Ernst Rüdin’s Unpublished Family Study of “Manic-Depressive Insanity” and the Genetics of Bipolar Disorder

Jay Joseph, Psy.D.
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In a previous posting I described Swiss-German “Munich School” psychiatric genetics founder Ernst Rüdin’s long career as an advocate of racial hygienic (eugenic) policies in Germany, both well before and during the National Socialist era (1933-1945). I summarized the evidence pointing to the crimes that he and others committed in the 1930s and 1940s, which included the forced sterilization of hundreds of thousands of Germans, and his later involvement in the killing of adults and children labelled “defective,” “incurable,” and “feeble-minded.”1 I also documented Rüdin’s failure to produce scientifically valid evidence in support of his belief that psychiatric conditions are caused by inherited disordered genes, a failure that continues in psychiatric genetics to the present day.

A group of researchers headed by Gundula Kösters wrote an article in November, 2015 on Rüdin’s 1920s-era family study of “Manic-depressive insanity” (now called bipolar disorder)—a study that Rüdin never published.2 Following up on his (published) 1916 schizophrenia (dementia praecox) family study, Kösters and colleagues described Rüdin’s unpublished manic-depression study as consisting of “approximately 160 pages of unbound typescript, each chapter paginated separately, with Rüdin’s hand-written corrections, and numerous large-format, hand-written charts.” The study was referenced in a 1936 article by Munich-trained British psychiatric geneticist Eliot Slater, who wrote that “the investigations of Rüdin have never been published, and [therefore] cannot be criticized.”3

The main statistical method used by Rüdin and his colleagues was the “empirical genetic prognosis” (empirische Erbprognose), which involved calculating the probability that (presumably hereditary) psychiatric disorders would eventually appear in the biological relatives and descendants of people diagnosed with these disorders. These calculations, which were based mainly on family studies and family pedigree diagrams, produced age-corrected “morbid risk” percentage figures for various groups of relatives biologically related to the diagnosed “proband.” In these studies the researchers did not assess relatives blindly, did not use control groups, and used vague and differing definitions of the psychiatric disorder in question. Moreover, as Mary Boyle has argued, it is probable that many people labeled “insane” in this era suffered from undiagnosed or unknown medical conditions such as Parkinson’s disease, and a viral infection called encephalitis lethargica.4

Like their fellow eugenicists in the United States, who based many of their theories and policy recommendations on alleged “hereditarily tainted family lines” such as the “Jukes” and the “Kallikaks,” Rüdin and his colleagues committed the crucial fallacy of assuming that hereditary factors explain the finding that psychiatric disorders tend to “run in the family.” As most contemporary psychiatric genetic and behavioral genetic researchers now understand, behavioral characteristics and disorders can run in families for environmental (non-genetic) reasons, because family members share a common environment as well as common genes. This runs-in-the-family-equals-genetic fallacy was repeated by Slater who, lacking any twin or adoption data, believed that “it is fairly certainly established” that “manic-depressive insanity” is “inheritable.” He supported acceptance of the “simplest possible theory” to account for the condition running in families, which holds that “the inheritance” is based on “a single dominant autosomal gene.”5 Previously, the founder of modern psychiatry Emil Kraepelin had written that the condition appeared to be caused by a “morbid predisposition,” and that he could establish the presence of “hereditary taint” in about 80% of the cases he investigated.6

According to Kösters and colleagues’ description of the unpublished manuscript, Rüdin’s sample consisted of 661 German “probands” from 650 families, and included 4351 siblings in total. In 566 families both parents were “healthy,” and in 84 families one parent had an affective disorder. Rüdin compared the morbid risks he calculated in these families against “the proportions expected from a Mendelian crossing in order to prove Mendelian inheritance and thereby the inheritance of affective disorders.”

Kösters and colleagues, who discussed some of the crimes Rüdin committed in the National Socialist era, concluded that Rüdin decided against publishing this study because the results did not fit his theories of Mendelian inheritance, and failed to support his advocacy of eugenic policies:

“Rüdin’s 1922–1925 study on the inheritance of ‘manic-depressive insanity’ was completed in manuscript form, but never published. It failed to prove a pattern of Mendelian inheritance, counter to the tenets of eugenics of which Rüdin was a prominent proponent. It appears he withheld the study from publication, unable to reconcile this contradiction, thus subordinating his carefully derived scientific findings to his ideological preoccupations.”

Although Kösters et al. questioned Rüdin’s decision not to publish his study, they did not question psychiatric genetic methods and theories, and considered Rüdin’s research to be “reasonably sound” by today’s standards. They also did not question contemporary claims that bipolar disorder is “highly heritable.” However, as I showed in Chapter 10 of my 2006 book The Missing Gene, genetic claims in this area, similar to claims for other diagnoses, are shaky at best. Given almost 50 years of causal gene discovery claims that were not confirmed by replication attempts,7 we must assume by default that current gene finding claims are false-positive results as well, until proven otherwise. Kösters and colleagues could not name any confirmed gene discoveries, noting that “the search for replicable gene variants leading to the onset of affective disorders continues.” Nevertheless, it is axiomatic in psychiatry that genetic factors are involved in bipolar disorder, and that they play a predominant role.

The Genetics—Or Lack Thereof—of Bipolar Disorder

As I showed in The Missing Gene, the widespread claim that bipolar disorder is “highly heritable” is based mainly on twin studies, and on two adoption studies. Readers of my previous postings are aware that I am critical of genetic interpretations of twin data in general, and of psychiatric twin data in particular.8 Genetic interpretations of twin studies are based on the utterly false assumption that MZ and DZ twin pairs grow up experiencing “equal environments,” and they are therefore invalid.9 The adoption studies are Julien Mendlewicz and John Rainer’s 1977 Belgian study, and a 1986 Danish-American study by Paul Wender, Seymour Kety, David Rosenthal and their Danish colleagues.10 Although these two adoption studies are cited in countless publications in support of the genetic basis of bipolar disorder, a close look at them suggests nothing of the kind. (A more recent study based entirely on Swedish registers and hospital diagnoses, which included adoption data, was published in 2009.11 This study showed an elevated rate of bipolar disorders among the adopted-away offspring of people with the same diagnosis, but is subject to many of the problems found in psychiatric adoption studies in general.12)

Mendlewicz and Rainer found a significantly higher rate of psychological disturbance and affective disorders among their “index” (experimental group) biological versus adoptive parents, leading them to conclude in favor of the importance of genetic influences on “manic-depressive illness.” They believed that a “comparison of adoptive parents of persons with a psychiatric disorder with their biological parents provides a unique opportunity to separate the interacting etiological roles of heredity and environment.”13

However, although overlooked by the investigators and most subsequent reviewers, a higher rate of disorder in the biological parent group is easily explained by non-genetic factors. This is because adoptive parents constitute a population screened for mental health as part of the adoption process. For reasons having nothing to do with genetics, we would expect to find less psychological disturbance among adoptees’ adoptive (rearing) parents —a population screened for mental health — versus adoptees’ (unscreened) biological parents, whose psychological distress may have compelled them or others to give up their child for adoption in the first place. As one group of psychiatric genetic researchers correctly pointed out, it is “unreasonable to infer a genetic component” from this comparison.14

Because Mendlewicz and Rainer’s finding of more psychiatric and affective disorders among their adoptees’ biological versus adoptive parents could reflect nothing more than adoption agencies having screened prospective adoptive parents for mental disorders, the study’s design is invalid on its face. In a rare dissenting view in psychiatry, psychiatric genetic researcher Elliot Gershon correctly observed that “comparisons of adoptive with biological relatives reveal little because of the careful screening that is traditional in adoption placements.”15

Leaving aside the invalid design of the study and the major issues in adoption studies in general, Mendlewicz and Rainer’s results do not support a genetic basis for bipolar disorder. Their biological and adoptive parents groups consisted of 57 parents each, and there were four bipolar diagnoses among the biological parents (7.0%), and one bipolar diagnosis among the adoptive parents (1.7%).16 This comparison is not statistically significant, meaning that the study found no difference in bipolar diagnoses between these two groups.17 This should have led the researchers (and the reviewers and editors of the prestigious journal Nature) to conclude that the study found no evidence supporting a genetic basis for manic-depressive (bipolar) disorder. Instead, these genetically oriented researchers illogically concluded, on the basis of their decision to create an “affective spectrum” that included several other diagnoses, that “the results demonstrate the importance of genetic factors in the etiology of manic-depressive illness.”18

Wender and colleagues’ study is the other frequently cited adoption study of bipolar disorder. Wender et al. started with adoptees, and then diagnosed their adoptive and biological relatives. There were 71 index “proband” and 71 control adoptees. However, only 10 (14%) of the 71 index adoptees were diagnosed with bipolar disorder. Wender and colleagues compared the diagnostic status of the index versus control biological relatives. Their results showed a higher (though statistically non-significant) rate of bipolar disorder among the control biological relatives. There were 2 (0.5%) bipolar diagnoses among 387 index biological relatives, versus 3 (0.9%) diagnoses among 344 control biological relatives, and both rates are comparable to general population expectations.19 However, like Mendlewicz and Rainer, the investigators decided to combine all affective disorders to create an “affective disorders spectrum,” and found many more index versus control biological relatives diagnosed with “uncertain major mood disorder” and “unipolar depression.” Attempting to justify their decision to create a spectrum of different disorders, they wrote, “These illnesses were considered together, since they have generally been regarded as the most dependent on internal (genetic or biological) factors.”20 This is a classic example of psychiatric genetic researchers’ use of illogical circular reasoning, since their conclusions in favor of genetic influences on affective disorders depended on their prior assumption of both the genetic basis and genetic relationship of these disorders.

But even after deciding to combine various affective disorders into a spectrum, Wender and colleagues still found no statistically significant results.21 To find such results, they decided to count “uncertain” cases. This after-the-fact juggling of diagnoses allowed them to conclude that “increased frequency of affective-spectrum disorder… has been found among the biological relatives of the adoptees with affective disorder. This finding is consistent with the hypothesis that genetic factors play a role in at least some of these disorders.”22 However, looking specifically at bipolar disorder, they recognized their “failure to find such a differential for bipolar illness” (italics added).23

Contrary to common claims in the mainstream literature, these two adoption studies do not come close to providing evidence that bipolar disorder (manic-depressive disorder) is caused by disordered genes. As Gershon wrote in 1990, understatedly in my view, “We would conclude that the adoption data do not provide a broad base of supportive data on the hypothesis that [bipolar] disorders are transmitted before the age of adoption.”24

Although psychiatric genetic studies in Rüdin’s era were unsound and biased for many different reasons, he at most showed that “manic-depressive insanity” runs in families, a finding that can be explained completely by non-genetic (environmental) factors. Like all other psychiatric disorders, whose validity and reliability already rest on shaky ground,25 there currently exists little if any scientifically acceptable evidence that bipolar disorder and other “affective disorders” have an underlying genetic component.

* * *

If Rüdin were alive today, it is likely that he would attempt to publish his manic-depression family study. Given the lack of accountability of how researchers conduct their studies before submitting them for publication, he would be able to redefine diagnoses and methods after the fact, choose statistical methods and comparisons to obtain the desired results, and then conclude that the findings fit his and psychiatry’s theories completely. Few psychiatrists would actually read Rüdin’s study, and instead would rely on textbooks’ and other secondary sources’ uncritical and often inaccurate descriptions of it. This has been the basic script of the bipolar disorder adoption studies, in addition to the famous yet massively flawed Danish-American schizophrenia adoption studies that I and others have described and critiqued in detail elsewhere, and continues today as the “state of the science” in psychiatry and psychiatric genetics.26

* * * * *

Footnotes:

  1. Joseph, J., & Wetzel, N, (2013), Ernst Rüdin: Hitler’s Racial Hygiene Mastermind, Journal of the History of Biology, 46, 1-30.
  2. Kösters et al., (2015), Ernst Rüdin’s Unpublished 1922-1925 Study “Inheritance of Manic-Depressive Insanity”: Genetic Research Findings Subordinated to Eugenic Ideology, PLoS Genetics, 11(11): e1005524. doi:10.1371/journal.pgen.1005524 
  3. Slater, E., (1936), The Inheritance of Manic-Depressive Insanity, Proceedings of the Royal Society of Medicine, 29, 981-990, p. 982.
  4. Boyle, M., (2002), Schizophrenia: A Scientific Delusion? (2nd ed.), Hove, UK: Routledge, pp. 69-76.
  5. Slater, 1936, p. 986.
  6. Kraepelin, E., (1976), Manic-Depressive Insanity and Paranoia, New York: Arno Press, p. 164. (Originally published in English in 1921)
  7. Turkheimer, E., (2015), Arsonists at the Cathedral, PsycCRITIQUES, 60 (40), 1-4. DOI: http://dx.doi.org/10.1037/a0039763. For a response to Turkheimer, see my November, 2, 2015 MIA blog posting.
  8. See also Fosse, R., Joseph, J., & Jones, M., (2015), Schizophrenia: A Critical View on Genetic EffectsPsychosis (published online September 14th). DOI: 10.1080/17522439.2015.1081269 
  9. Joseph, J., (2015), The Trouble with Twin Studies: A Reassessment of Twin Research in the Social and Behavioral Sciences, New York: Routledge.
  10. Wender et al., (1986), Psychiatric Disorders in the Biological and Adoptive Families of Adopted Individuals with Affective Disorders, Archives of General Psychiatry, 43, 923-929; Mendlewicz, J., & Rainer, J. D., (1977), Adoption Study Supporting Genetic Transmission in Manic-Depressive Illness, Nature, 268, 327-329.
  11. Lichtenstein et al., (2009), Common Genetic Determinants of Schizophrenia and Bipolar Disorder in Swedish Families: A Population-Based Study, Lancet, 373, 234–39.
  12. Joseph, J., (2004), The Gene Illusion: Genetic Research in Psychiatry and Psychology under the Microscope, New York: Algora; Joseph, J., (2006); The Missing Gene: Psychiatry, Heredity, and the Fruitless Search for Genes, New York: Algora.
  13. Mendlewicz & Rainer, 1977, p. 327.
  14. Clerget-Darpoux et al., (1986), Clinical Methods in Psychiatric Genetics, Acta Psychiatrica Scandinavica, 74, 305-311, p. 306.
  15. Gershon, E. S., (1990), “Genetics,” in F. Goodwin & K. Jamison, Manic-Depressive Illness (pp. 373-401), New York: Oxford University Press, p. 377.
  16. Mendlewicz & Rainer, 1977, p. 328, Table 3.
  17. 4/57 vs. 1/57, probability = .18, Fisher’s Exact Test, one-tailed. Not statistically significant at the conventional 0.05 level of significance.
  18. Mendlewicz & Rainer, 1977, p. 329. The investigators also used three control groups: (1) the parents of non-adopted people diagnosed manic-depressive, (2) the adoptive and biological parents of normal adoptees, and (3) the parents of people who had contracted polio. However, they based their conclusions in favor of genetics primarily on a diagnostic comparison between the biological and adoptive parents of adoptees diagnosed with manic-depressive disorder.
  19. Wender et al., 1986, p. 926, Table 3.
  20. Wender et al., 1986, p. 926.
  21. 7.5% index vs. 4.7% control, probability = .074. See Wender et al., 1986, p. 927, Table 4.
  22. Wender et al., 1986, p. 929.
  23. Wender et al., 1986, p. 928.
  24. Gershon, 1990, p. 378.
  25. Kirk, S. A., Gomory, T., & Cohen, D., (2013), Mad Science: Psychiatric Coercion, Diagnosis, and Drugs, New Brunswick, NJ: Transaction.
  26. Critical analyses of the Danish-American schizophrenia adoption studies can be found in Boyle, 2002; Joseph, 2004; Joseph, 2006; Joseph, J., (2013), “‘Schizophrenia’ and Heredity: Why the Emperor (Still) Has No Genes,” in J. Read & J. Dillon (Eds.), Models of Madness: Psychological, Social and Biological Approaches to Psychosis (2nd ed.; pp. 72-89), London: Routledge; Lewontin et al., (1984), Not in Our Genes, New York: Pantheon; Lidz, T., (1976), Commentary on a Critical Review of Recent Adoption, Twin, and Family Studies of Schizophrenia: Behavioral Genetics Perspectives, Schizophrenia Bulletin, 2, 402-412; Lidz, T., & Blatt, S., (1983), Critique of the Danish-American Studies of the Biological and Adoptive Relatives of Adoptees who Became Schizophrenic, American Journal of Psychiatry, 140, 426-435; Lidz et al., (1981), Critique of the Danish-American Studies of the Adopted-Away Offspring of Schizophrenic Parents, American Journal of Psychiatry, 138, 1063-1068; Pam, A., (1995), “Biological Psychiatry: Science or Pseudoscience?,” in C. Ross & A. Pam (Eds.), Pseudoscience in Biological Psychiatry: Blaming the Body (pp. 7-84), New York: John Wiley & Sons.

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9 COMMENTS

  1. Jay,
    Thanks for your continuing work.

    We should ask the question: How many people diagnosed with supposed bipolar or schizophrenia have benefitted in terms of better functional outcomes, from the hundreds of millions of dollars poured into genetic research of psychiatric disorders over the last 50 years?

    Answer: Zero.

    In reading this I mentally stepped back and asked myself, “Why are psychiatrists even trying to find the heritability for illusory illnesses that don’t exist as separable entities?” This research always seems silly because they are assuming conditions reliably or discretely exist for which we have no biomarkers or clear etiology (outside of trauma). This research brings to mind astrology research or witchcraft research or ECat research (nuclear fusion with no heat source, a pipe dream). In other words, supposed bipolar and schizophrenia symptoms are not evidence of discrete illnesses, but rather are highly individual and variable-over-time experiences that are caused differently by many different stresses. Since there’s no one illness in either case, you can’t break it down numerically by genetic contributions. That’s one reason why this research is doomed. I would bet a lot of money that it will continue to fail.

    Then I imagined the answer to why are they researching this, “Because it supports the narrative that bipolar and schizophrenia actually exist as discrete illnesses, and this legitimizes continued sale of neuroleptic drugs and continued profits to psychiatrists, drug companies, and shareholders and continued funding to researchers.” A host of other reasons too including the need for coercion/oppression of undesirable elements and the fact that considering a strong parental/social role in causing psychosis is threatening emotionally to many in our society.

    But the fact remains: Abusive and neglectful parents do contribute very much to an increased chance of a young person getting diagnosed bipolar or schizophrenic, as the ACE studies and John Read’s research shows.

    How sad to spend your whole career researching something (genetic contribution to “bipolar” as a discrete illness) that is essentially a delusion, and to die without ever knowing how fraudulent your life’s work really was. Kind of like the scientists who spent their career studying how sun revolved around the Earth.

  2. I’m curious, given today’s current “gold standard” treatment guidelines for “bipolar,” which include combining the antidepressant drugs, benzos, and antipsychotic drugs:

    http://www.mayoclinic.org/diseases-conditions/bipolar-disorder/basics/treatment/con-20027544

    And the reality that combining these same drug classes are known to create “psychosis” via the central symptoms of anticholinergic intoxication syndrome:

    “Central symptoms [of anticholinergic intoxication syndrome] may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures.”

    “Substances that may cause [anticholinergic] toxidrome include the four ‘anti’s of antihistamines, antipsychotics, antidepressants, and antiparkinsonian drugs[3] as well as atropine, benztropine, datura, and scopolamine.”

    Isn’t it likely most “bipolar” today is the completely iatrogenic illness, anticholinergic toxidrome, rather than the theorized “bipolar”?

    Even Wiki confesses, “An example of a partially iatrogenic condition due to common misdiagnosis is bipolar disorder, especially in pediatric patients.”

    • I think manic states of mind are real, but rare, and not an illness certainly.

      I recently had a conversation via email with an experienced psychoanalyst who works with bipolar people and helps them get off drugs and get well. I asked him how his psychoanalytic training taught him to view bipolar states, and he said,

      “From the PA-viewpoint bipolarity is part of the normal personality development. The little child divides and in fact needs to divide his experiences and the events into good and bad ones, as he does with the things and people around him. The good experiences are to start with often grossly idealized and the bad ones grossly demonized depending on how bad and frustrating they have been for the child. This is called the paranoid-schizoid position. Gradually the wide gap between these blissful omnipotent states of extreme happiness on the other had the paranoid dread of facing annihilation and death (falling into a death, dissolving into nothingness, or the like) melt into a new slightly more mature type of bipolarity that is manic triumph and narcissistic self idealization on one hand and deep depression that is feelings of total worthlessness and inadequacy or the like. The changes happen over many years gradually little by little. Then this continues to transform and become more moderate and realistic when the person begins to realize that he is both good and bad at the same time and there is an eternal balance, no-one is totally good or totally bad resulting in normal balanced life where the amplitude between swings between the extreme states diminish and integration to normal maturity ushers in. ”

      Then I asked him about his own work with people experiencing bipolar states and he said,

      “I have. Indeed every patient of mine has needed to go through a phases of bipolarity when leftovers of their childhood relating to their problems have been touched upon. Many had medication at arrival but the medication was finishes in a few months. Most have not had any medication. It is almost everyday stuff on a small in analysis. One very ill psychotically disturbed bipolar man who attended only twice weekly kept on his lithium all through the too short treatment. He had a very deprived and traumatized childhood and did easily fall into deep depressions due to very small triggers or errors, disappointments etc. He gained a lot and finished treatment too early against my recommendation. I heard that some 4-5 years later he had needed to be hospitalized again. He did not return into psycho analytic psychotherapy. I am by no means saying that the treatment of major psychotic bipolar states is easy. I am however, saying that it is possible and in a small way part of every therapy or analysis. Indeed they become free from their manic states when they realize how unrealistic psychotic and cruel this grandiose self aggrandizing triumphant and arrogant states are and how they create the depression and destroy their social relationships and often their economy. Some manage to use their manic states for creative work and may be able to limit the mood swings and hold it in some proportion without becoming so unrealistic that they make a mess of everything. ”

      I also think it’s true what you say that drugs can trigger and excacerbate so-called bipolar symptoms. Mainstream psychiatric treatment (or creation) of bipolar mental states is a dangerous waste of time that usually produces chronicity and suffering rather than cure.

  3. Good to know all this. Additionally, we should not forget that social influences, as well as ‘mind’ related interventions change the expression of genes in expected directions.
    I posted some links in an earlier post – here are a few additional ones:
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1550735/
    http://www.ncbi.nlm.nih.gov/pubmed/16095592
    http://www.ncbi.nlm.nih.gov/pubmed/22777883
    http://www.nature.com/neuro/journal/v15/n5/full/nn.3093.html

  4. Ironically, England had a leader who protected the British people from NAZI Germany–One who experienced times of deep depression–followed by periods of enormous energy…

    Had he lived in today’s period of disgnosis–Prime Minister Winston Churchill would have likely been put on drugs, and would not have been able to fiercely defend his country.

    Duane

  5. One factor in this type of discussion that is rarely talked about is the period of time and experiences of a fetus PRIOR to birth. What is the impact on the development of a fetal brain from depression, wide mood swings with periods of elation, and extreme stress and anxiety in the pregnancy experience of the birth mother?

    All this must be factored into any scientific examination of the nature/nurture debate and it would be next to impossible to measure this in any meaningful way.