BCS 246, Biology of Mental Disorders

Biology of Mental Disorders, BCS 246
Fall 1996

Meeting room: Meliora Hall, Room 221
Instructor: Steven B. Schwarzkopf, MD
Office/phone: Meliora 171, 275-8463
Meeting times: Tuesday and Thursdays 9:40 am to 10:55 am

Required text: Trimble, M.R. (1996) Biological Psychiatry, Second Edition, John Wiley & Sons, New York, NY.

Recommended text: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (1994) American Psychiatric Association, Washington DC.

Prerequisites: Neural Foundations of Behavior (BCS 110), Biopsychology (Psych 141) or Machinery of the Human Brain (NSC/PSY 152)

General description of course:

The course will be divided into three parts, each taking approximately one-third of the semester. (A detailed lecture schedule will be posted.)

Section I will focus on a series of videotaped case vignettes that illustrate the signs and symptoms of a variety of psychiatric syndromes. There will be an initial emphasis on the history of psychiatry, linking these cases to how they would have been viewed through the ages. Further, during this section, descriptive terminology will be reviewed that most accurately describes the phenomena of these syndromes. The current diagnostic classification, using the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM IV), for these syndromes/disorders will then be addressed along with the rationale for these classifications.
Section II of the course will overview the neuroscience concepts particularly relevant to psychiatric symptomatology and review research methods particularly useful in psychiatric research. Phenomena resulting from "limbic" pathology with be emphasized, as well as the current concept of a limbic system and its neural circuitry. The theorized neural substrates of arousal, attention, coordinated movement and thought, hedonic capacity, and goal directed behavior will be covered. This section will provide a rationale for the research findings covered in the last section of the course.
Section III will specifically examine biological findings in mental disorders, including: anxiety and phobic conditions, obsessive compulsive disorder, depression, mania, and chronic psychotic states (particular emphasis on schizophrenia). If time permits, other syndromes, including attention deficit and eating disorders, post-traumatic stress syndrome, and substance abuse findings will be touched upon. Time allowing, some of these topics will be chosen based on class interest. This section will also include a brief overview of the most effective biological treatment modalities for specific syndromes and some of the advances in biological treatments showing promise for the future. We will attempt to synthesize the research findings, neuroscience knowledge, and effective treatments in a way that is theoretically sound and results in testable hypotheses that suggests additional research that would either confirm/reject this synthesis.

Additional readings selected and distributed from:

Bloom FE, Kupfer DJ (1995) Psychopharmacology: The Fourth Generation of Progress, Raven Press,: New York.. (pharmacologic and neurotransmitter findings in major syndromes)
Kaplan HI & Sadock BJ (1989) Comprehensive Textbook of Psychiatry, Fifth Edition,: Williams and Wilkins, Baltimore MD.
Mesulam M (1985) Principles of Behavioral Neurology, F.A. Davis Company, Philadelphia,: pp. 1-59, 125-162. (overview of cortical function, limbic system, state/channel functions, hemispheric lateralization)
Selected recent review articles pertaining to biological findings in psychiatric syndromes.: These articles will be selected generally from the Archives of General Psychiatry, Biological Psychiatry, Biological Psychology, Psychiatry Research, and the British Journal of Psychiatry.

Class format:

Two one hour and fifteen minute meetings per week, divided into two sections. The first 45 minutes will consist of a lecture on the topic material assigned, or presentation of a case directly relevant to the reading material or lecture. It is expected that readings be done prior to lecture in order to facilitate class discussion/participation. After a 5 minute break, there will be a 25 minute period for: discussion of the topic of the lecture/case vignette, audio or videotape of material providing further background for the topic, or discussion of the clinical case and assigned readings. In section III of the class, each student will be expected to present briefly a current article (detailed outline for presentation will be provided) on a psychiatric syndrome of interest to him/her. I will help with the necessary literature search for this project, using the Medline database.

Assessment of performance:

There will be two tests and two quizzes during the semester. Tests will consist of multiple choice and short answer questions, with one essay question. Exams will count for 40% of the grade, quizzes 20%, research paper presentation 20%, and class preparation and participation 10%, and paper presentation 10%. Though not required, those interested and desiring additional credit may submit a 5 page paper on the neurobiology of a selected psychiatric syndrome.

Outline of topics for Biology of Mental Disorders:

Section I: Cases, historical perspectives, terminology, and diagnostics classification, with disorders presented in order of least to most severe symptomatology and disability.

Case vignettes:

Adjustment disorder with anxiety: Case presentation, historical (environmental stressor: causing imbalance of humors etc.), mental status terminology, DSM IV criteria.
Dysthymic disorder: Case presentation, historical (melancholic personality),: mental status terminology, DSM IV criteria.
Hypomania: Case presentation, historical (choleric personality vs. in this case vacillation: between depression and hypomania), mental status terminology, DSM IV criteria.
Schizoid personality: Case presentation, historical (phlegmatic), mental status: terminology, DSM IV criteria.
Generalized anxiety: Case presentation, historical (neurasthenia etc.), mental status terminology,: DSM IV criteria. Personality change due to medical condition: Case presentation, historical, mental status terminology, DSM IV criteria.
Panic attacks: Case presentation, historical, mental status terminology, DSM IV criteria.
Depression: Case presentation, earliest theorizing (again Hippocrates excess black bile -> melancholia;: treatment with diet, bathing, personal hygiene as well as biologic treatments [strong cathartic: hellbore, emetics, and if necessary, bleeding]), mental status terminology, current DSM IV criteria.
Mania: Case presentation, historical, mental status terminology, DSM IV criteria.
Schizophrenia: Case presentation, historical, mental status terminology, DSM IV criteria.

Introduction to history of psychiatry: Greek "psychiatry" (Ionians first to depart from theological concepts), then Hippocrates (or most likely a group of writers whose work was later attributed to Hippocrates) first to theorize on specific imbalances and relation to illness and extremes of temperament or personality; major components: blood, phlegm, yellow bile, black bile; with excesses phlegm -> dementia, yellow bile -> manic rage, black bile -> melancholia; with lesser excesses causing temperament variations: blood -> sanguine (cheerful), phlegm -> phlegmatic (calm, stoic, unemotional), yellow bile -> choleric (irritable), black bile -> melancholic personality types, Plato, Aristotle, Epicurians, Pneumaticists (influenced by Stoics). Roman "psychiatry" with mostly following lead of Greeks, but original work by Galen (particularly melancholia writing), Medieval Period, with demonology/witches etc. probably describing many mentally ill, The Renaissance!!, hope of rational thought and emphasis on nosology, reforms of treating mentally ill ("moral therapy": Pinel in Paris, Chaiarugi in Italy, Tuke in England, Rush in U.S.), Mesmer and hypnotism (also Braid), Gall and Phrenology, Greisinger (felt psychiatry was part of neurology and brought asylums to university), Kraepelin (excellent descriptions and distinction of manic-depressive psychosis and dementia praecox, emphasis on observation, course of illness), Pavlov (experiments on conditioned reflexes), Bleuler and schizophrenia, Freud (emphasis on unconscious conflict causing illness and major change in emphasis from empiricism to description of individual cases and theorizing from these), body types and mental illness (Dretschmer in Germany and Sheldon in US; ectomorph, endomorph, mesomorphs with differing vulnerability to mental illnesses), Julius von Wagner-Jauregg (fever for insanity, malarial treatment, good for general paresis not mental illness, only psychiatrist to receive Nobel prize), shock therapy (insulin, metrozol, electro-shock all used and found to help some patients), psychosurgery (Moniz, neurosurgeon also given Nobel prize for this!!), psychopharmacology (early 1950s) began the modern era of understanding mental illness as potentially imbalances of neurotransmitters and ability to explore this systematically.

Section II: Overview of neuroscience concepts relevant to psychiatric symptomatology and review of research methods particularly useful in psychiatric research.

Why limbic regions of neural connections with strong links to these areas might be important in: psychiatric illness. Limbic stimulation during neurosurgery, temporal lobe epilepsy, epilepsy/psychiatric phenomena relationship, psychosis after development of TLE, septal abnormalities in chronic schizophrenia
Overview of cortical function: General schema of cortical specialization, neural connectivity: between primary sensory -> primary association cortex -> secondary association cortex, with discussion of how this knowledge is obtained (neurosurgery stimulation, neural pathway definitions (retrograde/anterograde tracers etc.), lesions, human clinical syndromes.
Association cortex and limbic regions: Continued discussion of overall schema, multi-modal or: heteromodal associations areas, paralimbic regions, and limbic region. The breakdown of the stimulus response bond, internal template of external reality, ability to access memory and chose appropriate action given differing environmental "contexts".
Sub-cortical regions: Basal ganglia and thalamus, Parallel processing of motor and cognitive: information, cortico-striato-thalamo-cortical loops, motor/cognitive/motivational aspects of these loops (dorsal vs. ventral striatum and lateral vs. medial thalamus).
Channel vs. state functions: Likelihood that regions critical to "state" functions may be implicated in: psychiatric syndromes, neurotransmitters linked to these regions, interaction of channel and state in deficits (often both present), theory of temperament being based on three dimensions: negative affectivity (stress reactivity), positive affectivity (sense of well being), and constraint (overall inhibition level). Another similar theory links neurotransmitter systems predominantly to each of these dimensions (Cloninger's theory).
Attention and cortical lateralization: Attentional apparatus may be dependent particularly on certain: cortical areas including the right parietal lobe, frontal lobes. Lateralization of verbal language functioning, as well as prosody (affective processing of language). Lateralization of affective functioning
Neurologic illnesses with psychiatric symptomatology: Stroke, multiple sclerosis, Parkinson's: disease, Huntington's disease and effects on brain circuitry, esp. cortico-striato-thalamo-cortical loops.
Medication and dietary manipulations resulting in "psychiatric" phenomena: Reserpine: induced depressive symptoms, tryptophan depletion diet, dopaminergic blockers, noradrenergic stimulation effects, GABAergic false transmitters, lactate infusion in panic prone patients, acute amphetamine effects, cocaine effects, LSD, anticholinergics (Ditran).
Research methods in psychiatric research: Epidemiologic studies; family, adoption, and: twin studies; genetic linkage work, psychophysiologic research, peripheral and central neurochemical studies, in vivo brain imaging studies, post-mortem tissue analysis

Section III: Neurobiologic findings linked to specific mental disorders, including evidence for etiologic theories for the following syndromes. An attempt will be made to cover the most pertinent genetic, physiologic, neurochemical/neurotransmitter, and brain imaging findings. In addition, a brief discussion of the most effective biological treatments will be covered for each of the syndromes. Additional lectures covering findings in some other syndromes (attention deficit, addictive disorders etc.) and medical treatments for them will be given if time permits.

Anxiety/phobic disorders: Overview of findings, recent promising preliminary findings,: biological treatments
Obsessive compulsive disorder: Overview of findings, recent promising preliminary findings,: biological treatments
Depression (typical and atypical): Overview of findings, recent promising preliminary findings,: biological treatments
Mania: Overview of findings, recent promising preliminary findings, biological treatments
Schizophrenia: Overview of findings, recent promising preliminary findings, biological treatments

Calendar for BCS 246, Biology of Mental Disorders

Dates, readings, cases, and topics (readings for day of lecture for purpose of discussion)

(1) 9/5 No readings (can you believe it?), Class overview, videos (case vignettes) of extremes of psychopathology (adjustment disorder to schizophrenia), Introduction to history of Biological Psychiatry, Recurring themes through history (continuing today), Discussion of reading assignments
Lecture

(2) 9/10 Readings: Trimble C1 (pp.1-2), Kaplan & Sadock (pp. 2132-2133 to Galen), DSM IV mental status terms (read carefully) and diagnostic criteria of cases (overview, not to be memorized)
Lecture & Discussion: Case vignettes: dysthymic disorder, hypomania; History of Biological Psychiatry; DSM IV terminology and criteria

(3) 9/12 Readings: Trimble C1 (pp.2-7, 20-22), Kaplan & Sadock (pp. 2133-2135, up to 18th century), DSM IV mental status terms, diagnostic criteria of cases
Lecture & Discussion: Case vignettes: schizoid personality, personality change secondary to medical condition; History of Biological Psychiatry; DSM IV terminology and criteria

(4) 9/17 Readings: Trimble C1 (pp. 7-12, 23-25), Kaplan & Sadock (pp. 2135-2137, up to 19th century), DSM IV mental status terms, diagnostic criteria of cases
Lecture & Discussion: Case vignettes: generalized anxiety disorder, panic attacks; History of Biological Psychiatry; DSM IV terminology and criteria

(5) 9/19 Readings: Trimble C1 (pp. 12-16, 25-28), Kaplan & Sadock (pp. 2137-2139, up to Freud), DSM IV mental status terms, diagnostic criteria of cases
Lecture & Discussion: Case vignettes: post-traumatic stress disorder, obsessive compulsive disorder; History of Biological Psychiatry; DSM IV terminology and criteria

(6) 9/24 Readings: Trimble C1 (pp. 16-19, 28-30), Kaplan & Sadock (pp. 2139-2141, up to Institutional Care), DSM IV mental status terms, diagnostic criteria of cases
Lecture & Discussion: Case vignettes: recurrent depression, mania; History of Biological Psychiatry; DSM IV terminology and criteria

(7) 9/26 Readings: Trimble C1 (pp. 31-40), Kaplan & Sadock (pp. 2141-2143, end of text), DSM IV mental status terms, diagnostic criteria of cases
Lecture & Discussion: Case vignettes: amphetamine psychosis, chronic paranoid schizophrenia, History of Biological Psychiatry (focus on history of present categories of psychosis, dopamine theory of psychosis; DSM IV terminology and criteria

(8) 10/1 *Quiz 1* (covers above material: history, terminology, some diagnostic questions)
Readings: no readings, Mesulam chapter for next class (only use pp. 1-49!! rest F.Y.I.)
Lecture & Discussion: Introduction to Mesulam concepts, cortical organization, how much of this data derived (research techniques), discussion of quiz (no h.o.)

(9) 10/3 Readings: Mesulam pp. 1-30 (up to paralimbic areas)
Lecture & Discussion: Cortical organization, histology, Extrapersonal Space <-> Internal Milieu, primary sensory/motor areas, unimodal association areas, heteromodal (higher order) association areas

Fall break

(10) 10/10 Readings: Mesulam pp. 1-30 continued 30-49 (up to "Concept of a Limbic System)
Lecture & Discussion: Paralimbic areas and breakdown of stimulus-response bond, memory, drive, affect, and higher autonomic control; (gustation and olfaction not critical sections), basal ganglia, thalamus ("cortico-striato-thalamo-cortical" loops, not in readings but I will discuss this), concept of limbic system, and channel vs. state functions (neurotransmitters involved)

10/15 - > Overview of psychopharmacology, Dr. Guttmacher if possible

10/17 (out of town), time for reviewing for test 1!!
Review Trimble Chap 1-2, Kaplan & Sadock, DSM IV terms, Mesulam pp. 1-49
** Test on Mesulam and concept emphasis but lesions and specific outcome important

(11) 10/22 Readings: Finish Mesulam (state/channel functions) Trimble C.3 Chemistry and Physiology; pp. 41-59 (up to receptors)
Lecture & Discussion: Overview of biopsychology relevant to psychiatric syndromes, physiology and chemistry, genetics will be stressed less than cell metabolism and physiology.

(12) 10/24 Readings: Continue Trimble C. 3 pp. 59-75; start pp. 76-107 (receptors, neurones)
Lecture & Discussion: Physiology continued, receptors,

(13) 10/29 Readings: Trimble C.3 pp. 76-107 (receptors, neurones)
Consider C.4 some relationships between structure and function and behavior (107-115)
Lecture & Discussion: classic neurotransmitters, and neuropeptides. Brief discussion of some early and recent neurotransmitter theories and psychiatric syndromes (DA hypothesis, action of antipsychotics). Discussion of Trimble C.4: Brain structure/function and behavior. Aggression, anxiety, memory, sexual behavior, arousal, sleep, attention, motivation related to Mesulam.

(14) 10/31 Test 1** over previous readings/handouts/lectures (see above)

(15) 11/5 Readings: Trimble C.4 107-115 briefly, anatomy/behavior relationships; Start Trimble C.5 Investigations; pp. 116-141.
Lecture & Discussion: Anatomical regions and possible specificity for behaviors relevant to psychiatric conditions; Types of investigations: clinical interview, "typical" laboratory tests in clinical setting, (phenomenology, genetic studies, not mentioned here), examples of neuroendocrine, neurochemical, psychophysiology, brain imaging techniques.

(16) 11/7 Readings: Trimble C.5 Investigations; pp. 116-141; Trimble C.7 Personality disorders and neuroses; pp. 159-182; Trimble C. 12 Minor tranquilizers pp. 358-363.
Lecture & Discussion: Tests back. Genetics of neurosis (and normal variability of personality; Minnesota twin study and others). Broad overview of biology of anxiety, aggression, obsessive compulsive disorder. Pharmacologic treatment of anxiety disorders, OCD, and aggression.

(17) 11/12 Readings: Continue Trimble C.7 Personality disorders and neuroses; pp. 159-182; Trimble C.12 Minor tranquilizers pp. 358-363. Decide on Weinberger and E. Walker presenters.
Lecture & Discussion: Continue overview of biology of anxiety, aggression, obsessive compulsive disorder and pharmacologic treatment of anxiety disorders, OCD, and aggression.

(18) 11/14 Readings: Tellegen article on personality; genetic/shared & unshared environment.
Lecture & Discussion: Presentation of Tellegen article. How might this fit with the data in Trimble's chapter? Decide on presenters for Weinberger and Swerdlow & Koob article.

(19) 11/19 Readings: Trimble C.8 Schizophrenia, pp. 183-225 (schizophrenia). Weinberger article.
Lecture & Discussion: Genetics, neurochemical, early hypotheses, psychophysiologic, neuroanatomic findings (post-mortem), in vivo brain imaging findings.

(20) 11/21 Readings: Weinberger article.
Lecture & Discussion: Presentation of Weinberger article. Schizophrenia as a neurodevelopmental disorder, with early developmental dysfunction that does not become obvious until after adolescence. Theory of frontal lobe dysfunction and dopaminergic involvement, integrated with developmental knowledge regarding this system. Discuss in terms of previous neuranatomical data (Mesulam etc.)

(21) 11/26 Readings: Elaine Walker article (schizophrenia)
Lecture & Discussion: Presentation of Walker article on motoric/cognitive symptoms and neurodevelopment; cortical and subcortical "loops"; relationship to schizophrenia; Discuss in terms of Weinberger and Trimble.

(22) 12/3 Readings: Trimble C.9 Affective disorders; pp. 226-265.
Lecture & Discussion: Course evaluation, no lecture (time to read Trimble?)

(23) 12/5 Readings: Brain Imaging in Affective Disorders
Lecture & Discussion: Presentation of above and discussion of Swerdlow & Koob notion of corticostriato-thalamo-cortical loops and relevance to affective disorders (as per Walker article).

(24) 12/10 (last class) Readings: Brain Imaging in Anxiety Disorders
Lecture & Discussion: Presentation of above and brief affective disorder lecture on Trimble material. Need to read this for test (genetics, metabolic, neuropeptides, neurochemical, psychophysiologic, brain imaging findings, serotonin, norepinephrine, and other neurotransmitter theories). Will discuss dopamine theory of depression and mania that is not emphasized much in Trimble.

Scheduled Final Exam: 12/18 at 4 PM, Meliora room 221

To be covered on final:

Trimble chapters 4 (pp. 107-115), 5 (pp 116-141), 7 (159-182), 8 (183-225), 9 (226-265)
Class discussion of variability of course, symptomatology in schizophrenia
Presentation info from class on: Tellegen, Weinberger, Walker, Brain imaging in affective disorders and anxiety disorders

Events during semester affecting schedule (that I'm aware of):

Fall break:     10/4 - 10/8
Election day:   11/5 (very pleased vs. very bummed lecturer; blood/phlegm vs. yellow bile?)
Thanksgiving:   11/28
Reading period: 12/12 to 12/15
Final exams:    12/16 - 12/20

Presentations:

11/14/96: Tellegen et al. (Personality similarity/differences in twins .....)
David Capodicasa (genetics overview, good)
Jennifer Ettel (lit. review, good)
Faith Horten (intro and analysis, excellent)
Karin McCoy (wrap up, excellent)

11/21/96: Weinberger 1987
William Raes
Scott Neurberger
? Jill Knott

11/26/96: Walker schizophrenia theoretical and review article
Christa Ambrose
Amy Angleman
Jason Hamilton
Dave Vago

12/5/96: Affective disorder paper
???

Rest of semester:
11/19; 11/21 (schizophrenia)
11/26 (schizophrenia)
12/3; 12/5: (affective disorder)
12/10: (review)
Final test: 12/18

December 5, 1996

Biology of Mental Disorders, BCS 246 Fall 1996