Antidepressants, Emotions and Personality
Condition: Antidepressive Agents, Second-Generation
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Citalopram; Placebo
Intervention type(s): Drug; Drug
Intervention MeSH terms: Citalopram
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Neuroticism; Emotion processing; Eye gaze movements; Heart Rate Variability