Imaging Dopamine Release in Depression
Information source: New York State Psychiatric Institute
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Major Depressive Disorder
Intervention: Pramipexole (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: New York State Psychiatric Institute Official(s) and/or principal investigator(s): Franklin Schneier, MD, Principal Investigator, Affiliation: NYSPI
Overall contact: Franklin Schneier, MD, Phone: 646-774-8041, Email: Fschneier@nyspi.columbia.edu
Summary
This study aims to determine whether ventral striatal dopamine release is a mechanism of
reward motivation in major depression, whether dopamine release is low in depression, and
whether DA release and reward motivation predict response to dopamine-targeted treatment
with pramipexole.
Clinical Details
Official title: Ventrostriatal Dopamine Release and Reward Motivation in MDD
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Change in Hamilton Rating Scale for Depression
Secondary outcome: Change in Snaith Hamilton Pleasure ScaleChange in Temporal Experience of Pleasure Scale Change in Mood and Anxiety Symptom Questionnaire, Short Form Change in the Apathy Evaluation Rating Scale Change in Items on Side Effect Checklist Change in Columbia Suicide Severity Rating Scale Clinical Global Improvement - Change Scale
Detailed description:
Better understanding of the basic neurobiology of mood dysfunction appears necessary to
enable further progress in the treatment of depression. Reward motivation (and the closely
related construct of "reward learning") is a core neurobehavioral domain.(1,2) In major
depressive disorder (MDD), low reward motivation is a key aspect of anhedonia, a cardinal
symptom of MDD, and is related to resistance to treatment.(2,3) Although much has been
learned about reward motivation's neurobiology and relevance to psychopathology, important
gaps in our knowledge have impeded the application of basic science findings to improving
treatment of MDD. Reward motivation in healthy subjects involves ventrostriatal (VST)
dopamine (DA)(4,5), and reduced reward motivation is linked to MDD and anhedonia.(3,6) These
data suggest that VST DA dysfunction might be present in MDD and manifested clinically by
anhedonia. While DA neuroreceptor imaging studies have failed to verify this, they have been
methodologically compromised. Limitations include imaging methods with poor resolution of
functional striatal subregions, MDD samples heterogeneous for antidepressant use, and use of
self-report measures of anhedonia, rather than objective behavioral testing of the specific
domain of reward motivation. This will be the first study of both VST DA release (by PET
imaging) and reward motivation, and will include patients with MDD and healthy volunteers.
Reward motivation will be captured and operationalized as reward learning in a probabilistic
reward task (prior to imaging). This will clarify if VST DA dysfunction is linked to
impaired motivation in MDD. To test clinical implications in MDD patients, we will assess
the relationship of VST DA release, reward motivation, and anhedonia to outcome of
subsequent open label treatment with the DA D2 receptor agonist pramipexole.
Eligibility
Minimum age: 18 Years.
Maximum age: 50 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Weight between 44 kg and 115 kg
- Meets DSM-IV criteria for principal diagnosis of MDD, current major depressive
episode, without psychotic features
- Score of >16 and <29 on 17-item Hamilton Rating Scale for Depression
- Psychotropic-naïve, as defined by lifetime <2 weeks treatment with antidepressants,
anxiolytics or antipsychotics
- Able to tolerate a treatment-free period during study participation
- Able to provide informed consent
Exclusion Criteria:
- A principal diagnosis of any current Axis I psychiatric disorder other than the MDD
- Lifetime diagnosis of any psychotic disorder, bipolar disorder, mental retardation,
attention deficit/hyperactivity disorder, or substance use disorders (including
nicotine use disorders)
- Serious suicidal risk or history of violent behavior which would make participation
in the protocol unsafe
- Any tobacco use in the prior three months (if not already excluded for
abuse/dependence by #1)
- Illicit drug use in the prior three months, as evidenced by history or urine
toxicology screen
- Women who are pregnant, nursing, postmenopausal, or using hormonal methods of birth
control
- Women who are not using an effective birth control method or sexual abstinence during
the ten days before the scan
- Any medical or neurological problem that might affect interpretation of findings or
safety of participation (e. g., blood dyscrasias, lymphomas, hypersplenism,
endocrinopathies, renal failure or chronic obstructive lung disease, malignancy,
neurological diseases of the brain, history of seizures or head trauma), low
hemoglobin (Hb < 12 gm/dL in males, Hb < 10. 5 gm/dL in females))
- Blood donation within 4 weeks of study
- Metal implants or paramagnetic objects in the body that might affect safety of
undergoing MRI (e. g., heart pacemaker, shrapnel, bullets, surgical prostheses or
surgical clips), as determined in consultation with a neuroradiologist and according
to the guidelines set forth in the reference: "Guide to MR procedures and metallic
objects" Shellock; Lippincott Williams and Wilkins, NY, 2001
- More than one major risk factor for coronary artery disease (e. g. hyperlipidemia,
sedentary lifestyle). Smokers are already excluded by #4 above, and diabetics by #8
above
- Systolic blood pressure > 140 or diastolic blood pressure > 90 based on at least two
readings at rest
- History of untoward reaction to amphetamine or other stimulant medication, or
pramipexole
- Any psychotropic treatment in the past 3 weeks (or depot medication in the past 6
months), except for lorazepam,which may be administered as needed prior to imaging
day
- Current, past or anticipated exposure to radiation in the workplace, or participation
in nuclear medicine procedures, including research protocols (In case of previous
exposure to activity due to research studies, subjects will be eligible if all
conditions listed below are fulfilled: 1) The injected dose and dosimetry of the
radiotracer are known; 2) Except for research studies, the subject has not been
exposed to radiation (workplace and medical); 3) Adding prior exposure to the
exposure due to the study will result in a yearly cumulative exposure lower than the
FDA limit for research studies
- Family history of schizophrenia in parents, siblings, or children
- Ongoing cognitive-behavioral or interpersonal psychotherapy for depression
(Supportive therapy is not an exclusion)
Locations and Contacts
Franklin Schneier, MD, Phone: 646-774-8041, Email: Fschneier@nyspi.columbia.edu
New York State Psychiatric Institute, New York, New York 10032, United States; Recruiting Franklin Schneier, MD, Principal Investigator
Additional Information
Related publications: Sanislow CA, Pine DS, Quinn KJ, Kozak MJ, Garvey MA, Heinssen RK, Wang PS, Cuthbert BN. Developing constructs for psychopathology research: research domain criteria. J Abnorm Psychol. 2010 Nov;119(4):631-9. doi: 10.1037/a0020909. Treadway MT, Zald DH. Reconsidering anhedonia in depression: lessons from translational neuroscience. Neurosci Biobehav Rev. 2011 Jan;35(3):537-55. doi: 10.1016/j.neubiorev.2010.06.006. Epub 2010 Jul 11. Review. Vrieze E, Pizzagalli DA, Demyttenaere K, Hompes T, Sienaert P, de Boer P, Schmidt M, Claes S. Reduced reward learning predicts outcome in major depressive disorder. Biol Psychiatry. 2013 Apr 1;73(7):639-45. doi: 10.1016/j.biopsych.2012.10.014. Epub 2012 Dec 8. Forbes EE, Hariri AR, Martin SL, Silk JS, Moyles DL, Fisher PM, Brown SM, Ryan ND, Birmaher B, Axelson DA, Dahl RE. Altered striatal activation predicting real-world positive affect in adolescent major depressive disorder. Am J Psychiatry. 2009 Jan;166(1):64-73. doi: 10.1176/appi.ajp.2008.07081336. Epub 2008 Dec 1. Kumar P, Waiter G, Ahearn T, Milders M, Reid I, Steele JD. Abnormal temporal difference reward-learning signals in major depression. Brain. 2008 Aug;131(Pt 8):2084-93. doi: 10.1093/brain/awn136. Epub 2008 Jun 25. Pizzagalli DA, Iosifescu D, Hallett LA, Ratner KG, Fava M. Reduced hedonic capacity in major depressive disorder: evidence from a probabilistic reward task. J Psychiatr Res. 2008 Nov;43(1):76-87. doi: 10.1016/j.jpsychires.2008.03.001. Epub 2008 Apr 22.
Starting date: February 2014
Last updated: April 14, 2015
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