Pathophysiology: Introduction to Neuropsychiatry


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This presentation was given to first year pharmacy students as part of a course on medical physiology and pathophysiology.

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  • Neurons in mouse brain (likely pyramidal).
  • Pinel did away with bleeding, purging, and blistering in favor of a therapy that involved close contact with and careful observation of patients. Pinel visited each patient, often several times a day, and took careful notes over two years. He engaged them in lengthy conversations. The actual removal of the shackles may have been done by someone else  Jean-Baptiste Pussin(1745-1811), the superintendent.Pinel's classification of mental disorders included four basic types: melancholia, mania (insanity), dementia, and idiotism. 
  • Charcot provided key descriptions of ALS/MS. He also promoted the otherwise obscure writings that led to (James) Parkinson’s Disease & (George) Huntington’s Disease.
  • The International Classification of Diseases is published by the World Health Organization (WHO) and used worldwide for morbidity and mortality statistics and reimbursement systems. In 1893, a French physician, Jacques (joc) Bertillon, introduced the Bertillon Classification of Causes of Death at a congress of the International Statistical Institute in Chicago.  Many countries and cities adopted Dr. Bertillon’s system, which was based on the principle of distinguishing between general diseases and those localized to a particular organ or anatomical site, as was used by Paris for classifying deaths. Includes a 6 digit code for insurance reimbursement.The ICD-9 contained 17K codes for diseases & procedures. ICD-10 = 155K!
  • Loss of energy or change in appetite; feelings of worthlessness or excessive guilt; difficulty concentrating, thinking, or making decisions.
  • Reliability was a problem with the Rosenhan schizophrenia study.
  • The eight pseudopatients were a varied group. One was a psychology graduate student in his 20's and there were three psychologists, a pediatrician, a psychiatrist, a painter, and a housewife (5 male).35/118 patients were skeptical (e.g. you’re a journalist)0:37-3:30:
  • An older school of thought for the origins of psychiatric disorders was poor parenting (e.g. “refrigerator mother” & autism).
  • Pathophysiology: Introduction to Neuropsychiatry

    1. 1. Introduction to Neurological & Psychiatric Disorders Brian J. Piper, Ph.D., M.S. October 16, 2012
    2. 2. Learning objectivesPharmacy students should be able to:1. Compare and contrast psychiatry & neurology (historical figures & diagnostic systems).2. Provide examples of animal models of human neurobehavioral conditions.3. Evaluate evidence of neurobiological substrates of psychiatric conditions.
    3. 3. Neurology Psychiatryfounder Jean Martin Charcot Philippe Pineldiagnostic system International Diagnostic & Classification Statistical of Diseases (ICD) Manual (DSM)examples epilepsy, migraine, MS/ALS, depression, schizophrenia, Parkinson’s sleep, dementia, autismpathophysiology moderate lowlaboratory tests common uncommondevelopment of moderate moderateanimal models (Parkinson’s, migraine) (drug addiction, schiz)
    4. 4. Father of Psychiatry: Philippe Pinel• moral treatment• classification: 4 Tony Robert-fleury (1876 ): Philippe Pinel releasing 1745 - 1826 lunatics from their chains at the Salpetriere asylum for women in Paris.
    5. 5. Father of Neurology: Jean Charcot• Described: – ALS – Multiple Sclerosis – Parkinson’s Disease – Huntington’s disease – Tourette syndrome
    6. 6. International Classification of Diseases • UN/WHO • International List of Causes of Death 1: 1900 • International Statistical Classification of Diseases 6: 1949 • ICD-10: 1994 • ICD-11: 2015
    7. 7. Diagnostic & Statistical Manual of Mental Disorders (DSM)• Published by American Psychiatric Association• DSM-I: 1952: consists of 106 mental disorders• DSM-II: 1968: psychodynamic• DSM-III: 1980: descriptive, removal of homosexuality• DSM-IV: 1994: 297 disorders• DSM-5: 2013: ≈300 disorders!
    8. 8. Major Depressive Disorder • At least one: • At least five: – sad mood – ↑/↓sleeping – anhedonia – psychomotor agitation/retardation – loss of energy – weight loss – excessive guilt • Symptoms are present – thoughts of nearly every day for at death/suicide least 2 weeks.Kring et al. (2012). Abnormal Psychology, p. 134.
    9. 9. Criticisms of DSM• economic conflicts of interest• too subjective (interview, not laboratory based)• qualitative or quantitative• comorbidity (anxiety/depression; anorexia/bulimia)• reliable• valid – out: Asperger’s, Catatonic Schizophrenia – in: Premenstrual Dysphoric Disorder
    10. 10. Rosenhan Study • 8 pseudopatients show up at psychiatric facilities (12) with one symptom (hearing voices) • all diagnosed with schizophrenia • institutionalized for 7 -52 days • patients, but not staff, were suspiciousRosenhan, D. L. (1973). On being sane in insane places. Science, 179, 250-258.
    11. 11. Accuracy of Diagnosis Decision • 8 healthy pseduo-patients presented to SCZ- SCZ+ 12 psychiatric hospitals with complaint SCZ- Correct Type I of hearing voices Reality Diagnosis error • Acted normal but 11 diagnosed as schizophrenic SCZ+ Type II Correct error Diagnosis • Fellow patients, but not staff, were suspicious • Released after 7-52 days (mean = 19) 1929-2012Rosenhan (1973). Science, 179, 250-258.
    12. 12. Neuropsychopharmacology
    13. 13. Genain Sisters “Genain”: Greek “dire birth”, born 1930, allhospitalized for schizophrenia by early 20s, probability = 1.5 billion Nora: intermediate (jobs, no family) Iris: intermediate (jobs, no family) Myra: secretary, married, 2 sons Hester: showed signs at age 11, institutionalized Genetics: identical Environment: identical (schizophrenic mom) Prenatal: ?
    14. 14. Genetics & Schizophrenia The likelihood of an individual suffering from schizophrenia is 50% if their identical twin has the disorder. 0 10 20 30 40 50 Identical Both parents Fraternal One parent SiblingNephew or niece Unrelated
    15. 15. Genetics & Schizophrenia The following shows the prevalence ofschizophrenia in identical twins as seen in different countries.
    16. 16. Heritability of Psychiatric DisordersBritish Medical Journal 1999; 319 : 37
    17. 17. Structural Changes & Depression• Rat research indicate that persistent increases in cortisol are toxic to hippocampal neurons.• Studies examining the volume of the hippocampus in MDD were inconsistent.• A meta-analysis showed that the left (-4.5%) and right hippocampus (-4.0%) showed reductions.Cole et al. (2011). Journal of Affective Disorders, 134, 483-487.
    18. 18. Brain Morphology & Schizophrenia Some schizophrenia patients exhibit morphological changes in the brain like enlargement of fluid-filled ventricles. Both Photos: Courtesy of Daniel R. Weinberger, M.D., NIH-NIMH/ NSC
    19. 19. Individual Differences in SCZ
    20. 20. Meta-Analysis • 58 studies Region (Left or Right) % of Control • 1,588 SCZ patients L Lateral Ventricle 130 R Lateral Ventricle 120 Gray Matter 96 White Matter 98 L Frontal Lobe 95 L Hippocampus 95 L Amygdala 91 L Thalamus 96 R Thalamus 96Wright et al. (2000). American Journal of Psychiatry, 157, 16-25.
    21. 21. Concern: Cause or Correlate? • Adult monkeys received typical (haloperidol) or * atypical (olanzapine) * antipsychotics for 2 years at doses similar to schizophrenics. • Gray matter in parietal cortex was examined.Konopaske et al. (2007). Neuropsychopharmacology, 32, 1216-1223.
    22. 22. Wisconsin Card Sorting Test• Developed by Esta Berg in 1950s• Measures cognitive flexibility and perseverative behaviors (number, color, shape)
    23. 23. Hypofrontality During WCST
    24. 24. Example Animal Models• Psychiatry: Forced Swim Test (depression) b5U• Neurology: Roto-rod (PD/motor function) XlBQ
    25. 25. Current: Mental Health “Care”U.S. Patients in Psychiatric Hospitals, by year.U.S. Census, 2007.