Lecture 22 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. (email@example.com) at Willamette University. Focus is on typical and atypical antipsychotics.
SchizophreniaThe Greek translation is schizein “split” and phren “mind” which refers to a split from reality. A group of severe disorders characterized by atypical: 1. Cognition 2. Behavior NOT Multiple Personality Disorder 3. Emotions
Symptoms of SchizophreniaPositive symptoms: the presence of inappropriatebehaviors delusions hallucinations: auditory >>> visual > other disorganized talking: “word salad” movementsNegative symptoms: the absence of appropriatebehaviors flat affect: joy, anger, disgust anhedonia catatonia: waxy flexibility
Disorganized & Delusional ThinkingThis morning when I was at Hillside [Hospital], I wasmaking a movie. I was surrounded by movie stars …I’m Mary Poppins. Is this room painted blue to get meupset? My grandmother died four weeks after myeighteenth birthday.” (Sheehan, 1982)Other forms of delusions include, delusions ofThis monologue illustrates fragmented, bizarrethinking with (“someone is following delusions persecution distorted beliefs called me”) or grandeur (“I am a king”). (“I’m Mary Poppins”).
Example PatientHaldol: classic antipsychotic drugDelusions of grandeur: inappropriate beliefs about one’s self-worth or special powersGerald (upto 2:30): http://www.youtube.com/watch?v=gGnl8dqEoPQ
Auditory HallucinationsFor almost 7 years, except during sleep, I continue to hear voices. They accompany me to every place and at all times, when I’m in conservations with other people, they persist,undeterred, even when I concentrate on other things, for instance, read a book, play thepiano, etc. Only when I’m talking aloud to other people or to myself are they drowned by the stronger sound of the spoken word and therefore inaudible to me. Recounted by Ann M. Kring, Ph.D. Pros & Cons Behavioral strategies (& family discord) Command Hallucinations
DSM5 Diagnosis of Schizophrenia• Two or more of the following, including 1, 2, or 3 1. Delusions 2. Hallucinations 3. Disorganized speech 4. Grossly abnormal psychomotor behavior 5. Negative symptoms• Duration: 1 month during last 6• Social/occupational dysfunction• Exclusion: medical condition or drug
Typical?The relationship between schizophrenia and aggression iscontroversial.Renfrew (1996). Aggression & Its Causes.
John W. Hinckley, Jr. Jared Lee LoughnerThe relationship between schizophrenia and aggression iscontroversial.Disorganized: Increased risk of victimizationParanoid: small increaseRenfrew (1996). Aggression & Its Causes.
Accuracy of Diagnosis Decision • 8 healthy pseduo-patients SCZ- SCZ+ presented to 12 psychiatric SCZ- Correct Type I hospitals with complaint of hearing Reality Diagnosis error voices • Acted normal but 11 diagnosed as SCZ+ Type II Correct schizophrenic error Diagnosis • Fellow patients, but not staff, were suspicious • Released after 7-52 days (mean = 19) 1929-20120:37-3:30: http://www.youtube.com/watch?v=Kq-7uvVOoykRosenhan (1973). Science, 179, 250-258.
Abnormal Brain Morphology Some schizophrenia patients exhibitmorphological changes in the brain like enlargement of fluid-filled ventricles. Both Photos: Courtesy of Daniel R. Weinberger, M.D., NIH-NIMH/ NSC
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). Am J Psychiatry, 157, 16-25.
Genetic Factors The following shows the prevalence ofschizophrenia in identical twins as seen in different countries.
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: ?
Wisconsin Card Sorting Test• Developed by Esta Berg in 1950s• Measures cognitive flexibility and perseverative behaviors (number, color, shape)
Neuropsych Testing of Genain Sisters at age 68• Digit Span: working memory• Trail Making Test: set shifting• Continuous Performance Test: attention Mirsky et al. (2000). Schizophrenia Bulletin, 26, 699-708.
Concern • 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.
Beyond D2• the dopaminergic (or serotonergic) model of schizophrenia may be too simplistic Kerwin et al. (1999). Neuroscience, 39, 25-32.
Schizophrenia in Children • More frequently recognized8 min: http://www.youtube.com/watch?v=UTUMt05_nCI9 min: http://www.youtube.com/watch?v=B9v4FsKXmj8
Reduced Lifespan (N = 5,036,662)! Male Male Female Female Life Expectancy Years Life Years Lost Lost ExpectancyAll (Psychiatric 76.5 NA 80.9 NAHistory - )Schizophrenia 57.8 18.7 64.6 16.3Bipolar 62.9 13.6 68.8 12.1 Laursen (2011). Schizophrenia Research, 131, 101-104 .
Reduced Lifespan (N = 5,036,662)! Male Male Female Female Life Expectancy Years Life Years Lost Lost ExpectancyAll (Psychiatric 76.5 NA 80.9 NAHistory - )Schizophrenia 57.8 18.7 64.6 16.3Bipolar 62.9 13.6 68.8 12.1 Contributing Factors suicide, accident, homicides, self-care, metabolic (?) Laursen (2011). Schizophrenia Research, 131, 101-104 .
Art During Disease Progression• A English artist, who was fascinated by cats, painted these pictures over a period of time in which he became mentally ill.• Pro – Paranoia – Disorganization• Con Louis Wain (1860-1939) – Schizophrenia – Order
VideocastOverman, Gerald (2010). Antipsychotic treatment & tolerability. Starts about 4:40 (ends abruptly):http://videocast.nih.gov/Summary.asp?File=15991What are the pros and cons of the typical and atypicalantipsychotics?What is EPS? What areas of the brain are important for this?If you had a family member that was recently diagnosed withSCZ, what drug (or drug class) would you hope that thepsychiatrist would prescribe?