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Unformatted text preview: 10/20/10 Schizophrenia Dr.
Fred
Rose
 Nature
of
Schizophrenia
and
Psychosis:

 An
Overview
 •  Schizophrenia
vs.
Psychosis
 –  Psychosis
–
Cluster
of
disorders;
hallucina5ons
and/or
 loss
of
contact
with
reality
 –  Schizophrenia
–
A
type
of
psychosis
 •  Affects
1
in
100
persons,
$65
Billion
annually
 •  Historical
Background
 –  Emil
Kraeplin
–
1896;
Used
the
term
demen5a
praecox,
 focused
on
onset
and
outcomes
 –  Eugene
Bleuler
–
1911
he
introduced
the
term
 “schizophrenia”
or
“spliJng
of
the
mind”

 1 10/20/10 Prevalence
of
Schizophrenia
 •  Prevalence
of
1%
worldwide
 –  2
×
Alzheimer’s
 –  5
×
Mul5ple
Sclerosis
 –  6
×
Insulin‐dependent
Diabetes
 –  60
×
Muscular
Dystrophy
 •  Schizophrenia
Is
Generally
Chronic
 –  Moderate‐to‐severe
lifelong
impairment
 –  Life
expectancy
is
slightly
less
than
average
 •  Equal
Gender
DistribuLon
 –  Women
‐
beWer
long‐term
prognosis
 –  Onset
differs
between
men
and
women
 Gender differences in onset of schizophrenia in a sample of 470 patients Howard et al., 1993 2 10/20/10 •  Symptoms
(2
or
more):
 Diagnosis:
DSM
IV
 –  Delusions
(content)
 –  Hallucina5ons
 –  Disorganized
speech
(form)
 –  Disorganized
or
catatonic
behavior
 –  Nega5ve
symptoms
(flat
affect
etc.)
 •  Social/Occupa5onal
Dysfunc5on
 •  Dura5on:
6‐months
(1
month
of
symptoms)
 •  Not
caused
by
substances
 •  Not
Schizoaffec5ve/Mood
Disorder
 The
“PosiEve”
Symptoms
 •  Ac5ve
manifesta5ons
of
abnormal
 behavior
or
distor5ons
of
normal
behavior
 •  Delusions
‐
90%
 –  Soma5c:

“Snake
living
inside
my
abdomen”

 –  Grandeur:
“Chosen
by
God”
 –  Persecu5on:

“
‘They’
are
monitoring
me”
 –  Manifesta5ons:

Thought
broadcas5ng,
ideas
 of
reference,
thought
withdrawal
 3 10/20/10 The
“PosiEve”
Symptom
Cluster

 •  HallucinaLons
 –  Sensory
events
without
environmental
input
 –  Auditory
are
the
most
common
(can
be
any
 sensory
modality)
 –  Normal
volume,
known,
external,
nega5ve
 –  Speech
vs.
auditory
processing
studies
 Some major language areas of the cerebral cortex 4 10/20/10 The
“NegaEve”
Symptom
Cluster

 •  Absence
or
insufficiency
of
normal
behavior
 •  Spectrum
of
NegaLve
Symptoms

 –  Avoli5on
(or
apathy)
–
Inability
to
ini5ate
and
persist
in
 ac5vi5es
 –  Alogia
–
A
rela5ve
absence
of
speech

 –  Anhedonia
–
Inability
to
experience
pleasure
or
engage
in
 pleasurable
ac5vi5es
 –  Flat
affect
–
Show
liWle
expressed
emo5on,
but
may
s5ll
 feel
emo5on

 “Disorganized”
Symptoms
 •  Severe
and
excess
disrup5ons
in:
 •  Speech

 –  Cogni5ve
slippage
–
Illogical
and
incoherent
 speech
 –  Tangen5ality
–
“Going
off
on
a
tangent”
and
not
 answering
a
ques5on
directly

 –  Loose
associa5ons
or
derailment
–
Taking
 conversa5on
in
unrelated
direc5ons
 5 10/20/10 “Disorganized”
Speech
 


“I
have
also
killed
my
ex‐wife,
[name],
in
a
2.5
to
3.0
 hours
sex
bout
in
Devon
Pennsylvania
in
1976,
 while
two
Pitcairns
were
residing
in
my
next
room
 closet,
hearing
the
event.
Enclosed,
please
find
my
 urology
report,
indica5ng
that
mymale
genitals,
 specifically
my
penis,
are
within
normal
size
and
 that
I’m
capable
of
normal
intercourse
with
any
 woman,
signed
by
Dr.
[name],
a
urologist
and
 surgeon
who
performed
a
circumcision
on
me
in
 1982.
Conclusions:
I
cannot
be
a
nincompoop
in
a
 physical
sense
(unless
Society
would
feed
me
 chemicals
for
my
picture
in
the
nincompoop
book).”
 “Disorganized”
Symptoms
 •  Affect
 –  Inappropriate
affect
(e.g.,
crying
when
one
 should
be
laughing)
 •  Behavior

 –  Disrup5on
in
goal
directed
behavior
 –  Decline
in
rou5ne
daily
func5oning
 –  Catatonia
–
Spectrum
from
wild
agita5on,
waxy
 flexibility,
to
complete
immobility

 6 10/20/10 Symptoms
of
Schizophrenia
 Positive (Type 1) Negative (Type II) Disorganized Thematic Delusions Avolition (apathy) Grossly Bizarre Behavior Thematic Hallucinations Alogia (Poverty of Speech/ Incoherent hallucinations Content) or delusions Bizarre Behavior Anhedonia Flat Affect Asociality Disorganized Affect Disorganized Speech Lenzenweger, Dworkin & Wethington (1991) Subtypes
of
Schizophrenia
 •  Paranoid
Type
 –  Intact
cogni5ve
skills
and
affect,
and
do
not
show
 disorganized
behavior
 –  Hallucina5ons
and
delusions
thema5c
(e.g.,
grandeur
or
 persecu5on)
 •  Disorganized
Type
 –  Marked
disrup5ons
in
speech,
behavior,
affect
 –  Fragmented
hallucina5ons
and
delusions
 –  Develops
early,
tends
to
be
chronic,
lacks
periods
of
 remissions
 7 10/20/10 Subtypes
(cont.)
 •  Catatonic
Type
 –  Unusual
motor
responses
and
odd
mannerisms
(e.g.,
 echolalia,
echopraxia)
 –  ?
Need
for
consistency
 –  Tends
to
be
severe
and
quite
rare
 •  UndifferenLated
Type
 –  Symptoms,
but
don’t
meet
criteria
for
another
type
 •  Residual
Type
 –  One
past
episode
of
schizophrenia
 –  Con5nue
to
display
less
extreme
residual
symptoms
(e.g.,
 odd
beliefs)
 Problems
with
Diagnosis
 “Schizophrenia appears to be a disorder with no particular symptoms, no particular course, no particular outcome and which responds to no particular treatment” [Bentall, 1990] •  Heterogeneity
of
symptoms
 –  Symptoms
change
as
the
disorder
develops
 –  Schizophrenics
‘slip
back
into
reality’
 •  Treatement
response
varies
 •  Is
it
a
unitary
disorder?
 •  Is
it
disLnct
from
normal
experience?
 8 10/20/10 Other
PsychoEc
Disorders
 •  Schizophreniform
Disorder
 –  Schizophrenic
symptoms
for
less
than
6
months
 –  Associated
with
good
premorbid
funcEoning;
 most
resume
normal
lives
 •  Schizoaffec3ve
Disorder
 –  Symptoms
of
schizophrenia
and
a
mood
disorder
 –  10‐year
outcome
beQer
than
Schizophrenia
 (Harrow
et
al.,
2000)
 Other
PsychoEc
Disorders
 •  Delusional
Disorder
 –  Delusions
without
other
major
schizophrenia
 symptoms
 –  May
show
other
negaEve
symptoms
 –  Type
of
delusions
include
erotomanic,
grandiose,
 jealous,
persecutory,
and
somaEc
 –  This
condiEon
is
extremely
rare
 9 10/20/10 AddiEonal
Disorders
with
PsychoEc
 Features
 •  Brief
PsychoLc
Disorder
 –  One
or
more
posi5ve
symptoms
of
schizophrenia
 –  Usually
precipitated
by
extreme
stress
or
trauma
 –  Lasts
<
1
month
 •  Shared
PsychoLc
Disorder
 –  Delusions
from
one
person
manifest
in
another
person
 –  LiWleis
known
about
this
condi5on
 •  Schizotypal
Personality
Disorder
 –  May
reflect
a
less
severe
form
of
schizophrenia
 GeneEcs
Influences
 •  Family
Studies
 –  Inherit
a
tendency
for
schizophrenia
 –  Schizophrenia
increases
risk
in
other
family
members

 •  Twin
Studies
 –  Risk
of
schizophrenia
in
MZ
twins
ranges
from
15%
to
 65%,
with
an
average
of
28%
(Fuller‐Torrey,
1994).
 –  Risk
of
schizophrenia
drops
to
6%
for
dizygo5c
twins
 •  AdopLon
Studies

 –  Risk
remains
high
in
adopted
children
with
a
biological
 parent
suffering
from
schizophrenia
 10 10/20/10 Risk of developing schizophrenia GoQesman,
1991
 GeneEc
Influences
(cont.)
 •  Summary
of
GeneLc
Research

 –  Risk
of
schizophrenia
increases
as
a
func5on
of
 gene5c
relatedness
 –  Mul5ple
genes
involved
 –  One
need
not
show
symptoms
of
schizophrenia
 to
pass
on
relevant
genes
 –  Schizophrenia
has
a
strong
gene5c
component,
 but
genes
alone
are
not
enough
 11 10/20/10 GeneEc
Influences
(cont.)
 •  Genes
scaWered
15
of
23
chromosomes
have
been
 implicated
 •  Most
important:

 –  Neuregulin
1:
NMDA,
GABA,
&
Ach
receptors
 –  Dysbindin:
synap5c
plas5city
 –  Catechol‐O‐methyl
transferase:
DA
metabol.
 –  G72:
regulates
glutamatergic
ac5vity
 –  Others:
myelina5on,
glial
func5on
 •  Paternal
age:
more
cell
divisions
in
sperm
 Biological
Markers
 •  Smooth‐Pursuit
Eye
Movement
 – Tracking
a
moving
object
visually
with
the
 head
kept
s5ll
 – Tracking
is
impaired
in
persons
with
 schizophrenia,
including
their
rela5ves

 12 10/20/10 EEology
 •  The
Dopamine
Hypothesis
 –  Overac5vity
of
dopamine
(DA)
neurons
in
 the
brain
causes
schizophrenia
 13 10/20/10 The
Dopamine
Hypothesis
 •  Support
 –  Drugs
that
block
dopamine
receptors
reduce
 posi5ve
receptors
 –  Amphetamines,
which
increase
dopamine,
 create
posi5ve
symptoms
 –  High
number
of
D2
receptors
in
schizophrenic
 brains
 The
Dopamine
Hypothesis
 •  Problems
 –  Dopamine
antagonists
don’t
treat
nega5ve
 symptoms
 –  Time
lapse
‐
immediately
in
brain
but
no
 improvement
for
2
weeks
 –  Parkinson’s
disease
(but…)
 •  Substan5a‐Nigra,
Caudate‐Putamen
‐
PD
 •  Ventral
Tegmentum,
Nucleus
Accumbens,
Septal
 area
‐
Schiz.
 –  Neurolep5cs
increase
D2
receptors
 –  PET
scan
studies
inconclusive
 14 10/20/10 The
Dopamine
Hypothesis
 •  Revised:
 –  Overac5vity
of
dopamine
neurons
in
the
 mesolimbic
pathway
may
cause
posi5ve
 symptoms.
 •  An5psycho5cs
which
block
dopamine
receptors
 lessen
posi5ve
symptoms
 – but…
 The
Dopamine
Hypothesis
 •  Revised:
 –  Underac5vity
of
dopamine
neurons
in
the
 mesocor5cal
pathway
in
the
prefrontal
 cortex
may
cause
nega5ve
symptoms.

 •  An5psycho5cs
have
liYle
or
no
effect
on
nega5ve
 symptoms.
 15 10/20/10 Dopamine
Pathways
 Other
Neurobiological
Influences
 •  Structural
and
FuncLonal
AbnormaliLes
in
 the
Brain

 –  Enlarged
ventricles
and
reduced
5ssue
volume
 •  Inverse
rela5onship
between
ventricle
size
and
 response
to
medica5on

 –  Abnormal
neural
migra5on
 –  Gray
maWer
loss
in
adolescence
 –  Hypofrontality
–
Less
ac5ve
frontal
lobes
(a
 major
dopamine
pathway)

 16 10/20/10 Enlarged
Ventricles
in
Schizophrenia
 Source: Daniel Weinberger, M.D. 17 10/20/10 18 10/20/10 19 10/20/10 FuncEonal
changes
in
brain
 •  Hypofrontality
hypothesis
 –  Discordant
twins:
low
frontal
blood
flow
only
in
 affected
twin
 –  CogniEve
Flexibility
 •  Schizophrenics
can’t
shi_
aQn.
to
other
criterion
 •  FuncEonal
imaging:
frontal
lobe
acEvity
lower
at
rest,
 esp.
in
right
hemisphere,
does
not
increase
during
task.
 •  Drug
treatment
increased
acEvaEon
of
frontal
lobes
 20 10/20/10 Psychosocial
Influences
 •  The
Role
of
Stress
 –  May
ac5vate
underlying
vulnerability
and/or
increase
 risk
of
relapse
 •  Family
InteracLons
 –  Families
of
people
with
schizophrenia
show
 ineffec5ve
communica5on
paWerns
 –  High
expressed
emo5on
in
the
family
is
associated
 with
relapse

 •  The
Role
of
Psychological
Factors

 –  Likely
exert
only
a
minimal
effect
in
producing
 schizophrenia

 21 10/20/10 Gene‐Environment
InteracEon
 •  Tienari
et
al.
(1985,
1987);
Tienari
(1991,
 1994)
 –  Children
of
schizophrenic
and
“normal”
mothers
 adopted
out
at
birth)
 –  Tracked
family
communicaEon
paQerns
 Communication Good High Schizo. Risk Low No Impairment No Impairment LOWEST Impairment! Poor High Impairment Medical
Treatment
 •  AnLpsychoLc
(NeurolepLc)
MedicaLons
 –  Dopamine
antagonists
are
owen
the
first
line
of
 treatment
for
schizophrenia
 –  Began
in
the
1950s
 –  Most
medica5ons
reduce
or
eliminate
the
posi5ve
 symptoms
of
schizophrenia
 –  Acute
and
permanent
extrapyramidal
and
Parkinson‐like
 side
effects
are
common
 –  Poor
compliance
with
medica5on
is
common

 –  Risperdal,
Olanzapine
are
“atypical”
neurolep5cs
with
 beWer
side‐effect
profile
than
“ Throrazine”
 22 10/20/10 Psychosocial
Treatment
 •  Psychosocial
Approaches:

Overview
and
Goals
 –  Behavioral
(i.e.,
token
economies)
on
inpa5ent
units
 –  Community
care
programs
 –  Social
and
living
skills
training
 –  Behavioral
family
therapy

 –  Voca5onal
rehabilita5on

 •  Psychosocial
Approaches
Are
Usually
a
Necessary
 Part
of
Treatment
 Summary
 •  Schizophrenia
Includes
a
Spectrum
on
CogniLve,
EmoLonal,
 and
Behavioral
DysfuncLons
 –  Posi5ve,
nega5ve,
and
disorganized
symptom
clusters
 •  DSM‐IV‐TR
Divides
Schizophrenia
Into
Five
Subtypes
 •  Other
DSM‐IV‐TR
Disorders
Include
PsychoLc
Features

 •  GeneLc,
Biological,
and
Environmental
CausaLve
Factors
 Have
Been
Implicated
for
Schizophrenia
 •  Successful
Treatment
Rarely
Includes
Complete
Recovery

 23 ...
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