Schizophrenia is a devastating psychotic disorder, which affects about 1% of the population worldwide. Currently there is no known cure and the prognosis is bleak for most patients. In fact it is often said that schizophrenia is to psychiatry what cancer is to medicine: a sentence as well as a diagnosis. However, recent developments in neuroscience, genetics, psychology and psychiatry have dramatically transformed and energized the field of schizophrenia research so much that the quest for the origins and cure seems within our reach. We will cover the basic ground as well as some of the more controversial topics in schizophrenia research in this course.

The format of the course is a combination of formal lectures, presentations and discussions. The first half of the course consists of lectures to get you solidly grounded in current research. The other half of the course consists of formal student presentations and discussions. Therefore, formal student presentations on a special topic (15 minutes) will form the core of the classes after a test in October. There will be a mid term test based on readings and lectures. The questions will be very straight-forward and factual (multiple choices and short answers). The test is there to make sure that you know the basic facts so that when we start class discussions and presentations, you are fully equipped to participate and enjoy the debates. After the test, we will assign the presentation slots but if you want to, you can sign up any time before. It might be best to sign up early so that you get your pick. The same student(s) who present will also lead the discussion. Based on your presentation, you will write a term paper (around 10-15 pages). The paper is due 1 week after your presentation.

Evaluation:

1. Mid-term test 30%

2. Participation in class discussion 10%

3. Presentation 30%

3. Paper 30%

Readings:

You are expected to have read all the required material and at least browse the recommended readings. Recommended readings will be useful for your presentation, discussion and paper.

All readings will be available at least a week before the class in the file cabinet in the Xerox room in Wilson. Many of them can be downloaded as pdf files from my website. I recommend the following books if you are serious about studying schizophrenia. They are also on reserve in the Wilson Xerox room.

E. Fuller Torrey. Surviving Schizophrenia

S. Matthysse, D. Levy, J. Kagan & F. Benes (1996) Psychopathology.

Gottesman, I. (1991) Schizophrenia Genesis.

Highly Recommended

1. The lost years of a Nobel laureate. The New York Times, Sunday Nov.13^th1994 by Sylvia Nasar. Or, read her book, Nasar, S. (1999) A Beautiful Mind. The film version is very different from the book.

2. The Quiet Room by Lori Schiller. We will read this together in class so don’t buy the book.

3. The Professor and the mad man (1998) by Simon Winchester. The bizarre history of the making of the Oxford English dictionary and William Minor’s contributions.

Details of the course and the reading list

Before the first class please download and read the following brochure published by the NAMI. UnderstandingSchizophrenia.pdf

Go to my website WWW.PSY.VANDERBILT.EDU/faculty/sohee/ and look under the “Courses”

Week 1

8/26 Th

Introduction and overview

Original formulation of the concept of the schizophrenias.

Gottesman. I. (1991) Schizophrenia Genesis. Ch. 3

Week 2

8/31 Tu

History and background. Is this a new disease?

Gottesman. I. (1991) Schizophrenia Genesis. Ch. 1

9/2 Th

Definitions, diagnosis and symptoms. How do we know if someone has it?

Gottesman. I. (1991) Schizophrenia Genesis. Ch. 2.

Week 3

9/7 Tu

Epidemiology. Where do we see this and when?

Gottesman. I. (1991) Schizophrenia Genesis. Ch. 4.

9/9 Th

Positive Symptoms: hallucinations

Most psychotic patients live with hallucinations every day. But hallucinations can also occur as the result of drug use, fever, brain injury, sensory deprivation and so on. The most interesting models of hallucination integrate cognitive theories with functional neuroimaging data, as well as paying meticulous attention to the phenomenology. We will discuss current models of hallucination including faulty source monitoring (Frith), neural network model (Hoffman), callosal abnormalities (David) among others.

Required

Shergill, S, Brammer, M, Murray, R, McGuire, P (2000) Mapping Auditory Hallucinations in Schizophrenia Using Functional Magnetic Resonance Imaging. Archives of General Psychiatry. Vol 57(11) pp 1033-1038.

McGuire, P.K et al., (1995) Abnormal monitoring of inner speech: a physiological basis for auditory hallucinations.The Lancet. 346, Sep, 596-600.

Cahill, C & Frith C. (1996) False perceptions of false beliefs? Hallucinations and delusions in schizophrenia. In Marshall, J.C. & Halligan, P. W.(Eds) Methods in Madnness. Blackwell. Ch 13.267-291

Week 4

9/14 Tu.

Hallucinations. (contd)

Hoffman, R.E. & McGlashan , T.H. (1997) Synaptic elimination, neurodevelopment and the mechanism of hallucinated " Voices" in schizophrenia. Am. J. Psychiatry, 154:12, Dec, 1683-1689.

David, A.S. (1994) The neuropsychological origins of auditory hallucinations. In: A.S. David & J.C. Cutting (Eds) The Neuropsychology of Schizophrenia. LEA. pp. 269-313.

Recommmended for Hallucination section : The phenomenon of "Feeling-of-Presence" is common in the general population. What are the possible neural correlates of this feeling?

Brugger, P., Regard, M. & Landis, T. (1997) Unilaterally felt "presences": The neuropsychiatry of one's invisible Doppelgänger. Neuropsychiatry, Neuropsychology and Behavioral Neurology, 9(2), 114-122.

9/16 Thu.

Positive Symptoms: Delusions

To understand delusions, we need to study both normal and abnormal reasoning processes. It is possible that delusions are the product of normal cognition and occur in response to anomalous or unusual sensory data. Therefore we need to examine cognitive biases and abnormal beliefs in the context of culture. Delusions occur in a range of psychiatric disorders (eg. Schizophrenia, manic depression, depression, eating disorders, OCD etc). There are also fascinating delusional misidentification syndromes which result from brain damage (e.g. Frégoli, Capgras & Cotard delusions). But delusions also occur frequently in every day life.

Required:

Weinstein E (1996) Reduplicative misidentification syndromes. In: Marshall, J.C. & Halligan, P.W. (Eds) Methods in Madnness. Blackwell. Ch 1. 13-36.

Ellis, H.D. & Szulecka, K.T. (1996) The Disguised Lover: A case of Frégoli delusion. In: Marshall, J.C. & Halligan, P.W. (Eds) Methods in Madnness. Blackwell. Ch 2. pp.37-50.

Halligan, P. W. & Marshall, J.C. (1996) The wise prophet makes sure of the events first: Hallucinations, amnesia and delusions. In: Marshall, J.C. & Halligan, P. W.(Eds) Methods in Madnness. Blackwell. pp.237-266.

Week 5

9/21 Tu

Delusions (contd)

Theories of how delusions are formed and maintained

Brugger, P. & Graves, P. (1997) Testing and believing hypotheses: Magical ideation in the judgment of contingencies. Cognitve Neuropsychiatry, 2(4), 251-272.

Bentall, R.P. (1994) Cognitive biases and abnormal beliefs. Towards a model of persecutory delusions. In: A.S. David & J.C. Cutting (Eds) The Neuropsychology of Schizophrenia. LEA. p.337-360.

Fleminger, S. (1994) Top-down preconscious perceptual processing and delusional misidentification in neuropsychiatric disorder. In: A.S. David & J.C. Cutting (Eds) The Neuropsychology of Schizophrenia. LEA. pp.361-379.

Recommended:

Phillips, ML & David AS (1995) Facial processing in schizophrenia and delusional misidentification: cognitive neuropsychiatric approaches. Schizophrenia Research, 17, 109-114.

Cahill, C., Silbersweig, D.A. & Frith, C.D. (1996) Psychotic experiences induced in deluded patients using distorted auditory feedback. Cognitive Neuropsychiatry, 1(3), 201-211.

Burgess, P.W., Baxter, D., Rose, M. & Alderman, N. (1996) Delusional paramnesic misidentification. In: Marshall, J.C. & Halligan, P. W.(Eds) Methods in Madnness. Blackwell. pp.51-78.

Ellis, H. & de Pauw, K. (1994) The cognitive neuropsychiatric origins of the Capgras delusion. In: A.S. David & J.C. Cutting (Eds) The Neuropsychology of Schizophrenia. LEA. pp. 317-335.

Young, A.W. & Leafhead, K.M. (1996) Betwixt life and death: Case studies of the Cotard delusion. In: Marshall, J.C. & Halligan, P. W.(Eds) Methods in Madnness. Blackwell. pp.147-171.

9/23 Th

Prefrontal Abnormalities: Negative Symptoms

The most problematic factor in rehabilitation of schizophrenia is the presence of negative symptoms. Those with severe negative symptoms do not show any interest in the environment around them. What might be the causes of this type of withdrawal?

Required

Brown RG and Pluck G (2000) Negative symptoms: the pathology of motivation and goal directed behaviour. TINS 23(9) 412-417

Recommended

Liddle, P. (1994) Volition and schizophrenia. In: A.S. David & J. Cutting (Eds) Neuropsychology of schizophrenia. LEA. pp.39-49.

Week 6

9/28 Tu

Prefrontal Abnormalities: Working Memory

What are some of the consequences of working memory abnormalities? Schizophrenia patients and their relatives show deficits in working memory, which may lie at the core of their clinical symptoms. But what are the possible mechanisms ? Do they have reduced capacity for maintaining information? Is the deficit modality specific or more global? What brain systems are involved and can we improve working memory in schizophrenia patients?

Required

Goldman-Rakic, P.S.(1996) The functional parcellation of dorsolateral prefrontal cortex and the heterogeneous facets of schizophrenia. In: S. Matthysse, D. Levy, J. Kagan & F. Benes (Eds) Psychopathology. pp.7-33.

Park, S. & O'Driscoll G.A. (1996) Components of working memory deficit in schizophrenia. In: S.W. Matthysse, D.L. Levy, J. Kagan & F.Benes (Eds) Psychopathology: pp.34-50.

Perlstein W, Carter C, Noll, D & Cohen JD (2001) Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia. American Journal of Psychiatry 158:1105-1113.

9/30 Thu

Sex differences; Puberty, laterality and development.

Why does schizophrenia usually emerge after puberty? Why do men and women have different courses of illness? We need to examine neurodevelopmental events during puberty.

Sex differences: Estrogen

Are women protected from more severe forms of psychosis by estrogen? Can we use estrogen as an antipsychotic agent?

Required:

Seeman, M.V.& Lang, M. (1990) The role of estrogen in schizophrenia gender differences. Schizophrenia Bulletin, 16(2), 185-193.

Seeman M. (1997) Psychopathology in women and men. Am J of Psychiatry 154:1641-1647.

Kulkarni J, Riedel A, de Castella AR, Fitzgerald PB, Rolfe TJ, Taffe J, Burger H (2001) Estrogen - a potential treatment for schizophrenia. Schizophrenia Research 48 (1): 137-144

Recommended

Kopala, L. & Clark, C. (1990) Implication of olfactory agnosia for understanding sex differences in schizophrenia. Schizophrenia Bulletin, 16(2), 255-261.

Walker, E. & DiForio, D. (1997) Schizophrenia: A neural diasthesis-stress model. Psychological Review. 104 (4): 667-685

Kulkarni J, deCastella A, Smith D, Taffe J, Keks N, Copolov D (1996) A clinical trial of the effects of estrogen in acutely psychotic women. Schizophrenia Research 20 (3): 247-252

Gruzelier, J.H. & Kaiser, J. (1996) Syndromes of schizotypy and timing of puberty. Schizophrenia Research . 21.183-194 (download it from Jane and Alexander Heard Library electronic journal)

Benes, F.M. (1989) Myelination of cortico-hippocampal relays during late adolescence: Anatomical correlates to the onset of schizophrenia. Schizophrenia Bulletin, 15, 585-594.

Week 7

Oct 5 Tue

Language, laterality and hemispheric domaninance

What are the most striking features of schizophrenic language ?

Is schizophrenia the price we pay for language ? Crow's theory of schizophrenia is based on sexual selection & language. What is the relationship between language vs. intentionality ? What are the pragmatics and social functions of language. Psycholinguistic analyses of mania and schizophrenia speech patterns. Is it possible to separate language disorder from thought disorder in psychosis ?

Crow, T.J. (1997) Schizophrenia as failure of hemispheric dominance for language. Trends in Neuroscience, 20 (8), 339-343.

Cutting, J. (1992) The role of right hemisphere dysfunction in psychiatric disorders. British J of Psychiatry, 160, 583-588.

Crow, TJ, Done, DJ and Sacker, A. (1996) Cerebral lateralization in children who later develop schizophrenia. Schizophrenia Research. 22, 181-185

Shenton, M. et al. (1992) Abnormalities of the left temporal lobe and thought disorder in schizophrenia. New England Journal of Medicine, 327, 604-612.

Recommended:

Crow, T.J. (1995) A continuum of psychosis, one human gene, and not much else - the case for homogeneity. Schizophrenia Research, 17, 135-145. (download it from Jane and Alexander Heard Library electronic journal)

Spitzer M., Thimm M., Hermle L., et al. (1996) Increased activation of indirect semantic associations under psilocybin. Biological Psychiatry 39, No. 12, 1055-1057. (download it from http://www.elsevier.nl/cgibin/cas/tree/store/bps/cas_free/browse/browse.cgi )

Kwapil, T., Hegley, D., Chapman, L. & Chapman, J. (1990) Facilitation of word recognition by semantic priming in schizophrenia. J of Abnormal Psychology, 99 (3), 215-221.

Brown, R. (1995) Politeness and schizophrenia. In: Matthysse, S. et al. (Eds) Experimental psychopathology. Cambridge University Press. pp.336-350.

Spitzer, M., Braun, U., Hermle, L & Maier, S. (1993) Associative semantic network dysfunction in thought-disordered schizophrenic patients: Direct evidence from indirect semantic priming. Biological Psychiatry. 34, 864-877.

Oct 7 Thu

Mid term test (20-25 questions) DO NOT WORRY !!!

Week 8

Oct 12^th Tue

Intentionality and Evolution of the Mind

How do we navigate through the everyday social world ? How do people with schizophrenia or autism differ from healthy people in this context ? How useful is the Theory of Mind in the context of psychiatric illnesses ? What do we mean by Intentionality, Mindblindness and Mindreading ? Is it possible for a "mindblind" individual to be depressed ? Can we study theory of mind by using cognitive paradigms ? When and how did schizophrenia or psychosis emerge ?

Required

Frith, C.D. (1994) Theory of Mind in Schizophrenia. In: A.S. David & J.C. Cutting (Eds) The Neuropsychology of Schizophrenia. LEA. pp.147-161.

Corcoran, R., Mercer, G. & Frith, C. (1995) Schizophrenia, symptomatology and social inference: Investigating "theory of mind" in people with schizophrenia. Schizophrenia Research, 17, 5-13.

Povinelli, D. & Preuss, T. (1995) Theory of Mind: Evolutionary history of a cognitive specialization. Trends in Neuroscience, 18, 418-424.

Recommended:

Rosse, R., Kendrick, K., Wyatt, R.J. et al. (1994) Gaze discrimination in patients with schizophrenia. American J of Psychiatry, 151 (6), 919-921.

Crow, T.J. (1997) Sexual selection as the mechanism of evolution of Machiavellian intelligence: a Darwinian theory of the origins of psychosis. J. Psychopharmacology, 10(1), 77-87.

Baron-Cohen, S. (1996) Mindblindness. MIT Press. Ch. 1, 2, 4, 5.

Oct 14^th Thu

Prenatal effects on the origins of schizophrenia

Do early neural insult result in adult schizophrenia ? Discussion of birth complications, viral infections, neural development.

Required

Torrey, E.F. et al. (1994) Schizophrenia and Manic-Depressive disorder. Ch. 4. pp 79-101. Basic Books.

Mednick, S., Machon, R.A., Huttunen, M.O. & Bonett, D.(1988) Adult schizophrenia following prenatal exposure to an influenza epidemic. Archives of General Psychiatry, 45, 189-192.

Cannon,T.D., Mednick, S.A., Parnas, J., Schulsinger, F., Praestholm, J. & Vestergaard, A (1993) Developmental brain abnormalities in the offsprings of schizophrenic mothers. Archives of General Psychiatry, 50,551-564. (download it from http://www.mc.vanderbilt.edu/biolib/journals/#A )

Torrey EF. Miller J. Rawlings R. Yolken RH. Seasonality of births in schizophrenia and bipolar disorder: a review of the literature. Schizophrenia Research. 28(1):1-38, 1997 Nov 7.

Recommended

Hollister, J.M., Mednick, S.A., Brennan, P. & Cannon, T.D. (1994) Impaired autonomic system habituation in those at genetic risk for schizophrenia. Archives of General Psychiatry, 51, 552-558 (download it from http://www.mc.vanderbilt.edu/biolib/journals/#A )

Week 9

Oct 19^th Tue

Class Presentations

Some suggestions for class presentation

1. Stress, cortisol and HPA axis

2. Emotion/affect abnormalities

3. Attention (latent inhibition, prepulse inhibition, sensory gating) and psychosis

4. Creativity in schizophrenia patients & their relatives

5. Neurological soft signs, finger ridge counts, nail plexus visibility etc

6. Schizotypal personality disorder

7. Pain perception and negative symptoms

8. Pestivirus hypothesis