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16 September, 2003

To: Bruce Spring, M.D.
Department of Psychiatry
Room 209 IRD
LAC+USC Medical Center
2020 Zonal Avenue
Los Angeles, CA 90033-1011

Dear Dr. Spring,

It has been brought to our attention that, in a recent conversation with supporters of the MindFreedom Support Coalition International hunger strike, you stated that "the Danish twin study" supplied important evidence supporting the APA's position that schizophrenia is caused by biological factors. As members of the Panel of Experts supporting the strikers, we subsequently sent you an e-mail requesting that you provide us with a reference for this study. Unfortunately, in an e-mail dated 9/10/2003, you replied, "I do not have that reference readily available, and regrettably I do not have the time to seek it out for you. As the study is fairly widely known, it may well be among the references already provided to your organization by the APA." Because you are unable to provide a reference, we take this opportunity to briefly respond to your original verbal comment on the "Danish twin study."

Of the 15 schizophrenia twin studies, one was performed in Denmark. The investigator was Margit Fischer, who in 1973 found pairwise schizophrenia concordance rates of monozygotic (MZ) 36%, and dizygotic (DZ) 18% (using the probandwise concordance method and a wider definition of schizophrenia, Fischer reported higher rates). The other 14 studies also found higher concordance rates among MZ versus DZ twins. Fischer's study merely adds to this finding, and is rarely cited as a particularly noteworthy study when compared with the others. Moreover, although rarely mentioned in psychiatry textbooks, conclusions about genetic factors derived from MZ/DZ comparisons are confounded by the much more similar physical, psychological, social and treatment environments experienced by MZ twins. Almost every study looking into the matter has found that MZ environments are much more similar than DZ environments. Because twin studies are as confounded by environmental factors as family studies, there is no valid reason to accept that psychiatric twin studies measure anything other than the more similar environments of MZ versus DZ twins, plus error and bias.

It is also possible that you were referring to the Danish schizophrenia adoption studies of Seymour Kety, David Rosenthal, Paul Wender, and their Danish associates, whose original publications appeared in the 1960s and 70s. Unlike Fischer's Danish twin study, these adoption studies are frequently cited in support of genetic and biological influences on schizophrenia. However, the authors of several critical investigations have shown that these studies are far too flawed to be able to conclude that they support the genetic/biological argument (Boyle, 1990; Breggin, 1991; Cassou et al., 1980; Colbert, 2001; Joseph, 2001, 2003; Lewontin et al., 1984; Lidz, 1976; Lidz & Blatt, 1983; Lidz et al., 1981; Pam, 1995). One member of the Panel has recently published a detailed examination of all schizophrenia adoption studies, where he concluded that their numerous flaws and doubtful assumptions invalidate any conclusions in favor of genetics (Joseph, 2003). The following bulleted list highlights flaws which, taken together, invalidate genetic findings from the Danish adoption studies:

• The Danish-American investigators widened the definition of schizophrenia to include non-psychotic "schizophrenia spectrum disorders." Not only was this procedure questionable, there is no published evidence that Kety and colleagues arrived at this expanded definition of schizophrenia before adoptees were diagnosed and relative diagnoses were assigned to their respective categories The studies would not have found statistically significant differences without greatly expanding the definition of schizophrenia. Among the 65 identified first-degree biological relatives of adoptees diagnosed with a spectrum disorder in the Kety et al. 1968 study, not one was diagnosed with chronic schizophrenia (Kety et al., 1968, p. 354). In Rosenthal and colleagues study (Rosenthal et al., 1971), only 1 of the 76 adopted-away biological offspring of parents diagnosed with a schizophrenia spectrum disorder had received a hospital diagnosis of schizophrenia.

• The investigators used inconsistent and biased methods of counting relative diagnoses.

• Second-degree biological relatives were counted with the same weight as first-degree biological relatives.

• No information was provided on the life histories or environmental conditions experienced by adoptees and relatives.

• The investigators' most important conclusions were derived from counting relatives individually, even if they were reared in the same family. Because family members are more similarly exposed to environmental and rearing factors, this procedure violates the assumption of independent observations underlying the statistical procedures used (Benjamin, 1976).

• It is clear that the investigators' bias in favor of genetic explanations had an important influence on their methods and conclusions.

• In the Rosenthal et al. study, manic depressive disorder was included in the schizophrenia spectrum despite the investigators' insistence elsewhere that this condition is genetically unrelated to schizophrenia (for example, see Kety et al, 1976; Rosenthal, 1971).

• The Danish-American investigators used substandard interviews to make diagnoses. In the Kety et al. studies many of the "interviews" never occurred, and were simply fabricated by the investigators (Lewontin et al., 1984; Kendler & Gruenberg, 1984). In the raw data they were called "pseudo-interviews" by Kety et al., but no mention of them appeared in any of the Danish-American investigators' publications. Of the interviews that were conducted, a five-minute doorstep conversation sometimes was deemed sufficient to diagnose someone with schizophrenia (see Paikin et al., 1974, pp. 308-310).

• According to Wender et al., the purpose of their Danish "Crossfostering" study was to answer the question, "Can psychopathology in rearing parents produce psychopathology in the offspring when the offspring do not carry a genetic load for schizophrenia?" (Wender et al. 1974, p. 122). Problems with Wender's study include, (1) the use of global mental health ratings in place of diagnosing schizophrenia, (2) the use of post-hoc comparisons which were used to support the genetic position, (3) the failure to find statistically significant differences between important comparison groups, (4) the investigators' failure to consider alternative explanations of their results, and (5) that the mean age of the crossfostered adoptees at the time their adoptive parents were diagnosed with a spectrum disorder was 12-years-old (based on a subsample reported by Van Dyke et al., 1975). By the 1980s, Wender himself would admit that, in his 1974 study, "the question of what would happen if children born of normal parents were placed in the homes of typical schizophrenics cannot be answered" (Wender & Klein, 1981, p. 175).

• The most important problem in all Danish adoption studies, however, is the likelihood that the selective placement of adoptees confounded the results. Adoption study results are based on the assumption that factors relating to the adoption process (including the policies of adoption agencies) did not lead to the placement of index adoptees into environments contributing to a higher rate of the condition or trait in question. The investigators assume that selective placement did not occur in their sample, meaning that children were not placed into homes correlated with the psychiatric status of their biological family. It is unlikely that this condition was met, however, because during the period when the adoptees were placed (1924-1947), eugenic ideas in Denmark were very strong and the sterilization of people diagnosed with schizophrenia was permitted by law (Hansen, 1976; Joseph 2003). Moreover, it is clear that Danish adoption agencies of the time used the psychiatric status of a potential adoptee's biological family as a matching criterion (Mednick & Hutchings, 1977). Thus, the higher rate of spectrum diagnoses among index versus control biological relatives found in the Danish adoption studies might reflect little more than the agencies' placement of children with "schizophrenia-tainted" biological relatives into more psychologically harmful adoptive homes. Environmental and psychosocial theories of schizophrenia postulate, and empirical evidence confirms (Tienari et al., 1987), that these types of homes are more likely to produce psychologically unstable (and possibly "schizophrenic") adults.

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