The effects of single session Competitive Memory Training (COMET) and yohimbine on the saliency of positive autobiographical memories.

Increasing the accessibility and emotional intensity of positive
autobiographical episodic memories may improve the wellbeing of clinical
populations who suffer from positive memory deficits (e.g., depression and
PTSD) or anhedonia (e.g., depression, social phobia and schizophrenia). In this
study we combine two novel methods to increase the saliency of positive
autobiographical memories: Competitive Memory Training (COMET) and
administration of the cognitive enhancer Yohimbine. COMET is an
autobiographical episodic memory training and has proven to be effective for
increasing self-esteem and decreasing specific symptomology in several
internalizing clinical samples. It is assumed that COMET increases self-esteem,
because it increases memory saliency. However, a proof-of-principle study is
lacking. We investigate the effect of COMET on memory and hypothesize that
COMET procedures increase the ease of recollection, specificity, vividness and
positive affectivity of positive autobiographical memories. The efficacy of
COMET may be maximized by short-acting medication that enhances emotional
arousal. One such enhancer is yohimbine, which facilitates the release of
noradrenaline in the amygdala. Yohimbine has been found to enhance the
(re)consolidation of emotional memory and boost exposure therapy effectiveness.
Therefore, we hypothesize that yohimbine administration will boost COMET memory
effects.

The first goal of the present research proposal is to investigate whether
single session COMET imagery procedures, relative to no intervention control,
increase the ease of recollection, the specificity, vividness and positive
affectivity of positive autobiographical memories in healthy subjects. The
second goal is to investigate whether the induction of emotional arousal
(noradrenaline) by yohimbine vs. placebo can boost these memory effects. The
third goal is to investigate whether noradrenaline/arousal levels prior to and
during the intervention are related to changes in memory after the
intervention. This is the first study to test the efficacy of yohimbine on
positive autobiographical material.

The study will use a double-blind, placebo-controlled, experimental, repeated
measures, cross-over design. Medication group (yohimbine, placebo),
intervention (COMET, control) and time (pre-test, post-test, 2-day follow-up)
will serve as within-subjects independent variables.

Participants select four mildly positive autobiographical memories. They
receive two intervention sessions. During each session, one memory will be
activated using COMET procedures and one memory will receive no intervention.
During one of these sessions, yohimbine HCL (20mg) will be administrated and
during the other session placebo. In total there are four within-subjects
conditions: yohimbine+COMET, yohimbine+no intervention, placebo+COMET, and
placebo+no intervention.

This project involves a low risk study. The low dosage (20mg) of yohimbine HCL
has minimal side-effects (see IB for an overview), and serious adverse events
are very unlikely. Participants are screened for contraindicative conditions
and medication use. The intervention (recalling positive autobiographical
memories) is unlikely to produce psychological discomfort. sAA levels are
measured by chewing on a cotton swab, which is not painful. Another burden for
the subjects is that they have to invest some time (4 visits; approximately 5
hours) in participating in the study. The burdens of the test can be justified
by the clinical and scientific relevance of the study. Participants can
withdraw at any time.