An Investigation of the Relationship Between Omega-3 Fatty Acid Nutrition and Mental Health in Children and Adolescents

An Investigation of the Relationship Between Omega-3 Fatty Acid Nutrition and Mental Health in Children and Adolescents: A Case-control Study

This is an observational case-control add-on study to an investigator-initiated clinical trial (IICT) (ClinicalTrials.gov Identifier: NCT03167307): Omega-3 fatty acids as firstline treatment in pediatric depression. A 36-week multi-centre, double-blind, placebo-controlled randomized superiority study.

This project will recruit a healthy control group matched for age and sex to a sub-group of patients with diagnosed pediatric major depressive disorder (pMDD) enrolled in the IICT. The aim is to investigate the relationship of n-3 FA intake and status with mental health in children and adolescents with and without diagnosed pMDD, and explore potential biochemical mechanisms underlying this relationship by measuring biomarkers related to n-3 FA metabolism, mental health and cognitive function.

Study Overview

• Status: Completed
• Conditions: Depression; Major Depressive Disorder; Child Mental Disorder

Detailed Description

According to a recent school survey, one out of ten adolescents in Zurich have moderate to marked depressive symptoms. Early onset of paediatric major depressive disorder (pMDD) is a risk factor for chronic and recurrent forms of depression in adulthood (MDD). MDD is associated with difficulties in relationships, impaired school and work performance, and an increased risk of substance abuse. Furthermore, MDD is a major contributor to the burden of suicide and poor long-term health late in life. The emerging potential of n-3 polyunsaturated fatty acids (n-3 PUFAs), also known in short as omega-3 fatty acids (n-3 FAs), for the treatment of MDD is being investigated in several studies. Previous observational studies suggest a link between the consumption of n-3PUFA-rich food and the level of depressive symptoms. However, studies that investigated the potential beneficial effects of n-3 PUFA supplementation for the treatment of MDD compared with placebo showed inconsistent findings.

Primary objectives of this project are:

1. To determine the relationship of n-3 FA intake and status with mental health in children and adolescents with and without diagnosed pMDD.
2. To explore biochemical mechanisms underlying this relationship by measuring biomarkers related to n-3 FA metabolism, mental health, cognitive function, and potential pathways linking n-3 FA intake/status and brain health (e.g. immune system, gut microbiome-brain-axis).

Participants meeting the following criteria are eligible for the study:

Inclusion criteria:

• Participants of female and male sex
• Children aged 8 to ≤ 13 years or teenagers 13 to < 18 years at time of study entry
• Written informed assent of the subject and written informed consent from the subject's parents/legal representatives
• No present primary diagnosed psychiatric disorder according to the M.I.N.I. KID Test

Exclusion criteria:

• More than 4 weeks of regular n-3 FA supplementation
• Women who are self-reported pregnant or breast feeding
• Pre-existing neurological or medical conditions likely to be a risk factor for developing depressive symptoms

In a first step participants will be screened for in- and exclusion criteria. If participants can be included into the study we will

• Measure participant's mental health with behavioural and cognitive assessments
• Collect biological samples from participants (blood, urine, saliva, hair, and stool)

This study aims to recruit a total of 200 participants: 100 cases (from IICT) and 100 controls (recruited for this study).

There will be a total recruiting period of 18 months.

• Study Type: Observational
• Enrollment (Actual): 190

Contacts and Locations

Study Locations

• Switzerland
  • Zürich, Switzerland, 8092
    • ETH Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 17 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children/adolescents in German speaking Switzerland

Description

For cases: participants enrolled in the IICT and therefore meeting the criterie for participation in the IICT will be selected.

For controls, participants fulfilling all of the following inlclusion criterie are eligible for the study

Inclusion Criteria:

• Participants of female and male sex
• Children aged 8 to ≤ 13 years or teenagers 13 to < 18 years at time of study entry
• Written informed assent of the subject (appendix informed consent forms) and written in formed consent form from the subjects' parents/legal representatives
• No present primary diagnosed psychiatric disorder according to the M.I.N.I. KID Test.
• No use of chronic medication
• Able to communicate in German; degree of understanding sufficient to comply with trial procedure

Exclusion Criteria:

• More than 4 weeks of regular n-3 FA supplementation (>2 daily capsules standard strength providing > 600 mg combined EPA/DHA) within the last 6 months.
• Women who are self-reported pregnant or breast feeding.
• Self-reported pre-existing neurological (such as e.g. brain tumour, temporal lobe epilepsy, HIV encephalopathy) or medical conditions (ICD-10 F06-F07) likely to be a risk factor for developing depressive symptoms
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cases; Patients with pMDD, enrolled in the Investigator-initiated clinical trial IICT (ClinicalTrials.gov Identifier: NCT03167307)
Controls; Controls matched to cases according to age, sex and school education

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
n-3 fatty acid intake	Estimation of dietary omega-3 intake with a validated self-reported Omega-3 Food Questionnaire	6 months
n-3 fatty acid status	Measurement of relative amount of n-3 fatty acids	1 day
Pediatric depressive symptoms	Quantification of depressive symptoms with "Children's Depression Rating Scale - Revised" (CDRS-R) total score; Scale from 17 to >72; values >40 rated as moderate depression	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatty acid metabolism	Measurement of lipid mediators	1 day
Biomarkers related to brain health	Measurement of brain-derived neurotrophic factor (BDNF), kynurenine pathway metabolites, and monoamine neurotransmitters	1 day
Biomarkers related to systemic inflammation	Measurement of C-reactive Protein (CRP), alpha-1-acid glycoprotein, and cytokines	1 day
Biomarkers related to gut microbiota	Measurement of; gut microbiome composition with 16S rRNA sequencing; Faecal calprotectin; Intestinal fatty acid binding protein	1 day
Biomarkers related to nutritional status	Measurement of iron and iodine status	1 day

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Verbal learning and memory test (VLMT)	Differences in scores between cases and controls	1 day
Behavior Rating Inventory of Executive Function (BRIEF)	Differences in the overall score between cases and controls	1 day
Digit span measured by the Wechsler Intelligence Scale for children (WISC-IV)	Differences in scores between cases and controls	1 day
Emotion recognition measured with the Amsterdam Neuropsychological Task (ANT) program	Differences in scores between cases and controls	1 day
Attentional flexibility measured with the shifting attentional set of the Amsterdam Neuropsychological Task (ANT) program	Differences in reaction times between cases and controls	1 day
Regensburg Word Fluency Test (RWT)	Differences in scores between cases and controls	1 day
Reynolds Intellectual Assessment Scales (RIAS)	Differences in scores between cases and controls	1 day
Suicidal ideation Questionnaire (SIQ)	Differences in scores between cases and controls	1 month
Scale of Impulsivity and Emotion Dysregulation (IES-27)	Differences in scores between cases and controls	1 month
Childhood Trauma Questionnaire (CTQ)	Differences in scores between cases and controls	1 day
Strenght and Difficulty Questionnaire (SDQ)	Differences in scores between cases and controls	1 day
Perceived Stress Scale (PSS-10)	Differences in scores between cases and controls	1 month
Children's Depression Inventory (DIKJ)	Differences in scores between cases and controls	1 month
Connor Davidson Resilience Scale (CDRS)	Differences in scores between cases and controls	1 month
Beck Anxiety Inventory (BAI)	Differences in scores between cases and controls	1 month

Collaborators and Investigators

• Sponsor: Swiss Federal Institute of Technology
• Collaborators: Psychiatric University Hospital, Zurich
• Investigators: Study Chair: Gregor Berger, Dr. med., Psychiatrische Universitätsklinik Zürich; Principal Investigator: Jeannine Baumgartner, Dr., Swiss Federal Institute of Technology; Principal Investigator: Isabelle Herter-Aeberli, Dr., Swiss Federal Institute of Technology; Principal Investigator: Michael B Zimmermann, Dr. med., Swiss Federal Institute of Technology

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 16, 2019
• Primary Completion (ACTUAL): December 22, 2020
• Study Completion (ACTUAL): December 22, 2020

Study Registration Dates

• First Submitted: April 18, 2019
• First Submitted That Met QC Criteria: November 6, 2019
• First Posted (ACTUAL): November 12, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 11, 2022
• Last Update Submitted That Met QC Criteria: January 7, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: n-3 fatty acids; pediatric Major Depressive Disorder
• Additional Relevant MeSH Terms: Behavioral Symptoms; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Mental Disorders; Depressive Disorder, Major; Neurodevelopmental Disorders
• Other Study ID Numbers: n-3 case-control study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: A BioBank will be established. Access to the Biobank can be requested upon completion of the IICT and the add-on study contacting the principal investigator Dr. Jeannine Baumgartner
• IPD Sharing Time Frame: upon study completion of the IICT and the add-on study.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No