identicals do indeed experience more similar environments than fraternals, identical pairs “create” or “elicit” more similar environments for themselves because they are more similar genetically.1 However, this “twins create their own environment” argument is a circular one, because twin researchers’ conclusion that identical pairs behave more similarly because they are more similar genetically is based on the assumption that identical pairs behave more similarly because they are more similar genetically. This means that twin researchers’ position that genetic factors explain the greater behavioral resemblance of identical twin pairs is, illogically, both a conclusion and a premise of the twin method. In defending the validity of the twin method, modern twin researchers refer to the premise in support of the conclusion, and then refer back to the conclusion in support of the premise, in a continuously circular loop of faulty reasoning.
Another argument twin researchers put forward in support of the equal environment assumption is that, while again conceding that identicals grow up experiencing more similar environments than fraternals, in order to invalidate the EEA it must be shown that identical and fraternal environments differ in aspects that are relevant to the trait in question. This is known as the “trait-relevant” definition of the equal environment assumption. (For example, witnessing trauma is a trait-relevant environmental factor contributing to PTSD.) However, even if it is shown that identical pairs experience more similar trait-relevant environments than fraternal pairs, twin researchers could still argue (and have argued) in favor of the validity of the twin method and the equal environment assumption by reverting to their previous circular argument that identical pairs “create” or “elicit” more similar “trait-relevant” environments for themselves because they are more similar genetically.2
In addition, there are many other methodological problems and unsupported assumptions associated with the twin method, which critics have described since its development nearly 100 years ago.3
The question of whether the twin method is a valid instrument for the detection of genetic influences comes down to two basic positions, which have been put forward by twin researchers and their critics respectively: (1) based on the acceptance of the equal environment assumption, the greater behavioral similarity of identical versus fraternal twin pairs demonstrates that important genetic influences underlie variation in most human behavioral traits; or (2) based on the rejectionof the equal environment assumption, the greater behavioral similarity of identical versus fraternal twin pairs is caused by non-genetic influences.
The bottom line is this: despite being cited in countless textbooks, scholarly journal publications, and popular books and articles, the little-disputed finding that identical pairs experience much more similar environments than fraternal pairs means that non-genetic factors plausibly explain twin method results. The fact that psychiatric twin studies continue to be cited in support of genetics, largely uncritically, speaks volumes about the scientific status of psychiatry in the 21rst century. Psychiatry’s acceptance of twin studies is even more remarkable in the context of the decades-long failure of molecular genetic research to uncover genes that investigators believe cause psychiatric disorders (see my February 15th MIA posting)—research that is based largely on genetic interpretations of the results of psychiatric twin studies.
In 2011, journalist Brian Palmer wrote an article in an edition of the U.S.-based online magazineSlate, entitled “Double Inanity: Twin Studies are Pretty Much Useless.”4 This article, which as its title suggests was critical of twin research, produced over one hundred comments, mainly in opposition to what Palmer wrote. Although Palmer’s conclusion that the assumptions underlying the twin method are “deeply flawed” is accurate, his article had some glaring holes in it, which opened the field for the critics.
Twin researcher Nancy L. Segal and her colleagues, including behavioral geneticist Eric Turkheimer and longtime twin researchers Irving Gottesman and Nicholas Martin, provided their own response to Palmer in an online comment entitled “The Value of Twin Studies: A Response to SlateMagazine.” Segal and colleagues wrote that Palmer’s article was “one of the most inaccurate, misleading and uninformative essays on twin research to come along in a while.” Regardless of their opinion of the article, it doesn’t necessarily follow that Palmer’s conclusion that twin studies are “useless” for detecting genetic influences is wrong. Segal and colleagues referred to themselves as “scientists who have been involved in twin research for decades,” and signed their response using the title “Dr.” before their names, invoking the authority of Ph.D. level experts in twin research and implying that they deserve to have the authoritative last word on the validity of the twin method. “The Value of Twin Studies” was subsequently reposted in Segal’s Psychology Today “Twofold” blog, and was published in the journal Twin Research and Human Genetics with a some additional comments by Segal.5
Segal and colleagues attempted to answer some of Palmer’s main points while presenting twin researchers’ typically weak arguments in support of the equal environment assumption and the twin method, based on how the EEA supposedly has been tested and validated by other twin researchers. The flaws of Palmer’s article provided Segal and colleagues with an opportunity to successfully counter some of his points, but in general their argument was largely based on the implied authority of these eminent twin researcher co-authors. However, appeals to authority of this type do not validate twin research any more than the existence of heaven and hell would be validated by an open letter authored by the College of Cardinals proclaiming that they exist.
After reprinting “The Value of Twin Studies” in her Twin Research and Human Geneticspublication, Segal mentioned two articles by a pair of critics “unsympathetic to twin research.”6 She wrote that “such work should not go unanswered by our membership,” referring to the International Society for Twin Studies (ISTS). Despite calling on her colleagues to answer the critics, in practice Segal and colleagues grabbed the low hanging fruit of a journalist’s weak attempt to critique twin research, while continuing to largely ignore or dismiss detailed scholarly critical assessments of twin research by others. Although Segal and other twin researchers at times discuss selected arguments by “critics,” they often fail to answer detailed arguments by specific critical experts.7
During the past 15 years, in two books and several peer reviewed articles and chapters, I have described the methodological errors and false theoretical assumptions underlying twin research.8 Segal is well aware of my work, having referred to me by name in her most recent book as a “harsh critic of behavior genetics” and citing some of my publications.9 And in a different publication Turkheimer referred to a textbook chapter I wrote in 2010 that included a detailed critique of the twin method and its assumptions.10
Even in the context of the responses to Palmer’s Slate article, Segal failed to answer serious criticism of the twin method and the equal environment assumption. Following Palmer’s article, I posted several online comments outlining the main problems with twin studies, as did psychologist Ken Richardson. Following this, Segal posted “The Value of Twin Studies,” which failed to specifically address these points. Segal and colleagues took offense to Palmer’s (overstated) claim that “One of the main messages of science over the last couple of decades is that genes are destiny.” They angrily asked, “Who exactly is supposed to have said this?” In response, I quoted four leading genetic researchers who did make published statements implying that genes are all-important, including Nobel Laureate James D. Watson’s 2003 forward to a behavioral genetics textbook published by the American Psychological Association, where he wrote, “The older one gets…the more most of us conclude that children come into the world with fixed personalities that are hard to ascribe to specific home or school environmental influences. Particularly happy children almost seem to be born that way.” There were no responses to my postings by Segal or her colleagues. This prompted commenter (and MIA blogger) Jonathan Leo to write,
“This is a great discussion, but I think it is only fair that once a researcher like Dr. Segal decides to enter a discussion like this, especially when they have very harsh words for those who disagree with her, that it is only proper that they also reply to those, like Jay Joseph, who point out the problems in their logic. Take Dr. Segal’s first point that the idea that genes are destiny is ‘a grotesque caricature of genetic research in general and twin studies in particular.’ Joseph pretty much shows that this is not at all a caricature and that indeed there are prominent researchers who do have this view. If researchers [such as Segal, Turkheimer and colleagues] are going to come down from the ivory tower and take pot shots, then they should also be willing to take the heat and defend their ideas when someone as knowledgeable as Joseph also enters the discussion.”
Yet Segal and the others did not respond, even after Jonathan Leo publically challenged them to do so.
Following Segal’s reposting of “The Value of Twin Studies” in her Psychology Today blog, on September 7th, 2011 Ken Richardson and I posted a response where we highlighted the main arguments against the equal environment assumption, including the position that the twin method is based on a circular argument. Neither Segal nor any other twin researcher responded to our posting, which as I mentioned appeared in connection to her own Psychology Today blog. This failure to respond flies in the face of Segal’s position that such criticism “should not go unanswered” by twin researchers, and suggests that she has few convincing arguments with which to respond. In fact, I am unaware of any twin researcher attempting to argue against the published position that the twin method is based on circular reasoning. Nevertheless, Segal and her colleagues continue to uphold the validity of the twin method.
It is clear that the twin method is no more able to disentangle the potential roles of genetic and environmental influences on behavioral traits and disorders than is the finding from family studies that such traits and disorders tend to “run in the family.” Given that both research methods are confounded by environmental factors, the results of family studies and studies using the twin method should be evaluated in exactly the same way, leading to the conclusion that neither provides scientifically acceptable evidence in support of genetic influences on psychiatric disorders and behavioral traits. The acceptance of this conclusion does not mean, as twin researchers sometimes write, that the twin method might “overestimate heritability,” or that the equal environment assumption should be tested “trait-by-trait,” but rather that genetic interpretations of all twin method data produced by psychiatry and psychology, and social science fields such as political science and economics, must be rejected outright. It follows that the claim that genes play a significant role in explaining behavioral differences in these fields must undergo a thorough public reexamination.
In the spirit of her stated desire to answer the works of twin research critics, I encourage Nancy Segal and other twin researchers to respond to each and every major point that I and other critics have raised, and to engage in an ongoing public discussion of whether genetic interpretations of twin method findings should be accepted or rejected.
Citations
1 For example, see Kendler, K. S. (1983). Overview: A Current Perspective on Twin Studies of Schizophrenia. American Journal of Psychiatry, 140, 1413-1425; see also Joseph, J. (2012). The “Missing Heritability” of Psychiatric Disorders: Elusive Genes or Non-Existent Genes? Applied Developmental Science, 16, 65-83
2 Examples of twin researchers arguing in support of the equal environment assumption and the twin method by claiming that identicals’ more similar “trait relevant” environments are elicited by their greater genetic resemblance include Derks et al. (2006). A Test of the Equal Environment Assumption (EEA) in Multivariate Twin Studies. Twin Research and Human Genetics, 9, 403-411; Smith et al. (2012). Biology, Ideology, and Epistemology: How Do We Know Political Attitudes are Inherited and Why Should We Care? American Journal of Political Science, 56, 17-33; True et al. (1993). A Twin Study of Genetic and Environmental Contributions to Liability for Posttraumatic Stress Symptoms. Archives of General Psychiatry, 50, 257-264.
3 Political scientist Evan Charney argues that many previously accepted biological and genetic assumptions underlying twin research may not be true, which is “necessitating a rethinking of every one of the assumptions of the classical twin study methodology.” See Charney, E. (2012). Behavior Genetics and Postgenomics. Behavioral and Brain Sciences, 35, 331-358; quotation from Charney, E., & English, W. (2012). Candidate Genes and Political Behavior. American Political Science Review, 106, 1-34.
4 Palmer, B. (2011, August 24th). Double Inanity: Twin Studies are Pretty Much Useless. Slate.Retrieved from http://www.slate.com/articles/life/twins/2011/08/double_inanity.html
5 Segal, N. L. (2011). The Value of Twin Studies: A Response to Slate Magazine / Research Reviews / Twin News Worth Noting. Twin Research and Human Genetics, 14, 593-597.
6 The twin research critics Segal mentioned were W. Joseph Wyatt and Donna M. Midkiff. See Wyatt, W. J., & Midkiff, D. M. (2006). Biological Psychiatry: A Practice in Search of a Science.Behavior and Social Issues15, 132–151; Wyatt, W. J., & Midkiff, D. M. (2007). Psychiatry’s Thirty-Five Year, Non-Empirical Reach for Biological Explanations. Behavior and Social Issues16, 197–213.
7 Segal, like most leading twin researchers, has put forward the “twins create their own environment” defense of the twin method. For example, in 2009 she wrote, “It is important to note that if MZ twins are treated more alike than DZ twins, it is most likely associated with their genetically based behavioral similarities.” See Segal, N. L., & Johnson, W. (2009). Twin Studies of General Mental Ability. In Y. Kim (Ed.), Handbook of Behavior Genetics (pp. 81-99). New York: Springer.
8 Critical analyses of twin research that I have published since 1998 include: Joseph, J. (1998). The Equal Environment Assumption of the Classical Twin Method: A Critical Analysis. Journal of Mind and Behavior, 19, 325-358; Joseph, J. (2002). Twin Studies in Psychiatry and Psychology: Science or Pseudoscience? Psychiatric Quarterly, 73, 71-82; Joseph, J. (2004). The Gene Illusion: Genetic Research in Psychiatry and Psychology under the Microscope. New York: Algora. (2003 United Kingdom Edition by PCCS Books); Joseph, J. (2006). The Missing Gene: Psychiatry, Heredity, and the Fruitless Search for Genes. New York: Algora;  Joseph, J. (2010). Genetic Research in Psychiatry and Psychology: A Critical Overview. In K. Hood et al. (Eds.), Handbook of Developmental Science, Behavior, and Genetics (pp. 557-625). Malden, MA: Wiley-Blackwell; Joseph, J. (2012), “Missing Heritability” (see Footnote 1); Joseph, J., & Ratner, C. (2013). The Fruitless Search for Genes in Psychiatry and Psychology: Time to Re-examine a Paradigm. In S. Krimsky & J. Gruber (Eds.), Genetic Explanations: Sense and Nonsense (pp. 94-106). Cambridge, MA: Harvard University Press; Joseph, J. (forthcoming). The Use of the Classical Twin Method in the Behavioral Sciences: The Fallacy Continues. Journal of Mind and Behavior.
9 Segal, N. L. (2012). Born Together—Reared Apart: The Landmark Minnesota Twin Study.Cambridge, MA: Harvard University Press.
10 Joseph, J. (2010), “Genetic Research in Psychiatry and Psychology” (see Footnote 8); Turkheimer, E. (2011). Still missing. Research in Human Development, 8, 227-241.
11 Watson, J. D. (2003). A Molecular Genetics Perspective. In R. Plomin et al. (Eds.), Behavioral Genetics in the Postgenomic Era (pp. xxi-xxii). Washington, DC: American Psychological Association Press.
12 In psychology, so-called studies of “twins reared apart” are frequently cited in support of major genetic influences on traits such as IQ and personality. Over the years, however, critics have pointed to many potentially invalidating problems and biases found in these studies. See Joseph, J. (2001). Separated Twins and the Genetics of Personality Differences: A Critique. American Journal of Psychology, 114, 1-30; Joseph, J. (2004), The Gene Illusion (referenced in Footnote 8); Joseph, J. (2010), “Genetic Research in Psychiatry and Psychology” (referenced in Footnote 8).

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