STUDY: FMRI, AUDITORY
HALLUCINATION VS AUDITORY
STIMULATION
Nota:
They took patients with BRIEF AUDITORY HALLUCINATIONS
-then looked at BLOOD OXYGENATION ACTIVITY in the brain
only 3 patients
-pressed button when the hallucinations began and then when they ended
-scanned them while experiencing their hallucinations
-also scanned them when they were listening to a tone
RESULT: -Similar areas in the brain were activated for BOTH CONDITIONS!!
STUDY: non-clinical
hallucinations vs. hearing voices
in healthy individuals
Nota:
did FMRI with these individuals
-they looked at TIMING of brain activity
RESULT:
STS: activated when we hear human voices
IFG: aka BROCA'S area, involved in language production and comprehension
SMA: controls INTERNALLY generated motor movements and speech
people imagining: first SMA activated, then other areas kicked in 1-3 seconds later
healthy individuals with non-clinical hallucinations: SMA LIGHTS AT SAME TIME AS OTHER AREAS
==> *basically, the SMA doesn't warn you that "hey, this is coming from you"
SMA
"this action is
coming from
me!"
TICKLING STUDY
SZ can tickle themselves
disorganized symptoms
disorganized speech
ex. neologisms
disorganized + catatonic behaviour
catatonia
unusual and
uncomfortable
position for long
period of time
negative symptoms
flat, blunted affect
alogia
avolition
more negative symptoms=
WORSE PROGNOSIS
EPIDEMIOLOGY
older father
>45-50
certain
ethnic
groups
sex differences
men= EARLIER ONSET
av age men 25, women 29
ESTROGEN
women's negative
symptoms get worse after
menopause
related disorders
schizoaffective disorder
features of BOTH
schizophrenia + severe mood
disorder
schizophreniform disorder
same criteria as SZ
but SHORTER
DURATION of
symptoms
neurodevelopmental
disorder
STUDY: Walker et al,
CHILDHOOD HOME
MOVIES OF PPL WITH SZ
participants: SZ or Major
Affective Disorder
6 groups
Nota:
1. patients with SZ
2. healthy siblings of SZ
3. patients with affective
4. affective siblings
5. healthy controls
result: MORE MOTOR
ABNORMALITIES +
MORE NEGATIVE FACIAL
EMOTION IN SZ
PATIENTS
*specifier: facial
abnormalities on LEFT
SIDE
take-home: there
are abnormalities
present since birth
GENETICS
DANISH ADOPTION
STUDY, Kety et al
5500 adoptees,
interviewed their
families
blindly
interviewed
them and gave
diaagnoses
SZ related diagnoses found in
biological relatives not adoptive
phenotype
focus on PSYCHOTIC SYMPTOMS
endophenotype
intermediate
phenotype, marks
risk
examples of deficits
deficit in smooth
pursuit eye
movements
verbal memory
sensory gating
reduced hippocampal
volume
DIATHESIS-STRESS MODEL
diathesis:
DOPAMINE
DYSFUNCTION
all meds for SZ
block dopamine in
STRIATUM (dopamine antagonists)
effective dose depends onto
how well it binds with
dopamine receptor
give healthy
controls
DOPAMINE
AGONISTS=
PSYCHOSIS
give sz patients dopamine
agonists= worsens their
symptoms
STUDY: Breir et al, DOPAMINE AGONIST
Nota:
Gave healthy controls and SZ patients AMPHETAMINE (dopamine agonist)
amphetamine: increases availability of dopamine
patients: MORE DOPAMINE RELEASE relative to controls
STUDY:
dopamine
depletion
Nota:
depleted dopamine in healthy controls and SZ patients
-this exposes receptors
-compare binding of radio ligand at BASELINE and after depletion
-estimate proportion of D2 receptors masked at baseline
**ENDOGENOUS levels of dopamine have been reduced after depletion
-increased binding, increased number of RECEPTORS
Unmedicated patients had more dopamine
receptors available in STRIATUM compared
to health controls
binding of radio-ligand
HIGHER in DLPFC OF SZ
PROSPECTIVE
LONGITUDINAL
STUDY
5 X INCREASE in
psychotic symptoms
for methamphetamine
users
ex. suspiciousness, hallucinations
GLUTAMATE
Antagonists of NMDA receptor
of glutamate (GLU)
given to healthy
controls
produces symptoms
similar to SZ patients
PCP
another antagonist of
NMDA receptor subtype
of glutamate
KETAMINE
similar to PCP, less potent
emotional withdrawal, blunted affect
STUDY: effects of
ketamine +
amphetamine
HEALTHY CONTROLS ONLY!
tested them over 4 days
positive symptoms: 2 drugs produced
greater effects COMBINED
negative symptoms:
KETAMINE
INCREASED THEM,
not amphetamine
cognitive symptoms:
each had effect, but NO
EFFECT WHEN
COMBINED
amphetamine
grandiosity and
suspiciousness
SEROTONIN
antipsychotic-naive patients
and healthy controls
NEG.CORRELATION between
serotonin binding and positive
symptoms
ONLY FOUND THIS IN MALES
FRONTAL
CORTEX, lower
serotonin binding
more positive symptoms
ENLARGED
LATERAL and
3RD ventricles
SMALLER THALAMUS
Low
dopaminergic
activity in PFC
Neurocognitive
deficits
attention
eye-tracking deficits
smooth pursuit
deficits, saccadic
sensorimotor gating
working
memory +
executive
function
STUDY: birth complications
swedish national
birth register
238 cases of SZ
complications like
preeclampsia, vacuum
extraction,
malfromations
increased risk of SZ
PROJECT ICE STORM
LONGTERM
PROSPECTIVE STUDY
objective + subjective stress
objective: how many days did
you not have power?
lower MDI SCORES
OBJECTIVE STRESSORS 1ST + 2ND TRIMESTER
subjective: how
stressed did you feel
followed kids
from 6 months to
2 yrs and looked
at their IQ (MDI
cuz they too
young)
LOW SES
SOCIOGENIC HYPOTHESIS
being in LOW SES can cause SZ
SOCIAL DRIFT HYPOTHESIS
the illness itself can cause a
downward shift in SES