Cognitive vs. Emotional Psychopharmacological Manipulations of Fear vs. Anxiety
| Status: | Completed |
|---|---|
| Conditions: | Anxiety |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 50 |
| Updated: | 10/3/2018 |
| Start Date: | May 31, 2014 |
| End Date: | September 26, 2018 |
Cognitive vs. Emotional Psycho-Pharmacological Manipulations of Fear vs. Anxiety
Background:
Stress and anxiety can interfere with how well people perform tasks. But performing a task
can sometimes lessen anxiety by distracting people from the stress. Researchers want to
examine the interaction between attention and stress. They will use two drugs with different
effects on stress and concentration.
Objective:
- To better understand how thinking and emotion affect anxiety and performance. Also, to
study the effects of methylphenidate and propranolol on performance.
Eligibility:
- Adults age 18 50.
Design:
- First, participants will be screened with a test in which they hear loud, sudden noises
through headphones. Sticky pad electrodes will be placed on the skin under one eye.
These electrodes will tell us how sensitive participants are to the noises.
- Second, participants will complete questionnaires about their mood, thinking, and
anxiety. They will give a saliva sample. For this, a cotton swab will be placed in their
mouth for 2 minutes.
- Third, participants will take a single dose of one of the study pills or a placebo. They
will then look at words, shapes, and letters on a computer monitor. They will answer
questions about what they remember. They may receive a shock or hear loud noises during
the tests.
- For the shocks, small metal disk or sticky pad electrodes will be taped to a wrist or
finger. For recording bodily responses, additional electrodes will be placed on the
arms, body, and under each eye.
- Blood pressure and pulse will be measured during the tests. More saliva samples will be
taken.
- At the end of the study, participants will answer questions about their reaction to the
study testing and about any effects they noticed from the study pill.
- After the experiment, participants will be evaluated for effects of the study pill.
Stress and anxiety can interfere with how well people perform tasks. But performing a task
can sometimes lessen anxiety by distracting people from the stress. Researchers want to
examine the interaction between attention and stress. They will use two drugs with different
effects on stress and concentration.
Objective:
- To better understand how thinking and emotion affect anxiety and performance. Also, to
study the effects of methylphenidate and propranolol on performance.
Eligibility:
- Adults age 18 50.
Design:
- First, participants will be screened with a test in which they hear loud, sudden noises
through headphones. Sticky pad electrodes will be placed on the skin under one eye.
These electrodes will tell us how sensitive participants are to the noises.
- Second, participants will complete questionnaires about their mood, thinking, and
anxiety. They will give a saliva sample. For this, a cotton swab will be placed in their
mouth for 2 minutes.
- Third, participants will take a single dose of one of the study pills or a placebo. They
will then look at words, shapes, and letters on a computer monitor. They will answer
questions about what they remember. They may receive a shock or hear loud noises during
the tests.
- For the shocks, small metal disk or sticky pad electrodes will be taped to a wrist or
finger. For recording bodily responses, additional electrodes will be placed on the
arms, body, and under each eye.
- Blood pressure and pulse will be measured during the tests. More saliva samples will be
taken.
- At the end of the study, participants will answer questions about their reaction to the
study testing and about any effects they noticed from the study pill.
- After the experiment, participants will be evaluated for effects of the study pill.
Objective:
The overall aim of this protocol is to examine the effect of pharmacological manipulations of
affective and cognitive processes on anxiety and task performance. Ultimately, the goal is 1)
to provide insight into the relative influence of cognitive and affective states on anxiety,
2) generate theoretical models that can be applied to a better understanding of the
interaction between cognition and emotion, 3) develop a better screening approach to
candidate anxiolytics, and 4) help formulate novel therapeutic interventions for clinical
anxiety.
Excessive or inappropriately sustained anxiety and fear lead to the most common group of
psychiatric disorders. A number of theoretical models have been proposed to understand the
mechanisms engaged in these maladaptive behaviors. Most recent emphasis has focused on the
synergistic contribution of cognitive and emotional processes. Our laboratory has been
instrumental in delineating aspects of behavioral and neural processes that are associated
with fear and anxiety, using psychophysiological and neuroimaging measures of fear and
anxiety. Evidence shows that levels of anxiety modulate cognitive performance, such as
working memory or perceptual discrimination, and that, conversely, cognitive engagement
influences severity of experimentally induced anxiety. The exact contribution of emotional
processes vs. cognitive processes to the experience of anxiety is not clear, similarly to the
neural mechanisms underlying these interactions.
In this protocol, we propose to manipulate pharmacologically separately cognitive and
emotional processes to dissociate their contribution to fear/anxiety, while using
state-of-the-art measures of anxiety derived from translational work. Indeed, we already
developed integrative experimental models of fear and anxiety via the manipulation of
predictable and unpredictable shock, respectively. We already employed successfully these
models to measure anxiolytic and anxiogenic effects of various compounds such as alprazolam,
citalopram, hydrocortisone, and oxytocin in healthy participants.
We propose in a first step (step-1) to start with a simple proof-of-concept study, using two
pharmacological compounds in a double-blind randomized parallel design, each preferentially
acting respectively on the cognitive (methylphenidate) or affective (propranolol) domain, and
using a single cognitive process (working memory). In a second step (step-2), we propose to
extend this work to the fMRI to examine the cognitive correlates of the effects seen in the
step-1 behavioral study, specifically with methylphenidate. Whereas the comparison among
three drugs is planned for the electrophysiology study, we plan to study only the drug that
improves cognition in the fMRI. The reason we will focus on methylphenidate in step 2 is that
our overall goal is to study the effect of improving cognitive functions on anxiety using
neuroimaging. To reach this goal, we plan to use different approaches to boost cognitive
functions in the coming years, including psychopharmacology, direct current stimulation,
mindfulness. Methylphenidate is our first psychopharmacological study towards this
objective.. Future work will also expand to other compounds and cognitive processes, as well
as vary the strategy to induce anxiety. Presently, anxiety will be induced using the threat
of shock, while participants perform the task. We will examine in step-1 whether 1) the
reduction of induced-anxiety with propranolol improves cognitive performance, and 2) the
facilitation of cognitive performance with methylphenidate reduces induced-anxiety. In
step-2, we will identify the neural mechanisms underlying the effects of methylphenidate, the
drug having beneficial effects on cognitive function.
Study population:
Medically and psychiatrically healthy adult males and females, aged 18 to 50 years.
Design:
The study is a double-blind design. For step-1, three groups of healthy participants will
come for one experimental session. During this session, they will be asked to perform a
working memory task under the threat of shock, i.e., while anticipating unpleasant electric
shocks. Each group will receive one drug challenge, either placebo, propranolol (40 g) or
methylphenidate (20 mg). For step-2, the study tasks will be conducted in a 3T fMRI scanner.
In this step, only methylphenidate and placebo will be compared. Two groups will come for one
experimental session, one will receive placebo and the other one will receive methylphenidate
(20 mg). In a follow-up study for the step-2 fMRI the two groups will come for one
experimental fMRI session one will receive methylphenidate (60 mg).
Outcome measures:
In step-1, the primary outcome measures are the startle reflex and performance on the working
memory task. In step-2, the primary outcome measures are the startle reflex and the cerebral
fMRI blood-oxygen-level dependent (BOLD) responses. For both step-1 and step-2, secondary
measures include skin conductance, heart rate, and subjective measures of anxiety.
The overall aim of this protocol is to examine the effect of pharmacological manipulations of
affective and cognitive processes on anxiety and task performance. Ultimately, the goal is 1)
to provide insight into the relative influence of cognitive and affective states on anxiety,
2) generate theoretical models that can be applied to a better understanding of the
interaction between cognition and emotion, 3) develop a better screening approach to
candidate anxiolytics, and 4) help formulate novel therapeutic interventions for clinical
anxiety.
Excessive or inappropriately sustained anxiety and fear lead to the most common group of
psychiatric disorders. A number of theoretical models have been proposed to understand the
mechanisms engaged in these maladaptive behaviors. Most recent emphasis has focused on the
synergistic contribution of cognitive and emotional processes. Our laboratory has been
instrumental in delineating aspects of behavioral and neural processes that are associated
with fear and anxiety, using psychophysiological and neuroimaging measures of fear and
anxiety. Evidence shows that levels of anxiety modulate cognitive performance, such as
working memory or perceptual discrimination, and that, conversely, cognitive engagement
influences severity of experimentally induced anxiety. The exact contribution of emotional
processes vs. cognitive processes to the experience of anxiety is not clear, similarly to the
neural mechanisms underlying these interactions.
In this protocol, we propose to manipulate pharmacologically separately cognitive and
emotional processes to dissociate their contribution to fear/anxiety, while using
state-of-the-art measures of anxiety derived from translational work. Indeed, we already
developed integrative experimental models of fear and anxiety via the manipulation of
predictable and unpredictable shock, respectively. We already employed successfully these
models to measure anxiolytic and anxiogenic effects of various compounds such as alprazolam,
citalopram, hydrocortisone, and oxytocin in healthy participants.
We propose in a first step (step-1) to start with a simple proof-of-concept study, using two
pharmacological compounds in a double-blind randomized parallel design, each preferentially
acting respectively on the cognitive (methylphenidate) or affective (propranolol) domain, and
using a single cognitive process (working memory). In a second step (step-2), we propose to
extend this work to the fMRI to examine the cognitive correlates of the effects seen in the
step-1 behavioral study, specifically with methylphenidate. Whereas the comparison among
three drugs is planned for the electrophysiology study, we plan to study only the drug that
improves cognition in the fMRI. The reason we will focus on methylphenidate in step 2 is that
our overall goal is to study the effect of improving cognitive functions on anxiety using
neuroimaging. To reach this goal, we plan to use different approaches to boost cognitive
functions in the coming years, including psychopharmacology, direct current stimulation,
mindfulness. Methylphenidate is our first psychopharmacological study towards this
objective.. Future work will also expand to other compounds and cognitive processes, as well
as vary the strategy to induce anxiety. Presently, anxiety will be induced using the threat
of shock, while participants perform the task. We will examine in step-1 whether 1) the
reduction of induced-anxiety with propranolol improves cognitive performance, and 2) the
facilitation of cognitive performance with methylphenidate reduces induced-anxiety. In
step-2, we will identify the neural mechanisms underlying the effects of methylphenidate, the
drug having beneficial effects on cognitive function.
Study population:
Medically and psychiatrically healthy adult males and females, aged 18 to 50 years.
Design:
The study is a double-blind design. For step-1, three groups of healthy participants will
come for one experimental session. During this session, they will be asked to perform a
working memory task under the threat of shock, i.e., while anticipating unpleasant electric
shocks. Each group will receive one drug challenge, either placebo, propranolol (40 g) or
methylphenidate (20 mg). For step-2, the study tasks will be conducted in a 3T fMRI scanner.
In this step, only methylphenidate and placebo will be compared. Two groups will come for one
experimental session, one will receive placebo and the other one will receive methylphenidate
(20 mg). In a follow-up study for the step-2 fMRI the two groups will come for one
experimental fMRI session one will receive methylphenidate (60 mg).
Outcome measures:
In step-1, the primary outcome measures are the startle reflex and performance on the working
memory task. In step-2, the primary outcome measures are the startle reflex and the cerebral
fMRI blood-oxygen-level dependent (BOLD) responses. For both step-1 and step-2, secondary
measures include skin conductance, heart rate, and subjective measures of anxiety.
- INCLUSION CRITERIA:
- Ages 18-50
- Males and females
- Subjects give their own consent
EXCLUSION CRITERIA:
- Clinically significant prior exposure to medications, that based on the investigator s
judgment, may impact the study, such as Ritalin (MPH) and Inderal (PRO).
- Any significant medical or neurological problems (e.g. cardiovascular illness,
respiratory illness, neurologic illness, seizure, etc.)
- Raynaud syndrome
- IQ < 80
- Sinus bradycardia (P<50), or tachycardia (P>90)
- Significant ECG abnormality (i.e., greater than first-degree block etc.)
- Active broncho-spastic lung disease
- A history of visits to the emergency room because of asthma, or with recent history of
asthma symptoms in the past year, which required medication treatment
- High or low blood pressure (SBP>140 or SBP<90; SDP<50 or SDP>90)
- A first-degree family history of mania, schizophrenia, or other psychoses based on
verbal reports
- Significant past psychopathology (e.g., hospitalization for psychiatric disorders,
recurrent depression, suicide attempt, psychoses)
- Current psychiatric disorders according to DSM-IV
- Past alcohol/drug dependence and alcohol/drug abuse in past one year or lifetime
alcohol or drug dependence
- Current use of psychotropic medication
- Impaired hearing
- Pregnancy or positive pregnancy test
- Neurological syndrome of the wrist (e.g., carpal tunnel syndrome)
- Breastfeeding
- Significant lab abnormalities (i.e., CBC with differential, acute care and mineral
panel, hepatic panel, thyroid panel)
- Positive urine toxicology screen
- You have been in another study with an experimental medication within the previous
month
- Small startle reactivity (a change in EMG activity that is less than 3 times the
baseline EMG activity)
- Glaucoma
- Current use of anti-acid medications
- For fMRI participants: Any medical condition that increases risk for fMRI:
- Any metal implants (clips, screws, plates, pins, etc) or metal fragments cause by
injuries or metal working
- Any sort of medical implants (aneurysm clips, pacemaker, insulin pump, Hickman
line, etc.)
- Permanent eye liner and tattoos above the neck
- Patients who have difficulty lying flat on their back for up to 90 min in the
scanner
- Participants who are uncomfortable in small closed spaces (have claustrophobia)
and would feel uncomfortable in the MRI machine
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
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