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Autour de la grippe et de la schizophr?nie
Petite histoire de la nosologie en psychiatrie
Depuis le d?but du XXe si?cle, la psychiatrie a ?t? anim?e de diff?rents courants de pens?e. Chacun s?accompagne de son lot d?avanc?es et de retours en arri?re. De surprises aussi comme cette curieuse association lors de l??pid?mie de grippe espagnole.
TOUTE L?HISTOIRE d?bute dans les ann?es 1920. Tr?s exactement deux ans plus t?t, en 1918, alors que l?effroyable ?pid?mie de grippe espagnole vient de d?cimer entre 50 et 100 millions de jeunes adultes ?g?s entre 20 et 40 ans. Le psychiatre Karl Menninger note une curieuse association entre grippe et maladies psychiatriques chez 80 patients admis au Boston Psychopathic Hospital. L??tude est publi?e dans le ? JAMA ? en 1919 et est encore c?l?bre aujourd?hui. Mais pas tant sur la physiopathologie de la grippe dans les psychoses, que comme une ?tape clef dans l?histoire de la psychiatrie? Des sujets au diagnostic de ? dementia pr?cox ? vont en effet retenir l?attention du psychiatre. Et l?, ? sa grande surprise, au cours d?un suivi de cinq ans, 35 parmi 50 sujets r?cup?rent totalement et 5 sont consid?rablement am?lior?s. Ces patients ?tiquet?s ? dementia pr?cox ? ne seraient-ils pas d?ments en r?alit? ? Cette constatation l?am?ne ? penser que ? de nouveaux crit?res de diagnostic ou de nouvelles conceptions pronostiques sont n?cessaires ?. Et c?est le point de d?part de la classification moderne des maladies psychiatriques.
De la dementia pr?cox ? la schizophr?nie.
Au d?but du XXe si?cle, le psychiatre Kr?pelin popularise le terme de ? dementia pr?cox ?, qu?il d?finit comme une maladie c?r?brale d?g?n?rative commen?ant ? la fin de l?adolescence et dont les sympt?mes vont en s?aggravant. Puis arrive le Suisse Bleuler, tr?s influenc? par Freud, qui croit, lui, ? un d?s?quilibre mental d? ? des fonctions normales surexprim?es. Bleuler rebaptise la ? dementia pr?cox ? en schizophr?nie, ou ? esprit scind? ?, pour traduire les contradictions intrapsychiques du trouble.
Avec la d?ferlante psychanalytique, les courants plus normatifs sont mis de c?t? jusqu?aux ann?es 1970. La nosologie, l??pid?miologie mais aussi les neurosciences et la neurobiologie sont rel?gu?es aux oubliettes. Le concept de la m?re schizophr?nog?nique illustre le caract?re extr?me pris par ce mode de pens?e. Le trouble mental y est expliqu? comme la r?sultante d?un comportement maternel ambivalent, ? la fois surprotecteur et rejetant. En pratique, aucune am?lioration chez le patient mais une culpabilit? aggrav?e du c?t? des m?res.
Retour ? la classification du DSM.
Devant le tournant subjectif et trop peu rationnel pris par la sp?cialit?, l?American Psychiatric Association prend le contre-pied dans les ann?es 1970 et organise la r?daction de la troisi?me ?dition du Diagnostic and Statistical Manual of Mental Disorders (DSM-III). L?ouvrage a pour mission de cat?goriser les troubles psychiatriques et de d?finir des crit?res diagnostiques prouv?s. Depuis les multiples d?couvertes r?alis?es ces vingt derni?res ann?es dans des champs aussi divers que la biologie mol?culaire et cellulaire, la g?n?tique, l?imagerie et l??pid?miologie, la classification du DSM-IV montre ses limites ? son tour. Une cinqui?me ?dition programm?e pour 2 012 devrait compl?ter, voire remplacer, la d?finition de la schizophr?nie.
Alors la boucle est-elle boucl?e ? Entre grippe et schizophr?nie, Menninger avait formul? plusieurs hypoth?ses, mais pas celle de l?exposition au virus in utero. Et pourtant? Le risque de schizophr?nie serait plus ?lev?, 3 fois plus sur l?ensemble des ?tudes ? ce sujet et jusqu?? 7 fois plus dans l??tude de Brown. Certaines formes de schizophr?nie pourraient ?tre ?vit?es en vaccinant les femmes enceintes. Un bel exemple de recherche accomplie en d?pit des turpitudes de la discipline.
? Dr IR?NE DROGOU
Yudofsky S. JAMA, 21 janvier 2009. Contracting schizophrenia.
Le Quotidien du M?decin du : 23/01/2009
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Contracting SchizophreniaLessons From the Influenza Epidemic of 1918-1919
<nobr>Commentary by Stuart C. Yudofsky, MD</nobr>
JAMA. 2009;301(3):324-326.
<!--startindex--><sup> </sup> Commentary<sup> </sup>
The Spanish influenza pandemic of 1918-1919 was contracted by<sup> </sup>more than 500 million individuals worldwide, between 50 million<sup> </sup>and 100 million individuals died in just 1 year, and the preponderance<sup> </sup>of deaths was among 20- to 40-year-olds.<sup>1</sup> One of the few silver<sup> </sup>linings in the dark, devastating cloud of this epidemic has<sup> </sup>been its value as a probe for elucidating conceptual approaches<sup> </sup>for diagnosing and treating subsequent psychiatric illnesses<sup> </sup>among those who were infected and survived. Paradoxically, each<sup> </sup>advance in the diagnostic classification systems of psychiatric<sup> </sup>disorders during the 20th century has also brought coincident<sup> </sup>conceptual limitations that have impaired research into the<sup> </sup>understanding and treatment of individuals with mental illnesses.<sup> </sup>
In 1919, JAMA published a classic article by Karl A. Menninger<sup> </sup>on the association of influenza and psychoses in patients who<sup> </sup>were admitted to the Boston Psychopathic Hospital from September<sup> </sup>15, 1918, through December 15, 1918, the apogee of this scourge<sup> </sup>in New England.<sup>2</sup> Menninger's professional life was in transition<sup> </sup>in 1918 (as was the field of psychiatry in the era in which<sup> </sup>this paper was written): he was in the internship year between<sup> </sup>graduation from Harvard Medical School and founding the legendary<sup> </sup>Menninger Clinic in Topeka, Kansas (with his father C. F. Menninger,<sup> </sup>MD). In this Classic, Menninger reported the clinical courses<sup> </sup>of 80 patients admitted to the psychiatric hospital with "mental<sup> </sup>disturbances" associated with influenza, of whom 16 were diagnosed<sup> </sup>with delirium, 25 with dementia praecox, 23 with "other types<sup> </sup>of psychosis," and 16 who were not able to be classified.<sup>2</sup> It<sup> </sup>was the group of patients diagnosed with dementia praecox who<sup> </sup>captured Menninger's primary interest in this article<sup>2</sup> and in<sup> </sup>others he published about this series of patients. In 1926,<sup> </sup>Menninger published a follow-up study of 50 patients diagnosed<sup> </sup>with dementia praecox (at Boston Psychopathic Hospital) after<sup> </sup>the 1918 influenza outbreak.<sup>3</sup> To his surprise, 35 of these patients<sup> </sup>completely recovered within a 5-year follow-up period and 5<sup> </sup>others showed improvement. He wrote, "The astonishing indication<sup> </sup>of these data is that the vast majority of cases regarded as<sup> </sup>?dementia praecox? did not dement, but actually<sup> </sup>recovered," and concluded, "This would seem to indicate the<sup> </sup>need of new diagnostic criteria or new prognostic conceptions."<sup>3</sup><sup> </sup>
Diagnosing Schizophrenia at the Turn of the 20th Century <table border="0" cellpadding="0" cellspacing="0" width="100%"> <tbody><tr> <td bgcolor="#6a90aa" width="100%"></td><td></td></tr></tbody></table>
Dementia praecox, a term popularized in the late 19th and early<sup> </sup>20th centuries by German psychiatrist Emil Kraepelin, MD, was<sup> </sup>thought to be a degenerating disease of the brain that began<sup> </sup>with patients in their late teens and comprised a constellation<sup> </sup>of diverse and usually progressively worsening symptoms.<sup>4</sup> Kraepelin's<sup> </sup>diagnostic classification was largely based on clusters of signs<sup> </sup>and symptoms exhibited by patients he had observed during the<sup> </sup>protracted courses of their illnesses, as well as on a theory<sup> </sup>of causality, which, in the case of dementia praecox, was a<sup> </sup>hereditary "autointoxication" leading to cortical neuronal loss.<sup>4</sup><sup> </sup>He used symptomatic criteria and courses of illness to differentiate<sup> </sup>dementia praecox and manic depression into 2 distinct categories<sup> </sup>of psychotic disorders, and this process has comprised a categorical<sup> </sup>approach to the diagnostic classification system that is the<sup> </sup>prevailing method in the current Diagnostic and Statistical<sup> </sup>Manual of Mental Disorders (Fourth Edition, Text Revision [DSM-IV-TR]).<sup>5</sup><sup> </sup>
Swiss psychiatrist Eugen Bleuler, MD, who was strongly influenced<sup> </sup>by the ideas of Sigmund Freud, did not believe that dementia<sup> </sup>praecox was the result of an irreversible deterioration of the<sup> </sup>brain but, rather, the condition reflected "disharmonious" mental<sup> </sup>states that were exaggerations of normal psychic functions.<sup>6</sup><sup> </sup>Bleuler proposed renaming the condition "schizophrenia," or<sup> </sup>"split-mind," to reflect the contradictory intrapsychic influences<sup> </sup>he deemed to characterize the disorder. He also contended that<sup> </sup>schizophrenia actually encompassed a group of psychotic disorders<sup> </sup>that could be ameliorated, but not cured, by psychotherapeutic<sup> </sup>treatments.<sup>6</sup><sup> </sup>
1920-1970: What Happened to the Brain in Schizophrenia? <table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td bgcolor="#6a90aa" width="100%"></td></tr></tbody></table>
During the first two-thirds of the 20th century in the United<sup> </sup>States, Freud's psychoanalytically based conceptualizations<sup> </sup>principally shaped psychiatry's theoretical, etiological, diagnostic,<sup> </sup>and therapeutic approaches to schizophrenia and other mental<sup> </sup>illnesses.<sup>7</sup> Although psychoanalytic approaches have brought<sup> </sup>many tools to the armamentarium of psychiatry for understanding<sup> </sup>and treating patients with mental illnesses, there were also<sup> </sup>concomitant disadvantages of the predominant psychoanalytic<sup> </sup>emphasis during this period. These drawbacks were summarized<sup> </sup>by psychoanalyst Melvin Sabshin, MD, medical director of the<sup> </sup>American Psychiatric Association from 1974 to 1994 and one of<sup> </sup>the United States' most prominent psychiatrists both before<sup> </sup>and during this epoch, as follows: " . . . psychoanalysis<sup> </sup>developed enormous academic institutional power and affected<sup> </sup>significant hospitals, associations and their leaders . . . Epidemiology<sup> </sup>was essentially ignored as much as nosology, although without<sup> </sup>the opprobrium that many analysts cast upon the classificatory<sup> </sup>systems . . . Furthermore, the overwhelming<sup> </sup>majority of psychoanalysts demonstrated minimal interest in<sup> </sup>exploring the relationship between intrapsychic process and<sup> </sup>new biological concepts."<sup>7</sup> Nancy Andreasen, MD, PhD, a neuroscientist<sup> </sup>and psychiatrist, agrees: "In general, the psychoanalytic movement<sup> </sup>considered diagnosis and classification to be a fruitless endeavor.<sup> </sup>Defining the nature and source of intrapsychic conflicts was<sup> </sup>the goal instead."<sup>8</sup><sup> </sup>
A prototypic example and outcome of the overemphasis of mental<sup> </sup>processes in the putative etiology, diagnosis, and treatment<sup> </sup>of schizophrenia is the theory of the schizophrenogenic mother,<sup> </sup>as posited by prominent psychoanalyst Frieda Fromm-Reichmann,<sup> </sup>MD, and embraced by many others.<sup>9</sup> Fromm-Reichmann argued that<sup> </sup>schizophrenia was caused by mothers who were simultaneously<sup> </sup>overinvolved with and rejecting of their affected children,<sup> </sup>with the consequent recommendation of psychoanalysis as a primary<sup> </sup>treatment for the condition: "The schizophrenic is painfully<sup> </sup>distrustful and resentful of other people due to the severe<sup> </sup>early warp and rejection he encountered in important people<sup> </sup>of his infancy and childhood, as a rule, mainly a schizophrenogenic<sup> </sup>mother."<sup>9</sup> In addition to shaming and blaming mothers who already<sup> </sup>were experiencing stress and other problems from caring for<sup> </sup>severely disabled, distressed, and distressing offspring, the<sup> </sup>"opportunity costs" of failures in that era to conduct research<sup> </sup>on valid neurobiological etiologies and effective treatments<sup> </sup>for individuals with schizophrenia are incalculable.<sup> </sup>
DSM and Schizophrenia <table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td bgcolor="#6a90aa" width="100%"></td></tr></tbody></table>
US psychiatrists trained from the 1920s through the late 1960s<sup> </sup>were taught to diagnose schizophrenia, at least in part, based<sup> </sup>on the personal feeling states evoked by these patients while<sup> </sup>in their physical presence. Manifestly, these highly subjective<sup> </sup>emotional reactions varied greatly from clinician to clinician,<sup> </sup>and, thereby, significantly reduced the diagnostic reliability<sup> </sup>and, most likely, the validity of this approach. Additionally,<sup> </sup>neither a uniformly accepted diagnostic language nor categorization<sup> </sup>format existed whereby either clinicians or researchers could<sup> </sup>communicate reliably about patients in their care or participants<sup> </sup>in their research. This deficiency seriously impaired the abilities<sup> </sup>of scientists to conduct valid schizophrenia research of all<sup> </sup>types, especially across disparate cultures and nationalities.<sup>5</sup><sup> </sup>
In 1974, the American Psychiatric Association charged a group<sup> </sup>of psychiatrists and biometricians to develop a third edition<sup> </sup>of the Diagnostic and Statistical Manual of Mental Disorders<sup> </sup>(DSM-III) that would prioritize evidence-based, operationalized<sup> </sup>criteria for making diagnoses, as opposed to basing diagnoses<sup> </sup>on untested and nonvalidated etiological theories.<sup>5</sup> During the<sup> </sup>1990s through the present time, technological and methodological<sup> </sup>breakthroughs in brain imaging, molecular and cellular biology,<sup> </sup>genetics, and epidemiological research progressively have opened<sup> </sup>a multiplicity of exciting new avenues of understanding the<sup> </sup>etiologies and pathogeneses of many psychiatric disorders, including<sup> </sup>schizophrenia.<sup>10</sup><sup> </sup>
Although DSM-III and, currently, DSM-IV-TR are based on categorical<sup> </sup>diagnoses that have been broadly used and proven as valuable<sup> </sup>in outcome research of psychopharmacological and psychotherapeutic<sup> </sup>treatments of individuals with schizophrenia, the plethora of<sup> </sup>recent findings in neurobiology and neurogenetics has revealed<sup> </sup>limitations of this approach that constrain the progress of<sup> </sup>research in schizophrenia.<sup>11</sup> Specifically, the categorical diagnostic<sup> </sup>format of Kraepelin that distinguishes dementia praecox from<sup> </sup>bipolar illness is partially based on the longitudinal course<sup> </sup>of both illnesses. Categorical diagnostic classification of<sup> </sup>schizophrenia will likely be replaced or complemented in the<sup> </sup>fifth edition of DSM, scheduled to be published in 2012, by<sup> </sup>a dimensional approach that emphasizes the symptom continua<sup> </sup>that are common to varieties of psychosis, such as reality distortion,<sup> </sup>disorganization, negativity, catatonia, mania, and depression.<sup>11</sup><sup> </sup>
Can Influenza "Cause" Schizophrenia? <table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td bgcolor="#6a90aa" width="100%"></td></tr></tbody></table>
Although Menninger considered many avenues by which the Spanish<sup> </sup>Influenza of 1918 could lead to the development of dementia<sup> </sup>praecox, neither he nor any of his contemporary investigators<sup> </sup>raised the possibility that the influence of influenza on the<sup> </sup>etiology of schizophrenia could occur in utero. Although this<sup> </sup>idea has been debated in the scientific literature, many studies<sup> </sup>have documented that schizophrenia occurs more frequently in<sup> </sup>children born in winter and early spring when viral infections<sup> </sup>are more prevalent.<sup>12</sup> Among 25 investigations of the incidence<sup> </sup>of schizophrenia in the offspring of women who were thought<sup> </sup>to have contracted influenza during pregnancy, approximately<sup> </sup>50% reported positive associations.<sup>13</sup> Reliably documenting maternal<sup> </sup>influenza exposure in these studies has been challenging because<sup> </sup>viral exposure has been generally based on participants' self-reports<sup> </sup>of infection or on occurrences of influenza epidemics contemporaneous<sup> </sup>with their pregnancies. To counter this problem, Brown et al<sup> </sup>assayed for influenza antibodies in sera drawn from pregnant<sup> </sup>women whose children later developed schizophrenia, and compared<sup> </sup>these samples with ones from a matched control group of women<sup> </sup>whose children did not develop schizophrenia.<sup>14</sup> The study population<sup> </sup>was derived from 170 cases judged to have schizophrenia or "schizophrenia<sup> </sup>spectrum disease" from a cohort of 12 094 live births enrolled<sup> </sup>in the California Child Health and Development Study.<sup>15</sup> The<sup> </sup>results of the study by Brown et al<sup>14</sup> revealed a dramatic 7-fold<sup> </sup>increase in the risk of schizophrenia among the offspring of<sup> </sup>women who were exposed to influenza during their first trimester<sup> </sup>of pregnancy. Further analysis suggested a 3-fold increase of<sup> </sup>risk in women who were exposed to influenza from the midpoints<sup> </sup>of their first and second trimesters.<sup>14</sup><sup> </sup>
The finding that exposure to influenza during pregnancy may<sup> </sup>be an etiologic factor for schizophrenia may lead to new understanding<sup> </sup>of the pathogenesis, treatment, and prevention of this devastating<sup> </sup>condition. For example, vaccinating women of childbearing age<sup> </sup>against influenza might help prevent some forms of schizophrenia.<sup> </sup>In carrying to fruition this remarkable line of research, the<sup> </sup>90 years of progress in improving psychiatric diagnosis and<sup> </sup>classification since the original Menninger study<sup>2</sup> have been<sup> </sup>as important as the advances in modern laboratory techniques<sup> </sup>used to assay the influenza antigens in the sera of the cohorts.<sup> </sup>It certainly seems reasonable to speculate that Kraepelin, Bleuler,<sup> </sup>and Karl Menninger would be excited by this progress and pleased<sup> </sup>with their seminal roles in the evolution of the diagnosis and<sup> </sup>classification of psychiatric disorders.<sup> </sup>
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AUTHOR INFORMATION <table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td bgcolor="#6a90aa" width="100%"></td></tr></tbody></table>
Corresponding Author: Stuart C. Yudofsky, MD, Menninger Department<sup> </sup>of Psychiatry and Behavioral Sciences, Baylor College of Medicine,<sup> </sup>One Baylor Plaza, Room 115-D, Houston, TX 77030 (stuarty@bcm.tmc.edu<script type="text/javascript"><!-- var u = "stuarty", d = "bcm.tmc.edu"; document.getElementById("em0").innerHTML = '<a href="mailto:' + u + '@' + d + '">' + u + '@' + d + '<\/a>'//--></script>).<sup> </sup>
Financial Disclosures: Dr Yudofsky reports being the Neuroscience<sup> </sup>CME e-journal club moderator, which is sponsored by an educational<sup> </sup>grant from Eli Lilly; he also reports being co-chairman of the<sup> </sup>psychopharmacology annual update for the American Psychiatric<sup> </sup>Association annual meeting, supported by educational grants<sup> </sup>from Organon and Bristol-Myers Squibb.<sup> </sup>
<!--stopindex--> <!--null--> Author Affiliation: Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas.
REFERENCES <table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td bgcolor="#6a90aa" width="100%"></td></tr></tbody></table>
<!-- null -->1. Mamelund SE. Effects of the Spanish Influenza pandemic of 1918-1919 on later life mortality of Norwegian cohorts born about 1900. Memorandum No. 29/2003. Oslo, Norway: Department of Economics, University of Oslo; 2003.<!-- HIGHWIRE ID="301:3:324:1" --> <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->2. Menninger KA. Psychoses associated with influenza, I: general data: statistical analysis. JAMA. 1919;72(4):235-241.<!-- HIGHWIRE ID="301:3:324:2" --> <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->3. Menninger KA. Influenza and schizophrenia: an analysis of post-influenzal "dementia praecox," as of 1918, and five years later: further studies of the psychiatric aspects of influenza. Am J Psychiatry. 1926;5(4):469-529.<!-- HIGHWIRE ID="301:3:324:3" --> <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->4. Kraepelin E. Dementia praecox. In: Kraepelin E, Ayed S, trans-ed. Quen JM, ed. A Textbook for Students and Physicians: Vol 2 (1899). 6th ed. Canton, MA: Science History Publications; 1990:110-161.<!-- HIGHWIRE ID="301:3:324:4" --><!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->5. First MB, Frances A, Pincus HA. DSM-IV-TR Guidebook. Washington, DC: American Psychiatric Publishing Inc; 2004.<!-- HIGHWIRE ID="301:3:324:5" --><!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->6. Bleuler E. Dementia Praecox or the Group of Schizophrenias. Zinkin J, trans-ed. New York, NY: International Universities Press; 1950.<!-- HIGHWIRE ID="301:3:324:6" --><!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->7. Sabshin M. Turning points in twentieth-century American psychiatry. Am J Psychiatry. 1990;147(10):1267-1274.<!-- HIGHWIRE ID="301:3:324:7" --> <nobr>FREE FULL TEXT</nobr> <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->8. Andreasen NC. DSM and the death of phonomenology in America: an example of unintended consequences. Schizophr Bull. 2007;33(6):108-112.<!-- HIGHWIRE ID="301:3:324:8" --> <nobr>FREE FULL TEXT</nobr> <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->9. Fromm-Reichmann F. Notes on the development of treatment of schizophrenics by psychoanalysis and psychotherapy. Psychiatry. 1948;11(3):263-273.<!-- HIGHWIRE ID="301:3:324:9" --> PUBMED <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->10. Tamminga CA, Shad MU, Ghose S. Neuropsychiatric aspects of schizophrenia. In: Yudofsky SC, Hales RE, eds. The American Psychiatric Publishing Textbook of Neuropsychiatry and Behavioral Neurosciences. Washington, DC: American Psychiatric Publishing Inc; 2008:969-1001.<!-- HIGHWIRE ID="301:3:324:10" --><!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->11. Cuesta MJ, Peralta V. Current psychopathological issues in psychosis: towards a phenome-wide scanning approach. Schizophr Bull. 2008;34(4):587-590.<!-- HIGHWIRE ID="301:3:324:11" --> FREE FULL TEXT <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->12. Battle YL, Martin BC, Dorfman JH, Miller LS. Seasonality and infectious disease in schizophrenia: the birth hypothesis revisited. J Psychiatr Res. 1999;33(6):501-509.<!-- HIGHWIRE ID="301:3:324:12" --> PUBMED <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->13. Bagalkote H, Pang D, Jones PB. Maternal influenza and schizophrenia in the offspring. Int J Ment Health. 2001;29:3-21.<!-- HIGHWIRE ID="301:3:324:13" --> <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->14. Brown AS, Begg MD, Gravenstein S; et al. Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry. 2004;61(8):774-780.<!-- HIGHWIRE ID="301:3:324:14" --> <nobr>FREE FULL TEXT</nobr> <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->15. van den Berg BJ. The California Child Health and Development Studies: twenty years of research. World Health Stat Q. 1979;32(4):269-286.<!-- HIGHWIRE ID="301:3:324:15" --> PUBMED <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table>
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Petite histoire de la nosologie en psychiatrie
Depuis le d?but du XXe si?cle, la psychiatrie a ?t? anim?e de diff?rents courants de pens?e. Chacun s?accompagne de son lot d?avanc?es et de retours en arri?re. De surprises aussi comme cette curieuse association lors de l??pid?mie de grippe espagnole.
TOUTE L?HISTOIRE d?bute dans les ann?es 1920. Tr?s exactement deux ans plus t?t, en 1918, alors que l?effroyable ?pid?mie de grippe espagnole vient de d?cimer entre 50 et 100 millions de jeunes adultes ?g?s entre 20 et 40 ans. Le psychiatre Karl Menninger note une curieuse association entre grippe et maladies psychiatriques chez 80 patients admis au Boston Psychopathic Hospital. L??tude est publi?e dans le ? JAMA ? en 1919 et est encore c?l?bre aujourd?hui. Mais pas tant sur la physiopathologie de la grippe dans les psychoses, que comme une ?tape clef dans l?histoire de la psychiatrie? Des sujets au diagnostic de ? dementia pr?cox ? vont en effet retenir l?attention du psychiatre. Et l?, ? sa grande surprise, au cours d?un suivi de cinq ans, 35 parmi 50 sujets r?cup?rent totalement et 5 sont consid?rablement am?lior?s. Ces patients ?tiquet?s ? dementia pr?cox ? ne seraient-ils pas d?ments en r?alit? ? Cette constatation l?am?ne ? penser que ? de nouveaux crit?res de diagnostic ou de nouvelles conceptions pronostiques sont n?cessaires ?. Et c?est le point de d?part de la classification moderne des maladies psychiatriques.
De la dementia pr?cox ? la schizophr?nie.
Au d?but du XXe si?cle, le psychiatre Kr?pelin popularise le terme de ? dementia pr?cox ?, qu?il d?finit comme une maladie c?r?brale d?g?n?rative commen?ant ? la fin de l?adolescence et dont les sympt?mes vont en s?aggravant. Puis arrive le Suisse Bleuler, tr?s influenc? par Freud, qui croit, lui, ? un d?s?quilibre mental d? ? des fonctions normales surexprim?es. Bleuler rebaptise la ? dementia pr?cox ? en schizophr?nie, ou ? esprit scind? ?, pour traduire les contradictions intrapsychiques du trouble.
Avec la d?ferlante psychanalytique, les courants plus normatifs sont mis de c?t? jusqu?aux ann?es 1970. La nosologie, l??pid?miologie mais aussi les neurosciences et la neurobiologie sont rel?gu?es aux oubliettes. Le concept de la m?re schizophr?nog?nique illustre le caract?re extr?me pris par ce mode de pens?e. Le trouble mental y est expliqu? comme la r?sultante d?un comportement maternel ambivalent, ? la fois surprotecteur et rejetant. En pratique, aucune am?lioration chez le patient mais une culpabilit? aggrav?e du c?t? des m?res.
Retour ? la classification du DSM.
Devant le tournant subjectif et trop peu rationnel pris par la sp?cialit?, l?American Psychiatric Association prend le contre-pied dans les ann?es 1970 et organise la r?daction de la troisi?me ?dition du Diagnostic and Statistical Manual of Mental Disorders (DSM-III). L?ouvrage a pour mission de cat?goriser les troubles psychiatriques et de d?finir des crit?res diagnostiques prouv?s. Depuis les multiples d?couvertes r?alis?es ces vingt derni?res ann?es dans des champs aussi divers que la biologie mol?culaire et cellulaire, la g?n?tique, l?imagerie et l??pid?miologie, la classification du DSM-IV montre ses limites ? son tour. Une cinqui?me ?dition programm?e pour 2 012 devrait compl?ter, voire remplacer, la d?finition de la schizophr?nie.
Alors la boucle est-elle boucl?e ? Entre grippe et schizophr?nie, Menninger avait formul? plusieurs hypoth?ses, mais pas celle de l?exposition au virus in utero. Et pourtant? Le risque de schizophr?nie serait plus ?lev?, 3 fois plus sur l?ensemble des ?tudes ? ce sujet et jusqu?? 7 fois plus dans l??tude de Brown. Certaines formes de schizophr?nie pourraient ?tre ?vit?es en vaccinant les femmes enceintes. Un bel exemple de recherche accomplie en d?pit des turpitudes de la discipline.
? Dr IR?NE DROGOU
Yudofsky S. JAMA, 21 janvier 2009. Contracting schizophrenia.
Le Quotidien du M?decin du : 23/01/2009
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width="1"></td> </tr><tr><td bgcolor="#b1bdbf" width="138" height="1"></td> </tr></tbody></table></td></tr></tbody></table> </td></tr></tbody></table> Contracting SchizophreniaLessons From the Influenza Epidemic of 1918-1919
<nobr>Commentary by Stuart C. Yudofsky, MD</nobr>
JAMA. 2009;301(3):324-326.
<!--startindex-->
SUMMARY OF THE ORIGINAL ARTICLE Psychoses Associated With Influenza,<sup> </sup>I: General Data: Statistical Analysis
Karl A. Menninger, MS,<sup> </sup>MD
JAMA. 1919;72(4):235-241.
Menninger presented a series<sup> </sup>of 100 patients observed at the Boston Psychopathic Hospital<sup> </sup>from September 15, 1918, through December 15, 1918. All patients<sup> </sup>had mental disturbances associated with influenza.
See PDF<sup> </sup>for full text of the original JAMA article.
Karl A. Menninger, MS,<sup> </sup>MD
JAMA. 1919;72(4):235-241.
Menninger presented a series<sup> </sup>of 100 patients observed at the Boston Psychopathic Hospital<sup> </sup>from September 15, 1918, through December 15, 1918. All patients<sup> </sup>had mental disturbances associated with influenza.
See PDF<sup> </sup>for full text of the original JAMA article.
The Spanish influenza pandemic of 1918-1919 was contracted by<sup> </sup>more than 500 million individuals worldwide, between 50 million<sup> </sup>and 100 million individuals died in just 1 year, and the preponderance<sup> </sup>of deaths was among 20- to 40-year-olds.<sup>1</sup> One of the few silver<sup> </sup>linings in the dark, devastating cloud of this epidemic has<sup> </sup>been its value as a probe for elucidating conceptual approaches<sup> </sup>for diagnosing and treating subsequent psychiatric illnesses<sup> </sup>among those who were infected and survived. Paradoxically, each<sup> </sup>advance in the diagnostic classification systems of psychiatric<sup> </sup>disorders during the 20th century has also brought coincident<sup> </sup>conceptual limitations that have impaired research into the<sup> </sup>understanding and treatment of individuals with mental illnesses.<sup> </sup>
In 1919, JAMA published a classic article by Karl A. Menninger<sup> </sup>on the association of influenza and psychoses in patients who<sup> </sup>were admitted to the Boston Psychopathic Hospital from September<sup> </sup>15, 1918, through December 15, 1918, the apogee of this scourge<sup> </sup>in New England.<sup>2</sup> Menninger's professional life was in transition<sup> </sup>in 1918 (as was the field of psychiatry in the era in which<sup> </sup>this paper was written): he was in the internship year between<sup> </sup>graduation from Harvard Medical School and founding the legendary<sup> </sup>Menninger Clinic in Topeka, Kansas (with his father C. F. Menninger,<sup> </sup>MD). In this Classic, Menninger reported the clinical courses<sup> </sup>of 80 patients admitted to the psychiatric hospital with "mental<sup> </sup>disturbances" associated with influenza, of whom 16 were diagnosed<sup> </sup>with delirium, 25 with dementia praecox, 23 with "other types<sup> </sup>of psychosis," and 16 who were not able to be classified.<sup>2</sup> It<sup> </sup>was the group of patients diagnosed with dementia praecox who<sup> </sup>captured Menninger's primary interest in this article<sup>2</sup> and in<sup> </sup>others he published about this series of patients. In 1926,<sup> </sup>Menninger published a follow-up study of 50 patients diagnosed<sup> </sup>with dementia praecox (at Boston Psychopathic Hospital) after<sup> </sup>the 1918 influenza outbreak.<sup>3</sup> To his surprise, 35 of these patients<sup> </sup>completely recovered within a 5-year follow-up period and 5<sup> </sup>others showed improvement. He wrote, "The astonishing indication<sup> </sup>of these data is that the vast majority of cases regarded as<sup> </sup>?dementia praecox? did not dement, but actually<sup> </sup>recovered," and concluded, "This would seem to indicate the<sup> </sup>need of new diagnostic criteria or new prognostic conceptions."<sup>3</sup><sup> </sup>
Diagnosing Schizophrenia at the Turn of the 20th Century <table border="0" cellpadding="0" cellspacing="0" width="100%"> <tbody><tr> <td bgcolor="#6a90aa" width="100%">
</td><td></td></tr></tbody></table>Dementia praecox, a term popularized in the late 19th and early<sup> </sup>20th centuries by German psychiatrist Emil Kraepelin, MD, was<sup> </sup>thought to be a degenerating disease of the brain that began<sup> </sup>with patients in their late teens and comprised a constellation<sup> </sup>of diverse and usually progressively worsening symptoms.<sup>4</sup> Kraepelin's<sup> </sup>diagnostic classification was largely based on clusters of signs<sup> </sup>and symptoms exhibited by patients he had observed during the<sup> </sup>protracted courses of their illnesses, as well as on a theory<sup> </sup>of causality, which, in the case of dementia praecox, was a<sup> </sup>hereditary "autointoxication" leading to cortical neuronal loss.<sup>4</sup><sup> </sup>He used symptomatic criteria and courses of illness to differentiate<sup> </sup>dementia praecox and manic depression into 2 distinct categories<sup> </sup>of psychotic disorders, and this process has comprised a categorical<sup> </sup>approach to the diagnostic classification system that is the<sup> </sup>prevailing method in the current Diagnostic and Statistical<sup> </sup>Manual of Mental Disorders (Fourth Edition, Text Revision [DSM-IV-TR]).<sup>5</sup><sup> </sup>
Swiss psychiatrist Eugen Bleuler, MD, who was strongly influenced<sup> </sup>by the ideas of Sigmund Freud, did not believe that dementia<sup> </sup>praecox was the result of an irreversible deterioration of the<sup> </sup>brain but, rather, the condition reflected "disharmonious" mental<sup> </sup>states that were exaggerations of normal psychic functions.<sup>6</sup><sup> </sup>Bleuler proposed renaming the condition "schizophrenia," or<sup> </sup>"split-mind," to reflect the contradictory intrapsychic influences<sup> </sup>he deemed to characterize the disorder. He also contended that<sup> </sup>schizophrenia actually encompassed a group of psychotic disorders<sup> </sup>that could be ameliorated, but not cured, by psychotherapeutic<sup> </sup>treatments.<sup>6</sup><sup> </sup>
1920-1970: What Happened to the Brain in Schizophrenia? <table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td bgcolor="#6a90aa" width="100%">
</td></tr></tbody></table>During the first two-thirds of the 20th century in the United<sup> </sup>States, Freud's psychoanalytically based conceptualizations<sup> </sup>principally shaped psychiatry's theoretical, etiological, diagnostic,<sup> </sup>and therapeutic approaches to schizophrenia and other mental<sup> </sup>illnesses.<sup>7</sup> Although psychoanalytic approaches have brought<sup> </sup>many tools to the armamentarium of psychiatry for understanding<sup> </sup>and treating patients with mental illnesses, there were also<sup> </sup>concomitant disadvantages of the predominant psychoanalytic<sup> </sup>emphasis during this period. These drawbacks were summarized<sup> </sup>by psychoanalyst Melvin Sabshin, MD, medical director of the<sup> </sup>American Psychiatric Association from 1974 to 1994 and one of<sup> </sup>the United States' most prominent psychiatrists both before<sup> </sup>and during this epoch, as follows: " . . . psychoanalysis<sup> </sup>developed enormous academic institutional power and affected<sup> </sup>significant hospitals, associations and their leaders . . . Epidemiology<sup> </sup>was essentially ignored as much as nosology, although without<sup> </sup>the opprobrium that many analysts cast upon the classificatory<sup> </sup>systems . . . Furthermore, the overwhelming<sup> </sup>majority of psychoanalysts demonstrated minimal interest in<sup> </sup>exploring the relationship between intrapsychic process and<sup> </sup>new biological concepts."<sup>7</sup> Nancy Andreasen, MD, PhD, a neuroscientist<sup> </sup>and psychiatrist, agrees: "In general, the psychoanalytic movement<sup> </sup>considered diagnosis and classification to be a fruitless endeavor.<sup> </sup>Defining the nature and source of intrapsychic conflicts was<sup> </sup>the goal instead."<sup>8</sup><sup> </sup>
A prototypic example and outcome of the overemphasis of mental<sup> </sup>processes in the putative etiology, diagnosis, and treatment<sup> </sup>of schizophrenia is the theory of the schizophrenogenic mother,<sup> </sup>as posited by prominent psychoanalyst Frieda Fromm-Reichmann,<sup> </sup>MD, and embraced by many others.<sup>9</sup> Fromm-Reichmann argued that<sup> </sup>schizophrenia was caused by mothers who were simultaneously<sup> </sup>overinvolved with and rejecting of their affected children,<sup> </sup>with the consequent recommendation of psychoanalysis as a primary<sup> </sup>treatment for the condition: "The schizophrenic is painfully<sup> </sup>distrustful and resentful of other people due to the severe<sup> </sup>early warp and rejection he encountered in important people<sup> </sup>of his infancy and childhood, as a rule, mainly a schizophrenogenic<sup> </sup>mother."<sup>9</sup> In addition to shaming and blaming mothers who already<sup> </sup>were experiencing stress and other problems from caring for<sup> </sup>severely disabled, distressed, and distressing offspring, the<sup> </sup>"opportunity costs" of failures in that era to conduct research<sup> </sup>on valid neurobiological etiologies and effective treatments<sup> </sup>for individuals with schizophrenia are incalculable.<sup> </sup>
DSM and Schizophrenia <table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td bgcolor="#6a90aa" width="100%">
</td></tr></tbody></table>US psychiatrists trained from the 1920s through the late 1960s<sup> </sup>were taught to diagnose schizophrenia, at least in part, based<sup> </sup>on the personal feeling states evoked by these patients while<sup> </sup>in their physical presence. Manifestly, these highly subjective<sup> </sup>emotional reactions varied greatly from clinician to clinician,<sup> </sup>and, thereby, significantly reduced the diagnostic reliability<sup> </sup>and, most likely, the validity of this approach. Additionally,<sup> </sup>neither a uniformly accepted diagnostic language nor categorization<sup> </sup>format existed whereby either clinicians or researchers could<sup> </sup>communicate reliably about patients in their care or participants<sup> </sup>in their research. This deficiency seriously impaired the abilities<sup> </sup>of scientists to conduct valid schizophrenia research of all<sup> </sup>types, especially across disparate cultures and nationalities.<sup>5</sup><sup> </sup>
In 1974, the American Psychiatric Association charged a group<sup> </sup>of psychiatrists and biometricians to develop a third edition<sup> </sup>of the Diagnostic and Statistical Manual of Mental Disorders<sup> </sup>(DSM-III) that would prioritize evidence-based, operationalized<sup> </sup>criteria for making diagnoses, as opposed to basing diagnoses<sup> </sup>on untested and nonvalidated etiological theories.<sup>5</sup> During the<sup> </sup>1990s through the present time, technological and methodological<sup> </sup>breakthroughs in brain imaging, molecular and cellular biology,<sup> </sup>genetics, and epidemiological research progressively have opened<sup> </sup>a multiplicity of exciting new avenues of understanding the<sup> </sup>etiologies and pathogeneses of many psychiatric disorders, including<sup> </sup>schizophrenia.<sup>10</sup><sup> </sup>
Although DSM-III and, currently, DSM-IV-TR are based on categorical<sup> </sup>diagnoses that have been broadly used and proven as valuable<sup> </sup>in outcome research of psychopharmacological and psychotherapeutic<sup> </sup>treatments of individuals with schizophrenia, the plethora of<sup> </sup>recent findings in neurobiology and neurogenetics has revealed<sup> </sup>limitations of this approach that constrain the progress of<sup> </sup>research in schizophrenia.<sup>11</sup> Specifically, the categorical diagnostic<sup> </sup>format of Kraepelin that distinguishes dementia praecox from<sup> </sup>bipolar illness is partially based on the longitudinal course<sup> </sup>of both illnesses. Categorical diagnostic classification of<sup> </sup>schizophrenia will likely be replaced or complemented in the<sup> </sup>fifth edition of DSM, scheduled to be published in 2012, by<sup> </sup>a dimensional approach that emphasizes the symptom continua<sup> </sup>that are common to varieties of psychosis, such as reality distortion,<sup> </sup>disorganization, negativity, catatonia, mania, and depression.<sup>11</sup><sup> </sup>
Can Influenza "Cause" Schizophrenia? <table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td bgcolor="#6a90aa" width="100%">
</td></tr></tbody></table>Although Menninger considered many avenues by which the Spanish<sup> </sup>Influenza of 1918 could lead to the development of dementia<sup> </sup>praecox, neither he nor any of his contemporary investigators<sup> </sup>raised the possibility that the influence of influenza on the<sup> </sup>etiology of schizophrenia could occur in utero. Although this<sup> </sup>idea has been debated in the scientific literature, many studies<sup> </sup>have documented that schizophrenia occurs more frequently in<sup> </sup>children born in winter and early spring when viral infections<sup> </sup>are more prevalent.<sup>12</sup> Among 25 investigations of the incidence<sup> </sup>of schizophrenia in the offspring of women who were thought<sup> </sup>to have contracted influenza during pregnancy, approximately<sup> </sup>50% reported positive associations.<sup>13</sup> Reliably documenting maternal<sup> </sup>influenza exposure in these studies has been challenging because<sup> </sup>viral exposure has been generally based on participants' self-reports<sup> </sup>of infection or on occurrences of influenza epidemics contemporaneous<sup> </sup>with their pregnancies. To counter this problem, Brown et al<sup> </sup>assayed for influenza antibodies in sera drawn from pregnant<sup> </sup>women whose children later developed schizophrenia, and compared<sup> </sup>these samples with ones from a matched control group of women<sup> </sup>whose children did not develop schizophrenia.<sup>14</sup> The study population<sup> </sup>was derived from 170 cases judged to have schizophrenia or "schizophrenia<sup> </sup>spectrum disease" from a cohort of 12 094 live births enrolled<sup> </sup>in the California Child Health and Development Study.<sup>15</sup> The<sup> </sup>results of the study by Brown et al<sup>14</sup> revealed a dramatic 7-fold<sup> </sup>increase in the risk of schizophrenia among the offspring of<sup> </sup>women who were exposed to influenza during their first trimester<sup> </sup>of pregnancy. Further analysis suggested a 3-fold increase of<sup> </sup>risk in women who were exposed to influenza from the midpoints<sup> </sup>of their first and second trimesters.<sup>14</sup><sup> </sup>
The finding that exposure to influenza during pregnancy may<sup> </sup>be an etiologic factor for schizophrenia may lead to new understanding<sup> </sup>of the pathogenesis, treatment, and prevention of this devastating<sup> </sup>condition. For example, vaccinating women of childbearing age<sup> </sup>against influenza might help prevent some forms of schizophrenia.<sup> </sup>In carrying to fruition this remarkable line of research, the<sup> </sup>90 years of progress in improving psychiatric diagnosis and<sup> </sup>classification since the original Menninger study<sup>2</sup> have been<sup> </sup>as important as the advances in modern laboratory techniques<sup> </sup>used to assay the influenza antigens in the sera of the cohorts.<sup> </sup>It certainly seems reasonable to speculate that Kraepelin, Bleuler,<sup> </sup>and Karl Menninger would be excited by this progress and pleased<sup> </sup>with their seminal roles in the evolution of the diagnosis and<sup> </sup>classification of psychiatric disorders.<sup> </sup>
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AUTHOR INFORMATION <table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td bgcolor="#6a90aa" width="100%">
</td></tr></tbody></table>Corresponding Author: Stuart C. Yudofsky, MD, Menninger Department<sup> </sup>of Psychiatry and Behavioral Sciences, Baylor College of Medicine,<sup> </sup>One Baylor Plaza, Room 115-D, Houston, TX 77030 (stuarty@bcm.tmc.edu<script type="text/javascript"><!-- var u = "stuarty", d = "bcm.tmc.edu"; document.getElementById("em0").innerHTML = '<a href="mailto:' + u + '@' + d + '">' + u + '@' + d + '<\/a>'//--></script>).<sup> </sup>
Financial Disclosures: Dr Yudofsky reports being the Neuroscience<sup> </sup>CME e-journal club moderator, which is sponsored by an educational<sup> </sup>grant from Eli Lilly; he also reports being co-chairman of the<sup> </sup>psychopharmacology annual update for the American Psychiatric<sup> </sup>Association annual meeting, supported by educational grants<sup> </sup>from Organon and Bristol-Myers Squibb.<sup> </sup>
<!--stopindex--> <!--null--> Author Affiliation: Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas.
REFERENCES <table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td bgcolor="#6a90aa" width="100%">
</td></tr></tbody></table><!-- null -->1. Mamelund SE. Effects of the Spanish Influenza pandemic of 1918-1919 on later life mortality of Norwegian cohorts born about 1900. Memorandum No. 29/2003. Oslo, Norway: Department of Economics, University of Oslo; 2003.<!-- HIGHWIRE ID="301:3:324:1" --> <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td>
</td></tr></tbody></table><!-- null -->2. Menninger KA. Psychoses associated with influenza, I: general data: statistical analysis. JAMA. 1919;72(4):235-241.<!-- HIGHWIRE ID="301:3:324:2" --> <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->3. Menninger KA. Influenza and schizophrenia: an analysis of post-influenzal "dementia praecox," as of 1918, and five years later: further studies of the psychiatric aspects of influenza. Am J Psychiatry. 1926;5(4):469-529.<!-- HIGHWIRE ID="301:3:324:3" --> <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->4. Kraepelin E. Dementia praecox. In: Kraepelin E, Ayed S, trans-ed. Quen JM, ed. A Textbook for Students and Physicians: Vol 2 (1899). 6th ed. Canton, MA: Science History Publications; 1990:110-161.<!-- HIGHWIRE ID="301:3:324:4" --><!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->5. First MB, Frances A, Pincus HA. DSM-IV-TR Guidebook. Washington, DC: American Psychiatric Publishing Inc; 2004.<!-- HIGHWIRE ID="301:3:324:5" --><!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->6. Bleuler E. Dementia Praecox or the Group of Schizophrenias. Zinkin J, trans-ed. New York, NY: International Universities Press; 1950.<!-- HIGHWIRE ID="301:3:324:6" --><!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->7. Sabshin M. Turning points in twentieth-century American psychiatry. Am J Psychiatry. 1990;147(10):1267-1274.<!-- HIGHWIRE ID="301:3:324:7" --> <nobr>FREE FULL TEXT</nobr> <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->8. Andreasen NC. DSM and the death of phonomenology in America: an example of unintended consequences. Schizophr Bull. 2007;33(6):108-112.<!-- HIGHWIRE ID="301:3:324:8" --> <nobr>FREE FULL TEXT</nobr> <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->9. Fromm-Reichmann F. Notes on the development of treatment of schizophrenics by psychoanalysis and psychotherapy. Psychiatry. 1948;11(3):263-273.<!-- HIGHWIRE ID="301:3:324:9" --> PUBMED <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->10. Tamminga CA, Shad MU, Ghose S. Neuropsychiatric aspects of schizophrenia. In: Yudofsky SC, Hales RE, eds. The American Psychiatric Publishing Textbook of Neuropsychiatry and Behavioral Neurosciences. Washington, DC: American Psychiatric Publishing Inc; 2008:969-1001.<!-- HIGHWIRE ID="301:3:324:10" --><!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->11. Cuesta MJ, Peralta V. Current psychopathological issues in psychosis: towards a phenome-wide scanning approach. Schizophr Bull. 2008;34(4):587-590.<!-- HIGHWIRE ID="301:3:324:11" --> FREE FULL TEXT <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->12. Battle YL, Martin BC, Dorfman JH, Miller LS. Seasonality and infectious disease in schizophrenia: the birth hypothesis revisited. J Psychiatr Res. 1999;33(6):501-509.<!-- HIGHWIRE ID="301:3:324:12" --> PUBMED <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->13. Bagalkote H, Pang D, Jones PB. Maternal influenza and schizophrenia in the offspring. Int J Ment Health. 2001;29:3-21.<!-- HIGHWIRE ID="301:3:324:13" --> <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->14. Brown AS, Begg MD, Gravenstein S; et al. Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry. 2004;61(8):774-780.<!-- HIGHWIRE ID="301:3:324:14" --> <nobr>FREE FULL TEXT</nobr> <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table><!-- null -->15. van den Berg BJ. The California Child Health and Development Studies: twenty years of research. World Health Stat Q. 1979;32(4):269-286.<!-- HIGHWIRE ID="301:3:324:15" --> PUBMED <!-- /HIGHWIRE --><table border="0" cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td></td></tr></tbody></table> </td></tr></tbody></table>