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AP PSYCH
The Brain
Gone Bad
SCHIZOPHRENIA
Mr. Pustay
Prevention
Schizophrenia is a PSYCHOTIC
DISORDER
A severe mental disorder in which
thinking and emotion are so impaired that
the individual is seriously out of contact
with reality.
*Psychotic symptom is out of touch
with reality
Schizophrenia - symptoms
Positive Symptoms
Hallucinations
Delusions (bizarre, persecutory)
Disorganized Thought
Perception disturbances
Inappropriate emotions
FUNCTION
Cognition
New Learning
Memory
Negative Symptoms
Blunted emotions
Anhedonia
Lack of feeling
Mood Symptoms
Loss of motivation
Social withdrawal
Insight
Demoralization
Suicide
What is schizophrenia?
• A chronic severe brain disorder; often they
hear voices, believe media are
broadcasting their thoughts to the world or
may believe someone is trying to harm
them.
• In men it usually develops in teen years
and early 20s; in women it usually
develops in 20s and 30s.
Diagnosis
• Currently there is no physical or lab test
(although 2012 genome research is
showing some signs of success) that can
predict high risk to diagnose
schizophrenia.
– Cost ($3000-$4000)
• A psychiatrist usually comes to the
diagnosis based on clinical symptoms.
GENOME TESTING
• Researchers at the Indiana University School of
Medicine have developed a test that can predict how
likely an individual is to develop schizophrenia.
– The scientists combined data from several different
types of studies in order to identify and prioritize a
group of genes most associated with the disease
• "At its core, schizophrenia is a disease of decreased
cellular connectivity in the brain, precipitated by
environmental stress during brain development, among
those with genetic vulnerability."
Early onset schizophrenia: Wave of gray matter loss begins in parietal cortex and spreads forward STG = superior
temporal gyrus; DLPFC=dorsolateral prefrontal cortex
Prevalence of Schizophrenia
•
•
•
•
1-2% of U.S. population
2 million diagnosed in U.S.
Median age at diagnosis = mid-20’s
Men = Women prevalence
– Men earlier diagnosis
Prognosis of Schizophrenia
• 10% continuous hospitalization
• < 30% recovery = symptom-free for 5
years
• 60% continued problems in
living/episodic periods
Biological Finding
• The Dopamine Hypothesis
– Disturbed functioning in dopamine system
(i.e., excess dopamine activity at certain
synaptic sites)
Dopaminergic Pathways
Role of Dopamine
• Original theory proposed that an over
activation of DA led to schizophrenic
symptoms
• More recently it has been hypothesized
that
– Positive symptoms are caused by an over
activation of specific DA pathways
– Negative symptoms arise from and under
activation of different DA pathways
GABA
Gamma-aminobutyric acid
• GABA is the chief inhibitory neurotransmitter in
the brain
• Primarily has effects in the spine, brainstem and
retina--it is responsible for the vast majority of all
inhibitory neurotransmission in the CNS
• Between 20-50% of all central synapses use
GABA as their transmitter.
– The enzyme responsible for the formation of GABA
from the amino acid glutamate
– This chemical messenger is known to aid in relaxation
and sleep and regulate anxiety.
GLUTAMATE
AMINO ACID
• Glutamate sends chemical messages in the brain by
“exciting” neurons that are sensitive to it.
• It plays a vital role in learning, memory, and brain
development; too much glutamate can be toxic.
– When a person experiences a head injury or stroke,
glutamate floods the injured area and kills the
neurons by overexciting them, causing brain damage
– one of the reasons why schizophrenia occurs is
because people with schizophrenia have a deficiency
or a defect in this receptor and the receptor cannot be
properly stimulated by glutamate.
• Resembles those on PCP
SEROTONIN
• Acts by blocking the affects of serotonin at specific
receptors in the brain and therefore it can produce
amazing changes in the mind and mental processes and
behavior
– Internal processes in the brains of people with schizophrenia
showed similar behavior and mental processing as if on LSD
– Abnormally low levels of the serotonin receptors can cause
psychotic systems in behavior
Schizophrenia and
Antipsychotic Treatment
New Antipsychotics 2002-2014
•
•
•
•
•
•
•
•
•
•
•
•
•
2002
2003
2004
2005
2006
2007
2008
2009
Aripiprazole (ABILIFY); Nov 15
Risperidone LAI (RISPERDAL CONSTA); Oct 29
Paliperidone (INVEGA); Dec 19
Clozapine
Iloperidone (FANAPT); May 6
Paliperidone LAI (INVEGA SUSTENNA); Jul 31
Asenapine (SAPHRIS); Aug 13
Olanzapine LAI (ZYPREXA RELPREVV); Dec 11
2010 Lurasidone (LATUDA); Oct 28
2011
2012
2013
2014
AP PSYCH
The Brain
Gone Bad
SCHIZOPHRENIA
Mr. Pustay
Progression of Schizophrenia
Role of Dopamine
• Original theory proposed that an over
activation of DA led to schizophrenic
symptoms
• More recently it has been hypothesized
that
– Positive symptoms are caused by an over
activation of specific DA pathways
– Negative symptoms arise from and under
activation of different DA pathways
Cocaine Use
• Cocaine may
increase
symptoms of
schizophrenia
by increasing
dopamine
levels
GLUTAMATE
AMINO ACID
• Glutamate sends chemical messages in the brain by
“exciting” neurons that are sensitive to it.
• It plays a vital role in learning, memory, and brain
development; too much glutamate can be toxic.
– One of the reasons why schizophrenia occurs is
because people with schizophrenia have a deficiency
or a defect in this receptor and the receptor cannot be
properly stimulated by glutamate.
• FLAT EFFECT
SCHIZOPHRENIA
• By definition
Schizophrenia is most
likely characterized by
disorganized and
fragmented thinking
Selective Attention
• Selective Auditory
Attention
• How people are able
to track certain
conversations while
tuning others out, a
phenomenon he
referred to as the
"cocktail party"
effect.
• The "spotlight" model
– William James suggested
that this spotlight includes
a focal point in which
things are viewed clearly.
– The area surrounding this
focal point, known as the
fringe, is still visible, but
not clearly seen.
– Finally, the area outside of
the fringe area of the
spotlight is known as the
margin.
• The “Zoon lens” model
BRAIN AREAS INVOLVED IN
ANTIPSYCHOTIC TREATMENT
• The oversimplified version of what brain areas
are involved in anti-psychotic medication use is:
– Reticular Activating System: the effects on this area
generally moderate spontaneous activity and
decrease the patients reactivity to stimuli.
– The Limbic System: the effects on this area generally
serves to moderate or blunt emotional arousal.
– The Hypothalamus: the effects on this areas generally
serve to modulate metabolism, alertness, and muscle
tone.
Thalamus
• Vigorous activity in the
thalamus has been found to
be associated with hearing
voices
• Schizophrenics have smaller
than normal thalamus which
causes difficulty in focusing
attention
Schizophrenia Correlations
• Prenatal viral
infections contribute
to schizophrenia
• Low birth weight
• People born in North
America during the
month of February
are at increased risk
for schizophrenia
Seasonality of Schizophrenia
• One possible reason that researchers believe
may explain this seasonality of schizophrenia
risk is the association between winter/spring
births and schizophrenia may be related to
sunlight exposure.
• A lack of sunlight (for example, during the
shorter days of winter) can lead to vitamin D
deficiency, which scientists believe could alter
the development of a child's brain in the
mother's womb and after birth.
Genetic Studies
• Twin Studies
• Blood
(Family)relatives
• Adoption
• High-risk populations
(e.g., children of
schizophrenic
parents)
If identical twins have different placentas it is
only 1/10 probability versus 5/10
09_05
KH2F0905
60
First-Degree Relative
50
46%
Second-Degree Relative
48%
Third-Degree Relative
40
Percentage
30
of Risk
Unrelated Person
20
17%
13%
9%
10
1%
2%
2%
2%
5%
4%
6%
6%
0
Spouse
First
Cousin
General
Population
Grandchild Half
Sibling
Uncle
or Aunt
Nephew
or Niece
Parent
Offspring of Offspring of
One
Two
Schizophre- Schizophrenic Parent
nic Parents
Sibling
Relationship to Schizophrenic Person
Fraternal Twin
Identical
Twin
Early Course Schizophrenia
Initiation of Antipsychotic
5 years
1-2 years*
Positive Sx
Negative Sx
Depression
Psychosis
Threshold
Prodromal Period
Psychosis
Post-Psychotic Period
Based on Häfner, ABC Schizophreniestudie
Schizophrenia
• Symptoms of withdrawal following the
disappearance of hallucinations and
delusions are most indicative residual
schizophrenia (chronic)
Background
• It is believed that Schizophrenia must be
treated in a multifaceted treatment
– While medication is the first line treatment
counseling, social and family services should
be provided for proper treatment of patients
• Further developments in pharmacological
treatments should increase functioning of
patients in society by reducing side effects
with more selective drugs
Misdiagnosis
• This is a common problem since
schizophrenia shares a significant number
of symptoms with other disorders.
– DDs, Bipolar, Depression, Mania, etc.
• There is an average of 10 years from
onset to correct diagnosis & tx.
Two Categories of Symptoms in
Schizophrenia
• Positive symptoms
• Negative symptoms
• Positive symptoms are the presence of inappropriate
behaviors, and negative symptoms are the reduction of
appropriate behaviors
Positive Symptoms
• Distortions or excesses of normal functioning
– delusions,
– hallucinations,
– disorganized speech,
– thought disturbances,
– motor disturbances
• Positive symptoms are generally more responsive to
treatment than negative symptoms
• Auditory hallucinations (particularly "hearing voices") are
far more common than visual, with some estimating
prevalence of over 70%
Delusions
• False beliefs that are firmly and
consistently held despite disconfirming
evidence or logic
• Individuals with mania or delusional
depression may also experience
delusions.
– The delusions of patients with schizophrenia
are often more bizarre (highly implausible).
Types of Delusions
• Delusions of Grandeur
– Belief that one is a famous or powerful
person from the past or present
• Delusions of Control
– Belief that some external force is trying to take
control of one’s thoughts (thought insertion),
body, or behavior
Types of Delusions
• Thought Broadcasting
– Belief that one’s thoughts are being broadcast
or transmitted to others
• Thought Withdrawal
– Belief that one’s thoughts are being removed
from one’s mind
Types of Delusions
• Delusions of Reference
– Belief that all happenings revolve around
oneself, and/or one is always the center of
attention
• Delusions of (Paranoid) Persecution
– Belief that one is the target of others’
mistreatment, evil plots, and/or murderous
intent
Hallucinations
• Sensory experiences in
the absence of any
stimulation from the
environment
• Any sensory modality
may be involved
–
–
–
–
–
auditory (hearing);
visual (seeing);
olfactory (smelling);
tactile (feeling);
gustatory (tasting)
• Auditory hallucinations
are most common
Common Auditory Hallucinations in
Schizophrenia
• Hearing own thoughts spoken by another
voice
• Hearing voices that are arguing
• Hearing voices commenting on one’s own
behavior
Disorganized Speech /
Thought Disturbances
• Problems in organizing ideas and
speaking so that a listener can understand
• Loose Associations (cognitive slippage)
– continual shifting from topic to topic without
any apparent or logical connection between
thoughts
• Neologisms
– new, seemingly meaningless words that are
formed by combining words
– “Word Salad”
Negative Symptoms
• Behavioral deficits that endure
beyond an acute episode of
schizophrenia
• More negative symptoms are
associated with a poorer
prognosis
• Some negative symptoms might
be secondary to medications
and/or institutionalization
• An expressionless face is an
example of a negative symptom
Types of Negative Symptoms
• Anhedonia
– inability to feel pleasure; lack of interest or
enjoyment in activities or relationships
• Avolition
– inability or lack of energy to engage in routine
(e.g., personal hygiene) and/or goal-directed
(e.g., work, school) activities
Types of Negative Symptoms
• Alogia
– lack of meaningful speech, which may take
several forms, including poverty of speech
(reduced amount of speech) or poverty of
content of speech (little information is
conveyed; vague, repetitive)
• Asociality
– impairments in social relationships; few
friends, poor social skills, little interest in
being with other people
Types of Negative Symptoms
• Flat Affect (Catatonia)
– No stimulus can elicit an
emotional response
– Patient may stare vacantly, with
lifeless eyes and expressionless
face.
– Voice may be toneless.
– Echolalia (parrotlike repeating of
another’s speech or movements
– Flat affect refers only to outward
expression, not necessarily
internal experience.