Dr. Zahiruddin Othman discusses concepts and definitions related to psychosis. Psychosis has been conceptualized in various ways throughout history such as shamanism, demonic possession, lunacy, and witchcraft. Definitions of psychosis focus on symptoms such as delusions and hallucinations. Psychotic symptoms include hallucinations, delusions, disorganized speech, and disorganized or catatonic behavior. Schizophrenia, schizophreniform disorder, brief psychotic disorder, and other psychiatric disorders can involve psychotic symptoms.

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

2. 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

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)

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
AnswerQuestion
Normal: goal directed and linear
AnswerQuestion
Circumstantial
AnswerQuestion
Tangential
AnswerQuestion
Loosening of associations
AnswerQuestion
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

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

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
démence précoce 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 SymptomsCognitive 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

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
Relapse Rates Over 9 Months
Low EE High EE
<35h/wk
High EE
>35h/wk
Anti-
psychotic
12% 15% 53%
No Anti-
psychotic
15% 42% 92%

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
Amountofstress

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
ADIATHESIS-STRESSMODEL

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.