1. Chapter 14: Schizophrenia: The Most Dreaded Illness Abnormal Psychology Mar 12 & 24, 2009 Classes #17-18

2. Etiology ► Schizophrenia is a disease of the brain ► Changes in neurophysiological function that characterize schizophrenia have been identified ► Exact causes:  Unknown ► Prevention:  Unknown

3. Prevalence and Onset ► 1% of the general population ► Onset:  Young adulthood (although late onset is possible)

4. Risk Factors ► Equal numbers of men are women are diagnosed  In men, symptoms begin earlier and are more severe ► Rates of diagnosis differ by marital status  3% of divorced or separated people  2% of single people  1% of married people ► It is unclear whether marital problems are a cause or a result

5. Risk Factors ► Rates of the disorder differ by ethnicity and race  About 2% of African Americans are diagnosed, compared with 1.4% of Caucasians ► According to the census, however, African Americans are also more likely to be poor and to experience marital separation ► When controlling for these factors, rates of schizophrenia are equal for the two racial groups ► Genetic factors appear to play a role  We’ll take a close look at the numbers later

6. Famous People Diagnosed

7. Nash portrayed in media: “He saw the world in a way no one could have imagined”

9. DSM-IV Diagnostic Criteria 1. Individual has two or more of the following for a significant portion of time during a 1-month period (or less if successfully treated): a. Delusions b. Hallucinations c. Disorganized speech d. Grossly disorganized behavior or catatonic behavior e. Negative symptoms (affective flattening, alogia, or avolition) 2. Individual shows a decline in social or occupational functioning 3. Symptoms persist for at least 6 months. This 6-month period must include at least 1 month of symptoms (or less if successfully treated) that might criterion A (active-phase symptoms) and may include prodromal or residual symptoms. 4. Other psychotic disorders and medical conditions have been ruled out

10. Diagnosis ► The diagnosis of this disorder is difficult and controversial…  Schizophrenia is a "diagnosis of exclusion" which is made if no other psychotic disorder can account for the type of symptoms and their duration ► The following factors may suggest a schizophrenia diagnosis but do not confirm it:  Developmental background  Genetic and family history  Changes from level of functioning prior to illness

11. Types of Schizophrenia ► Paranoid ► Disorganized ► Catatonic ► Undifferentiated ► Residual

12. Paranoid type ► Delusional thoughts of a persecution or grandiose nature ► Anxiety ► Anger ► Violence ► Argumentative

13. Disorganized type ► Incoherence (not understandable) ► Regressive behavior ► Flat Affect ► Delusions ► Hallucinations (mostly auditory) ► Inappropriate Laughter ► Mannerisms ► Social Withdrawal

14. Catatonic type ► Motor disturbances ► Stupor ► Negativism ► Rigidity ► Excitement ► May be unable to take care of personal needs ► Decreased sensitivity to painful stimulus

15. Undifferentiated type ► May have symptoms of more than one subtype of schizophrenia

16. Residual type ► The prominent symptoms of the illness have abated but some features, such as hallucinations and flat affect, may remain

17. Symptoms of Schizophrenia ► Cognitive symptoms  Hallucinations  Delusions ► Delusions of persecution ► Delusions of reference ► Delusions of identity ► Delusions of grandiosity ► Delusions of thought-broadcasting

18. Symptoms of Schizophrenia ► Cognitive symptoms  Disturbed thought processes ► Word salad ► Dementia praecox ► Schizophrenic deficit  Cognitive flooding (stimulus overload)

19. Symptoms of Schizophrenia ► Mood symptoms  Depression  Inappropriate emotional responses ► Physical symptoms  Effects of drugs  Motor symptoms

20. Copyright 2001 by Allkyn and Bacon20 Positive and Negative Symptoms of Schizophrenia Schizophrenia Positive Symptoms Negative Symptoms Blunted and Flat Affect Poverty of speech (alogia) Inability to experience positive feelings Apathy Inattentiveness Psychoticism Hallucinations Delusions Heightened perceptions Disorganization Thought disorders Bizarre behaviors Inappropriate affect Loose associations Neologisms Clang Associations

21. Copyright 2001 by Allkyn and Bacon21 Characteristics Associated with Positive and Negative Symptoms OnsetLaterEarlier Stability over timeSymptoms fluctuateSymptoms consistent over time Frequency ofMore frequent inMore frequent in occurrencewomenmen Response to GoodPoor treatment CharacteristicPositive symptomsNegative symptoms

22. Issues Associated with Schizophrenia ► Sociocultural factors  Age  Gender  Ethnicity  Socioeconomic class ► Downward social drift ► Bias in diagnosis ► Bias in treatment ► Bias in self-presentation

23. Explanations for Schizophrenia ► Psychodynamic explanations  Problems with child-rearing  Stress

24. Physiological Explanations ► Problems with Neurotransmitters  The Dopamine Theory  The Serotonin Explanation ► Positive symptoms ► Negative Symptoms  High Neurological Activity and Symptoms ► Prefrontal Cortex ► Temporal Cortex ► Problems with Brain Development and Activity ► Genetic Factors ► Biological Traumas

25. Carlsson & Lindqvist (1963) ► The Dopamine Theory  Speculated that an abnormality in the brain processes causes there to be an excess of dopamine  A high level of dopamine receptors is related to positive symptoms

26. The Dopamine Explanation ► L-dopa  Used to treat Parkinson’s patients who are thought to have too low levels of dopamine causing motor problems  Unfortunately, although it helps with the motor problems it also can produce positive symptoms of schizophrenia in these individuals

27. The Serotonin Explanation (Positive Symptoms) ► When serotonin levels are low, inhibitory neurons become underactive and do not reduce the activity of the excitatory neurons ► Thus, the activity of the excitatory neurons becomes to high and we see positive symptoms

28. The Serotonin Explanation (Negative Symptoms) ► Low levels of serotonin can contribute to negative symptoms of schizophrenia because these low levels can cause depression ► The depression then provides the basis for the negative symptoms (apathy, poverty of thought, etc.)

29. High Neurological Activity and Symptoms ► Prefrontal Cortex  This is where information from different parts of the brain is integrated and where thought processes occur  Too much activity here causes positive symptoms (thought processes are disrupted) ► Evidence  Pet Scans  “Angel Dust”

30. High Neurological Activity and Symptoms ► Temporal Cortex  This is where memories for auditory and visual experiences are stored  High activity here can activate those memories and result in hallucinations  Causing people to believe that they are really hearing voices

31. High Neurological Activity and Symptoms ► PET scans reveal higher brain activity when people are hallucinating ► Strong evidence linking high neurological activity in prefrontal and temporal cortexes with positive symptoms

32. Specific neuronal circuits involving the thalamus, caudate-putamen, anterior cingulate, limbic cortex, auditory cortex, hippocampus and parahippocampal gyrus are activated in schizophrenics during auditory hallucinations. Hallucinations are associated with neuronal activity Part of Figure 60-2

33. Gross neuroanatomical abnormalities in schizophrenia Decreased cortical gray matter (not shown here) Decreased cortical gray matter (not shown here) Unaffected twin Schizophrenic twin Increased size of cerebral ventricles Increased size of cerebral ventricles Figure 60-5 (lateral and 3rd) and decreased brain volume is the most replicated finding. Ventricular enlargement is found in affected twins of monozygotic pairs discordant for schizophrenia. This enlargement appears to be stable when patients are followed up prospectively. Especially evident in superior temporal gyrus, dorsal prefrontal cortex and limbic areas such as the hippocampal formation and anterior cingulate cortex. These abnormalities may be present in first-episode, never-medicated patients.

34. Decreased numbers of neurons have been found in the hippocampus and the dorsolateral prefrontal cortex. In studies of monozygotic twins discordant for schizophrenia, there is diminished activation of the dorsolateral prefrontal cortex as measured by SPECT and PET. Cellular neuronal abnormalities in schizophrenia (not shown here) Abnormal dendridic spines in prefrontal cortex- layer 3 Subcellular neuronal abnormalities in schizophrenia Unaffected Schizophrenic #1 Schizophrenic #2

35. Problems with Brain Development and Activity ► Neurodevelopmental Theory  This theory suggests that areas of the brain do not develop adequately and/or deteriorate faster than normal ► Proposes that a proportion of schizophrenia is the result of an early brain insult  For example: difficult pregnancy, mother near starvation during pregnancy, flu during pregnancy, etc. (Mednick, 1970)

36. Problems with Brain Development and Activity ► Specific problems with brain structures causing negative symptoms  Reversed hemispheric dominance ► For most people their left hemisphere is larger ► Not so for many schizophrenia patients ► Idea here is that since the left (more verbal and analytical) is underdeveloped leading to negative symptoms

37. Problems with Brain Development and Activity ► Specific problems with brain structures causing negative symptoms  Failure of Neural Migration ► Neurons are not in right places ► This occurs during prenatal development and briefly after birth  Cortical Atrophy -- Progressive loss or deterioration of neurons ► Cerebral cortex is somewhat shrunken in about one-third of schizophrenics ► Cerebral ventricles are enlarged (these are canals that go through the brain and carry away waste materials) ► Basically, is a sign of brain deterioration and causes a loss of neurons (found in at least 20% of schizophrenics)

39. Problems with Brain Development and Activity ► Hypofrontality  Prefrontal cortex is underactive causing negative symptoms

41. Genain Quadruplets: 1 in 100,000,000

42. History of Treatment of Schizophrenia Psychosurgery –Prefrontal Lobotomy (introduced in 1935)

43. Transorbital Lobotomy (introduced in 1948) Referred to as “the icepick lobotomy” Before During

44. Transorbital Lobotomy After

45. History of Drug Treatment of Schizophrenia ► Until the mid-1950’s the prognosis for schizophrenics was very unfavorable ► Most were institutionalized for the rest of their lives in large mental hospitals  Only about 30% would ever be discharged after entering

46. History of Drug Treatment of Schizophrenia ► Medications brought tremendous “overnight” change -- ► Chlorpromazine was the first  These drugs don’t cure the illness but often can control it  Originally referred to as “mild tranquilizers”

47. Contemporary Treatments ► Today, a schizophrenia patient is often treated in an outpatient clinic and those that enter a mental institution have about a 90% chance of being discharged in a matter of weeks or months ► The primary goal of modern drug therapy is to reduce the high level of neurological activity ► This is accomplished with a group of drugs called neuroleptics  These drugs block the receptors on the postsynaptic neuron so that dopamine cannot enter the receptor and cause the neuron to fire  These drugs also reduce the sensitivity of the postsynaptic receptors – less sensitive, less likely to fire.  Some of the newer neuroleptics also increase the levels of serotonin

48. Types of Neuroleptics ► Neuroleptics  Low-potency Neuroleptics ► Mellaril ► Thorazine  High-potency Neuroleptics ► Haldol ► Navane  Atypical Neuroleptics ► Clozaril ► Risperidal ► Zyprexa

49. Low-Potency Neuroleptics ► Popular in 1960’s – 1970’s ► Blocks 75%-80% of dopamine receptors ► Helps with positive symptoms but not with negative symptoms

50. High-Potency Neuroleptics ► These drugs released in 1970’s ► Blocks about 80% of dopamine receptors ► Much more effective than LP meds but at a price ► Drastic side-effects  Parkinson-type symptoms ► No help with negative symptoms

51. Atypical Neuroleptics ► Released in 1980’s (Clozaril) ► Block less dopamine receptors (about 65%) ► More selective in their blocking  Block receptors leading to frontal and temporal lobes (as the LP and HP drugs do) but block fewer receptors in nerve tracts associated with movement ► Help with negative symptoms  Increases serotonin levels which can also help reduce dopamine activity  Can also reduce depression associated with illness ► Side-effect:  About 2% of those taking Clozaril experience sudden drop of white blood cells ► Newer drugs (Risperidal and Zyprexa) do not cause this  Big developments in 1990’s

52. Atypical Neuroleptics ► So why don’t why only use these now???

53. Side Effects of Drug Therapy ► Mild symptoms  Dryness of mouth or excessive salivation  Blurred vision  Grogginess  Constipation  Sensitivity to light  Reduced sexual arousal

54. Side Effects of Drug Therapy ► More serious symptoms  Tardive Dyskinesia ► Involuntary muscle movements  Akathisia ► Inability to sit still  Malignant Neuroleptic Syndrome ► Muscular rigidity ► Very high temperature leading to brain damage ► Fluctuating blood pressure leading to stroke or coma ► Most likely to occur with high-potency neuroleptics ► Occurs more often in women ► Is very rare as it occurs in less than 1% of patients taking these drugs

55. Complications ► Noncompliance with medication ► Physical illness ► Substance abuse ► Depression ► Suicide

56. Prognosis ► Bad news  Unfortunately, the rate of readmission is extremely high as about two-thirds again need help ► Good news  About one-third recover  Which technically means that they remain symptom-free for five years ► Bad news  Problems with non-compliance  These drugs are a life-long situation as patients that stop taking the drugs will see the symptoms return and most often worsen

57. Other Psychotic Disorders ► Brief Psychotic Disorder ► Schizophreniform Disorder ► Schizoaffective Disorder ► Delusional Disorder ► Shared Psychotic Disorder ► Psychotic Disorder due to a general medical condition ► Substance-induced Psychotic Disorder

58. Credits ► http://www.dmacc.cc.ia.us/instructors/acstevens/241ppts/comer5e_lecture_Ch 14.ppt#314,2,Psychosis http://www.dmacc.cc.ia.us/instructors/acstevens/241ppts/comer5e_lecture_Ch 14.ppt#314,2,Psychosis http://www.dmacc.cc.ia.us/instructors/acstevens/241ppts/comer5e_lecture_Ch 14.ppt#314,2,Psychosis ► http://www.its.caltech.edu/~lester/Bi-150/Lecture-23-2007-Bi- CNS150.ppt#408,6,Slide 6