Download Schizophrenia and Related Disorders

Schizophrenia
and
Related Psychotic Disorders
Diana O. Perkins, MD, MPH
Associate Professor of Psychiatry
Director, Schizophrenia Treatment and
Evaluation Program
Schizophrenia and Related Psychotic
Disorders
 Clinical
characteristics
 Epidemiology
 Etiology
Psychotic Disorders
Clinical Characteristics
Schizophrenia is
Heterogeneous...
 A syndrome
defined by a constellation of
clinical symptoms
 With
multiple causes, that are similarly
expressed
Show video tape
Schizophrenia: Clinical Features
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Positive Symptoms
a distortion or excess of normal function
Negative Symptoms
a decrease or loss in normal function
Disorganization
of thoughts and behavior
Cognitive Impairments
Mood Symptoms
Features of Schizophrenia
Positive symptoms
Negative symptoms
Functional Impairments
Work
Interpersonal relationships
Self-care
Cognitive deficits
Mood symptoms
Disorganization
Positive Symptoms (Psychosis)
 Disturbance
of Perception
(Hallucinations)
 Disturbance
(Delusions)
of Thought Content
Positive Symptoms
Disturbance of Perception
 may effect any sensory modality
Positive Symptoms: Hallucinations
Auditory Hallucinations
• involve voices or sounds
• single or multiple
• familiar or unfamiliar
• may make insulting remarks or be pleasant
• may comment on behavior
• may command person to perform acts
Positive Symptoms: Hallucinations
Other Sensory Modalities
• Tactile: may involve electrical, tingling, or
burning sensations
• Visual
• Gustatory
• Olfactory
Positive Symptoms: Delusions
Delusions
• fixed false beliefs
• examples:
-
persecutory delusions
delusions of reference
delusions of being controlled
thought broadcasting/insertion/withdrawal
grandiose
religious
nihilistic
somatic
Features of Schizophrenia
Positive symptoms
- Hallucinations
- Delusions
Negative symptoms
Functional Impairments
Work
Interpersonal relationships
Self-care
Cognitive deficits
Mood symptoms
Disorganization
Negative Symptoms
Negative symptoms include:
decreased expression of feelings
diminished emotional range
poverty of speech
decreased interests
diminished sense of purpose
diminished social drive
Differential Diagnosis of Negative Symptoms
Negative Symptoms primary to schizophrenia:
The “Deficit Syndrome”: primary and enduring negative
symptoms in individuals with schizophrenia
• The Deficit Syndrome occurs in about 20% of treated
patients
Differential Diagnosis of Negative Symptoms
Negative Symptoms may be secondary to:
antipsychotic EPS side effects
- decreased emotional expression and apathy may
be due to Parkinsonian side effects
- lack of initiation of activity may be due to
bradykinesia
psychosis
depression or anxiety
demoralization
Features of Schizophrenia
Positive symptoms
- Delusions
- Hallucinations
- Disorganization
Functional Impairments
Work
Interpersonal relationships
Self-care
Cognitive deficits
Negative symptoms
-  emotional range
-  expression of emotion
-  motivation/drive
-  interests
-  social drive
- poverty of speech
Mood symptoms
Disorganization
Positive Symptoms: Disorganization
• Disorganization of Speech
– tangential or circumstantial speech
– looseness of associations
• Disorganization of Behavior
– odd mannerisms
– catatonic stupor
Video Tape
 Positive
symptoms:
• Hallucinations
• Delusions
 Disorganization
• Speech
• Behavior
 Negative
symptoms:
Features of Schizophrenia
Positive symptoms
- Delusions
- Hallucinations
- Disorganization
Functional Impairments
Work
Interpersonal relationships
Self-care
Cognitive deficits
Disorganization
- speech
- behavior
Negative symptoms
-  emotional range
-  expression of emotion
-  motivation/drive
-  interests
-  social drive
- poverty of speech
Mood symptoms
Cognitive Domains:
Severe Impairment in Schizophrenia
–
–
–
–
–
Severe Impairments
Serial learning
Executive functioning
Vigilance
Motor speed
Verbal Fluency
–
–
–
–
–
Moderate Impairment
Delayed recall
Distractibility
Immediate memory span
Visuomotor skills
Working memory
Working Memory
– Aspects of Working Memory
• Temporary storage and manipulation of information
• “workspace” for holding items of information in mind
as recalled, manipulated, and associated with other
ideas and information
– Tests
• patients with schizophrenia tend to perform 1-2
standard deviations below the mean
• Tests: visual, spatial, auditory working memory
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Executive Function
– Aspects of Executive Function
• Focus attention
• Distinguish the important aspect of a task or a
situation from unimportant
• Prioritize
• Perform mental or physical activities proper sequence
• Modulate behavior based on social cues
– Tests:
• Patients perform 2-3 standard deviations below mean
• Examples: Trail Making Tests, Wisconsin Card Sort,
Tower of London
The Wisconsin Card Sorting Test
The Wisconsin Card Sorting Test
The Wisconsin Card Sorting Test
The Wisconsin Card Sorting Test
The Wisconsin Card Sorting Test
The Wisconsin Card Sorting Test
The Wisconsin Card Sorting Test
The Wisconsin Card Sorting Test
The Wisconsin Card Sorting Test
The Wisconsin Card Sorting Test
The Wisconsin Card Sorting Test
Vigilance
– Ability to monitor target stimuli over an
extended duration of time
• inability to attend to relevant stimuli and ignore
irrelevant stimuli
• inability to concentrate
• increased susceptibility to distractions
• inability to sustain effort and attention
– Tests of Vigilance:
• patients perform 2-3 standard deviations below the
mean
• example: CPT
Cognitive Functions:
Mild or No Impairment in Schizophrenia
Mild Impairment
No Impairment
• Word recognition
• Perceptual Skills
• Delayed recognition • Long-term factual memory
memory
• Confrontation naming
Features of Schizophrenia
Positive symptoms
- Delusions
- Hallucinations
- Disorganization
Cognitive deficits
- Attention
- Memory
- Verbal fluency
- Motor function
- Executive function
Negative symptoms
- Decreased experience and
expression of emotions
- Decreased motivation/drive
Functional Impairments - Decreased initiative
Work
Interpersonal relationships - Social withdrawal
Self-care
Disorganization
- speech
- behavior
Mood symptoms
Mood Symptoms
– Dsyphoric
• anger, hostility, fear, irritability, depression,
anxiety
• high risk of suicide
– Euphoric
• sense of power, control, exhilaration
Mood Symptoms
– Primary to schizophrenia
– “Reactive”
• psychosis is frightening
• reality of illness is demoralizing
– Co-morbid disorder
• major depressive episode
Features of Schizophrenia
Positive symptoms
Delusions
Hallucinations
Disorganized speech
Functional Impairments
Work
Interpersonal relationships
Self-care
Cognitive deficits
Attention
Memory
Verbal fluency
Executive function
(eg, abstraction)
Disorganization
- speech
- behavior
Negative symptoms
Anhedonia
Affective flattening
Avolition
Social withdrawal
Alogia
Mood symptoms
Depression/Anxiety
Aggression/Hostility
Suicidality
Diagnosis of Schizophrenia
Symptoms
Severity/Impairment/Distress
Duration
Differential Diagnosis of Schizophrenia
 Significant
psychotic symptoms for at least
one week

Continuous signs of the disturbance for at
least six months

Markedly impaired ability to function

Without known etiology
Differential Diagnosis of
Schizophrenia
Differential Diagnosis: related disorders
Schizophreniform Disorder
Brief Psychotic Disorder
Delusional Disorder
Schizoaffective Disorder
Schizoid Personality
Schizotypal Personality Disorder
Paranoid Personality Disorder
Differential Diagnosis of
Schizophrenia
Differential Diagnosis: Mood Disorders with
Psychotic Features
Major Depression
Bipolar Disorder
Differential Diagnosis of
Schizophrenia
Organic Mental Disorders
substance induced (e.g. PCP,
amphetamine, cocaine,
hallucinogens, cannabis, alcohol, a
variety of prescribed medications
most diseases affecting the
central nervous system
case
OVERVIEW
Demographics:
Vignette 1: Michael
Michael is a 23 year old single male. He lives with his father. He completed some college and
currently works at the shipping dock of a department store.
Occupational History:
Michael has worked for nearly a year at the shipping dock. He has had several other jobs that he
quit when he felt “frustrated”. He has also been unemployed for several long periods. He calls in
sick to work several times a month and is currently on probation at work.
Status of Current Treatment:
He is currently an outpatient in the psychiatric clinic. He was hospitalized for 4 days
approximately two months ago.
Chief Complaint and Description of Problem:
Michael reports that he has trouble fitting in and believes that all his co-workers are “weird”. He
reports feeling “a little confused” at work, but admits he usually goes to work “high” on
marijuana or crack.
History:
Michael had been in his usual state of good health until approximately three years ago. At the
time he was smoking crack cocaine and marijuana several times a week and reports several
episodes where he thought that the police were following him and bugging his phone. All of the
Vignette 1: Michael
episode occurred after a heavy episode of drug use, and resolved after one or two days. He
eventually went to the psychiatric clinic for help with the episodes of paranoia, but denied any
substance use to the clinic staff. He was prescribed haloperidol, which he took for two days, and
then stopped because the medication made him feel “weird”.
Prior to three years ago, the patient had no history of mental illness. However, over the past 3
years he has frequently used crack and marijuana and during periods of heavy use he has
consistently felt “more paranoid” and “cut-off from everyone”.
There are no other major life changes and there have been no deaths of close friends or relatives.
However, his relationship with this father is quite strained. His mother died over 10 years ago.
About 2 months ago Michael was admitted to the hospital after becoming very aggressive towards his
father. He accused his father of sabotaging his car, trying to kill him, and said he would “get dad before dad
got me”. In the emergency room Michael was agitated, and was fearful that sirens were the police coming
to arrest him. He also reported hearing “voices” telling him “bad stuff” while in the emergency room.
Urine toxicology screen was positive for marijuana, PCP, and cocaine. His agitation and paranoid ideation,
as well as the “voices” resolved by the third hospital day, without any medication treatment.
Treatment History:
Michael has had one prior substance abuse inpatient stay lasting 6 days, where, off substances
and without medication, his psychotic symptoms resolved.
Vignette 1: Michael
Other Current Problems:
He reports that he always feels “weird and anxious”. He smokes marijuana or crack 1-3 times a
day and drinks “several beers” daily.
Current Social Function:
Michael has no close friends although he will socialize with co-workers occasionally while at work. He is
estranged from his father who feels that he does not try hard enough to get better. Outside of work, he
watches TV and listens to music.
For the past several months, Michael has said he feels anxious and depressed most of
the time, because he feels he has no life and no future. He says he never feels interested in
anything, and he wishes that he were “more motivated”. His appetite is fine and he has had no
change in weight. He reports that his sleep is “pretty good” and he is sleeping 6-8 hours a night.
Vignette 1: Michael
He denies motor changes (either periods of agitation or motor slowing), and his movements and
rate of speech are normal during the SCID interview. He states his energy is “fine”. He feels
hopeless about the future, specifically that he will never get a “good job” or have a “decent place
to live” but denies feeling worthless or guilt. He blames his father for his current living and work
situation. He states that his concentration is “fine”, and there is no evidence of impaired
concentration during the interview. He denies recurrent thoughts of death or suicidal ideation.
He denies any other periods of depression or loss of interest/motivation in the past five years.
Michael denies any periods of time when he has felt euphoric or irritable.
He denies thoughts that others take special notice of him. He acknowledges “feeling
paranoid” at times when he smokes crack and marijuana. At these times he believes that the
police are bugging his phone, and following him and trying to “get him”. He denies any other
unusual beliefs. After smoking crack and marijuana he admits that he also occasionally hears
muffled voices coming up from the floor, but the voices are indistinct. He admits to hearing the
sirens in the emergency room, but he says “I think I was really hearing that”. He denies any other
perceptual abnormalities. He states that the paranoid ideas or the “voices” have always resolved
when he has stopped the drugs for a week or more, as is true during this hospitalization. On
examination, he is reasonably well dressed and well groomed. His motor behavior is normal and
well organized. He exhibits a full range and normal display of affect. His speech is normal in rate
and rhythm, and his thought form is generally well-organized. He exhibits poor eye contact .
watches TV and listens to music.
Schizophrenia: Epidemiology
Common disease:
One in every 100 people develops
schizophrenia
Each year, 100,000 people are newly
diagnosed with schizophrenia in the U.S.
On any given day, 600,000 people are in
active treatment for schizophrenia in the
U.S.
Etiology Risk Factors for Schizophrenia
 Genetic
Vulnerability Factors
 Environmental Risk Factors
• Obstetrical Trauma
• In-utero events
• Infectious Pathogens
• Nutritional Factors
• Substance Abuse
• Stressful life events
• College
• Boot Camp
Schizophrenia
is a genetic
neurodevelopmental
disorder
Schizophrenia
Schizophrenia
What does your baby’s future hold?
occurs in
all races
all cultures
all social classes
and both sexes
Schizophrenia
can be treated
but not cured
…yet!
Courtesy of Canadian Schizophrenia Society
Genetic Loci Linked to Schizophrenia
Schizophrenia: Course
Age of onset
may begin at any age
typically begins in late adolescents
and early adulthood
late onset form
males often have earlier age on
onset than females
Schizophrenia
Course
varies from recovery to severe
disability
in treatment settings commonly
see more severe, chronic course
Natural History Of Schizophrenia
Stages Of Illness
Premorbid
Prodromal
Onset/
Deterioration
Residual/
Stable
Healthy


Worsening
Severity Of
Signs And
Symptoms
Gestation/Birth
10
20
30
Years
40
50
Natural History of Schizophrenia
Stages of Illness
premorbid
prodromal
residual/
stable
onset/
deterioration
Healthy


Worsening Severity of
Signs and Symptoms
Gestation/Birth
10
20
30
40
50
Schizophrenia
Course: Variable
Complete recovery (~ 5-10%)
Complete, or almost complete
remission of symptoms, but with
periodic exacerbations of illness
symptoms
Chronic symptoms, serious impact in
function
Schizophrenia
Factors affecting prognosis:
age of onset
sex
premorbid function
abrupt versus insidious onset
family history of mood disorder
precipitating events
duration of untreated illness
substance abuse
Prospective Study of First Episode
Schizophrenia
Percent of Patients Remitting
100
Time to Remission
80
60
40
20
Remission Rate 87%
Median Time to Remission 11 wks
0
1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52
Weeks of Treatment
Robinson et al. 1999
First-Episode: Predictors of
Treatment Response
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
Duration of untreated illness :
Mean
Median
Active psychosis: 52 wks
11 wks
Prodrome:
151 wks
The longer the duration of pre-treatment symptoms,
the poorer the clinical outcome (r=.4, p=.0001)
The longer the duration of pretreatment symptoms,
the longer the time to respond to antipsychotic
medication treatment (p=.03)
Loebel et al. Am J Psychiatry 1992;149:1183-1188
Cumulative relapse rates by episode of
illness
90
80
1st Relapse(104 patients at risk)
70
2nd Relapse (63 patients at risk)
60
3rd Relapse (20 patients at risk)
50
40
30
20
10
0
Year 1
Year 2
* Refers to year(s) after recovery from the previous episode
Robinson et al 1999
Year 3
Year 4
Year 5
Mean Time to Response
Successive Episodes
Episode
(N=40)
1
2
Episode
(N=12)
1
2
3
0
20
40
60
80
Days to Therapeutic Response
Lieberman JA. J Clin Psychiatry. 1996;57(suppl):68-71
100
120
Alternative Pathways to the
Development of Residual Positive
Symptoms in Schizophrenia:

A Treatment Resistant Clinical Sub-type:
Patients who have persistent positive
symptoms despite treatment with
antipsychotics early in the course of illness.

Neuroprogressive Pathology:
Symptoms that are initially treatment
responsive and become unresponsive after
subsequent episodes of illness.