Antidepressive Agents, Second-Generation Clinical Trial
Official title:
Antidepressants, Emotions and Personality: Comparing the Neuropsychological Effects of the Antidepressant Citalopram in Healthy Volunteers With High and Low Neuroticism
Neuroticism is a personality trait described as an enduring tendency to experience negative
emotional states and to respond poorly to environmental stress. It has been shown that high
neuroticism can predispose, amongst other factors, to the development of depressive
episodes. Recent studies suggest that subjects with high neuroticism have a different
response to stimuli with an emotional content, showing both decreased processing of positive
or increased processing of negative emotionally salient cues. These differences in cognitive
processing of emotional stimuli are believed to underpin the psychological characteristics
that link high neuroticism with a higher risk for depression.
Preliminary data also indicate that modulation of serotonin function by antidepressant
treatment in healthy volunteers with high neuroticism traits could modify the brain activity
associated with the processing of emotional stimuli that is dysfunctional in this vulnerable
population.
The aim of this research is to investigate further whether modulation of serotonin function
via administration of serotonergic antidepressants (SSRIs) can revert the dysfunctional
emotion processing that characterises subjects with the personality trait of high
neuroticism.
In particular we hypothesise that SSRI administration will modify the abnormal patterns in
attention, physiological reactivity and regulation of emotional stimuli present in healthy
individuals with the vulnerable personality trait of high neuroticism.
Carrying out this research on healthy volunteers will enable us to understand if modulating
serotonin function by antidepressant administration has an effect not only on mood symptoms
- as is evident in depressed patients - but also on the predisposing psychological and
cognitive processes that sustain the depressed mood, such as the response to emotional
stimuli. We will also be able to verify if this effect is shown early treatment and prior to
any subjective changes in mood. This will be done by administering seven days of either the
antidepressant citalopram or placebo to subjects with high neuroticism scores and then
comparing them on a series of computer based psychological tests measuring various aspects
of how emotionally salient stimuli are processed.
Forty healthy volunteers with high scores on the Eysenck Personality Questionnaire
Neuroticism scale will be recruited from the general population using posters and
advertising in local newspapers and on internet. All advertisement will direct volunteers to
a specific website (http://weblearn.ox.ac.uk/site/users/psyc0390/public/) (hosted in the
Weblearn area of the University of Oxford) that will report the study Information Sheet.
People clicking on the "I agree to participate" link will then be able to leave their
contact details and fill in a shortened version of the Eysenck Personality Questionnaire.
Questionnaire results will be anonymous and only the researcher will access the data and the
correspondent contact details. Thus, only volunteers consenting to participate to the full
study will be screened for neuroticism scores and only suitable ones will be contacted for
the screening visit.
Participants will be requested to come to the Department of Psychiatry of the University of
Oxford for an initial screening assessment including basic medical examination and
structured psychiatric interview. On that occasion they will also be asked to complete a
number of questionnaires such as Beck Depression Inventory, Dysfunctional Attitudes Scale,
State-Trait Anxiety Inventory, Eysenck Personality Questionnaire, Parental Bonding
Instruments and Life Events Rating Scale.
Volunteers will be randomized to receive citalopram or placebo in a double blind between
groups design for 7 days. They will receive the treatment capsules to take home and will be
instructed to take the capsule every morning after breakfast around 8 am. Subjective mood
will be assessed on each day of treatment using the Befindlichskeit scale of mood and
energy, the State Anxiety Inventory and Visual Analogue Scales. Side-effects will be
registered every day using a specific side-effects report sheet.
On the day before starting the treatment (Day 0) and on the last day of treatment (Day 7)
participants will be asked to collect saliva sample to measure cortisol levels. Collection
of samples will be performed by participants in their own home and is non-invasive.
Participants will be provided with appropriate collection vessels containing a cotton swab.
They will be asked to roll this swab around in their mouths for a minute after waking and
take 4 further samples at 15 minute intervals, each on a separate cotton swab. The cotton
swabs will be put back in the collection vessel and participants will be asked to store
their saliva samples in the freezer and bring them back to the researcher on the day of
testing.
Participants will be given the mobile phone number of the Principal Investigator (PI) so
that they can immediately get in contact if they have any concerns when taking the drug. In
addition, the researcher will contact participants within the first few days to ensure that
they are not experiencing any side effects. Participants experiencing more than mild
transient side effects will be advised to stop taking the drugs and will be withdrawn from
the study.
On the last day of treatment (Day 7), participants will come to the Department of
Experimental Psychology of the University of Oxford around 2 pm, which corresponds to time
when the drug reaches its peak in blood levels. They will be asked to complete again part of
the questionnaires administered on the first day and then they will complete a battery of
neuropsychological tests including attentional tests, facial expression recognition tests
and emotional regulation tests, as used in our previous studies. During the emotional
regulation test an ECG will also be recorded. The testing session will last approximately 3
hours.
If the participant agreed, we would then also collect a blood sample to identify a
particular gene (the serotonin transporter polymorphism) that may influence some of those
measures and to assess the citalopram drug level in order to check that the treatment was
taken.
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Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science