Depressive Disorder, Major
Conditions
Keywords
Adolescents, Major Depressive Disorder, Proton Magnetic Resonance Spectroscopy, Immune System Activation, Omega-3 Fatty Acids
Brief summary
The purpose of this study is to examine the effects of a 10-week Omega-3 Fatty Acid treatment phase on brain chemistry of adolescents with major depressive disorder (MDD) using proton magnetic resonance imaging.
Detailed description
This study rests on a confluence of findings showing that: 1) Major depressive disorder (MDD), is a major public health concern that often emerges in adolescence; which entails 2) pathophysiological abnormalities in fronto-striatal structures resulting in death and atrophy of glia and neurons; 3) omega-3 fatty acids (FA) effects on brain function in adolescent MDD can be assessed by proton magnetic resonance spectroscopy (1H MRS); and, 4) it is critical that commonly used complementary and alternative medicines such as omega-3FA that have face validity be tested for their neurobiological effect in MDD. Using 1H MRSI, this study examines the effects of Omega-3FA on striatal and anterior cingulate cortex (ACC) concentrations of the neurocellular biomarkers total choline (tCho), total creatine (tCr), and γ-aminobutyric acid (GABA, ACC only) in adolescent MDD. Hypotheses are: 1) relative to placebo, omega-3FA treatment will result in significant reductions of striatal and ACC tCho and tCr concentrations, and increased ACC GABA; 2: Regardless of treatment condition (placebo or Omega-3FA), MDD adolescents who are improved at the end of 10-week treatment will exhibit a significant decrease in striatal and ACC tCho and tCr concentrations, and increases in ACC GABA relative to unimproved adolescents.
Interventions
The study medication will consist of combined EPA/DHA with a ratio of 2:1. Dosage will be titrated based on clinical response and side effects. The initial dose will be 1.2g/d. This will be increased gradually by 0.6 per 2 weeks to a possible maximum daily dose of 3.6 g/d. Patients will have to remain on a dose for 2 weeks to provide the opportunity to assess clinical response at any one dose. The total duration of the intervention will be 10 weeks.
DIETARY_SUPPLEMENTCorn oil
The dosage will correspond to the titration schedule of the Omega-3 Fatty Acid experimental treatment. Placebo (corn oil) and omega-3FA capsules will be identical in color and smell.
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 19 Years
Healthy volunteers
No
Inclusion criteria
* 12 to 19 years old (inclusive) of both sexes and all ethnic/racial groups. * DSM-IV-TR criteria for MDD * MDD Duration of at least 8 weeks and a severity score of at least 40 on the CDRS-R. * Age at first onset MDD of at least 12 years. * No significant medical or neurological disorder * For female subjects, negative pregnancy test at time of enrollment. * Female subjects who are sexually active and not using a method of birth control will be excluded. Use of hormonal contraceptives (such as prescribed birth control pills or a prescribed birth control implant) is not exclusionary. * Subjects must be able to swallow capsules. * A minimum IQ of 80 will be required.
Exclusion criteria
* Current or Past DSM-IV-TR diagnoses of bipolar disorder, schizophrenia, psychosis, autism/pervasive developmental disorder (PDD), and Tourette's disorder (TD). * Current diagnosis of eating disorder, panic disorder, obsessive-compulsive disorder (OCD), post traumatic stress disorder (PTSD), conduct disorder, and substance related disorders other than nicotine. * Current suicidal ideation with intent or plan, or who may pose a danger to themselves. * Current antidepressant treatment will be excluded. Past antidepressant treatment will not be exclusionary, so long as patients are off antidepressant medication for 60 days prior to study entry. No individual will be advised to terminate ongoing treatment. * Certain short half-life medications, such as vitamins that contain unidentified ingredients, St. Johns Wort, S-adenosyl Methionine (SAM), clonidine, and some over-the-counter medications. * A minimum of 90 days off of treatment with long half life medications, such as neuroleptics, prior to study entry is required. Stimulant medication treatment for ADHD will not be exclusionary. * If adolescents have been in psychotherapy prior to their entry in the study, they will be allowed to continue with the treatment. However, psychotherapy cannot be initiated at the time of study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ACC Glx/Water | baseline and 10-weeks | The data reflects the ratio of Glutamine-Glutamate and water in the brain (ratio divided by 10000 for analysis purposes). Glutamate is a precursor to Glutamine, an amino acid which functions as an excitatory neurotransmitter in the human brain. |
| ACC GABA/Water | baseline and 10-weeks | The ratio of gamma-Aminobutyric acid (GABA) and water in the brain (ratio divided by 10000 for analysis purposes), that was observed in MR Spectroscopy. GABA, an amino acid produced by cells of the central nervous system, is an inhibitory neurotransmitter, prominent in the human brain. |
Countries
United States
Participant flow
Recruitment details
Recruitment began in December 2005, with enrollment from January 2006 to June 2013. Participants recruited for this imaging from another study, GCO 12-1321.
Participants by arm
| Arm | Count |
|---|---|
| Corn Oil The dosage will correspond to the titration schedule of the Omega-3 Fatty Acid experimental treatment.
Corn oil: The dosage will correspond to the titration schedule of the Omega-3 Fatty Acid experimental treatment. Placebo (corn oil) and omega-3FA capsules will be identical in color and smell. | 7 |
| Omega-3 Fatty Acids The initial dose will be 1.2g/d. This will be increased gradually by 0.6 per 2 weeks to a possible maximum daily dose of 3.6 g/d.
Omega 3 Fatty Acids: The study medication will consist of combined EPA/DHA with a ratio of 2:1. Dosage will be titrated based on clinical response and side effects. The initial dose will be 1.2g/d. This will be increased gradually by 0.6 per 2 weeks to a possible maximum daily dose of 3.6 g/d. Patients will have to remain on a dose for 2 weeks to provide the opportunity to assess clinical response at any one dose. The total duration of the intervention will be 10 weeks. | 9 |
| Total | 16 |
Baseline characteristics
| Characteristic | Corn Oil | Omega-3 Fatty Acids | Total |
|---|---|---|---|
| Age, Continuous | 16.62 years STANDARD_DEVIATION 3.087 | 16.51 years STANDARD_DEVIATION 2.756 | 16.56 years STANDARD_DEVIATION 2.805 |
| Sex: Female, Male Female | 2 Participants | 7 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 2 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 9 |
| other Total, other adverse events | 0 / 7 | 0 / 9 |
| serious Total, serious adverse events | 0 / 7 | 0 / 9 |
Outcome results
Primary
ACC GABA/Water
The ratio of gamma-Aminobutyric acid (GABA) and water in the brain (ratio divided by 10000 for analysis purposes), that was observed in MR Spectroscopy. GABA, an amino acid produced by cells of the central nervous system, is an inhibitory neurotransmitter, prominent in the human brain.
Time frame: baseline and 10-weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Corn Oil | ACC GABA/Water | ACC GABA/Water Baseline | 28.37 ratio * 10^-4 | Standard Deviation 4.097 |
| Corn Oil | ACC GABA/Water | ACC GABA/Water 10 weeks | 28.93 ratio * 10^-4 | Standard Deviation 5.2 |
| Omega-3 Fatty Acids | ACC GABA/Water | ACC GABA/Water Baseline | 25.28 ratio * 10^-4 | Standard Deviation 2.845 |
| Omega-3 Fatty Acids | ACC GABA/Water | ACC GABA/Water 10 weeks | 28.84 ratio * 10^-4 | Standard Deviation 3.512 |
Primary
ACC Glx/Water
The data reflects the ratio of Glutamine-Glutamate and water in the brain (ratio divided by 10000 for analysis purposes). Glutamate is a precursor to Glutamine, an amino acid which functions as an excitatory neurotransmitter in the human brain.
Time frame: baseline and 10-weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Corn Oil | ACC Glx/Water | ACC Glx/Water Baseline | 19.21 ratio * 10^-4 | Standard Deviation 5.173 |
| Corn Oil | ACC Glx/Water | ACC Glx/Water 10 weeks | 19.28 ratio * 10^-4 | Standard Deviation 3.339 |
| Omega-3 Fatty Acids | ACC Glx/Water | ACC Glx/Water Baseline | 18.99 ratio * 10^-4 | Standard Deviation 2.989 |
| Omega-3 Fatty Acids | ACC Glx/Water | ACC Glx/Water 10 weeks | 20.61 ratio * 10^-4 | Standard Deviation 5.201 |