Clinical trial NCT01728194: Emotional and Cognitive Control in Late-Onset Depression
Official title: White Matter and Emotional and Cognitive Control in Late-Onset Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Depression
Keywords: Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Escitalopram
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Physiological Effects of Drugs
Muscarinic Antagonists
Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Serotonin Agents
Magnetic Resonance Imaging, Functional
fMRI
Magnetic Resonance Imaging
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2012-11-16
Enrollment: 121
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This study may help identify how abnormalities in brain systems that control the ability to ignore irrelevant information may contribute to the development of depression in older adults.

Detailed description: Approximately half of those who develop depression in late life never had depression before. The classic view is that changes taking place in our brains as we age contribute to the development of late-onset depression. This view is supported by the relative absence of family history for those with late onset depression. This research study will recruit 70 older adults with late life depression and 70 older adults without depression. All participants will receive a sub-clinical, non-contrast (magnetic resonance imaging (MRI) scan at the beginning of the study and then again 12 weeks later at the completion of the study. The depressed older participants will also receive a Food and Drug Administration (FDA)-approved antidepressant, escitalopram (Lexapro), as treatment for their depressive symptoms over 12 weeks. This MRI study may help the researchers identify how abnormalities in brain systems that control our ability to ignore distractions, control our emotions, and anticipate reward may contribute to the development of depression in older adults. The investigators hope that the findings promote the development of tests that may improve the detection of older adults at risk for poor treatment outcomes and eventually guide the development of novel treatments for depression.

Eligibility criteria: Inclusion Criteria:

* Age: 60-85 years, right-handed;
* Diagnosis: Major depression, unipolar (by Structured Clinical Interview for Diagnostic and Statistical Manual (DSM)IV (SCID-R) and DSM-IV criteria);
* Age of onset of first episode ≥ 50 years with up to three depressive episodes;
* Severity of depression: A 24-Item Hamilton Depression Rating Scale (HDRS) ≥ 20.

Exclusion Criteria:

* Psychotic depression by DSM-IV, i.e., presence of delusions with a SCID-R score higher than 2;
* High suicide risk, i.e. intent or plan to attempt suicide in near future;
* Presence of any Axis I psychiatric disorder (other than unipolar major depression) or substance abuse;
* History of psychiatric disorders other than unipolar major depression or generalized anxiety disorder (bipolar disorder, hypomania, and dysthymia are exclusion criteria);
* Dementia: Diagnosis of dementia by DSM-IV;
* Mild Cognitive Impairment (MCI);
* Acute or severe medical illness, i.e., delirium, metastatic cancer, decompensated cardiac, liver or kidney failure, major surgery, stroke or myocardial infarction during the three months prior to entry; or use of drugs known to cause depression, e.g., reserpine, alpha-methyl-dopa, steroids, sympathomimetics withdrawal;
* Neurological brain disease and/or history of electroconvulsive therapy;
* History of any use of citalopram or escitalopram during the current episode or need for drugs that may interact with these agents, i.e. drug metabolized by the 2D6 P450 isoenzyme system;
* Current involvement in psychotherapy;
* Contraindications to MRI scanning including cardiac pacemaker, metallic objects and metallic implants contraindicating MRI, cardiac stent, claustrophobia;
* Inability to speak English;
* Corrected visual acuity \< 20/70; Color blindness.

Primary outcomes:
measure: Change in Depression Severity (Measured by Montgomery Asberg Depression Rating Scale)
timeFrame: Baseline (Study Entry / Before Tx) and Week 12 (Following Tx)
Secondary outcomes:
measure: Change in Depression Severity (Measured by Hamilton Depression Rating Scale)
timeFrame: Baseline (Study Entry / Before Tx) and Week 12 (Following Tx)
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: White Plains
country: United States
facility: Weill Cornell Medical College - Westchester Division
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Faith Gunning, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Victoria LW, Alexopoulos GS, Ilieva I, Stein AT, Hoptman MJ, Chowdhury N, Respino M, Morimoto SS, Kanellopoulos D, Avari JN, Gunning FM. White matter abnormalities predict residual negative self-referential thinking following treatment of late-life depression with escitalopram: A preliminary study. J Affect Disord. 2019 Jan 15;243:62-69. doi: 10.1016/j.jad.2018.09.013. Epub 2018 Sep 11.
citation: Oberlin LE, Victoria LW, Ilieva I, Dunlop K, Hoptman MJ, Avari J, Alexopoulos GS, Gunning FM. Comparison of Functional and Structural Neural Network Features in Older Adults With Depression With vs Without Apathy and Association With Response to Escitalopram: Secondary Analysis of a Nonrandomized Clinical Trial. JAMA Netw Open. 2022 Jul 1;5(7):e2224142. doi: 10.1001/jamanetworkopen.2022.24142.
citation: Respino M, Hoptman MJ, Victoria LW, Alexopoulos GS, Solomonov N, Stein AT, Coluccio M, Morimoto SS, Blau CJ, Abreu L, Burdick KE, Liston C, Gunning FM. Cognitive Control Network Homogeneity and Executive Functions in Late-Life Depression. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Feb;5(2):213-221. doi: 10.1016/j.bpsc.2019.10.013. Epub 2019 Nov 7.
citation: Respino M, Jaywant A, Kuceyeski A, Victoria LW, Hoptman MJ, Scult MA, Sankin L, Pimontel M, Liston C, Belvederi Murri M, Alexopoulos GS, Gunning FM. The impact of white matter hyperintensities on the structural connectome in late-life depression: Relationship to executive functions. Neuroimage Clin. 2019;23:101852. doi: 10.1016/j.nicl.2019.101852. Epub 2019 May 3.