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Depressed Mood Improvement Through Nicotine Dosing 3 (DepMIND3)

Primary Purpose

Depressive Disorder

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Transdermal Nicotine Patch
Transdermal Placebo Patch
Sponsored by
Vanderbilt University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depressive Disorder focused on measuring geriatrics, aging, elderly, cognition, memory, nicotine transdermal patch, depression

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥ 60 years; diagnosis of major depressive disorder, single or recurrent episode (DSM5); On a stable therapeutic dose of an allowed SSRI or SNRI for at least 6 weeks; severity: at least mild active depression symptoms, defined as MADRS ≥ 15; cognition: MMSE ≥ 24; fluent in English Exclusion Criteria: Other Axis I psychiatric disorders, except for generalized anxiety disorder (GAD) or social phobia symptoms occurring in a depressive episode; Use of other augmentation medication treatments for depression (e.g., adjunctive bupropion or other augmenting agents) that the participant does not want to stop, although short-acting sedatives are allowed; Any use of tobacco or nicotine in the last year. Living with a smoker or regular exposure to secondhand smoke. History of alcohol use disorder or substance use disorder of moderate or greater severity (endorsing 4 or more of the 12 criteria) in the last 12 months. Acute suicidality. Acute grief (<1 month); Current or past psychosis. Primary central nervous system neurological disorder, including dementia, stroke, epilepsy, etc.; Presence of unstable medical illness requiring urgent treatment or intervention; MRI contraindication. Electroconvulsive therapy or transcranial magnetic stimulation in last 2 months; Current or planned psychotherapy where the potential participant does not want to pause therapy for the duration of the study; Allergy or hypersensitivity to nicotine patches; In the last 4 weeks, regular use of drugs with central cholinergic or anticholinergic properties or moderate / severe CYP2A6 inhibitors /inducers

Sites / Locations

  • Vanderbilt Psychiatric HosptialRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Transdermal Nicotine Patch

Transdermal Placebo Patch

Arm Description

Participants will be randomized to apply nicotine transdermal patches during waking hours. Active dose will titrate up from 3.5mg to 7mg in the first 3 weeks. Doses can be optionally titrated to a maximum of 14mg over 12 weeks, based on tolerability and perceived benefit. After 12 weeks, the patch dose will be tapered over 2-3 weeks.

Participants will be randomized to apply placebo transdermal patches during waking hours. Placebo patch titration will mirror the active arm, increasing the dose will titrate up from 3.5mg to 7mg in the first 3 weeks. Doses can be optionally titrated to a maximum of 14mg over 12 weeks, based on tolerability and perceived benefit. After 12 weeks, the patch dose will be tapered over 2-3 weeks.

Outcomes

Primary Outcome Measures

MADRS (Montgomery Asberg Depression Rating Scale) Score
Primary mood outcome measured by the total score of the clinician rated MADRS. MADRS will be measured every 3 weeks (baseline, week 3, week 6, week 9, and week 12). MADRS total score range is 0-60, where higher scores indicate greater depression severity.
Functional Magnetic Resonance Imaging (MRI)
MRI scans will be performed at baseline and week 6. MRI will measure cognitive control network function, operationalized as a reduction in the Stroop BOLD response in the middle and superior frontal gyri. The Stroop BOLD response is calculated as the activation difference between incongruent and congruent conditions of the emotional Stroop task. The primary outcome will be change in activation difference from baseline to week 6. This will be examined as both a continuous variable and a categorical variable, operationalized as those subjects will exhibit a middle / superior frontal gyri z-score reduction in activation over time of 0.5 or greater.
Continuous Performance Task (CPT) Performance
Primary cognitive outcome, the CPT is a neuropsychological test that measures attention conducted as part of the NIH EXAMINER Test Battery. In this test, participants are asked to respond to a target image and not to other images. This test is conducted at baseline and at week12. The specific primary outcome metric is standard error of change in the inter-stimulus hit reaction time or variability between different trials. There is not absolute range, but lower scores indicate decreased variability across trials and overall better performance.

Secondary Outcome Measures

NIH EXAMINER Test Battery
Secondary Cognitive Outcome: This neuropsychological test battery assesses a range of executive functions. We will examine its Executive Composite Score and the three factor scores (Cognitive Control, Fluency, and Working Memory). Higher scores indicate better performance.
Choice Reaction Time (CRT) Performance
Secondary cognitive outcome, a neuropsychological test measure of attention. We will examine the total response time for the CRT. Lower scores indicate better performance.
Selective Reminding Task
Secondary cognitive outcome, Selective Reminding Task as a test of immediate and delayed verbal memory. This is an 8-trial, 16-word test where the interviewer reads unrelated words to the participant who must recall them. Any missed items are then repeated before the next attempt. Alternative word lists are available for repeated assessments. A delayed trial is administered after 20 minutes. Change in the recall, failure to recall and consistency over 12 weeks reflect the verbal memory function.
Trait Adjectives Task
Participants view a series of randomized, rapidly presented positive and negative characteristics and quickly indicate whether each adjective does or does not apply to them. Positive and negative adjectives are balanced. Measures include number of adjectives endorsed or rejected, and RT for those trials. Task performance assesses self-referential negativity bias and is associated with antidepressant response. Anticipate increased endorsement of positive adjective and increased rejection of negative adjectives in the active arm.
Ruminative Response Scale
Secondary mood outcome: Change in rumination measured by the Ruminative Response Scale total score measured at Screening visit, week 6 and week 12. This is a self-report scale with a range of 0-66, where higher scores indicate higher levels of rumination.
Apathy Evaluation Scale (AES)
Secondary Mood Outcomes: Change in apathy as measured by the self-report AES, a questionnaire with a range of 0-54, where lower scores indicate greater apathy.
Insomnia Severity Index
Secondary Mood Outcomes: Change in the severity of insomnia measures as self-report, a questionnaire with the range of 0-21, where higher scores indicate increase in severity.
Penn State Worry Questionnaire (PSWQ)
Secondary mood outcome: Change in anxiety and worry measured by PSWQ, a self-report questionnaire with a range of 16-80, where higher scores indicate greater anxiety and worry.
Fatigue Severity Scale
Secondary fatigue out come :self-reported questionnaire that ranges from 0- 56;where higher scores indicate severe fatigue.
General Anxiety Disorder Scale (7 Item)
Secondary Mood outcome: self-reported questionnaire to measure the severity of anxiety. Questionnaire ranges 0-24, higher scores indicates greater anxiety state.
PROMIS Applied Cognition Abilities Short
Secondary Cognitive outcome:PROMIS (Patient reported outcome measurement information system) is a self-reported questionnaire to measure mental acuity, concentration, verbal and nonverbal memory, verbal fluency, and perceived changes in these cognitive functions, ranges from 0-32 , where higher scores indicate improvement.
Attentional Control Scale
Secondary Cognitive outcome: The Attentional Control Scale (ACS) is a self-report questionnaire that has been developed to measure individual differences in attentional control. These findings are discussed in relation to previous studies on attentional and executive control in anxiety and depression. Higher scores indicative of better attentional control.

Full Information

First Posted
February 14, 2023
Last Updated
October 6, 2023
Sponsor
Vanderbilt University Medical Center
Collaborators
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT05746273
Brief Title
Depressed Mood Improvement Through Nicotine Dosing 3
Acronym
DepMIND3
Official Title
Nicotinic Modulation of the Cognitive Control System in Late-Life Depression (R33 Phase)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 15, 2023 (Actual)
Primary Completion Date
October 31, 2025 (Anticipated)
Study Completion Date
September 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center
Collaborators
National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Deficits in cognitive control are core features of late-life depression (LLD), contributing both to emotion dysregulation and problems with inhibiting irrelevant information, conflict detection, and working memory. Clinically characterized as executive dysfunction, these deficits are associated with poor response to antidepressants and higher levels of disability. Improvement of cognitive control network (CCN) dysfunction may benefit both mood and cognitive performance, however no current pharmacotherapy improves Cognitive Control Network deficits in LLD. The study examines the hypothesis that nicotine acetylcholine receptor agonists enhance Cognitive Control Network function. This effect may resultantly improve mood and cognitive performance in LLD. Small, open-label studies of transdermal nicotine (TDN) patches have supported potential clinical benefit and provided support that transdermal nicotine administration engages the Cognitive Control Network. This blinded study will expand past open-label trials supporting potential benefit in LLD. It will examine TDN's effect on depression severity and cognitive control functions measured by neuropsychological testing. The study will evaluate 60 eligible and enrolled participants over a 3-year period.
Detailed Description
The purpose of the Depressed MIND3 study is to determine whether blinded, placebo-controlled administration of transdermal nicotine results in significant cognitive, clinical and functional improvement in participants with LLD. Neuronal nicotinic receptors have long been known to play a critical role in memory function in preclinical studies, with nicotine improving attention, learning, and memory function. This may be particularly relevant in LLD, which is characterized both by affective symptoms and broad cognitive deficits. The co-occurrence of cognitive deficits in LLD is a clinically relevant phenotype characterized by significant disability and poor antidepressant response. Cognitive deficits can persist even with successful antidepressant treatment and increase the risk of depression relapse. Despite the clinical importance of cognitive deficits in LLD, there are no established treatments that specifically target cognition in this population. The lack of clear pharmacologic targets and therapies aimed at improving cognitive deficits in depression is a substantial deficiency in current therapeutics. We propose that modulation of the cognitive control network by stimulation of cholinergic system nicotinic acetylcholine receptors will improve both mood and cognition in depressed elders. The study is a randomized double blind placebo control trial that will enroll 80 participants over a 3-year period. Participants will be randomized (2:1) to receive either active transdermal nicotine (TDN) patches or matching placebo patches. Participants will apply patches daily for 12 weeks, followed by a 3-week taper period. The Aims of this blinded trial are to: 1) validate target engagement and determine whether change in brain activation to an emotional Stroop task is related to improvement in depression severity and cognitive performance; and 2) determine the specificity of TDN's effects by examining whether changes in the default mode network (DMN) or other regions occur with TDN and if so, are they related to change in clinical measures. AIM 1: Examine how TDN's neural circuit changes affect depressive symptoms in a blinded RCT. Hyp 1A: Compared with placebo, TDN administration will significantly reduce the Stroop BOLD response on functional Magnetic Resonance Imaging. This change will be associated with reduction in depression severity by the Montgomery-Asberg Depression Rating Scale (MADRS). Hyp 1B: Change in the Stroop BOLD response of other brain regions with TDN administration, specifically the DMN, will not be significantly associated with change in depression severity. Hyp 1C: Compared with placebo, TDN will improve depression severity measured by MADRS (primary clinical outcome), reduce apathy and rumination measured by self-report, and reduce negative self-referential thinking measured by the Trait Adjectives Task (secondary outcomes). AIM 2: Examine how TDN's circuit changes affect CCN-mediated cognitive performance. Hyp 2A: Reduction in the Stroop BOLD response will be associated with improvement in attention, working memory, and episodic memory performance. Change in the Stroop BOLD response of other regions, specifically the DMN, will not be associated with change in task performance. Hyp 2B: Compared with placebo, nicotine will improve performance on tasks of attention, working memory, and episodic memory (secondary outcomes).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depressive Disorder
Keywords
geriatrics, aging, elderly, cognition, memory, nicotine transdermal patch, depression

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Double Blinded, using matching placebo patches.
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Transdermal Nicotine Patch
Arm Type
Experimental
Arm Description
Participants will be randomized to apply nicotine transdermal patches during waking hours. Active dose will titrate up from 3.5mg to 7mg in the first 3 weeks. Doses can be optionally titrated to a maximum of 14mg over 12 weeks, based on tolerability and perceived benefit. After 12 weeks, the patch dose will be tapered over 2-3 weeks.
Arm Title
Transdermal Placebo Patch
Arm Type
Placebo Comparator
Arm Description
Participants will be randomized to apply placebo transdermal patches during waking hours. Placebo patch titration will mirror the active arm, increasing the dose will titrate up from 3.5mg to 7mg in the first 3 weeks. Doses can be optionally titrated to a maximum of 14mg over 12 weeks, based on tolerability and perceived benefit. After 12 weeks, the patch dose will be tapered over 2-3 weeks.
Intervention Type
Drug
Intervention Name(s)
Transdermal Nicotine Patch
Other Intervention Name(s)
Nicoderm CQ, Nicotrol
Intervention Description
Participants will wear nicotine transdermal patches daily for 12-15 weeks. They will apply a study patch each morning and remove at bedtime. Active dose will titrate up from 3.5mg to 7mg, and then can optionally be further titrated to a maximum dose of 14mg. After week12, the dose will be slowly tapered over 2-3 weeks.
Intervention Type
Drug
Intervention Name(s)
Transdermal Placebo Patch
Other Intervention Name(s)
Placebo Patches
Intervention Description
Participants will wear placebo transdermal patches daily for 12-15 weeks. They will apply a study patch each morning and remove at bedtime. Placebo patch dose will titrate up from 3.5mg to 7mg, and then can optionally be further titrated to a maximum dose of 14mg. After week12, the dose will be slowly tapered over 2-3 weeks.
Primary Outcome Measure Information:
Title
MADRS (Montgomery Asberg Depression Rating Scale) Score
Description
Primary mood outcome measured by the total score of the clinician rated MADRS. MADRS will be measured every 3 weeks (baseline, week 3, week 6, week 9, and week 12). MADRS total score range is 0-60, where higher scores indicate greater depression severity.
Time Frame
Baseline to week 12
Title
Functional Magnetic Resonance Imaging (MRI)
Description
MRI scans will be performed at baseline and week 6. MRI will measure cognitive control network function, operationalized as a reduction in the Stroop BOLD response in the middle and superior frontal gyri. The Stroop BOLD response is calculated as the activation difference between incongruent and congruent conditions of the emotional Stroop task. The primary outcome will be change in activation difference from baseline to week 6. This will be examined as both a continuous variable and a categorical variable, operationalized as those subjects will exhibit a middle / superior frontal gyri z-score reduction in activation over time of 0.5 or greater.
Time Frame
Baseline to week 6.
Title
Continuous Performance Task (CPT) Performance
Description
Primary cognitive outcome, the CPT is a neuropsychological test that measures attention conducted as part of the NIH EXAMINER Test Battery. In this test, participants are asked to respond to a target image and not to other images. This test is conducted at baseline and at week12. The specific primary outcome metric is standard error of change in the inter-stimulus hit reaction time or variability between different trials. There is not absolute range, but lower scores indicate decreased variability across trials and overall better performance.
Time Frame
Baseline to Week 12
Secondary Outcome Measure Information:
Title
NIH EXAMINER Test Battery
Description
Secondary Cognitive Outcome: This neuropsychological test battery assesses a range of executive functions. We will examine its Executive Composite Score and the three factor scores (Cognitive Control, Fluency, and Working Memory). Higher scores indicate better performance.
Time Frame
Baseline to Week 12
Title
Choice Reaction Time (CRT) Performance
Description
Secondary cognitive outcome, a neuropsychological test measure of attention. We will examine the total response time for the CRT. Lower scores indicate better performance.
Time Frame
Baseline to Week 12
Title
Selective Reminding Task
Description
Secondary cognitive outcome, Selective Reminding Task as a test of immediate and delayed verbal memory. This is an 8-trial, 16-word test where the interviewer reads unrelated words to the participant who must recall them. Any missed items are then repeated before the next attempt. Alternative word lists are available for repeated assessments. A delayed trial is administered after 20 minutes. Change in the recall, failure to recall and consistency over 12 weeks reflect the verbal memory function.
Time Frame
Baseline to Week 12
Title
Trait Adjectives Task
Description
Participants view a series of randomized, rapidly presented positive and negative characteristics and quickly indicate whether each adjective does or does not apply to them. Positive and negative adjectives are balanced. Measures include number of adjectives endorsed or rejected, and RT for those trials. Task performance assesses self-referential negativity bias and is associated with antidepressant response. Anticipate increased endorsement of positive adjective and increased rejection of negative adjectives in the active arm.
Time Frame
Baseline to Week 12
Title
Ruminative Response Scale
Description
Secondary mood outcome: Change in rumination measured by the Ruminative Response Scale total score measured at Screening visit, week 6 and week 12. This is a self-report scale with a range of 0-66, where higher scores indicate higher levels of rumination.
Time Frame
Baseline to Week 12
Title
Apathy Evaluation Scale (AES)
Description
Secondary Mood Outcomes: Change in apathy as measured by the self-report AES, a questionnaire with a range of 0-54, where lower scores indicate greater apathy.
Time Frame
Baseline to Week 12
Title
Insomnia Severity Index
Description
Secondary Mood Outcomes: Change in the severity of insomnia measures as self-report, a questionnaire with the range of 0-21, where higher scores indicate increase in severity.
Time Frame
Baseline to Week 12
Title
Penn State Worry Questionnaire (PSWQ)
Description
Secondary mood outcome: Change in anxiety and worry measured by PSWQ, a self-report questionnaire with a range of 16-80, where higher scores indicate greater anxiety and worry.
Time Frame
Baseline to Week 12
Title
Fatigue Severity Scale
Description
Secondary fatigue out come :self-reported questionnaire that ranges from 0- 56;where higher scores indicate severe fatigue.
Time Frame
Baseline to Week 12
Title
General Anxiety Disorder Scale (7 Item)
Description
Secondary Mood outcome: self-reported questionnaire to measure the severity of anxiety. Questionnaire ranges 0-24, higher scores indicates greater anxiety state.
Time Frame
Baseline to Week 12
Title
PROMIS Applied Cognition Abilities Short
Description
Secondary Cognitive outcome:PROMIS (Patient reported outcome measurement information system) is a self-reported questionnaire to measure mental acuity, concentration, verbal and nonverbal memory, verbal fluency, and perceived changes in these cognitive functions, ranges from 0-32 , where higher scores indicate improvement.
Time Frame
Baseline to Week 12
Title
Attentional Control Scale
Description
Secondary Cognitive outcome: The Attentional Control Scale (ACS) is a self-report questionnaire that has been developed to measure individual differences in attentional control. These findings are discussed in relation to previous studies on attentional and executive control in anxiety and depression. Higher scores indicative of better attentional control.
Time Frame
Baseline to Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 60 years; diagnosis of major depressive disorder, single or recurrent episode (DSM5); On a stable therapeutic dose of an allowed SSRI or SNRI for at least 6 weeks; severity: at least mild active depression symptoms, defined as MADRS ≥ 15; cognition: MMSE ≥ 24; fluent in English Exclusion Criteria: Other Axis I psychiatric disorders, except for generalized anxiety disorder (GAD) or social phobia symptoms occurring in a depressive episode; Use of other augmentation medication treatments for depression (e.g., adjunctive bupropion or other augmenting agents) that the participant does not want to stop, although short-acting sedatives are allowed; Any use of tobacco or nicotine in the last year. Living with a smoker or regular exposure to secondhand smoke. History of alcohol use disorder or substance use disorder of moderate or greater severity (endorsing 4 or more of the 12 criteria) in the last 12 months. Acute suicidality. Acute grief (<1 month); Current or past psychosis. Primary central nervous system neurological disorder, including dementia, stroke, epilepsy, etc.; Presence of unstable medical illness requiring urgent treatment or intervention; MRI contraindication. Electroconvulsive therapy or transcranial magnetic stimulation in last 2 months; Current or planned psychotherapy where the potential participant does not want to pause therapy for the duration of the study; Allergy or hypersensitivity to nicotine patches; In the last 4 weeks, regular use of drugs with central cholinergic or anticholinergic properties or moderate / severe CYP2A6 inhibitors /inducers
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sarah Siddiqi
Phone
6159368297
Email
sarah.siddiqi@vumc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Carrie Williams
Phone
6159362162
Email
carrie.e.williams@vumc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Warren Taylor
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt Psychiatric Hosptial
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Siddiqi
Phone
615-936-8297
Email
sarah.siddiqi@vumc.org

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
This study will include clinical, cognitive, and neuroimaging data from older depressed subjects. The final dataset will include clinical information about subject psychiatric diagnoses, psychiatric and medical history, cognitive data, and response to transdermal nicotine. We will share data via the National Institute of Mental Health Data Archive (NDA). NDA provides a secure platform for data-sharing allowing for communication of research data, tools, and supporting documents. As required by NDA, we will obtain a Global Unique Identifier (GUID) for each participant. We will additionally follow NDA requirements to certify and review data, as well as timeline requirements for data submission and data sharing. Sharing of neuroimaging data will also be facilitated by an XNAT system (xnat.org). XNAT is an open-source informatics software platform that assists in the management and archiving of imaging data.
IPD Sharing Time Frame
Data will be shared according to policies from the NDA (NIMH Data Archive). Descriptive data, outcome measures and analyzed data will be shared will be shared within 4 months of when a publication is accepted. Study data will be shared through the NDA indefinitely.
IPD Sharing Access Criteria
The NIH will provide access to scientific investigators for research purposes. Qualified researchers who have completed a Data Use Certification and received approval from the NDA Data Access Committee (DAC) may be approved to access broadly shared data. A separate request process exists for access to data in federated sources. Additionally, the DAC and support staff at NIH have access to NDA shared data.
IPD Sharing URL
https://nda.nih.gov
Citations:
PubMed Identifier
30192444
Citation
Gandelman JA, Kang H, Antal A, Albert K, Boyd BD, Conley AC, Newhouse P, Taylor WD. Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in Nonsmokers With Late-Life Depression. J Clin Psychiatry. 2018 Aug 28;79(5):18m12137. doi: 10.4088/JCP.18m12137.
Results Reference
background
PubMed Identifier
25662104
Citation
Sutherland MT, Ray KL, Riedel MC, Yanes JA, Stein EA, Laird AR. Neurobiological impact of nicotinic acetylcholine receptor agonists: an activation likelihood estimation meta-analysis of pharmacologic neuroimaging studies. Biol Psychiatry. 2015 Nov 15;78(10):711-20. doi: 10.1016/j.biopsych.2014.12.021. Epub 2015 Jan 7.
Results Reference
background
PubMed Identifier
28859996
Citation
Gandelman JA, Newhouse P, Taylor WD. Nicotine and networks: Potential for enhancement of mood and cognition in late-life depression. Neurosci Biobehav Rev. 2018 Jan;84:289-298. doi: 10.1016/j.neubiorev.2017.08.018. Epub 2017 Aug 30.
Results Reference
background
PubMed Identifier
19001356
Citation
Aizenstein HJ, Butters MA, Wu M, Mazurkewicz LM, Stenger VA, Gianaros PJ, Becker JT, Reynolds CF 3rd, Carter CS. Altered functioning of the executive control circuit in late-life depression: episodic and persistent phenomena. Am J Geriatr Psychiatry. 2009 Jan;17(1):30-42. doi: 10.1097/JGP.0b013e31817b60af.
Results Reference
background
PubMed Identifier
22425432
Citation
Alexopoulos GS, Hoptman MJ, Kanellopoulos D, Murphy CF, Lim KO, Gunning FM. Functional connectivity in the cognitive control network and the default mode network in late-life depression. J Affect Disord. 2012 Jun;139(1):56-65. doi: 10.1016/j.jad.2011.12.002. Epub 2012 Mar 15.
Results Reference
background
PubMed Identifier
25251617
Citation
Taylor WD. Clinical practice. Depression in the elderly. N Engl J Med. 2014 Sep 25;371(13):1228-36. doi: 10.1056/NEJMcp1402180. No abstract available.
Results Reference
background

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Depressed Mood Improvement Through Nicotine Dosing 3

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