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JAMA Classics
January 21, 2009

Contracting Schizophrenia

Author Affiliations

Author Affiliation: Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas.

Author Affiliation: Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas.

JAMA. 2009;301(3):324-326. doi:10.1001/jama.2008.980

Psychoses Associated With Influenza, I: General Data: Statistical Analysis


Menninger presented a series of 100 patients observed at the Boston Psychopathic Hospital from September 15, 1918, through December 15, 1918. All patients had mental disturbances associated with influenza.

See PDF for full text of the original JAMA article .


The Spanish influenza pandemic of 1918-1919 was contracted by more than 500 million individuals worldwide, between 50 million and 100 million individuals died in just 1 year, and the preponderance of deaths was among 20- to 40-year-olds.1 One of the few silver linings in the dark, devastating cloud of this epidemic has been its value as a probe for elucidating conceptual approaches for diagnosing and treating subsequent psychiatric illnesses among those who were infected and survived. Paradoxically, each advance in the diagnostic classification systems of psychiatric disorders during the 20th century has also brought coincident conceptual limitations that have impaired research into the understanding and treatment of individuals with mental illnesses.

In 1919, JAMA published a classic article by Karl A. Menninger on the association of influenza and psychoses in patients who were admitted to the Boston Psychopathic Hospital from September 15, 1918, through December 15, 1918, the apogee of this scourge in New England.2 Menninger's professional life was in transition in 1918 (as was the field of psychiatry in the era in which this paper was written): he was in the internship year between graduation from Harvard Medical School and founding the legendary Menninger Clinic in Topeka, Kansas (with his father C. F. Menninger, MD). In this Classic, Menninger reported the clinical courses of 80 patients admitted to the psychiatric hospital with “mental disturbances” associated with influenza, of whom 16 were diagnosed with delirium, 25 with dementia praecox, 23 with “other types of psychosis,” and 16 who were not able to be classified.2 It was the group of patients diagnosed with dementia praecox who captured Menninger's primary interest in this article2 and in others he published about this series of patients. In 1926, Menninger published a follow-up study of 50 patients diagnosed with dementia praecox (at Boston Psychopathic Hospital) after the 1918 influenza outbreak.3 To his surprise, 35 of these patients completely recovered within a 5-year follow-up period and 5 others showed improvement. He wrote, “The astonishing indication of these data is that the vast majority of cases regarded as ‘dementia praecox’ did not dement, but actually recovered,” and concluded, “This would seem to indicate the need of new diagnostic criteria or new prognostic conceptions.”3

Diagnosing Schizophrenia at the Turn of the 20th Century

Dementia praecox, a term popularized in the late 19th and early 20th centuries by German psychiatrist Emil Kraepelin, MD, was thought to be a degenerating disease of the brain that began with patients in their late teens and comprised a constellation of diverse and usually progressively worsening symptoms.4 Kraepelin's diagnostic classification was largely based on clusters of signs and symptoms exhibited by patients he had observed during the protracted courses of their illnesses, as well as on a theory of causality, which, in the case of dementia praecox, was a hereditary “autointoxication” leading to cortical neuronal loss.4 He used symptomatic criteria and courses of illness to differentiate dementia praecox and manic depression into 2 distinct categories of psychotic disorders, and this process has comprised a categorical approach to the diagnostic classification system that is the prevailing method in the current Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision [DSM-IV-TR]).5

Swiss psychiatrist Eugen Bleuler, MD, who was strongly influenced by the ideas of Sigmund Freud, did not believe that dementia praecox was the result of an irreversible deterioration of the brain but, rather, the condition reflected “disharmonious” mental states that were exaggerations of normal psychic functions.6 Bleuler proposed renaming the condition “schizophrenia,” or “split-mind,” to reflect the contradictory intrapsychic influences he deemed to characterize the disorder. He also contended that schizophrenia actually encompassed a group of psychotic disorders that could be ameliorated, but not cured, by psychotherapeutic treatments.6

1920-1970: What Happened to the Brain in Schizophrenia?

During the first two-thirds of the 20th century in the United States, Freud's psychoanalytically based conceptualizations principally shaped psychiatry's theoretical, etiological, diagnostic, and therapeutic approaches to schizophrenia and other mental illnesses.7 Although psychoanalytic approaches have brought many tools to the armamentarium of psychiatry for understanding and treating patients with mental illnesses, there were also concomitant disadvantages of the predominant psychoanalytic emphasis during this period. These drawbacks were summarized by psychoanalyst Melvin Sabshin, MD, medical director of the American Psychiatric Association from 1974 to 1994 and one of the United States' most prominent psychiatrists both before and during this epoch, as follows: “ . . . psychoanalysis developed enormous academic institutional power and affected significant hospitals, associations and their leaders . . . Epidemiology was essentially ignored as much as nosology, although without the opprobrium that many analysts cast upon the classificatory systems . . . Furthermore, the overwhelming majority of psychoanalysts demonstrated minimal interest in exploring the relationship between intrapsychic process and new biological concepts.”7 Nancy Andreasen, MD, PhD, a neuroscientist and psychiatrist, agrees: “In general, the psychoanalytic movement considered diagnosis and classification to be a fruitless endeavor. Defining the nature and source of intrapsychic conflicts was the goal instead.”8

A prototypic example and outcome of the overemphasis of mental processes in the putative etiology, diagnosis, and treatment of schizophrenia is the theory of the schizophrenogenic mother, as posited by prominent psychoanalyst Frieda Fromm-Reichmann, MD, and embraced by many others.9 Fromm-Reichmann argued that schizophrenia was caused by mothers who were simultaneously overinvolved with and rejecting of their affected children, with the consequent recommendation of psychoanalysis as a primary treatment for the condition: “The schizophrenic is painfully distrustful and resentful of other people due to the severe early warp and rejection he encountered in important people of his infancy and childhood, as a rule, mainly a schizophrenogenic mother.”9 In addition to shaming and blaming mothers who already were experiencing stress and other problems from caring for severely disabled, distressed, and distressing offspring, the “opportunity costs” of failures in that era to conduct research on valid neurobiological etiologies and effective treatments for individuals with schizophrenia are incalculable.

DSM and Schizophrenia

US psychiatrists trained from the 1920s through the late 1960s were taught to diagnose schizophrenia, at least in part, based on the personal feeling states evoked by these patients while in their physical presence. Manifestly, these highly subjective emotional reactions varied greatly from clinician to clinician, and, thereby, significantly reduced the diagnostic reliability and, most likely, the validity of this approach. Additionally, neither a uniformly accepted diagnostic language nor categorization format existed whereby either clinicians or researchers could communicate reliably about patients in their care or participants in their research. This deficiency seriously impaired the abilities of scientists to conduct valid schizophrenia research of all types, especially across disparate cultures and nationalities.5

In 1974, the American Psychiatric Association charged a group of psychiatrists and biometricians to develop a third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) that would prioritize evidence-based, operationalized criteria for making diagnoses, as opposed to basing diagnoses on untested and nonvalidated etiological theories.5 During the 1990s through the present time, technological and methodological breakthroughs in brain imaging, molecular and cellular biology, genetics, and epidemiological research progressively have opened a multiplicity of exciting new avenues of understanding the etiologies and pathogeneses of many psychiatric disorders, including schizophrenia.10

Although DSM-III and, currently, DSM-IV-TR are based on categorical diagnoses that have been broadly used and proven as valuable in outcome research of psychopharmacological and psychotherapeutic treatments of individuals with schizophrenia, the plethora of recent findings in neurobiology and neurogenetics has revealed limitations of this approach that constrain the progress of research in schizophrenia.11 Specifically, the categorical diagnostic format of Kraepelin that distinguishes dementia praecox from bipolar illness is partially based on the longitudinal course of both illnesses. Categorical diagnostic classification of schizophrenia will likely be replaced or complemented in the fifth edition of DSM, scheduled to be published in 2012, by a dimensional approach that emphasizes the symptom continua that are common to varieties of psychosis, such as reality distortion, disorganization, negativity, catatonia, mania, and depression.11

Can Influenza “Cause” Schizophrenia?

Although Menninger considered many avenues by which the Spanish Influenza of 1918 could lead to the development of dementia praecox, neither he nor any of his contemporary investigators raised the possibility that the influence of influenza on the etiology of schizophrenia could occur in utero. Although this idea has been debated in the scientific literature, many studies have documented that schizophrenia occurs more frequently in children born in winter and early spring when viral infections are more prevalent.12 Among 25 investigations of the incidence of schizophrenia in the offspring of women who were thought to have contracted influenza during pregnancy, approximately 50% reported positive associations.13 Reliably documenting maternal influenza exposure in these studies has been challenging because viral exposure has been generally based on participants' self-reports of infection or on occurrences of influenza epidemics contemporaneous with their pregnancies. To counter this problem, Brown et al assayed for influenza antibodies in sera drawn from pregnant women whose children later developed schizophrenia, and compared these samples with ones from a matched control group of women whose children did not develop schizophrenia.14 The study population was derived from 170 cases judged to have schizophrenia or “schizophrenia spectrum disease” from a cohort of 12 094 live births enrolled in the California Child Health and Development Study.15 The results of the study by Brown et al14 revealed a dramatic 7-fold increase in the risk of schizophrenia among the offspring of women who were exposed to influenza during their first trimester of pregnancy. Further analysis suggested a 3-fold increase of risk in women who were exposed to influenza from the midpoints of their first and second trimesters.14

The finding that exposure to influenza during pregnancy may be an etiologic factor for schizophrenia may lead to new understanding of the pathogenesis, treatment, and prevention of this devastating condition. For example, vaccinating women of childbearing age against influenza might help prevent some forms of schizophrenia. In carrying to fruition this remarkable line of research, the 90 years of progress in improving psychiatric diagnosis and classification since the original Menninger study2 have been as important as the advances in modern laboratory techniques used to assay the influenza antigens in the sera of the cohorts. It certainly seems reasonable to speculate that Kraepelin, Bleuler, and Karl Menninger would be excited by this progress and pleased with their seminal roles in the evolution of the diagnosis and classification of psychiatric disorders.

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Article Information

Corresponding Author: Stuart C. Yudofsky, MD, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, One Baylor Plaza, Room 115-D, Houston, TX 77030 (stuarty@bcm.tmc.edu).

Financial Disclosures: Dr Yudofsky reports being the Neuroscience CME e-journal club moderator, which is sponsored by an educational grant from Eli Lilly; he also reports being co-chairman of the psychopharmacology annual update for the American Psychiatric Association annual meeting, supported by educational grants from Organon and Bristol-Myers Squibb.

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