Major Depressive Disorder Clinical Trial
Official title:
FMRI Study of Performance During a Probabilistic Reversal Learning Task in Depression
This study will examine how the brains of depressed people function during learning and
respond to feedback. Participants perform a "probabilistic reversal learning task" to
determine whether depressed people perform worse on a task than non-depressed people when
they sometimes receive misleading negative feedback.
Right-handed healthy volunteers, people with major depression who are currently depressed or
have previously been depressed and people with bipolar depression between 18 and 50 years of
age may be eligible for this study. Candidates are screened with a medical and psychiatric
history, physical examination, electrocardiogram, blood and urine tests. They are also
interviewed to evaluate mood, sleep, energy, work and school performance, and social
relationships, and asked to answer questions to investigate whether any history of paranoia,
panic attacks, obsession, compulsions, suicidal thoughts, eating disturbances, and alcohol or
drug abuse is present. They complete rating scales for depression, anxiety, and negative
thinking; history of alcohol and tobacco use; physical movement; socioeconomic status;
overall level of functioning; and depression type. Finally, they undergo a battery of
neuropsychological tests to assess general intelligence, handedness, and specific cognitive
abilities, including memory and concentration.
Participants perform the probabilistic reversal learning task either in a testing room seated
in front of a computer or lying down while undergoing functional magnetic resonance imaging
(FMRI). FMRI is a diagnostic test that uses a strong magnet and radio waves to obtain
pictures of brain structure and function. For the scan, the subject lies on a narrow bed with
a plastic-encased metal coil close to the head. The bed slides into the scanner - a small
tunnel about 6 feet long. All subjects, whether in the testing room or in the MRI scanner,
undergo the learning task as follows:
Two patterns are presented on a computer screen. One pattern is designated "correct" and the
other "incorrect." Subjects are asked to choose the correct pattern on each try and are
provided feedback as to whether the response was right or wrong. Sometimes the rule changes,
and the pattern that was correct is now wrong, and vice versa, so that the new correct
pattern must be chosen. In addition, misleading feedback is sometimes given intentionally,
indicating the subject chose the wrong pattern when in fact the response was correct.
Subjects should change their response only when they are sure that the rule has changed, and
not because they were incorrectly told that they were wrong. For patients undergoing MRI,
blood flow in the different areas of the brain is measured during the test.
After the test, outside the scanner, participants undergo additional tests of attention,
memory, and concentration like those that were administered during the screening procedures.
When depressed subjects perceive they have failed while performing a neuropsychological task
their performance on subsequent trials becomes impaired. Elliott et al. showed that MDD
subjects were far more likely to fail on subsequent tasks after failure on one task than
controls. This effect has been described as an "abnormal response' to negative feedback or a
'catastrophic response to perceived failure.'
Murphy et al. investigated this further using a probabilistic reversal learning task in which
subjects were faced with occasional negative feedback that was actually false. On each trial
of the task subjects choose one of two stimuli on screen, one considered correct and the
other incorrect, this is followed by feedback. Instructions prior to starting the task inform
the subject that sometimes the rule will change and the previously correct stimulus will be
incorrect, but sometimes the computer will give them incorrect feedback. They are instructed
to switch responding only when they are sure the rule has actually changed. MDD subjects
demonstrate intact acquisition and reversal of probabilistic learning but are impaired in
their ability to maintain a response in the face of misleading negative feedback. This
profile of impairment may be relatively specific to MDD as, for example, it is not found in
subjects with other neuropsychiatric conditions. This 'abnormal response' to negative
feedback may represent a significant link between negative affect and cognitive impairments
in depression.
During the proposed study functional magnetic resonance images will be acquired while
subjects perform a version of the probabilistic reversal learning task. Four groups will take
part: MDD, bipolar depressed, unmedicated MDD in remission and healthy control subjects.
These images will be used to investigate differences in neural activation between the four
groups, to clarify whether this specific profile of behavioral response extends to bipolar
depressed subjects and to assess the mood state dependences of this effect. This would
increase understanding of the specific profile of performance on this task and neural basis
of this abnormal response to negative feedback that contributes to impairment of cognitive
performance in depression.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05537558 -
Precision Medicine for the Prediction of Treatment (PROMPT) Response (PROMPT)
|
||
Terminated |
NCT02192099 -
Open Label Extension for GLYX13-C-202, NCT01684163
|
Phase 2 | |
Completed |
NCT03142919 -
Lipopolysaccharide (LPS) Challenge in Depression
|
Phase 2 | |
Recruiting |
NCT05547035 -
Identification of Physiological Data by a Wearable Monitor in Subjects Suffering From Major Depression Disorders
|
N/A | |
Terminated |
NCT02940769 -
Neurobiological Effects of Light on MDD
|
N/A | |
Recruiting |
NCT05892744 -
Establishing Multimodal Brain Biomarkers for Treatment Selection in Depression
|
Phase 4 | |
Recruiting |
NCT05537584 -
SMART Trial to Predict Anhedonia Response to Antidepressant Treatment
|
Phase 4 | |
Active, not recruiting |
NCT05061706 -
Multicenter Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder
|
Phase 3 | |
Completed |
NCT04479852 -
A Study of the Safety and Efficacy of SP-624 in the Treatment of Adults With Major Depressive Disorder
|
Phase 2 | |
Recruiting |
NCT04032301 -
Repeated Ketamine Infusions for Comorbid PTSD and MDD in Veterans
|
Phase 1 | |
Recruiting |
NCT05527951 -
Enhanced Measurement-Based Care Effectiveness for Depression (EMBED) Study
|
N/A | |
Completed |
NCT03511599 -
Cycloserine rTMS Plasticity Augmentation in Depression
|
Phase 1 | |
Recruiting |
NCT04392947 -
Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation
|
N/A | |
Recruiting |
NCT05895747 -
5-HTP and Creatine for Depression R33 Phase
|
Phase 2 | |
Recruiting |
NCT05273996 -
Predictors of Cognitive Outcomes in Geriatric Depression
|
Phase 4 | |
Recruiting |
NCT05813093 -
Interleaved TMS-fMRI in Ultra-treatment Resistant Depression
|
N/A | |
Recruiting |
NCT05135897 -
The Neurobiological Fundaments of Depression and Its Relief Through Neurostimulation Treatments
|
||
Enrolling by invitation |
NCT04509102 -
Psychostimulant Augmentation of Repetitive TMS for the Treatment of Major Depressive Disorder
|
Early Phase 1 | |
Recruiting |
NCT06026917 -
Assessing Dopamine Transporter Occupancy in the Patients With Depression Brain With Toludesvenlafaxine Hydrochloride Extended-Release Tablets Using 11C-CFT Positron Emission Tomography (PET)
|
Phase 4 | |
Recruiting |
NCT06145594 -
EMA-Guided Maintenance TMS for Depression
|
N/A |