Schizophrenia Research Study: Daniel, Weinberger, Jones et al. (1991) – a study into the effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia. Flashcards
Background
Several studies had shown low levels of activity in
the prefrontal cortexes of people with schizophrenia.
This had been linked to the activity of dopamine in
the brain. Studies had suggested that dopamine is
important in suppressing random brain activity and
helping to focus on specific stimuli in the environment.
Hypothesis
The researchers hypothesised that if dysfunction
in the prefrontal cortex was related to problems in
dopamine-controlled synaptic transmission, then a
substance that stimulated dopamine activity (known
as an agonist) should increase activity in that area
during a cognitive task. The agonist the researchers
chose was amphetamine, a chemical that increases
alertness and energy, and improves mood. The researchers used Single-Photon Emission-Computed Tomography (SPECT) to scan the participants’ brain
activity during the task.
Single-Photon Emission-Computed
Tomography
A type of nuclear imaging test that uses
gamma rays to show how blood flows to
tissues and organs.
Design
In this experiment, the independent variable was
whether participants had been given amphetamine or
not. The dependent variable was performance on the
Wisconsin Card Sorting Test
Sample
The participants were ten in-patients from the National
Institute of Mental Health research wards in Washington,
USA. The study had the approval of the institutional
review board and radiation safety committee, and the
participants all gave informed consent to take part in it.
Each patient met criteria for chronic schizophrenia.
Before receiving the amphetamine, the participants
had been stabilised for at least six weeks on a fixed
dose of an antipsychotic drug (haloperidol).
Although the participants were too ill to live
independently in the community, they were clinically
stable at the time of the study and able to cooperate
with the SPECT and testing procedures. They were
free of any illnesses that could have affected blood
flow in the brain, and free of alcohol or drug abuse.
Materials and Apparatus
Images of brain activity were recorded using SPECT
technology, which was capable of collecting a full set
of 80 projections in five seconds. Each participant
underwent two scans two to four days apart. During scanning, the participant was seated in a semi-reclined position in a comfortable chair, with their
head positioned in the scanner. The head was kept
still using foam-rubber inserts.
Each scan involved:
a mock test to get the participant used to the
set-up
a test of simple sensori-motor control, where the
participants match bars on screen based on their
orientation (the BAR task)
the prefrontal activation test (the WCST).
Procedure
Five participants did the BAR task first, and five did
the WCST first – this is known as counterbalancing.
On the two test days, each participant received
either a dose of amphetamine or a placebo, again
in an order that was counterbalanced between
participants. Both tasks were carried out on
computer and required similar motor responses.
Placebo
Cerebral blood flow
Placebo
A fake drug designed to have no effect (so it
can be tested against a real drug).
Cerebral blood flow
Supply of blood to the brain at any one given
time.
Results
The main results were:
Amphetamine had a minimal effect on regional
cerebral blood flow when participants completed
both the BAR task and the WCST.
There was no significant differences in the effects of
amphetamine and the placebo on brain activity when
completing the BAR task. However, there were some
significant differences in blood flow in particular
regions of the brain when completing the WCST. The
left dorsolateral prefrontal cortex, the occipital and
anterior cingulate cortices were all affected.
Amphetamine had a small but significant positive
effect on two performance measures of the WCST,
including the number of correct responses. There
was no such effect when the placebo was used. Behaviour changes caused by the amphetamine were highly variable and generally mild, ranging
from increased cooperation, optimism, and
improved mood to irritability and dysphoria. Three
patients showed clinically significant improvement,
whereas one patient significantly deteriorated.
Conclusion
Amphetamine significantly increased prefrontal cortex
activity during performance of a cognitive task, despite
it reducing blood flow in the brain. The results were
in line with animal studies . This
implies that some of the problems associated with
schizophrenia and prefrontal cortex dysfunction are, in
part, reversible through drug treatment.
- showed a link between brain function
and key symptoms of schizophrenia in support of the
biological theory.
2 Criticisms
The sample size was too small to draw reliable
conclusions. It is difficult to generalise the results
to other people with schizophrenia, as the sample
may not have been representative and the
participants were all volunteers.
The sample was potentially culturally biased. The
sample was drawn from a small area of the USA
and consisted mainly of white people. Because
there is evidence of different rates of schizophrenia
between different ethnic groups and different
countries, we should be cautious about making
generalisations about the relationship between the
brain and schizophrenia.
3 Criticisms
The study may lack temporal validity. The results
may become outdated over time because the
study used a different system for diagnosing
schizophrenia than the one that is used today.
Some psychologists would be concerned about
the ethics of using scans when we are unclear on
their long term consequences. This is especially
an issue because the participants were scanned
just for the sake of research and sometimes after
only being administered a placebo.
The difference in brain activity may have
been affected by the haloperidol given to the
participants before the other drugs. Although
haloperidol was necessary for stabilising the
patients, it becomes an extraneous variable that
makes it harder to establish cause and effect.
