1
Q
What is Schizophrenia NOT
A
“Split personality”
Violent/Dangerous/Unpredictable/Out-of-Control
Untreatable
All the same
Four people with schizophrenia
Why the misconceptions?
“Schizophrenic” has been used to describe the erratic behavior
of the weather, the stock market, and even the 2002 New
England Patriots’ football team.
2
Q
schizophrenia
A
category of psychotic disorders
Schizophrenia is the most common diagnosis in this group of disorders
3
Q
psychosis
A
impairment of reality testing
4
Q
Different types of symptoms
A
positive symptoms
negative symptoms
symptoms of disorganization
5
Q
positive symptoms
A
a. Sensory perception (hallucinations)
b. Ideations (delusions)
positive=psychotic
pathological excesses (50-70% experience)
! Delusions (firmly held beliefs)
! Hallucinations (sensory experience in absence of environmental stimuli or input)
6
Q
negative symptoms
A
a. Social/motivational deficits
b. Decreased expressions of emotion
7
Q
symptoms of disorganization
A
a. Disorganized speech/thought
b. Disorganized behavior
8
Q
schizophrenia prevalence
A
! Present in humans through recorded history ! 1% of most populations (roughly similar worldwide with some differences) ! About 2.5 million Americans currently have the disorder ! Appears in all socioeconomic groups; found more frequently in the lower levels ! Stress of poverty causes the disorder? ! Downward Drift? ! Disorder causes victims from higher social levels to fall to lower social levels and remain at lower levels
9
Q
making sense of schizophrenia
A
In 1960s: being sane in an insane world; constructive inward search
! R.D. Laing: “The experience and behavior that gets labeled schizophrenic is a
special strategy that a person invents in order to live in an unlivable situation.”
! Floyd Pinkerton: The Wall
! Half of people with schizophrenia will attempt suicide (role of
remission)
! Age
! Positive symptoms dwindle, negative symptoms come to forefront
! Late adolescence – early adulthood onset (20-32)
! Prodromal symptoms
! Stress plays major precipitating role
! No gender differences in prevalence, although men & women have
different courses
! Peak ages of onset: males 20–28 years and females 26–32 years
! More recent data suggest prevalence higher in MEN
10
Q
clinical features of schizophrenia
A
chart
11
Q
interesting schizophrenia fact
A
more severe course the less likely to kill themselves
12
Q
DSM-5 diagnosis
A
five key symptoms: 1) delusions 2) hallucinations 3) disorganized speech 4) disorganized or catatonic behavior 5) negative symptoms !two of these five symptoms are required AND at least one symptom must be one of the first three (delusions, hallucinations, disorganized speech).
13
Q
History-Emil Kraepelin
A
This illness develops relatively early
in life, and its course is likely deteriorating and
chronic; deterioration reminded dementia („Dementia
praecox“).
14
Q
History-Eugen Bleuler
A
He renamed Kraepelin’s dementia
praecox as schizophrenia (1911); he recognized the
cognitive impairment in this illness, which he named
as a „splitting“ of mind.
15
Q
Kurt Schneider
A
He emphasized the role of psychotic
symptoms, as hallucinations, delusions and gave
them the privilege of „the first rank symptoms”
16
Q
delusions
A
persecution, reference
Jesus, Satan, Heads of State
17
Q
hallucinations
A
Vast majority auditory (could be olfactory)
Command
Visual hallucinations are morphing what is already there
18
Q
edgar allen poe quote
A
“Have I not told you that what
you mistake for madness is but
the overacuteness of senses?”
19
Q
errotomania:
A
thinking you have a special relationship with someone who might not even know you exist
20
Q
disorganization in terms of speech
A
Rambling speech Jumping topic to topic
Word salad, “clanging”, loose associations
Neologisms
21
Q
disorganization in terms of behavior
A
Inappropriate affect
Agitation
Repetition (echolalia)
Bizarre Behavior (ex: pouring OJ on head)
22
Q
disordered thought
A
DISORDERED THOUGHT seems to be core of what disease is about
hallucinations more florid/dramatic…responsive to medications
23
Q
loose associations (derailment)
A
“The problem is insects. My brother used to collect insects. He’s now a man 5 foot 10 inches. You know, 10 is my favorite number; I also like to dance, draw, and watch TV.”
24
Q
Neologisms
A
(made-up words)
“This desk is a cramstile”
“He’s an easterhorned head”
Flusterated
25
Preservation symptom of disorganized speech
Patients repeat their words and statements again and again
26
Clang
rhymes
How are you? “Well, hell, it’s well to tell”
How’s the weather? “So hot, you know it runs on a cot”
27
word salad
“Much of abstraction has been left unsaid and undone in
these products milk syrup, and others, due to economics,
differentials, subsidies, bankruptcy, tools, buildings, bonds,
national stocks, foundation craps, weather, trades,
government in levels of breakages and fuses in electronics too
all formerly states not necessarily factuated”
28
negative symptoms
```
avolition
alogia
thought blocking
anhedonia
blunted/flat affect
social withdrawal
```
29
avolition
inability to initiate
| behavior (I.e. showering)
30
alogia
poverty of speech--difficult to access info
| ex: hit two bears with one stone -> do two things at once
31
anhedonia
no pleasure in things you use to enjoy
32
blunted/flat affect
toneless expression
33
social withdrawal
absence of social connectedness, absence of affect, apathy
34
psychomotor symptoms
People with schizophrenia sometimes experience
psychomotor symptoms
--Awkward movements, repeated grimaces, odd gestures
These symptoms may take extreme forms,
collectively called catatonia
-- Ranges from wild agitation to immobility
--Examples: pace excitedly or move fingers or arm in
stereotyped ways OR hold unusual postures (waxy flexibility)
35
schizophrenia & suicide
The general risk for suicide is higher at certain times in the
course of the disease:
! Within the first 5 years of onset of the disease
! During the first 6 months after hospitalization
! Following an acute psychotic episode
! The widespread use of antipsychotic drugs over the past
decade does not appear to have had much effect on suicide
rates. In fact, evidence suggests that the use of these drugs
as a way of reducing hospitalization time is increasing the
incidence of suicide. Depression, not delusions, appears to be
the most important motive for suicide in these patients.
36
course of schizophrenia
- continuous without temporary improvement
- episodic with progressive or stable deficit
- episodic with complete or incomplete remission
37
many sufferers experience three phases:
prodromal
active
residual
38
prodromal phase
beginning of deterioration; mild symptoms
| BIG prodromal phase
39
active phase
symptoms become increasingly apparent
40
residual phase
a return to prodromal levels
| - One-quarter of patients fully recover; three-quarters continue to have residual problems
41
Course
chart
42
early signs
```
! Social withdrawal
! Hostility or suspiciousness
! Deterioration of personal hygiene
! Flat, expressionless gaze
! Inability to cry or express joy
! Inappropriate laughter or crying
! Depression
! Oversleeping or insomnia
! Odd or irrational statements
! Forgetful; unable to concentrate
! Extreme reaction to criticism
! Strange use of words or way of speaking
```
43
North American Prodrome Longitudinal Study (NAPLS)
! Collaboration between 8 programs focusing on the psychosis
prodrome.
! Funded by the National Institute of Mental Health (NIMH), the sites
are located at Emory University, Harvard University, University of
Calgary, UCLA, UCSD, University of North Carolina Chapel Hill, Yale
University, and Zucker Hillside Hospital
! Combining different types of information—cognitive testing,
clinical features (e.g., unusual thoughts, suspiciousness,
decline in social functioning), a history of traumatic events,
and a family history of psychosis—over 70 percent of those
identified as high risk went on to develop psychosis.
! Accuracy appears equal to or better than our predictions of
heart disease or dementia.
44
Course and Prognosis
! Each phase of the disorder may last for days or years
! A fuller recovery from the disorder is more likely in people:
! With high premorbid functioning
! Whose disorder was triggered by stress
! With abrupt onset
! With later onset (during middle age)
--abrupt onset is more likely to get notice and treat quickly, but if there's a long onset, there might be a change in brain structure
45
Etiology
```
! The etiology and
pathogenesis of
schizophrenia is not known
! It is accepted, that
schizophrenia is „the group
of schizophrenias“ which
origin is multifactorial:
! internal factors – genetic,
inborn, biochemical
! external factors – trauma,
infection of CNS, stress
-factors occurring long before
the formal onset of the illness
(probably in gestation) disrupt
the course of normal brain
development resulting in subtle
alterations of specific neurons
and circuits
--high heritability rate
```
46
Developing country aspect
if you have schizophrenia, you better live in in developing country.
How can we interpret it?
-can anti-psychotic make the course worse?
-US in fact has great medical care
-Maybe US has worse patient (biological deficit) more severe population
47
Neurochemical causes
Dopamine Hypothesis
!Antipsychotic meds work (block dopamine receptors)
!Symptoms worsen with drugs that increase dopamine
! L-Dopa for Parkinson’s (low dopamine in substantia
nigra)
! dopamine levels raised everywhere in brain – become
psychotic
! Overmedicate schizophrenia – Parkinson’s symptoms
!Post-mortem brain studies show more dopamine
receptors in frontal cortex
!Amphetamines can cause psychotic symptoms
48
Dopamine problem
too much dopamine could be a cause but too little creates a tremor
49
Schizophrenia and drugs
people with schizophrenia don't tend to do cocaine or hallucinogens
50
Biochemical Abnormalities Cause
!Dopamine may be overactive in people with
schizophrenia because of a larger-than-usual number
of dopamine receptors (particularly D-2) or their
dopamine receptors may operate abnormally
! Autopsy findings have found an unusually large number of
dopamine receptors in people with schizophrenia
! Imaging studies have revealed particularly high occupancy
levels of dopamine at D-2 receptors in patients with
schizophrenia
! block dopamine receptors, specifically D2 receptors, reduce
schizophrenia symptoms.
(it is hard to find someone on schizophrenia who isn't on medication)
51
Brain Structure Cause
```
Early brain damage or
abnormalities? “Silent
lesions”
! Enlarged cranial ventricles
! Fewer neurons in frontal cortex &
lower levels of neurons affecting
frontal maturation
! Methodological limitations
! Malnutrition v. Disease
! Medications
! Rapid autopsy teams remove
brain ~30 minutes after death
! Unmedicated schizophrenia
patient (research gold)
```
52
Auditory Hallucinations
Wernicke's Area
Broca's Area
-misinterpreting own thoughts thinking its someone else or being paranoid
some people report hearing more than one voice
53
Wernicke's Area
understanding of written and spoken language
54
Broca's Area
production of language
55
Viral problems cause
```
--large number of people
with schizophrenia were
born in winter months
--mothers of children with
schizophrenia were more
often exposed to the
influenza virus during
pregnancy than mothers
of children without
schizophrenia
!inflammatory processes
!prenatal exposure to infection (winter births;
fingerprints)
!recent-onset schizophrenia increased
interleukin-1beta (IL-1B; proinflammatory
cytokine)
! The brain's immune defense system is activated in
schizophrenia
```
56
Feline Connection
toxoplasma gondii (parasite; toxoplasmosis) ! cat " schizophrenia connection
! Animals: infection with
Toxoplasma gondii can alter behavior & neurotransmitter
function.
! Human beings: acute
infection with T. gondii can produce psychotic
symptoms similar to those
displayed by persons with
schizophrenia
57
Gray matter brain structure
people with schizophrenia have less gray matter so ventricles swell to fill that space
58
Research gold
unmedicated schizophrenia
who just had first psychotic break
-not unique to schizophrenia
59
Schizophrenia and Cigarrettes
75% of schizophrenics smoke cigarrettes
60
People born around the equator
less schizophrenia cases in any months doesn't matter if its winder, maybe because not as distinct four seasons, more sun, more vitamin D
61
markers of inflammation
also present in PTSD and depression
62
Inflammation: Minocycline
remember schiz may be due to inflammatory processes in the brain
! Drug was prescribed to a young male patient with no previous
psychiatric history but became agitated and suffered auditory
hallucinations, anxiety and insomnia.
! Blood tests and brain scans showed nothing unusual and he
was started on the powerful anti-psychotic drug Halperidol.
! The treatment had no effect and he was still suffering from psychotic
symptoms a week later when he developed severe pneumonia and
was prescribed the antibiotic Minocycline to treat the infection.
! Researchers testing Minocycline in patients with schizophrenia
around the world
63
Gene Factors
```
!the concordance rate
in monozygotic twins is
greater than that
observed in dizygotic
twins
!adopted children of
schizophrenic parents
have the same risk of
schizophrenia as their
biological rather than
their adoptive parents
```
64
Strong Genetic Link
! Chances increase with number of relatives afflicted.
! MZ twins = 47%
! DZ twins = 17%
! Genain Quadruplets = 100%
65
Genain Quadruplets
Nora, Iris, Myra*, Hester**
! Nora and Myra were thought to be brighter
and taller, were treated better by their
parents, and were more successful
in life than the other two
! Iris/Hester - circumcision
! CT scans revealed no differences in brains
Genes and environment important!
66
Genetic factors
! Twins have received particular research study
! Studies of identical twins have found that if one twin develops the
disorder, there is a 48% chance that the other twin will do so as well
! If the twins are fraternal, the second twin has a 17% chance of developing
the disorder
! Very limited understanding of how genes alter brain development to
produce schizophrenia and other disorders.
! More specific knowledge would provide clues about mechanisms of
prevention and treatment.
! Gene variants that increase the risk for schizophrenia increase the
risk for other disorders, such as developmental delay, autism, and
bipolar disorder.
67
Cultural factors
! All cultures experience schizophrenia- including people in remote
locations
! Western Culture
! African-American men overdiagnosed (?) " Schizophrenia as political weapon
! Emotional disharmony (1920s-1950s)" assaultive & belligerent (civil rights) (DSM-II 1968)
! Jonathan M. Metzl: Protest Psychosis
! FBI & Malcom X
! Some fare better in certain cultures: psychosocial environments of
developing countries tend to be more supportive than developed
countries, leading to more favorable outcomes for people with
schizophrenia
! More acceptance
! Course & outcome in developing countries
! Social labeling – Rosenhan pseudo-patient study (1973) good interrator reliability
68
Psychological factors
Immigrant paradox NOT true for schizophrenia
! Stressful life events
! Prenatal stress (fetuses during famines china/netherlands= higher
incidence of schizophrenia), mechanical trauma at birth (brief hypoxia),
shared placenta by identical twins)
! Acute stressors
! Immigration
! Discrimination
! Social defeat (social exclusion)
! social rank or social economic status may be
exceptionally harmful
69
Expressed Emotion (EE)
–criticism, hostility, emotional overinvolvement
! Individuals who are trying to recover from schizophrenia are almost four
times more likely to relapse if they live with such a family
which is a modifiable risk factor
-families comment on negative symptoms mainly
Critical comments and hostility: ways in which family
members use their tone of voice to convey their feelings
(anger, rejection, irritability, ignorance, blaming, negligence,
etc)
70
sociocultural views
! EE is of interest to researchers and clinicians because it
predicts symptom relapse in patients and because familybased
interventions that seek to reduce EE have had success
in decreasing patients’ relapse rates
! Researchers have positioned EE within the diathesis-stress
model of psychopathology, characterizing it as an
environmental stressor that can potentially precipitate/cause
relapse of psychosis among people with a genetic
vulnerability.
71
emotional overinvolvement
behavior such as caregivers
blaming themselves, sacrificing things, being overprotective of
the identified patient, excessively being concerned for
identified patient, neglecting personal needs of self
72
etiological influences
```
Children born in urban environments are at an increased risk
for schizophrenia.
! dose-response effect
! Stress is a factor related to onset, severity, and expression of
schizophrenia.
! exacerbates symptoms, and may increase
psychotic episodes.
! research also shows that stress
is likely a casual factor for the
development of schizophrenia.
```
73
urbanicity
to be raised in an urban (people density) environment, higher schizophrenia risk
Why?
air quality, sickness, crime rate, nature, traumatic events, exposure to cats
74
Etiology take home message
! No evidence that schizophrenia is entirely caused by only
genetic or only social factors
! Intricate interplay of genetics/biology and social/
environmental factors is the culprit.
! Evidence for social factors has shown a dose-response effect,
! The more of the social factor present (dose), the greater the risk for
schizophrenia (response).
BIG GENETIC COMPONENT
75
Treatment
divided into three phases
1. acute: reduce severity of symptoms (meds)
2. stabilization: consolidate treatment gains & help patient attain stabile living situation
3. maintenance(symptoms are in partial or complete remission): reduce residual symptoms, prevent relapse, and improve functioning
76
Medication
is primary most successful intervention (antipsychotics)
--Neuroleptics: first effective meds (haldol, thorazine; 60% benefit)
--Atypicals: milder side effects? (abilify, risperdone, zyprexa, seroquel, geodon)
weight gain, diabetes and high blood
cholesterol
clozapine* = agranulocytosis and seizures
Minocycline(anti-biotic)
Medication non-compliance is an issue
77
agranulocytosis
a precipitous drop in white blood cell count
78
Tardive Dyskinesia
side effect causing involuntary movement around tongue and mouth-irreversible
79
Side effects
Extrapyramidal Side Effects
--akinesia (inability to initiate movement;
monotonous speech,
expressionless face)
--akathisia (inability to remain motionless)
--Tardive Dyskinesia - lick
smacking, chewing, etc
80
Clozapine Pros and Cons
- Superior efficacy for positive symptoms
- Possible advantages for negative symptoms
- Virtually no EPS or TD
- Advantages in reducing hostility, suicidality
- Associated with agranulocytosis (1-2%) ! WBC count monitoring required
- Seizure risk (3-5%)
- Warning for myocarditis
- Significant weight gain, sedation, orthostasis, tachycardia, sialorrhea, constipation
- Costly
- Fair acceptability by patients
81
Psychosocial treatment
Build social and self care skills (establishing routines)
! Family education
! Modify family communication
! Community support Programs
! Independent living skills (symptom management/med management)
82
CBT treatment in addition to meds
-- May be useful for avolition/apathy (symptom severity)
-- Adherence to medications – communicating with healthcare
professionals
--Help with weekly goals
--May be useful in reducing frequency or distress associated with positive symptoms, particularly auditory hallucinations.
Spring Semester
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