Schizophrenia has been described since ancient times, with formal diagnosis beginning in the late 19th century. Eugen Bleuler coined the term "schizophrenia" in 1911 to describe fragmented thinking. Research in the mid-20th century focused on family dynamics and genetics, finding that schizophrenia has genetic risk factors. Early treatments included sleep temple therapy, insulin shock therapy, bathing therapy, and electroconvulsive therapy, but these were replaced by first-generation antipsychotic drugs in the 1950s and later by second-generation atypical antipsychotics with fewer side effects.

1. Schizophrenia: Emerging from the Darkness Clista Clanton Baugh Biomedical Library University of South Alabama

2. History of Schizophrenia Symptoms associated with schizophrenia were described in the Book of Hearts in ancient Egypt. Dr. Emil Kraepelin introduced the term dementia praecox as a diagnostic entity in 1893: “the sub-acute development of a peculiar simple condition of mental weakness occurring at a youthful age.”

3. Eugen Bleuler, a Swiss psychiatrist, coined the term “schizophrenia” in 1911. Schizo (split) and phrene (mind) describe the fragmented thinking of people with the disorder. Mid-20 th century researchers focused on family dynamics, particularly the mother-child relationship and the onset of schizophrenia. Schizophenogenic mothers were: Cold Dominant Conflict inducing Rejecting Over protective Rigid and moralistic Fearful of intimacy

4. Early Therapies Sleep temple or dream temple therapy: the ill would spend the night in a holy place. Before falling asleep they were influenced by suggestions, in the hope of provoking dreams sent by the gods. With the knowledge generated from the dreams, incantations and prayers were used to invoke the healing powers of the gods. Sakel’s therapy (1930’s): patients were put into superficial coma’s with injections of insulin. Enjoyed great popularity with early findings indicating over 70% of patients improved after therapy. Further controlled studies showed no lasting improvement in symptoms. Some recipients of insulin shock therapy were James Forrestal (first US Secretary of Defense), Russian ballet dancer Vaslav Nijinski, Zelda Fitzgerald.

5. Bathing therapy (late 19 th century through the 1940’s): designed to calm anxiety, patients would stay in baths from several hours to several days.

6. Metrazol induced convulsions (1930’s): Ladislaus von Meduna studied the brains and mental health histories of schizophrenics and epileptics and noted that there seemed to exist a "biological antagonism" between these two diseases of the brain. He then reasoned that "pure" artificially induced epileptic convulsions could be able to "cure" schizophrenia. With the advent of other less dangerous therapies, metrazol was gradually discontinued in the late 40's and is no longer in use.

7. Electroconvulsive shock therapy (1930’s): Ugo Cerletti and Lucio Bini developed an apparatus that would deliver electric shocks to induce convulsions. Patients showed remarkable improvement and ECT became the shock therapy of choice in the majority of hospitals and asylums around the world. ECT was abused in many situations as a way to control problem patients and gradually fell out of favor. "ECT stands practically alone among the medical/surgical interventions in that misuse was not the goal of curing but of controlling the patients for the benefits of the hospital staff" (Medical Historian David J. Rothman, NIH Consensus Conference on ECT in 1985)

9. Research Landmarks Twin studies: demonstrate that genetics plays a role in the development of schizophrenia. (Gottesman, 1991)

10. Adoption studies: demonstrate that genetics play a role in the development of schizophrenia. Children of schizophrenic parents adopted by non-relatives early in life still develop schizophrenia at a significantly higher rate than the rest of the population. Smooth-pursuit eye movement: schizophrenics and their healthy blood relatives exhibit a smooth pursuit eye movement abnormality, again suggesting a genetic link for schizophrenia.

11. Approximately 10 gene variations are currently linked to the risk of developing schizophrenia. The more of these gene variations that a person has, acting in concert with environmental factors, the greater the risk of developing schizophrenia. Results of a study begun in 1990 show strong evidence for a schizophrenia susceptibility gene in 6p22-p24 and 11q21-22.

12. Brain abnormalities present in schizophrenics are larger ventricles and smaller medial temporal lobe structures. Studies suggest that prenatal infection and nutritional deficiencies as well as perinatal trauma can result in disrupted fetal brain development. Prenatal infection: schizophrenia is found 5-15% more in people born in winter and spring seasons. It is hypothesized that exposure to viral epidemics (particularly during the 2 nd trimester) during cold weather months contribute to the development of schizophrenia.

14. Pharmacotherapy First-generation or typical antipsychotics (FGA) 1952: modern era of pharmacotherapuetics in schizophrenia introduced with phenothiazine and chlorpromazine. Development of receptor binding techniques lead to discovery that the clinical potency of these drugs in treating psychotic behavior is related to the blockage of dopamine D2 receptors. 1980’s: new dopamine D2 receptor blockade drugs released. Worked well at treating the positive psychotic symptoms Induced dose-limiting extrapyramidal motor deficits (Parkinsonian symptoms to tardive dyskinesia) and exacerbated negative symptoms Failed to affect cognitive deficits

15. Second generation or atypical antipsychotic drugs (SGA) In an effort to mitigate against damaging side effects, over 30 SGA’s are now available. Clozapine, amisulpride, risperidone, and olanzapine produce greater size effects than FGAs on overall antipsychotic efficacy and reduced side effects.

16. References http://www.cerebromente.org.br/n04/historia/shock_i.htm#sakel The history of shock therapy in psychiatry. http://www.hubin.org/facts/history/1900_history/treatment/treatment_3_en.html Human brain informatics: your portal to schizophrenia.. http://www.schizophrenia.com/research/hereditygen.htm Heredity and genetics of schizophrenia. http://www.ns.purchase.edu/psych/Psychobio_of_Schizophrenia/default.htm Psychobiology of schizophrenia. McGue M, Gottesman II. The genetic epidemiology of schizophrenia and the design of linkage studies. Eur Arch Psychiatry Clin Neurosci. 1991;240(3):174-81. ):174-81 . Marek G, Merchant K. Developing therapeutics for schizophrenia and other psychotic disorders. J Am Soc Exp NeuroTher. 2005 Oct; 2:579-589.