Troubling Twin Studies

©: lightwise | 123RF.com

©: lightwise | 123RF.com

In 2004, Paula Bernstein received a call from the agency where she had been adopted. The message was that she had a twin who was looking for her. Elyse Schein—Paula’s twin—had been trying to find out information from the adoption agency about her birth mother when she learned she had a twin sister. They met for the first time in a café in New York City. They talked through lunch and dinner about the 35 years they had been apart. Among the things they discussed was why they were separated at five months old. It seems they were part of a one-of-a-kind study on nature versus nurture of twins separated at birth.

All Things Considered” said the study was headed up by Peter Neubauer, a noted child psychiatrist and Viola Bernard, a child psychologist. The study ended in 1980, a year before the state of New York began requiring that agencies keep siblings together. Neubauer realized that public opinion would be against the study so he didn’t publish it. The data and results have been sealed until 2066 and placed in an archive at Yale University.

The sisters tried to reach Neubauer, but he initially refused to speak with them. Eventually he did agree to meet with them. Paula hoped he would apologize for separating them. Instead he showed no remorse and offered them no apology.

Of the 13 children involved in his study, three sets of twins and one set of triplets have discovered one another. The other four subjects of the study still do not know they have identical twins.

Since the 1920s, researchers in psychology and psychiatry have used twin research (but not the above method) to assess the potential for genetic factors to underlie psychological traits and psychiatric disorders. In the Introduction to his new book, The Trouble with Twin Studies, Jay Joseph noted how this research method is seen as a scientifically valid research method that provides an ideally suited “natural experiment” to assess the relative importance of heredity and environment. According to one estimate, about 800,000 twin pairs had been studied by 2009. “In almost all cases these studies are based on twin pairs reared together in the same family, while an extremely small yet influential handful of studies, twin pairs were said to have been reared apart in different families.”

MZ (monozygotic, identical) twins have 100% of the same genes, where DZ (dizygotic, fraternal) twins share around 50%. Twin researchers have argued that the greater similarity between MZ pairs for behavioral traits and disorders (physical and psychiatric) than same-sex DZ pairs is caused by the greater genetic resemblance of the MZ pairs. Therefore, twin researchers reason, “the trait or the disorder has an important genetic component.” Underlying this is the basic assumption of the twin method, that MZ and DZ twin pairs experience equal environments.

Yet, even twin researchers have concluded that MZ pairs experience more similar environments than DZ pairs. Jay Joseph quoted twin researchers as saying, “the evidence of greater environmental similarity for MZ than DZ twins is overwhelming.” Nevertheless, twin researchers have perpetuated the twin method by using circular reasoning, denying ignoring or downplaying the evidence that MZ and DZ environments are different or changing the definition of what constitutes an equal environment.

In an article that was also titled: “The Trouble with Twin Studies,” Joseph noted how the circular argument in effect says that identical pairs “create” more similar environments because they are more similar genetically. When 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 tactic used to support the twin method is to first agree that identical twins grow up in more similar environments than fraternal twins. But then proponents say that it has to be demonstrated that identical and fraternal environments differ in ways that are relevant to the trait in question. If that cannot be done, then they argue the equal environment assumption is valid for that trait.

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 Joseph’s article, “Five Decades of Gene Finding Failures in Psychiatry”]—research that is based largely on genetic interpretations of the results of psychiatric twin studies.

There are a handful of studies whose twin pairs were supposedly reared apart from one another in different families. Advocates of twin studies assert that all behavioral similarities between reared-apart MZ twins (known as MZA pairs) must be the result of their 100% genetic similarity, since they have not had any environmental similarities.  Joseph said in “Studies of Reared-Apart (Separated) Twins: “Twin researchers and others view this occurrence as the ultimate test of the relative influences of nature (genes) and nurture (environment).”

Yet there were a variety of problems with these twins reared-apart (TRA) studies. Many twins experienced late separation and many twins were reared together in the same house for several years. Others had regular contact and/or a close emotional bond with each other. In one classic TRA study, twins separated as late as 9-years-old, or for only five years during childhood were counted as “separated twin pairs.” The same study counted a pair living next door to one another, brought up by different aunts, as a separated pair.

Far from being separated at birth and reared apart in randomly selected homes representing the full range of potential behavior-influencing environments, and meeting each other for the first time when studied, most MZA pairs were only partially reared apart, and grew up in similar cultural and socioeconomic environments at the same time.

In 1990, Peter Neubauer coauthored a book with his son, Alexander entitled: Nature’s Thumbprint. Within the Introduction was a tantalizing hint to what may have been information from Neubauer’s archived study. Father and son said that many years ago an opportunity arose to follow the development of identical twins from infancy. “With great curiosity a number of us decided to study the influence of the environment on the child.” No other identical twin study had explored twins reared apart as they matured and developed from birth on.

We could look at change as it happened. We would be there at birth and continue regular, intensive observations of separated twins and study their relationship with parents and siblings, collecting as much information as possible about behavior and growth. . . . In fact, it was our assumption that only by studying development as it happened could these disorders be accurately understood. Our study would therefore be useful to the investigation of both healthy and pathological growth, as well as to the ways the environment influences that growth.

Twin studies do not provide definitive evidence for the genetic basis of psychiatric conditions. The twin method is no more able to tease apart the potential roles of genetic and environmental influences for behavioral traits and “disorders” than family studies. As Jay Joseph noted, both research methods are confounded by environmental factors and should be evaluated in the same way: “neither provides scientifically acceptable evidence in support of genetic influences on psychiatric disorders and behavioral traits.”


Chasing Ghosts

© : Vera Kuttelvaserova Stuchelova | 123RF.com

© : Vera Kuttelvaserova Stuchelova | 123RF.com

Jay Joseph, a licensed psychologist, has written extensively on the failure of researchers to find scientific evidence that even one psychiatric condition has a genetic basis. In “The Crumbling Pillars of Behavioral Genetics,” he followed the history of failed predictions by Robert Plomin, a genetics researcher, who claimed repeatedly that we were “at the dawn of a new era” in molecular genetics; that “genes associated with behavioral dimensions and disorder are beginning to be identified;” that “within a few years psychology will be awash with genes associated with behavioral disorders.” So far, Plomin and other researchers have got nothing.

Despite the hope that the Human Genome Sequencing Project would “revolutionize the understanding, diagnosis and treatment of most human disorders,” acknowledged polymorphisms (common gene variants) for psychiatric conditions are still nonexistent. In “Still Chasing Ghosts,” Evan Charney said: “Not a single polymorphism has been reliably associated with any psychiatric conditions nor any aspect of human behavior within the ‘normal’ range.” Instead, researchers in psychiatry see schizophrenia and other psychiatric conditions as “multifactorial complex disorders,” meaning that they are caused by a complex interaction of multiple genes and environmental risk factors.

Within an editorial announcing that changes to the journal Neuropsychiatric Genetics, S.S. Farone et al. proudly announced that their journal “has become a leading venue for the publication of high quality research on the genetic basis of neuropsychiatric phenotypes.” But they also acknowledged: “It is no secret that our field has published thousands of candidate gene association studies but few replicated findings.” Joseph commented that in a practical sense, these results are a secret. After the initial results are hyped in the media, the replication failures rarely receive the same media attention. See “The Reproducibility Problem.”

The public has been misled by sensationalized reporting in the popular press, often in concert with leading researchers, to believe that genes for the major psychiatric disorders have been found.

Reluctant to believe the foundational heritability estimates were wrong, genetic researchers have instead hypothesized there is “missing heritability.” Proponents of this position argue that genes (heritability) are present, but cannot be identified (are “missing”) because each gene has such a small effect. So small in fact, that its effect cannot be identified by standard genome-wide association studies (GWAS). Joseph noted that by the summer of 2011 this failure to discover genes underlying psychiatric disorders led 96 of the leading psychiatric researchers to publically plead for potential funding sources to not “give up” on GWAS.

As Joseph pointed out in “Five Decades of Gene Finding Failures in Psychiatry,” the belief in “missing heritability” ignores the possibility that previous conclusions from family, twin and adoption studies could be wrong, all the while assuming that the genes have to exist. Despite evidence that many people diagnosed with “schizophrenia and other psychotic disorders are impacted by trauma, abuse, and other adverse experiences,” there continues to be an almost exclusive focus on “the genetic and biological bases of psychosis.” He suggested that although some researchers claim that several genes for the major psychiatric disorders have now been discovered, “these claims are likely to suffer the same fate as similar non-replicated claims we have heard for decades.” He then quoted John Horgan, a science journalist, who said that since 1990:

Researchers have announced the discovery of ‘genes for’ attention-deficit disorder, obsessive-compulsive disorder, manic depression, schizophrenia, autism, dyslexia, alcoholism, heroin addiction, high IQ, male homosexuality, sadness, extroversion, introversion, novelty seeking, impulsivity, violent aggression, anxiety, anorexia, seasonal affective disorder, and pathological gambling. So far, not one of those claims has been confirmed.

Evan Charney and Jay Joseph (Twin Studies and the “Nonreplication Curse”) described a new methodology, the genome-wide complex trait analysis (GCTA), which has been developed to replace the problems with GWAS. Like a typical GWAS, GCTA scans hundreds of thousands of polymorphisms of thousands of persons. But it does not identify which SNPs [single-nucleotide polymorphisms, common types of genetic variation] are responsible for a trait. Rather, it estimates the total genetic variance by comparing the genetic profiles of a large group of unrelated people. “In other words, it can produce a ‘finding’ of genes even when no specific genes are identified.”

Joseph indicated the GCTA method, like the GWA studies, is based upon two faulty assumptions: 1) the validity of heritability estimates for human behavioral traits and 2) that twin studies and adoption studies have established the genetic basis of psychiatric disorders.

Charney noted that the twin study methodology has been critiqued for making faulty assumptions, like assuming that the environments of MZ (identical) twins were no different than those of DZ (fraternal) twins. In fact, several studies have shown that MZ twins have more similar environments than DZ twins. The equal environment assumption was shown to be false. This environmental difference means that: “trait similarities ascribed to the greater genetic similarity of MZ twins might in fact be due to greater environmental similarity, significantly inflating heritability estimates.” In The Journal of Mind and Behavior, Joseph commented that:

Conclusions in favor of genetics based on twin studies (as well as family studies) were confounded by environmental factors, suggesting that the twin method should have been discarded as an instrument for the detection of genetic influence.

Charney suggested that chasing these “polymorphisms of tiny effect,” in ever-larger studies involving hundreds of thousands of persons, “is the last gasp of a failed paradigm.” It is like chasing ghosts. “Do we really want to squander our time and resources chasing ghosts?”