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

National Science Council, Taiwan

Status: Completed

Conditions: Major Depressive Disorder

Treatments: Dietary Supplement: DHA; Dietary Supplement: EPA; Dietary Supplement: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02615405

NSC101-2628-B-039-001-MY3

Details and patient eligibility

About

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.

Full 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).

Enrollment: 240 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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240 participants in 3 patient groups, including a placebo group

EPA

Experimental group

Description:

3.5 g/day in Studies 1 & 2

Treatment:

Dietary Supplement: EPA

DHA

Active Comparator group

Description:

1.75 g/day in Studies 1 & 2

Treatment:

Dietary Supplement: DHA

Placebo capsules

Placebo Comparator group

Description:

oleic oil in Study 1

Treatment:

Dietary Supplement: Placebo