Phospholipid Hypothesis of Depression: From Molecular Biology, Neuroimaging to Behaviour

With the dissatisfaction of monoamine-based pharmacotherapy and the high comorbidity of physical illness in depression, the serotonin hypothesis seems to fail in approaching the etiology of depression. Based upon the evidence from epidemiological data, case-control studies of PUFAs compositions, and antidepressant effects in clinical trials, phospholipid polyunsaturated fatty acids (PUFAs) is enlightening a promising path to discover the unsolved of depression.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Dietary supplement: EPA; Dietary supplement: DHA; Dietary supplement: Placebo

Detailed Description

There are several important questions to answer regarding phospholipid polyunsaturated fatty acids (PUFAs) hypothesis of depression. Firstly, although case-control studies revealed that depressive patients had lower levels of omega-3 PUFAs, the abnormal findings in individual PUFA of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) or arachidonic acid (AA) are not consistent. Secondly, the deficits in n-3 PUFAs are related to their metabolic enzymes. However, the association study of polymorphisms of PUFA-metabolism related genes in depression is limited. Thirdly, the active component of antidepressant effect in n-3 PUFAs is still in debate. Fourthly, the molecular mechanisms of n-3 PUFAs' antidepressant effects have yet to be elucidated in human brain functional neuroimaging or in cellular models.

This 3-year proposal is divided into 2 clinical studies. In study 1, the investigators aim to test the clinical and biological effects of n-3 PUFAs (EPA: 3.5 g/d and DHA: 1.75 g/d versus placebo: high oleic oil) for depressive symptoms in a 12-week, double-blind, placebo-controlled trial of patients with drug-free MDD. In study 2, the investigators will measure the biological and neuroimaging markers to investigate the biological mechanisms of EPA (3.5 g/d) versus DHA (1.75 g/d) in 12-week, double-blind, randomized-controlled trial with patients with drug-free major depression disorder (MDD).

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taichung, Taiwan, 403
    • China Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnostic and Statistical Manual (DSM)-IV criteria for major depressive disorder
• Age being age 18-65.
• Capacity and willingness to give written informed consent.
• Free from antidepressants, mood stabilizers, and antipsychotics for more than 4 weeks.

Exclusion Criteria:

• Any major medical illnesses.
• A recent or past history of any Axis-I diagnoses besides major depressive disorder, including psychotic disorders; cognitively impaired mental disorders; impulse control disorders; substance use disorder or substance abuse (last 6 months prior to the studies); primary anxiety disorders, including post-traumatic stress disorder and panic disorder; and bipolar disorders; or Axis-II diagnoses, i.e. borderline and antisocial personality disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EPA; 3.5 g/day in Studies 1 & 2	Dietary supplement: EPA; A daily treatment of 5 identical capsules of EPA (3.5 g/d) for Studies 1 & 2.; Other Names: Fish oil EPA
Active Comparator: DHA; 1.75 g/day in Studies 1 & 2	Dietary supplement: DHA; A daily treatment of 5 identical capsules of DHA (1.75 g/d) for Studies 1 & 2.; Other Names: Fish oil DHA
Placebo Comparator: Placebo capsules; oleic oil in Study 1	Dietary supplement: Placebo; A daily treatment of 5 identical capsules of placebo (high oleic oil) in single or divided administration for Study 1.; Other Names: oleic oil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes from Baseline Hamilton Depression Rating Scale (HDRS) at 12 weeks	Week 12
Remission rate	Week 12
Response rate	Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in Beck Depression Inventory (BDI)	Week 12
Changes in Neurotoxicity Rating Scale (NRS)	Week 12

Collaborators and Investigators

• Sponsor: National Science Council, Taiwan

Publications and helpful links

General Publications

• Su KP, Yang HT, Chang JP, Shih YH, Guu TW, Kumaran SS, Galecki P, Walczewska A, Pariante CM. Eicosapentaenoic and docosahexaenoic acids have different effects on peripheral phospholipase A2 gene expressions in acute depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jan 3;80(Pt C):227-233. doi: 10.1016/j.pnpbp.2017.06.020. Epub 2017 Jun 23.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: November 24, 2015
• First Submitted That Met QC Criteria: November 25, 2015
• First Posted (Estimate): November 26, 2015

Study Record Updates

• Last Update Posted (Estimate): November 26, 2015
• Last Update Submitted That Met QC Criteria: November 25, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: NSC101-2628-B-039-001-MY3