Psychoses [2002]

Lecture 2002

1. PSYCHOSES Dr Zahiruddin Othman Department of Psychiatry School of Medical Sciences University Science Malaysia

2. What is Psychosis? Concepts Definitions Psychopathology

3. Concept of Psychosis Shamanism Demonic possession Lunacy Witchcraft and charm Unpredictable and dangerous Major mental illness Unsound mind Break with reality Premature mental weakness

4. Definitions of Psychosis Symptoms Delusions or prominent hallucinations in the absence of insight into their pathological nature Delusions and prominent hallucinations Delusion, hallucinations and other schizophrenic symptoms – disorganized speech, grossly disorganized or catatonic behavior Narrowest Broader

5. Definitions of Psychosis Symptoms Delusions or prominent hallucinations in the absence of insight into their pathological nature Delusions and prominent hallucinations Delusion, hallucinations and other schizophrenic symptoms – disorganized speech, grossly disorganized or catatonic behavior Functional impairment “…impairment that grossly interferes with the capacity to meet ordinary demands of life” Concept Loss of ego boundaries or a gross impairment in reality testing Narrowest Broadest Broader

6. What is Psychotic Symptom?

7. Psychotic Symptoms Hallucinations Perceptual disturbance Modality – auditory, visual, tactile, olfactory, gustatory Delusions Thought content disorder Theme – persecutory, grandiosity, nihilistic, reference, religious, amorous, jealousy etc Disorganized speech Formal thought disorder E.g., circumstantial, tangential, loosening of association, word salad Grossly disorganized or catatonic behavior Goal directed behavior disorder E.g., disorganized, non-purposeful, childlike, silly, socially inappropriate behavior Perception Thought Behavior

8. Since Time Immemorial, Delusion Has Been Taken As the Basic Characteristic of Madness. To Be Mad Was to Be Deluded. Karl Jaspers

9. Delusions: A Critical Understanding Delusion - definition Fixed, false, belief not amenable to logic inconsistent with cultural background Delusion - phenomenology Not what you think but how you came to believe it Loss of normal logical boundaries Objects can have dual meanings (two memberness)

10. Perception Cognition Perception Cognition Pathologic cognition Normal and Delusional Thinking (Delusional Perception) Normal cognition delusional perception two memberness

11. Delusional Atmosphere (Trema State) Unbearable tension, uncanny, portentous feeling - (Delusional mood) State of anxiety leads to a autoplastic restructuring of the world- attempt to make sense of the world view of the patient in the state of anxiety A regression from a mature, “Copernican” view of the world as independent forces to a primitive, “Ptolemaic” view (related to idea of reference) – (Magical thinking) Sometimes followed by sense of relief (with “crystallization”) (ah ha)

12. Primary Delusions Delusional intuition “bolt of lighting”, primary, autochthonous Delusional perception two stage, two memberness Delusional memory retrospective, restructuring of the events to portray a pathological meaning

13. Delusion Form or process more important than content Continuum: normal belief to Over valued ideas to 2 ° delusion to a 1° delusion

14. Overvalued Idea A solitary, abnormal belief neither delusional or obsessional (not experienced as senseless by the sufferer) Comparison to delusions: occur in isolation, more mundane themes. Conviction is less Dominates the thought life of the subject a/w strong affect, abnormal personality e. g. , Anorexia nervosa, hypochondriasis, paranoid personality disorder

15. Delusions – Some Screening Questions for Various Types Have you ever felt that people were out to get you or deliberately trying to harm you? Have you ever seen things in magazines or on TV that seemed to refer specifically to you or contain a special message for you? Have you ever had a change in your body or the way that it was working for which the doctor could find no cause? Have you had any religious beliefs or experiences that other people didn’t share? Have you ever felt you had any special powers, talents, or abilities much more than other people?

16. Disorders of Perception Intensity Hyperaesthesia Hypoaesthesia Quality color Spatial form dysmegalopsia SENSORY DISTORTIONS Illusions Pseudohallucinations Hallucinations SENSORY DECEPTIONS Stimulus Clarity Control Insight Space pareidolia

17. Hallucinations Sensory perception or experience without any stimulus Normal is absence of hallucinations, or limited to hypnagogic (while falling asleep) or hypnopompic (while waking up) settings

18. Special Kinds of Hallucinations Functional hallucinations A stimulus causes the hallucination, but it is experienced as well as the hallucination Reflex hallucinations A stimulus in one sensory modality produces hallucination in another Extracampine hallucinations Hallucination outside the sensory the limits of sensory field Autoscopy or phantom mirror-image

19. Pseudohallucinations According to Kadinsky and Jaspers (1913) Especially vivid mental images , i.e. lack the quality of representing external reality and seem to be within the mind rather than external space. However, cannot be changed substantially by effort or will (i.e. no control ) According to Hare and Taylor (1979) The experience of perceiving something as in the external world, while recognizing that there is no such correlate to the experience (i.e. no insight )

20. Hallucinations - Screening Questions for Various Types Have you ever heard sounds or voices that other people could not hear? Have you ever heard voices that described or commented on what you were doing or thinking? Have you ever heard two or more voices talking with each other? Have you ever had visions or seen things that other people could not see? Have you ever had unusual sensations or other strange feelings in your body?

21. What Schizophrenia Does A 20th-century artist, Louis Wain, who was fascinated by cats, painted these pictures over a period of time in which he developed schizophrenia. The pictures mark progressive stages in the illness and exemplify what it does to the victim's perception.

22. Disorganized Speech (Formal Thought Disorder) Must be severe enough to substantially impair effective communication Types include tangential, circumstantial, loosening of associations, incoherence Normal is goal directed (e.g., going from point A to point B, or from a question to an answer) and linear (i.e., in a fairly direct and efficient manner)

23. Disorganized Speech - Geometrical Analogy Answer Question Normal: goal directed and linear Answer Question Circumstantial Answer Question Tangential Answer Question Loosening of associations Answer Question Incoherence

24. Disorganized Speech - Examples Tangentialty: A patient with depression is being evaluated. MD: “Have you had trouble sleeping through the night lately?” Pt: “I usually sleep in my bed, but now I’m sleeping on the sofa. Circumstantialty: A patient is describing her headaches. Pt: “They usually start in the morning. I’ll wake up at 6 or 6:30, and then by the time I have my coffee … well sometimes I’ll have tea. I like it with lemon and a bit of sugar … or honey sometimes. I always take milk with coffee. And like I was saying, after coffee I may turn on the TV for half an hour or so. Well, unless there is something really good. If I’m watching the news, I may not even notice the headaches, but by lunch they’re so bad I have to lie down. … … … ” Loosening of associations (also known as derailment): A patient with a first psychotic episode describes the week at home before coming into the hospital. Pt: “I … I watched TV, but the newspaper didn’t come. I … David is at school, too. Sometimes it’s better to be alone, you know, to save for a rainy day.”

25. Disorganized or Catatonic Behavior - I Grossly disorganized behavior Can be with any form of goal directed behavior Problems lead to difficulties in “activities of daily living” Not just aimless or generally non-purposeful behavior

26. Disorganized or Catatonic Behavior - II Catatonia Marked decrease in reactivity to the environment, if complete unawareness = catatonic stupor Maintaining a rigid posture and resisting efforts to be moved = catatonic rigidity ; or maintaining a new posture after being moved by another = waxy flexibility Active resistance to instructions or attempts to be moved = catatonic negativism Assumption of inappropriate or bizarre postures = catatonic posturing Purposeless and unstimulated excessive motor activity = catatonic excitement Also: immobility, mutism, stereotypy (repetitive non-goal directed movements like rocking), mannerisms (repetitive goal directed movements that are odd in appearance or context), echolalia, echopraxia

27. Grossly Disorganized Behavior - Examples Childlike silliness Unpredictable and untriggered agitation Markedly disheveled appearance Very unusual dress (e.g., wearing many coats) Clearly inappropriate sexual behavior (e.g., public masturbation) Collecting or hoarding generally useless things

28. Negative or Deficit Symptoms Account for much of the morbidity Take care to distinguish from antipsychotic medication side effects and from depressive symptoms Affective flattening (~absent affect) Alogia (poverty of speech) Avolition / apathy (lack of goal-directed activity) Anhedonia / asociality

29. Negative or Deficit Symptoms - Examples The patient’s face appears wooden -- changes less than expected as emotional content of discourse changes. The patient’s replies to questions are restricted in amount, tend to be brief, concrete, unelaborated. The patient has difficulty seeking or maintaining employment, completing school work, keeping house, etc. The patient may have few or no interests. Both the quantity and quality of the interests should be taken into account. The patient may have few or no friends and may prefer to spend all his time isolated.

30. Symptom, Syndrome and Disorder Sign / symptom Individual sign or symptom Syndrome Recognized constellation of signs and symptoms + qualifiers (threshold) Disorder Disease Symptom

31. Symptom, Syndrome and Disorder Sign / symptom Individual sign or symptom Syndrome Recognized constellation of signs and symptoms + qualifiers (threshold) Disorder Syndrome + presumed etiology Disease Definite etiology Etiology Symptom

32. Psychotic Symptom, Syndrome and Disorder Sign / symptom Hallucinations, delusions, disorganized speech, grossly disorganized or catatonic behavior Syndrome Paranoid, disorganized, catatonic, toxic, organic, pleomorphic etc. Disorder Schizophrenia and Other Psychotic Disorders

33. Psychotic Syndromes Paranoid Delusions and hallucinations (auditory) Disorganized / Hebephrenic Disorganized speech, grossly disorganized behavior and inappropriate affect Catatonic Catatonic behavior Toxic / Organic Delusions and hallucinations (visual, olfactory or tactile) + cognitive symptoms Acute / Pleomorphic Rapid change Psychotic Syndromes Prominent Symptoms

34. What Are Disorders Associated With Psychosis?

35. Disorders Associated With Psychotic Symptoms “Organic” or Secondary Delirium and Dementia General Medical Conditions Substance-induced “Functional” or Primary Other Primary Mental Disorders Primary Psychotic Disorders

36. Delirium and Dementia Delirium Delirium must be present Psychotic symptoms fluctuate They are fragmented and unsystematized Visual hallucinations are common Dementia Dementia must be present Delusions are common, especially persecutory Among hallucinations, visual predominates

37. General Medical Conditions (GMC) -I Catatonic Disorder Due to a GMC Psychotic Disorder Due to a GMC Hallucinations and/or delusions Have the symptom picture, not delirious , evidence “that the disturbance is the direct physiological consequence of a GMC”

38. General Medical Conditions (GMC) -II Neurological (especially temporal lobe and subcortical) Neoplasm, vascular, seizure, infection, autoimmune, … Endocrine Thyroid, parathyroid, adrenal Metabolic Hypoxia, hypercarbia, hypoglycemia Hepatic , renal , other electrolyte problems

39. Substance-induced Psychotic Disorder - I Have the symptom picture, not delirious , evidence that the symptoms developed during or within a month of substance (or medication) use, intoxication, or withdrawal “Not better accounted for” by another disorder Symptoms precede substance use Symptoms persist more than a month after stopping Symptoms are substantially excessive for expectation given the type, amount, or duration of use

40. Substance-induced Psychotic Disorder - II Intoxication : alcohol, amphetamine, cannabis, cocaine, hallucinogens, inhalants, phencyclidine Withdrawal - alcohol, sedative / hypnotics / anxiolytics Medications - steroids, antiparkinsonian agents, anticholinergic agents, others / unknown Toxins - anticholinesterases, organophosphates, volatiles, carbon monoxide, others / unknown

41. Other Primary Mental Disorders - I Bipolar Disorder - often psychotic during a manic episode, especially grandiose delusions Major Depressive Disorder - can be a psychotic depression, especially guilt or somatic delusions and/or derogatory auditory hallucinations; Also may appear catatonic in a severe mood episode Pervasive Developmental Disorders - can include hallucinations and delusions of < one month; Along with language, affective, and interpersonal deficits; Age of onset helps differentiate

42. Other Primary Mental Disorders - II Borderline Personality Disorder - may have “transient, stress-related paranoid ideation” or so-called “micro-psychotic episodes” Cluster A Personality Disorders (Schizotypal, schizoid, and paranoid) have various attenuated “criterion A” schizophrenia symptoms, which are basically the same level as would be referred to as prodromal or residual in schizophrenia

43. Primary Psychotic Disorders Schizophrenia Schizophreniform Disorder Brief Psychotic Disorder Delusional Disorder Schizoaffective Disorder

44. DSM-IV Schizophrenia Symptoms Hallucinations, delusions, disorganized speech, grossly disorganized or catatonic behavior, and negative symptoms Number :  2 of 5 symptoms Qualifiers Function : significant social/occupational impairment Duration : active phase  1/12, illness  6/12 Etiology Exclusion : mood, schizoaffective, GMC, substance Special : pervasive developmental disorder (PDD) A B C D&E F

45. DSM-IV Schizophrenia Subtypes Catatonic Motoric immobility, excessive motor activity, excessive negativism, peculiarities of voluntary movement, and echolalia or echopraxia Disorganized Prominent – disorganized speech and behavior, and flat/inappropriate affect Catatonic not prominent Paranoid Delusions or prominent hallucinations Not prominent - disorganization, catatonic, or flat/inappropriate affect Undifferentiated Criteria are not met for the Paranoid, Disorganized, or Catatonic type Residual Absence of positive psychotic symptoms Negative symptoms or attenuated positive symptoms (e.g., odd beliefs, eccentric behavior, or mildly disorganized speech) Subtype Diagnostic Criteria

46. DSM-IV Schizophreniform Disorder Symptoms Hallucinations, delusions, disorganized speech, grossly disorganized or catatonic behavior, and negative symptoms Number :  2 of 5 symptoms Qualifiers Duration : active  1/12, 1/12  illness > 6/12 Etiology Exclusion : mood, schizoaffective, GMC, substance A B

47. Schizophreniform Disorder Course, prognosis - limited information ~1/3 recover, ~2/3 progress to schizophrenia or Schizoaffective disorder Treatment - like schizophrenia, except: Only 3 to 6 months antipsychotic medications Tendency to respond more rapidly Provisional Schizophrenia

48. DSM-IV Brief Psychotic Disorder Symptoms Hallucinations, delusions, disorganized speech, and grossly disorganized or catatonic behavior Number :  1 of 4 symptoms Qualifiers Duration : 1 day > illness > 1 month Function : eventual full return of premorbid level Etiology Exclusion : mood, schizoaffective, schizophrenia, GMC, substance A B C

49. Brief Psychotic Disorder Course, prognosis - usual onset is late adolescence or early adulthood, often after marked stressor(s) , prognosis is good (over half recover with no further major psychiatric problems) Treatment - often hospitalization, acute use of antipsychotic medications, psychotherapy

50. DSM-IV Delusional Disorder Symptoms Non-bizarre delusions Criterion A for schizophrenia never been met Qualifiers Function : not markedly impaired, behavior not obviously odd or bizarre Duration :  1/12 Etiology Special : Mood episodes Exclusion : GMC, substance A B C D E

51. Delusional Disorder Types - erotomanic, grandiose, jealous, persecutory, somatic, mixed, unspecified Course, prognosis - onset usually middle to late adulthood, course is quite variable, persecutory and jealous most common types Treatment - usually outpatient, antipsychotic medication, reliable supportive psychotherapy

52. Schizoaffective Disorder - I Diagnosis Uninterrupted illness containing period(s) concurrently meeting “Criterion A” of Schizophrenia plus a major mood episode (depressed, manic, or mixed) Other period(s) of at least two weeks meeting “Criterion A” of Schizophrenia in the absence of prominent mood symptoms Mood episodes are a “substantial” portion of the total Relationship to Schizophrenia and Mood Disorders Biological relatives are at increased risk for both Schizophrenia and for Mood Disorders

53. Schizoaffective Disorder - II Course, prognosis Depressive and bipolar types Onset in early adulthood is typical Prognosis is intermediate between schizophrenia and mood disorders ~10% suicide Treatment Antidepressant or antimanic medications depending on type of Schizoaffective Disorder and current episode Antipsychotic medications often are needed also Psychosocial treatments, and hospitalization as needed

54. A disorder with psychotic feature Psychosis as the defining feature COGNITIVE DISORDERS Delirium and Dementia MOOD DISORDERS Bipolar Disorder Major Depressive Disorder PERSONALITY DISORDERS Borderline Personality Cluster A Personality PERVASIVE DEVELOPMENTAL DISORDERS PSYCHOTIC DISORDERS General Medical Condition Substance-induced Schizoaffective SCHIZOPHRENIA Schizophreniform Disorder Brief Psychotic Disorder Delusional Disorder yes no

55. Psychosis Prototype- Schizophrenia

56. Early Figures in the History of Schizophrenia 1801 -1809 Philippe Pinel A French physician who described cases of schizophrenia 1852 Benedict Morel A French physician who used the term d é mence pr é coce meaning early or premature loss of mind to describe schizophrenia 1898 -1899 Emil Kraepelin A German psychiatrist who unified the distinct categories of schizophrenia (hebephrenic, catatonic, and paranoid) under the name dementia praecox 1908 Eugen Bleuler A Swiss psychiatrist who introduced the term schizophrenia , meaning splitting of the mind Historical Figure Contribution

57. Historical Figures - I Emil Kraepelin Grouping together catatonia, hebephrenia and paranoia into dementia praecox Separated schizophrenia (which he called dementia praecox) from bipolar disorder (which he called manic-depressive psychosis) largely on the basis of the clinical course of the syndromes

58. Historical Figures - II Eugen Bleuler Coined the term schizophrenia, meaning splitting of the mind Four A’s Ambivalence - describes the splitting of the Mental state Autism - describes idiosyncratic logic and meanings Affect - described the blunting and inappropriate nature of the affect Association - describes the formal thought disorder

59. Epidemiology - I Lifetime prevalence ~1%; Male = female Seen in all cultures at similar frequency (refutes "myth" concept), though a few geographical pockets of higher prevalence exist Onset usually late adolescence to young adulthood, earlier in males than females Increased chance of being born in the winter or early spring

60. Epidemiology - II Increased mortality rate from accidents and natural causes: Life span is shortened by about a decade Some under-diagnosis of medical illness is present ~ 10-15% suicide; ~50% attempt; Prominent risks: Early in illness and young age High premorbid function Depression The latter two often contributing to demoralization Illness seems concentrated in urban settings, i.e., It is somewhat correlated with population density in larger cities Illness seems concentrated in lower socioeconomic classes Downward drift vs. Social causation

61. Epidemiology - III Increased use vs. Abuse vs. Dependence: ~75% nicotine; ~40% alcohol; ~20% marijuana; ~10% cocaine Substance use comorbidity worsens prognosis ~1/3 or more of homeless population Disabling (over 50% unemployed) High number years of productive life lost 2.5% of all health care expenditures 50% of all inpatient psychiatry beds 30% of all hospitalizations $50 billion annual cost to US (direct + indirect)

62. Clinical Course Prodrome Acute index episode (~first hospitalization) Relapsing, remitting course and prognosis Clinical presentation Positive and negative symptoms Type I and type II Schneider’s first rank symptoms Functional outcomes Violence

63. Prodrome Attenuated “Criterion A” symptoms of schizophrenia They can also be thought of as the symptoms of Cluster A (“odd & eccentric”) Personality Disorders, e.g., Paranoid, Schizoid, and/or Schizotypal Personality Disorders Schizoid Personality Disorder fits well with attenuated forms of “negative symptoms” Schizotypal Personality Disorder fits well with attenuated forms of “positive symptoms” Generalized anxiety Mild degrees of depression and preoccupation Loss of interest in work & social activities Neglect of personal appearance

64. Acute Index Episode Often, but not always, preceded by months to years of prodromal symptoms Usually no “stressor” is identifiable Patient develops Criterion A symptoms, i.e, an acute psychosis This usually leads to behavior seen as serious enough by family or other social supports to initiate some sort of medical contact Often some form of impetus (other than the patient) is needed, up to the point of legal coercion, e.g., involuntary hospitalization

65. Course Classically, course consists of exacerbations and remissions, though often not to “baseline” premorbid level of functioning Illness progression often plateau at about 5 years after initial diagnosis Antipsychotic medications improve acute and long-term outcome About 1/4 have a good outcome, 1/4 continue to have moderate symptoms, and 1/2 remain significantly impaired with current treatment

66. Course and Outcome in Schizophrenia (8 Types) Onset Exacerbation End state % of patient 10 24 10 5 1 2 3 4

67. Course and Outcome in Schizophrenia (8 Types) Onset Exacerbation End state % of patient 5 8 25 12 5 6 7 8

68. John F. Nash, Jr. Nobel Prize Winner Nash was a professor at the Massachusetts Institute of Technology when he developed a psychiatric disability (1959, age 30). After 25 years of disability, he returned to his research and received the Nobel prize in 1994 for his work.

69. Prognosis Better prognosis Poorer prognosis Good premorbid personality and social function Family history of bipolar affective disorder Poor premorbid personality Family history of schizophrenia Low IQ and SE class Perinatal trauma and childhood difficulties Onset in mid-life years Abrupt onset Precipitating events Symptoms of mood disturbance Presentation under 15 years Insidious onset Negative, disorganized, and neurological symptom/signs Good compliance with medication Good support system and married Poor compliance with medication Social isolation

70. Typical Gender Difference in Schizophrenia Variable Men Women Age of onset Earlier (18-25) Later (25-35) Premorbid adjustment Poor social functioning; more schizotypal traits Good social functioning; fewer schizotypal traits Typical symptoms More negative symptoms; more withdrawn and passive More hallucinations and paranoia; more emotional and impulsive Course More often chronic; poorer response to treatment Less often chronic; better response to treatment

71. Clinical Presentation POSITIVE SYMPTOMS : represent a distortion or exaggeration of a normal function and include delusions, hallucinations and abnormalities of language and behavior. Positive symptoms tend to DECREASE in severity with time SYMPTOM FUNCTION DISTORTED Hallucinations Perception Delusions Inferential thinking Formal thought disorder Language Behavioral disorganization Behavior control

72. Clinical Presentation NEGATIVE SYMPTOMS : represent a diminution or loss of function including poverty of speech and content of speech (alogia), affective blunting, asociality, anhedonia, and avolition. Negative symptoms tend to INCREASE in severity over the years SYMPTOM FUNCTION DISTORTED Alogia Fluency of expression Affective blunting Emotional expression Avolition-asociality Volition and drive Anhedonia Hedonic capacity Attentional impairment Attention

73. Type I and Type II (Crow 1980) Symptoms Positive symptoms Negative symptoms Premorbid adjustment Relatively good Relatively poor Responsiveness to traditional antipsychotics Good Poor Outcome of disorder Fair Poor Biological features Abnormal neurotransmitter activity Abnormal brain structure Type I Type II

74. Schneider’s First Rank Symptoms Auditory hallucinations Audible thoughts Voices arguing or discussing or both Voices commenting Passivity phenomena ‘Made affect’ ‘Made impulse’ ‘Made volition’ Thought alienation Thought broadcasting Thought insertion Thought withdrawal Somatic passivity Delusional perception Characteristic but not pathognomonic of schizophrenia 88% specificity, 91% positive predictive value, and 27% sensitivity

75. Social/Occupational Dysfunction work interpersonal relationships self-care Impact of Schizophrenia Symptoms on Functional Outcomes Positive Symptoms Mood Symptoms Cognitive Symptoms Negative Symptoms

76. Violence Media distortions and sensationalism contribute to the idea that most schizophrenics are violent, but this is untrue. However, after factoring out comorbid disorders well known for increasing violence (e.g., alcoholism, antisocial personality disorder), an elevated risk remains compared to the general population Best predictors are history of previous violence, along with dangerous behavior while hospitalized and hallucinations or delusions involving violence

77. Media Distortions and Sensationalism

78. What Causes Schizophrenia?

79. Etiology and Pathophysiology Genetics Neuropathology Neuroanatomy Functional brain imaging Neurophysiology Neurotransmitters Neuropsychiatry Neurodevelopmental Psychological Social Diathesis-stress

80. Genetics Epidemiology Genetic counseling Linkage studies Association studies Overall, evidence is most consistent with significant genetic influence, likely by complex genetic mechanisms, e.g., multiple genes and important interactions with the environment

81. Genetic Epidemiology Family studies Show increased risk for illness to relatives of probands (schizophrenics) vs. relatives of controls This risk falls off rapidly as the relationship becomes more distant “Schizophrenia spectrum”, such as schizotypal personality disorder Twin studies Show increased diagnostic concordance rate for monozygotic (identical) vs. dizygotic (fraternal) twins; usually a 3-4:1 ratio Heritability estimates are around 80% Monozygotic concordances of 40-50% are strong evidence for the importance of environmental components Adoption studies Show increased risk for biological vs. adoptive relatives of patients with schizophrenia Segregation analyses Attempt to fit observed families with modes of inheritance, but have not succeeded with schizophrenia

82. Genetic Counselling The Genain quadruplets all have schizophrenia, but the specific forms of schizophrenia differs among the sisters

83. Neuropathology (Postmortem Studies) Limbic system Decreased size of amygdala, hippocampus, and parahippocampal gyrus Disorganized neurons in hippocampus Basal ganglia  Number of D2 receptors Temporal and frontal lobes Some evidence for abnormal neuronal migration

84. Neuroanatomy (CT & MRI) Increased ventricular brain ratio (VBR) is commonly seen, especially lateral and third ventricular enlargement Correlation with severity of disease (deficit symptoms, worse premorbid function, more neurological signs) Not diagnostic and large group overlaps Decreased volumes of amygdala, hippocampus, and parahippocampal gyrus

85. Functional Brain Imaging (PET, SPECT, rCBF) Failure to increase blood flow to the dorsolateral prefrontal cortex while performing the activation task of the Wisconsin Card Sorting Test Reduced blood flow to the left globus pallidus (an even earlier finding in the course of illness) suggests a problem in the system connecting the basal ganglia to the frontal lobes Correlation with severity of disease present

86. Liddle’s Syndrome (1987) Syndrome Symptom rCBF by PET Psychomotor Poverty Syndrome Poverty of speech, flat affect and decrease spontaneous movement  Left dorsal PFC , medial PFC and anterior cingulate cortex  Head of caudate nucleus Reality Distortion Syndrome Delusions and hallucinations  Left parahippocampal region and left striatum Disorganization Syndrome Formal thought disorder and inappropriate affect  Right ventral PFC  Anterior cingulate and dorsomedial thalamic nuclei

87. Brain Areas and Functions Frontal Lobe Temporal Lobe Basal Ganglia Limbic System Drive and Ambition Problem solving Cognitive flexibility Capacity to plan Time sequential thinking Social awareness Empathy Mood Insight Impulsivity Judgment Abstraction Working memory Perception Reality Orientation Memory Inhibit unwanted sensory input Filter out irrelevant sensory input Regulate arousal Govern concentration Understanding emotional events Linking current perception to past memories Learning from experience

88. Neurophysiology Minor nonlocalizing neurological dysfunction (soft signs) common Several nonspecific electroencephalographic (EEG) findings Subset of patients drink water to excess & develop hyponatremia Some neurophysiological traits are strongly associated with illness and may be biological markers: Abnormal smooth pursuit eye movements Deficits in sensorimotor gating of auditory stimuli Other problems with information processing at higher levels (more like neuropsychology): Halstead-Reitan and Luria-Nebraska batteries Consistent with bilateral frontal & temporal dysfunction Impairments in attention, retention time, & problem-solving Some decreased intelligence as measured by IQ tests as a group

89. Neurotransmitters - I Dopamine Hypothesis - strengths: Substances leading to increased dopaminergic states cause psychosis. Another way of stating this is that L-DOPA, amphetamine, and cocaine are psychotomimetic. Antidopaminergic agents are antipsychotic, and there is a good correlation for classical antipsychotics between their potency and their D2 dopamine receptor binding Pretreatment correlations of plasma homovanillic acid (major dopamine metabolite) with severity of psychotic symptoms and treatment response Dopamine Hypothesis - weaknesses: Antipsychotics work for psychosis due to many other etiologies besides just schizophrenia The atypical antipsychotics are not as well correlated with respect to D2 dopamine receptor binding and clinical potency Time of onset vs. receptor occupancy

90. Dopaminergic Pathways and Innervation Nuc Acc = nucleus accumbens SN = substantia nigra VTA = ventral tegmental area

91. Neurotransmitters - II Other neurotransmitters with decent cases: Serotonin (5-hydroxytryptamine) Atypical antipsychotics notably block serotonin, especially at HTR2A (2A serotonin receptor) LSD (lysergic acid diethylamide) affects the serotonin system and is psychotomimetic Glutamate (one type of receptor is the NMDA class) Phencyclidine (PCP) intoxication often manifests with psychosis and can elicit sensorimotor gating deficits in rodents Ketamine is also a glutamate/NMDA antagonist, which induces psychosis in healthy volunteers mimicking schizophrenia Others with some support: Norepinephrine, gamma aminobutyric acid (GABA)

92. Serotonergic Pathways and Innervation Hypo = hypothalamus SN = substantia nigra Thal = thalamus

93. Ketamine is a glutamate/NMDA antagonist In healthy volunteers, it causes many psychotic symptoms: disorganization, perceptual changes, deficit symptoms PET shows focal activation of prefrontal cortex Adler CM et al. Comparison of ketamine-induced thought disorder in healthy volunteers and thought disorder in schizophrenia. Am J Psychiatry. 1999 Oct;156(10):1646-9. Ketamine Challenge

94. Neuropsychiatry Delusions - most common in neurological diseases bilaterally affecting the temporal lobes or basal ganglia Hallucinations - visual modality is more commonly found in neurological illnesses Individual symptoms, e.g., auditory hallucinations, are now being mapped in various neuroimaging protocols

95. Neurodevelopment Obstetrical complications and prenatal infections are two potential non-genetic early influences on neurodevelopment Genes influencing neuronal migration and other aspects of brain development are also candidates to explain abnormalities in neurodevelopment in schizophrenia Is schizophrenia neurodevelopmental or neurodegenerative or some combination?

96. Psychological Attempts to explain the origin of schizophrenic symptoms Loosening of association (Cameron, 1938) Concrete thinking (Goldstein, 1944) Over-inclusive thinking (Payne & Friedlander, 1962) Inconsistent concept (Bannister & Fransella, 1966) Defective filter theories (Broadbent) Faulty internal monitoring (Frith, 1992)

97. The Underlying Malfunction That Gives Rise to Positive Symptoms Intention Experience due to faulty monitor Symptom To act Unintended act Delusion of control To think Unintended thought Thought insertion To switch attention Switch elicited by irrelevant stimulus Delusion of reference To think (subvocal speech) Unexpected subvocal speech Thought broadcasting, auditory hallucinations Positive symptoms occur when information about self-generated intentions is not monitored. As a consequence, acts occur which are apparently unintended (Frith)

98. Social Theories Family processes: Double bind communication (Bateson, 1956) Parent giving conflicting messages, can not escape or respond to both  irrational / ambiguous behaviour  schizophrenia Skew and schism (Lidz, 1957) Caused by shifts in the traditional power roles in a family Skew: mother dominant, father submissive Schism: parents hostile towards each other  split psyche in child  schizophrenia

99. Social Theories Family processes: Life Events relapse preceded by an excess of life events (compared to normal controls, but not compared to other psy. patients) High Expressed Emotion (EE): relapse risk increasing: hostility emotional over-involvement critical comments relapse risk reducing: positive remarks warmth

100. Social Theories Socio-economic status higher in lower SES, urban areas (industrialized countries) social drift hypothesis: effected individuals move to lower SES due to social and occupational incompetence (parents normally higher SES) social causation hypothesis: stresses related to SE deprivation causes Schizophrenia immigrants: Afro-Carribean in UK have higher rates of Schizophrenia ? Stresses of leaving own country, adapting to new environment

101. Diathesis-Stress Model Vulnerability to a disorder (inherited or acquired) combines with the impact of stressors to produce the disorder It calls attention to the role of both biological and psychological factors in schizophrenia Disorder manifested Disorder not manifested Low Low High High Predisposition for the disorder Amount of stress

102. Genetic and/or Environmental Factors Abnormal Brain Structure or Functioning Reduced available processing capacity Autonomic hyperreactivity to aversive stimuli Social competence and coping deficits Enduring Vulnerability Characteristics Nonsupportive social network Social stressors Environmental Stimuli Processing capacity overload Autonomic hyperarousal Deficient processing of social stimuli Transient Immediate States Schizophrenic Psychotic Symptoms Outcome Behaviors A DIATHESIS-STRESS MODEL

103. Treatment Psychopharmacologic Classical (= typical = conventional) antipsychotics “Atypical” antipsychotics Other agents Psychosocial Supportive therapy Social skills training Case management Working with families

104. Classical (Typical) Antipsychotics - I Synonyms for antipsychotics are neuroleptics or major tranquilizers Henri Laborit, an anesthesiologist, discovered that chlorpromazine had a marked calming effect Their introduction in the 1950’s was a major revolution in psychiatry Classical antipsychotics are dopamine receptor antagonists They are most effective for positive symptoms Depot (long acting) forms are available

105. Classical (Typical) Antipsychotics - II They are divided into a high potency and a low potency group. Potency refers to the amount (mg) of drug to give the antipsychotic effect. Examples of high potency antipsychotics include haloperidol (Haldol) and of low potency antipsychotics include chlorpromazine (Thorazine). The high potency group is worse with extrapyramidal symptom (EPS) side effects, and the low potency group is worse with most of the other side effects (anticholinergic, sedation, orthostatic hypotension). A minimum therapeutic trial is 4-6 weeks of adequate dose.

106. “Atypical” Antipsychotics “Atypical” antipsychotics are serotonin-dopamine receptor antagonists They are as effective for positive symptoms and more effective for negative symptoms Clozapine is notable in particular: It is effective in treatment refractory cases It is worse for most non-EPS side effects It has a ~1-2% risk of inducing agranulocytosis The others (e.g., risperidone) generally produce fewer side effects than classical antipsychotics

107. Other Agents Other agents may be added for augmentation purposes to the antipsychotic: Lithium, valproate, carbamazepine Benzodiazepines Electroconvulsive therapy (ECT) is used on occasion, especially when the patient is catatonic

108. Psychosocial Supportive therapy This is well supported as an adjunct to medication. (Insight-oriented approaches are contraindicated.) Social skills training This especially focuses on amelioration of negative symptoms by means of cognitive-behavioral methods. Case management This greatly aids in coordination of care and optimization of treatment compliance. Working with families Besides education, the primary goal is to reduce high levels of expressed emotion to improve illness course.