Depression, InvolutionalNCT00084162
Neurocardiac Control in Major Depression
An observational study of Depression, Involutional, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
This study will examine how depression may influence the way the brain regulates heart function. Some researchers believe that depression may be a risk factor for some forms of heart disease. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Depression, Involutional
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Mar 2004to 17 Mar 2010
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Two groups of right-handed subjects, male or premenopausal female, who are drug-naive or who have not received psychotropic drugs for at least 3 weeks (8 weeks for fluoxetine), will be recruited for studies under this protocol: unipolar depressives and healthy controls individually matched to depressives by age, gender and smoking status. Because effective treatment will not be discontinued for the purposes of this protocol, subjects in the patient groups will be identified who have never been treated for or who have discontinued medication due to lack of efficacy, noncompliance, physician order or other reason prior to study entry.
- The presence of inclusion and exclusion criteria will be established using both an unstructured clinical interview with a psychiatrist and the Structure Clinical Interview for DSM-IV (SCID). Family history of mental illness will be obtained using the Family Interview of Genetic Studies.
Who cannot join
- Subjects will be excluded if they have:
- serious suicidal ideation or behavior;
- inability to provide informed consent;
- medical or neurological illnesses likely to affect physiology or anatomy;
- a history of drug or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM-IV criteria);
- current or past history of other axis I disorders that preceded the onset of MDD;
Show all 15Show fewer
- current pregnancy (documented by pregnancy testing prior to scanning);
- current breast feeding;
- general MRI exclusion criteria;
- vision and/or hearing problems severe enough to interfere with testing.
- Exposure within two weeks to medications likely to affect cerebral blood glow or heart rate.
- Any condition that may prevent the subject from performing the run/walk test, or
- Irregular menstrual cycles so that menstrual phase cannot be reliably determined, or
- Any ECG finding that would contraindicate PET scanning or run/walk testing (e.g. non-sinus rhythm, significant tachycardia, ST segment elevation or depression, Q waves) or arrhythmia that would obviate accurate calculation of HRV indices. Cardiology consultation will be obtained for abnormal ECG findings unless it is unequivocally clear in the judgment of the study physician that such consultation is medically unnecessary.
- Subjects who are beyond age 50 who are either postmenopausal or perimenopausal are excluded to reduce the biological heterogeneity in autonomic function which may be associated with difference in menstrual status.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
This study will examine how depression may influence the way the brain regulates heart function. Some researchers believe that depression may be a risk factor for some forms of heart disease.
Right-handed healthy volunteers and patients with major depressive disorder who are between 18 and 50 years of age may be eligible for this study. Female candidates must be premenopausal. Patients must currently be experiencing a major depressive episode. All candidates are screened with a medical history and physical examination, electrocardiogram, and blood and urine tests. They are interviewed about their psychiatric and medical history, current emotional state and sleep pattern, and family history of psychiatric disorders. They complete symptoms ratings scales for depression, anxiety, and negative thinking; history of alcohol and tobacco use; level of physical activity; socioeconomic status; overall level of functioning; and, for depressed patients, their depression type. Women candidates have their menstrual phase determined by the timing of their recent menstrual cycles and may undergo testing to determine the time of their ovulation.
Read more
Participants undergo the following tests and procedures:
- 12-minute walk/run test - This test measures the subject's general level of cardiorespiratory fitness. In a gymnasium in the NIH Clinical Center, the subject walks or runs as far as he or she can in 12 minutes. Blood pressure is measured before and after the exercise test, and heart rate is measured during exercise with a monitor worn around the chest.
- Magnetic resonance imaging (MRI) - A brain MRI scan is done to obtain pictures of the brain anatomy. Electrocardiogram leads are placed on the subject's chest to measure the electrical activity of the heart during the scanning session. The subject lies on a narrow bed in the scanner, which is a narrow metal cylinder about 6 feet long. The scanning session takes up to 90 minutes.
- Positron emission tomography (PET) - PET scanning produces images of the brain's blood flow. The subject is injected with a radiotracer (small amount of drug labeled with a radioactive substance) that is detected by a special camera to trace blood flow. During the scanning session, the subject lies still on a table. EKG leas are placed on the subject's chest to measure the electrical activity of the heart during the scan. A mask with holes for the eyes, ears, and mouth is placed over the subject's face to keep the head f...
Read the detailed description
The presence of major depression, with or without pre-existing coronary artery disease, predicts increased mortality from myocardial infarction (MI) and sudden cardiac death (SCD). Decreased parasympathetic vagal outflow, especially in the presence of elevated cardiac sympathetic tone, has been proposed as a mechanism for the increased risk of SCD. Multiple lines of evidence suggests that fronto-limbic areas are actively engaged in the robust optimization of autonomic balance between sympathetic and parasympathetic cardiac outflow over a broad range of cognitive and physical demands. We propose that dysfunction of these forebrain neurocardiac networks in MDD mediates maladaptive cardiac autonomic control and the increased risk of cardiovascular mortality. In this model, neurocardiac control networks exhibit a systemic bias toward increased sympathetic relative to parasympathetic outflow. Increased amygdalar activity in MDD will promote this imbalance. Additionally, dysfunction in posterior orbitofrontal cortex (OFC) and ventral anterior cingulated cortex (ACC), areas associated with abnormal histopathological changes in MDD, will lead to reduced capacity for generating adaptive levels of cardioinhibitory, parasympathetic tone. This reduced capacity in depressives will be evidenced by abnormally large withdrawals of parasympathetic outflow, compared to healthy controls, as cognitive or physical demands increase. This dynamic model is potentially consistent with functional neuroimaging and post mortem histopathological findings in MDD and the knowledge gained through testing this protocol may ultimately elucidate how brain dysfunction in MDD mediates significantly increased clinical risk of spontaneous ventricular arrhythmias and sudden cardiac death.
We propose to combine H (2) (15) O positron emission tomography (PET) and analysis of heart rate variability (HRV) in order to study in vivo the neural structures underlying normal forebrain control of cardiac autonomic function. We further aim to show whether regional functional abnormalities in amygdala, ventral anterior cingulate cortex, and orbitofrontal cortex-areas in which functional abnormalities have been identified in previous neuroimaging studies of major depressives-are associated with impaired modulation of cardiac autonomic function during major depression.
- Conditions
- Depression, Involutional
- Keywords
- PET, Heart Rate Variability, N-Back Task, Isometric Handgrip, MRI, Depression, MDD, Heart
- Medical subject headings
- Depressive Disorder, Major, Depression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2004 (estimated)
- Study start30 Mar 2004
- Study completion17 Mar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Depression, InvolutionalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00084162
- Sponsor's protocol ID
- 040136
- Other IDs
- 04-M-0136
- Status last verified
- 17 Mar 2010
- First submitted
- 8 Jun 2004
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation. 1999 Apr 27;99(16):2192-217. doi: 10.1161/01.cir.99.16.2192.
PubMed 10217662Billman GE. Left ventricular dysfunction and altered autonomic activity: a possible link to sudden cardiac death. Med Hypotheses. 1986 May;20(1):65-77. doi: 10.1016/0306-9877(86)90087-3.
PubMed 3636581Hull SS Jr, Evans AR, Vanoli E, Adamson PB, Stramba-Badiale M, Albert DE, Foreman RD, Schwartz PJ. Heart rate variability before and after myocardial infarction in conscious dogs at high and low risk of sudden death. J Am Coll Cardiol. 1990 Oct;16(4):978-85. doi: 10.1016/s0735-1097(10)80351-1.
PubMed 2212380
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurocardiac Control in Major Depression
- ClinicalTrials.gov ID
- NCT00084162
- Acronym / sponsor ID
- 040136
- Conditions
- Depression, Involutional
- Keywords
- PET, Heart Rate Variability, N-Back Task, Isometric Handgrip, MRI, Depression, MDD, Heart
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 30 Mar 2004
- Study completion
- 17 Mar 2010
- First posted
- 8 Jun 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine how depression may influence the way the brain regulates heart function. Some researchers believe that depression may be a risk factor for some forms of heart disease.
Right-handed healthy volunteers and patients with major depressive disorder who are between 18 and 50 years of age may be eligible for this study. Female candidates must be premenopausal. Patients must currently be experiencing a major depressive episode. All candidates are screened with a medical history and physical examination, electrocardiogram, and blood and urine tests. They are interviewed about their psychiatric and medical history, current emotional state and sleep pattern, and family history of psychiatric disorders. They complete symptoms ratings scales for depression, anxiety, and negative thinking; history of alcohol and tobacco use; level of physical activity; socioeconomic status; overall level of functioning; and, for depressed patients, their depression type. Women candidates have their menstrual phase determined by the timing of their recent menstrual cycles and may undergo testing to determine the time of their ovulation.
Participants undergo the following tests and procedures:
- 12-minute walk/run test - This test measures the subject's general level of cardiorespiratory fitness. In a gymnasium in the NIH Clinical Center, the subject walks or runs as far as he or she can in 12 minutes. Blood pressure is measured before and after the exercise test, and heart rate is measured during exercise with a monitor worn around the chest.
- Magnetic resonance imaging (MRI) - A brain MRI scan is done to obtain pictures of the brain anatomy. Electrocardiogram leads are placed on the subject's chest to measure the electrical activity of the heart during the scanning session. The subject lies on a narrow bed in the scanner, which is a narrow metal cylinder about 6 feet long. The scanning session takes up to 90 minutes.
- Positron emission tomography (PET) - PET scanning produces images of the brain's blood flow. The subject is injected with a radiotracer (small amount of drug labeled with a radioactive substance) that is detected by a special camera to trace blood flow. During the scanning session, the subject lies still on a table. EKG leas are placed on the subject's chest to measure the electrical activity of the heart during the scan. A mask with holes for the eyes, ears, and mouth is placed over the subject's face to keep the head f...
Detailed description
The presence of major depression, with or without pre-existing coronary artery disease, predicts increased mortality from myocardial infarction (MI) and sudden cardiac death (SCD). Decreased parasympathetic vagal outflow, especially in the presence of elevated cardiac sympathetic tone, has been proposed as a mechanism for the increased risk of SCD. Multiple lines of evidence suggests that fronto-limbic areas are actively engaged in the robust optimization of autonomic balance between sympathetic and parasympathetic cardiac outflow over a broad range of cognitive and physical demands. We propose that dysfunction of these forebrain neurocardiac networks in MDD mediates maladaptive cardiac autonomic control and the increased risk of cardiovascular mortality. In this model, neurocardiac control networks exhibit a systemic bias toward increased sympathetic relative to parasympathetic outflow. Increased amygdalar activity in MDD will promote this imbalance. Additionally, dysfunction in posterior orbitofrontal cortex (OFC) and ventral anterior cingulated cortex (ACC), areas associated with abnormal histopathological changes in MDD, will lead to reduced capacity for generating adaptive levels of cardioinhibitory, parasympathetic tone. This reduced capacity in depressives will be evidenced by abnormally large withdrawals of parasympathetic outflow, compared to healthy controls, as cognitive or physical demands increase. This dynamic model is potentially consistent with functional neuroimaging and post mortem histopathological findings in MDD and the knowledge gained through testing this protocol may ultimately elucidate how brain dysfunction in MDD mediates significantly increased clinical risk of spontaneous ventricular arrhythmias and sudden cardiac death.
We propose to combine H (2) (15) O positron emission tomography (PET) and analysis of heart rate variability (HRV) in order to study in vivo the neural structures underlying normal forebrain control of cardiac autonomic function. We further aim to show whether regional functional abnormalities in amygdala, ventral anterior cingulate cortex, and orbitofrontal cortex-areas in which functional abnormalities have been identified in previous neuroimaging studies of major depressives-are associated with impaired modulation of cardiac autonomic function during major depression.
Study design
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Two groups of right-handed subjects, male or premenopausal female, who are drug-naive or who have not received psychotropic drugs for at least 3 weeks (8 weeks for fluoxetine), will be recruited for studies under this protocol: unipolar depressives and healthy controls individually matched to depressives by age, gender and smoking status. Because effective treatment will not be discontinued for the purposes of this protocol, subjects in the patient groups will be identified who have never been treated for or who have discontinued medication due to lack of efficacy, noncompliance, physician order or other reason prior to study entry.
- The presence of inclusion and exclusion criteria will be established using both an unstructured clinical interview with a psychiatrist and the Structure Clinical Interview for DSM-IV (SCID). Family history of mental illness will be obtained using the Family Interview of Genetic Studies.
Key exclusion criteria (15 listed)
- serious suicidal ideation or behavior;
- inability to provide informed consent;
- medical or neurological illnesses likely to affect physiology or anatomy;
- a history of drug or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM-IV criteria);
- current or past history of other axis I disorders that preceded the onset of MDD;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 10217662Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation. 1999 Apr 27;99(16):2192-217. doi: 10.1161/01.cir.99.16.2192.
- Background: PubMed 3636581Billman GE. Left ventricular dysfunction and altered autonomic activity: a possible link to sudden cardiac death. Med Hypotheses. 1986 May;20(1):65-77. doi: 10.1016/0306-9877(86)90087-3.
- Background: PubMed 2212380Hull SS Jr, Evans AR, Vanoli E, Adamson PB, Stramba-Badiale M, Albert DE, Foreman RD, Schwartz PJ. Heart rate variability before and after myocardial infarction in conscious dogs at high and low risk of sudden death. J Am Coll Cardiol. 1990 Oct;16(4):978-85. doi: 10.1016/s0735-1097(10)80351-1.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Depression, Involutional, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00084162, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.