Psychopathology

1. Psychopathology Rains Chapter 13

2. What is Psychopathology • Major psychiatric disorders can severely disrupt behavior and cause enormous suffering. • Biological factors • medical model • illness • lesion responsible for disorder • psychosocial factors • Problems in living

3. What is Psychopathology • Gleitman (1995) example • individual with no cognitive disability but has simply not been taught to read. • Someday may identify brain circuits for reading and be able reprogram them through microsurgery or gene therapy • Probably better to understand inability to read in terms of lack of training

4. What is Psychopathology • General paresis as an example • syphilis caused by bacterial infection • in a few cases, symptoms seem to clear up then later general paresis appears • at first, thought general paresis was psychological disorder • progressive general decline of physical and psychological functioning culminating in personality changes, disturbed gait, delusions, dementia, and death

5. The Schizophrenic Disorders • 1-1.5% of population • 400,000 persons hospitalized in US • about 30% of all hospital beds • Typically chronic • symptoms may be more or less intense but seldom recover completely • Onset in early 20’s

6. Positive Symptoms • Delusions • Hallucinations • Bizarre behavior • Formal thought disorder • loose associations • word salad

7. Negative Symptoms • Apparent absence of motivation (avolition) • social withdrawal • diminished emotional expression (blunted affect) • diminished verbal expression (alogia) • poor judgment • poor personal hygiene • decrease in level of attention • decrease in activity level • decrease in self direction

8. The hypothesis of multiple etiologies of schizophrenia • May be a group of disorders • Perhaps with different underlying neurobiological abnormalities

9. Genetic Factors • Twin studies • Concordance rate • 55% for monozygotic twins • 10% for dizygotic twins • Adoption studies • 15% of children of schizophrenic mothers become schizophrenic whether adopted by non schizophrenic mother or not

10. Dopamine Hypothesis of Schizophrenia • Schizophrenia due to abnormally increased dopamine activity in the brain

11. Evidence for Dopamine Hypothesis • Antipsychotic (neuroleptic) drugs such as chlorpromazine (Thorazine) or haloperidol (Haldol) control symptoms in many patients • neuroleptics block dopamine receptors • magnitude of therapeutic effect of different neuroleptics is proportional to the magnitude of dopamine blocking effect

12. Neuroleptics as Anti-schizophrenic • not just anti-anxiety or sedative • If sedatives then barbiturates should work but they don’t • If anti-anxiety then neuroleptics should work with anxiety disorders but virtually ineffective • Neuroleptics calm hyperactive patients and make withdrawn patients more active • Anti-anxiety drugs are not effective with schizophrenia

13. Amphetamine Psychosis • The only drug effect that is clinically indistinguishable from schizophrenia • True drug effect not a result of sleep loss or activation of latent schizophrenia • Phenothiazines are effective in treating amphetamine psychosis • Amphetamines in small doses activate schizophrenic symptoms

14. Schizophrenia and Parkinson’s Disease • Parkinson’s disease is a degenerative (progressive and incurable) disease which results from a deficiency of dopamine or at least an insensitivity to dopamine. It is treated with L-dopa a precursor of dopamine which in some patients results in relief of the symptoms during the early stages.

15. Schizophrenia and Parkinson’s Disease • In many ways schizophrenia is the opposite of Parkinson’s disease. Schizophrenics act as if they have too much dopamine. • Parkinson’s patients act as though they have a deficiency of dopamine

16. Schizophrenia and Parkinson’s Disease • Never been a case on record of a Parkinson’s patient developing schizophrenia although if Parkinson’s patients are overmedicated they show temporary schizophrenic symptoms

17. Schizophrenia and Parkinson’s Disease • The anti-schizophrenic drugs produce Parkinson like symptoms as a side effect, presumably because they block dopamine and cause the individuals brain to resemble a Parkinson’s patient

18. Evidence for Dopamine Hypothesis • Dopamine enhancing drugs (eg: amphetamines and L-dopa) may produce transient psychotic states indistinguishable from schizophrenia • autopsy evidence suggests overabundance of dopamine receptors rather than too much dopamine (studies include individuals who have never been on neuroleptics)

19. Problems with Dopamine Hypothesis • Blockade effect on dopamine occurs in hours, symptoms don’t start to effect symptoms for weeks • Some patients respond to dopamine blockers, others don’t • Positive symptoms seem to be more related to dopamine abnormality • Negative symptoms seem more related to structural abnormalities

20. Refinement of Dopamine Hypothesis • Recent development of atypical antipsychotics such as clozapine (Clozaril), risperidone (Risperdal), and olanzapine (Zyprea) • These block both dopamine and serotonin and are more effective (particularly with schizophrenics with mainly negative symptoms) • led to dopamine-serotonin interaction hypothesis

21. Gross Structural Abnormalities • Enlarged Ventricles • correlational • not all schizophrenics show it • Cortical Atrophy • generalized atrophy not in particular regions

22. Two-Syndrome Hypothesis • Type I • normal ventricle size and no atrophy • predominantly positive symptoms • Type II • enlarged ventricles and cortical atrophy • predominantly negative symptoms

23. Microstructural Abnormalities • Pyramidal cells show disorganized orientation • Disrupted connections in hippocampus • Also reports of problems in a number of other areas

24. Abnormalities from Functional Imaging • Hypofrontality • decreased frontal activity in schizophrenia • decreased activation of frontal and prefrontal areas in tasks that normally activate these areas

25. Neuropsychological Functioning • Attentional Impairment • poor performance on Continuous Performance Test (vigilance type task) • Temporal Lobe and Prefrontal dysfunction • tests of verbal and non-verbal memory, working memory, flexibility, and planning • Left Hemisphere Hypothesis • schizophrenia -- abnormality in left hemisphere • overactivity may produce positive symptoms • mood disorders -- abnormality in right hemisphere

26. Prefrontal Dysfunction Hypothesis • Positive symptoms result from excessive dopamine activity in limbic system • Negative symptoms result in decrease in dopamine activity in prefrontal cortex • working memory impaired

27. Pharmacological Treatment of Schizophrenia • Psychotherapy is virtually ineffective with the schizophrenic symptoms • Drugs are somewhat effective for about 60% • Once the drugs have taken effect patient is in need of therapy, rehabilitation, social skills training, and help getting re-integrated into society

28. Extrapyramidal Side Effects • Caused by blocking the dopamine in the basal ganglia and not blocking the cholinergic input from the cortex • Produces an inballance • Can use anticholinergic drugs such as Artane and Cogentin to bring the Acetylcholine levels in line with dopamine and stop the Parkinson like or extrapyramidal side effects • Anticholinergic psychosis can occur from overdose (dry mouth, dilated pupils, psychosis)

29. Side Effects • Dystonia: tonic movements, twist of body, looks like a seisure • Acute dyskinesia: ticks and smacking • Acathesia: motor restlessness, can’t sit still, pace floor • Psychic restlessness • Tardive dyskinesia • Fly catchers tongue • Smacking • Foot tapping • Irreversible particularly after a long time on high doses • Need to give drug holidays

30. Side Effects • Retinal Pigmentation • Jaundice • Leuconemia • Cardiac arythmia • Sexual difficulties

31. Mood Disorders • Affective disorders • Disorders that have a long-term disturbance of mood as predominant feature. • Major depressive disorder • Seasonal affective disorder • Bipolar disorder

32. Major Depressive Disorder • Also called unipolar depression • Lifetime risk – 12% • Prevalence – 5% of population at any given time • Suicide risk – 15%

33. Major Depressive Disorder • Older classification • Endogenous depression – biological component • Reactive depression – external (interpersonal and social) factors • Now realize most disorders are result of both • Vegitative symptoms: loss of appetite, diurnal mood variation, decreased sex drive, sleep disturbance

34. Monoamine Hypothesis of Depression • Monoamines • Catecholamines • Dopamine • Norepinephrine • Indolamine • Serotonin

35. Monoamine Hypothesis of Depression • Drugs that increase brain monoamine levels alleviate depression • Tricyclic antidepressants • Monoamine oxidase inhibitors • Drugs that decrease monoamine levels induce depression • Reserpine • Hypothesize that abnormally low levels of monoamines play role in depression

36. Major Depressive Disorder • Dopamine agonists don’t help major depression • So conclude it is serotonin and norepinephrine • Many depressives have low levels of serotonin metabolite • Selective serotonin reuptake inhibitors (SSRI’s) work on serotonin alone • Fluoxetine (Prozac) • Paroxetine (Paxil) • Sertaline (Zoloft)

37. Possible Endocrine Dysfunction in Depression • Some depressed patients release too much cortisol in response to stress • Don’t know what this means

38. Abnormalities Revealed by Functional Imaging • Hypofrontality similar to that found in schizophrenia but • Do not show absence of activation on specific tasks and • Do not show cognitive impairments associated with specific brain areas • Don’t know what this means

39. Genetic Factors in Depression • Concordance rate for major depression for monozygotic twins is four times higher than for dizygotic twins

40. Pharmacological Treatment of Depression • Tricyclic Antidepressants • Tofranil • Elavil • Sinequan • Side Effects • Dry mouth • Dizziness • Cardiovascular

41. Pharmacological Treatment of Depression • MAO Inhibitors • Phenelzine (Nardil) • Isocarboxazid (Marplan) • Tranylcypromine (Parnate) • Beer-Cheese reaction • Foods containing tryptamine • Nose spray

42. Pharmacological Treatment of Depression • SSRI’s • Prozac • Paxil • Zoloft • Dual Action Antidepressants • Nefazodone (Serzone) • Mirtazapine (Remeron)

43. Seasonal Affective Disorder • Some people become depressed during the winter when days are short and nights are long. • Treated with exposure to bright lights for several hours a day • Don’t know much about biological basis of this but data doesn’t seem to relate to cycling of hypothalamus

44. Bipolar Disorder • Manic-depressive disorder • 0.5-1% of population • Mania • Few hours to several months • Elevated, expansive, irritable mood • Inflated self-esteem, decreased need for sleep • Hypersexuality, flight of ideas, high risk taking

45. Bipolar Disorder • Neurochemical factors • Lithium carbonate (Eskalith) • Anti-convulsant drugs • Carbamazepine (Tegretol) • Sodium valproate (Depakote) • These drugs are highly effective, but • Don’t know how they work so doesn’t lead to a theory

46. Genetic Factors in Bipolar Disorder • Specific genetic links have been identified • No single mechanism accounts for all cases • We are a long way from understanding bipolar disorder

47. Anxiety Disorders • Phobic disorders • Specific (snake or spider) • Social phobia • Agoraphobia • Generalized Anxiety Disorder • Panic Disorder • Obsessive-Compulsive Disorder

48. Neurochemical Factors in Anxiety Disorders • Anxiolytics bind to benzodiazapine receptors that are part of the benxodiazepine-GABA complex • Serotonin agonists (Proxac) are effective also • Don’t know how this fits together

49. Simple Phobias • Preparedness theory of phobias • Phobias develop for snakes, spiders, and heights which people in modern civilization are rarely threatened by • Don’t develop to electric sockets and automobiles that are real threats • People are genetically programmed to rapidly learn to fear certain stimuli • Most people with phobias have never actually been harmed by the object they fear.

50. Dementing Diseases • Alzheimer’s Disease • Huntington’s Chorea • Parkinson’s Disease