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.
| Status | Completed |
| Enrollment | 42 |
| Est. completion date | November 2010 |
| Est. primary completion date | November 2010 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Both |
| Age group | 18 Years to 50 Years |
| Eligibility |
Inclusion Criteria: - Participant is willing and able to give informed consent for participation in the study. - Male or Female, aged 18 - 50 years - Eysenck Personality Questionnaire Neuroticism scale =15/24 - Fluent in English language (in order to understand all study instructions and tasks using verbal stimuli) Exclusion Criteria: - any significant medical condition - current or past history of psychiatric disorder - family history of mania - pregnancy or breastfeeding - taking any current medication (except the contraceptive pill) - having taken part in other trials involving psychotropic drug intake in the previous three months |
Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science
| Country | Name | City | State |
|---|---|---|---|
| United Kingdom | University of Oxford, Department of Psychiatry, Warneford Hospital | Oxford | Oxfordshire |
| Lead Sponsor | Collaborator |
|---|---|
| University of Oxford |
United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Change in waking salivary cortisol levels | Change in levels of waking salivary cortisol from baseline pre-treatment to after 7 days of treatment administration | Change from baseline (day 0) to day 7 of treatment | No |
| Primary | Eye gaze fixations over the region of the eyes and whole face region of facial expressions during a gender discrimination task of emotional facial expressions | Fixations were defined as a set of eye positions within a defined area for a selected amount of time. We adopted the default values defining a fixation to be within a 0.30 x 0.30 degree box for 100 ms and calculating fixations using a velocity/distance algorithm. In the calculation, subjects' eyes are allowed to drift during fixation as long as the amount of drift is less than this area per 100 ms. We calculated the number of fixations present within the Region of Interest (ROI) of the eyes of the facial expressions used as stimuli in the task. | Day 7 of treatment administration | No |
| Secondary | Scanpath length over the eye region and whole face region of facial expressions during a gender discrimination task of emotional facial expressions | Scanpath length refers to the summed distances travelled by the eye during scanning, and is typically measured in degrees of visual angle (expressed in pixels) | Day 7 of treatment | No |
| Secondary | Scanning time over the eyes region and whole face of facial expressions during a gender discrimination task of emotional facial expressions | Scanning time refers to the time spent by the eye travelling over the stimuli, and is calculated in ms. | Day 7 of treatment | No |
| Secondary | Gaze maintenance over the eyes region and whole face of facial expressions during a gender discrimination task of emotional facial expressions | The gaze maintenance calculation indicated whether gaze was or was not maintained in the selected ROI (eyes, whole face) for the entire duration of each trial (500ms). | Day 7 of treatment | No |
| Secondary | Accuracy and reaction time of emotional facial expressions recognition during a facial expressions recognition task | Correct labelling of emotional facial expressions presented on a screen for 500ms at intensities varying between 10% and 100%: correct responses and misclassifications are recorded, and accuracy is measured calculating the average expression intensity threshold needed to correctly identify each emotion. Reaction times to correctly label facial expressions is recorded in ms. | Day 7 of treatment | No |
| Secondary | Recall and recognition scores and reaction times during a memory task for emotionally valenced self-descriptors | Number of correctly recalled, false alarms and number of recognised positive and negative self-descriptors, and reaction time in ms. | Day 7 of treatment | No |
| Secondary | Eye-blink reflex magnitudes in response to pleasant, unpleasant and neutral pictures during an emotion potentiated startle task | Eye-blink reflex magnitudes in microvolts were calculated by subtracting the amount of integrated EMG at reflex onset from the first peak amplitude of integrated EMG between 20 and 120 ms following probe onset. Trials with no traceable eye-blink reflex were assigned a magnitude of zero and included in the analysis. Eye-blink reflexes with excessive noise during the 20-ms, pre-startle baseline period were excluded. This task provides a measure of the relative acoustic startle response during unpleasant, pleasant and neutral pictorial stimuli presentation. Eye-blink reflex magnitudes were z-transformed within subjects to allow comparison between these different conditions and minimise inter-subject variability. | Day 7 of treatment | No |
| Secondary | High Frequency Heart Rate Variability (HF-HRV) during an emotion regulation task of unpleasant pictures | HF-HRV for each condition in the task (i.e. while passively viewing unpleasant pictures, "maintain condition", and while down-regulating the emotion elicited by unpleasant pictures, "suppress condition") and for 1 min "pre-task" period was calculated by integrating the spectral power across the bandwidth 0.15-0.4 Hz; normalised HF and LF values (HFn and LFn) were also calculated by dividing the HF-HRV and LF-HRV by the total power in the range above 0.04 Hz ("normalisation power"). | Day 7 of treatment | No |
| Secondary | Affect ratings during an emotion regulation task of unpleasant pictures | Rating of negative affect on a 5-point Likert scale after passive viewing ("maintain emotion" condition) or active down-regulation of the emotion elicited by unpleasant pictures ("suppress emotion" condition). | Day 7 of treatment | No |