A randomised, controlled feasibility trial of dairy products for depression symptoms in adolescent girls

INTERVENTION: Arm 1 ‐ Participants allocated to the intervention yoghurt arm will consume one 90 g tub of yoghurt orally once daily for eight weeks (56 days). The yoghurt contains standard yoghurt starter cultures with added Bifidobacterium animalis subsp. lactis BB‐12 and provides approximately 1 × 10^9 colony‐forming units of BB‐12 per daily serve. Study products will be supplied by Bega Dairy & Drinks and dispensed to participants and their parent/guardian by authorised ZenZone study staff at approximately Weeks 0, 3, and 6. Participants will consume the product at home and may choose between the available flavours. Participants will record each day whether they consumed all, some, or none of their allocated study product using the WeGuide application. The research dietitian will review adherence data regularly and provide supportive follow‐up where missed or partial serves indicate possible adherence difficulties. CONDITION: Depression; ; Depression Mental Health ‐ Depression PRIMARY OUTCOME: Enrolment feasibility.[Proportion of screened participants who meet eligibility criteria and are successfully enrolled, calculated from the screening and recruitment log. Cumulative data assessed at the conclusion of the recruitment period.] Participant retention through completion of the eight‐week intervention and final assessment.[Proportion of enrolled participants who complete the full eight‐week intervention and Week 8 final assessment, determined from participant status and study completion records. Reasons for non‐completion, including withdrawal, intervention discontinuation, and loss to follow‐up, will be described as attrition categories. Week 8 after intervention commencement.] Recruitment feasibility.[Number of participants enrolled within the planned recruitment period, obtained from the screening and recruitment log. Cumulative data assessed at the conclusion of the recruitment period.] SECONDARY OUTCOME: Change in anxiety symptoms.[Anxiety subscale score of the Depression Anxiety Stress Scales – Youth Version (DASS‐Y). Baseline, Week 4, and Week 8 after intervention commencement.] Change in Bifidobacterium animalis species.[Relative abundance of derived from shotgun metagenomic sequencing of stool samples. Baseline, Week 4, and Week 8 after intervention commencement.] Change in depression symptoms measured by the DASS‐Y.[Depression subscale score of the Depression Anxiety Stress Scales – Youth Version (DASS‐Y). Baseline, Week 4, and Week 8 after intervention commencement.] Change in depressive symptom severity.[Total score on the Patient Health Questionnaire – Adolescent Version (PHQ‐A). Baseline, Week 4, and Week 8 after intervention commencement.] Change in emotional processing.[Performance on the Emotional Bias Task of CANTAB. Baseline and Week 8 after intervention commencement.] Change in executive function.[Performance on the Spatial Working Memory task of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Baseline and Week 8 after intervention commencement.] Change in faecal microbial alpha diversity.[Alpha diversity derived from shotgun metagenomic sequencing of stool samples. Baseline, Week 4, and Week 8 after intervention commencement.] Change in faecal microbial beta diversity.[Beta diversity derived from shotgun metagenomic sequencing of stool samples. Baseline, Week 4, and Week 8 after intervention commencement.] Change in gastrointestinal symptom severity.[Total score of the Gastrointestinal Symptom Rating Scale (GSRS). Baseline, Week 4, and Week 8 after intervention commencement.] Change in health‐related quality of life.[Health‐state profile measured using the EuroQol Five‐Dimension Youth Three‐Level questionnaire (EQ‐5D‐Y‐3L). Baseline, Week 4, and Week 8 after intervention commencement.] Change in hippocampal structure in participants completing the optional MRI sub‐study.[Hippocampal structure derived from magnetic resonance imaging. Baseline and Week 8 after intervention commencement.] Change in left hippocampal neurometabolites in participants completing the optional MRI sub‐study.[Left hippocampal single‐voxel proton magnetic resonance spectroscopy. Baseline and Week 8 after intervention commencement.] Change in overall emotional and behavioural difficulties.[Total difficulties score on the adolescent self‐report Strengths and Difficulties Questionnaire (SDQ). Baseline, Week 4, and Week 8 after intervention commencement.] Change in participant healthcare service use.[Total healthcare service use reported by the parent/guardian using the study‐specific Health Service Use questionnaire. Baseline and Week 8 after intervention commencement.] Change in resting‐state functional connectivity in participants completing the optional MRI sub‐study.[Resting‐state functional magnetic resonance imaging. Baseline and Week 8 after intervention commencement.] Change in salivary cortisol.[Laboratory measurement of cortisol concentration in saliva samples. Baseline, Week 4, and Week 8 after intervention commencement.] Change in salivary melatonin.[Laboratory measurement of melatonin concentration in saliva samples. Baseline, Week 4, and Week 8 after intervention commencement.] Change in sleep quality.[Global score on the Pittsburgh Sleep Quality Inde X(PSQI). Baseline, Week 4, and Week 8 after intervention commencement.] Change in stool form.[Stool type classified using the Bristol Stool Chart. Baseline, Week 4, and Week 8 after intervention commencement.] Change in stress symptoms.[Stress subscale score of the Depression Anxiety Stress Scales – Youth Version (DASS‐Y). Baseline, Week 4, and Week 8 after intervention commencement.] Change in sustained attention.[Performance on the Rapid Visual Information Processing task of CANTAB. Baseline and Week 8 after intervention commencement.] Change in visual recognition memory.[Performance on the Pattern Recognition Memory task of CANTAB. Baseline and Week 8 after intervention commencement.] Parent/guardian‐reported acceptability of the allocated study product and trial procedures.[Mean score on the Acceptability of Intervention Measure (AIM), completed independently by the participant’s parent/guardian. Week 2 after intervention commencement.] Parent/guardian‐reported appropriateness of the allocated study product and trial procedures.[Mean score on the Intervention Appropriateness Measure (IAM), completed independently by the participant’s parent/guardian. Week 2 after intervention commencement.] Parent/guardian‐reported feasibility of the allocated study product and trial procedures.[Mean score on the Feasibility of Intervention Measure (FIM), completed independently by the participant’s parent/guardian. Week 2 after intervention commencement.] Parent/guardian‐reported global impression of change in the participant.[Single‐item Carer Global Impression of Change (CGI‐C). Weeks 2, 4, 6, and 8 after intervention commencement.] Participant experience of the clinical trial.[Qualitative thematic analysis of transcripts from a semi‐structured interview. Week 8 after intervention commencement.] Participant‐reported acceptability of the allocated study product and trial procedures.[Assessment method ; Mean score on the Acceptability of Intervention Measure (AIM), completed by the adolescent participant. Week 2 after intervention commencement.] Participant‐reported appropriateness of the allocated study product and trial procedures.[Mean score on the Intervention Appropriateness Measure (IAM), completed by the adolescent participant. Week 2 after intervention commencement.] Participant‐reported feasibility of the allocated study product and trial procedures.[Mean score on the Feasibility of Intervention Measure (FIM), completed by the adolescent participant. Week 2 after intervention commencement.] Participant‐reported global impression of change.[Single‐item Patient Global Impression of Change (PGI‐C). Weeks 2, 4, 6, and 8 after intervention commencement.] Primary feasibility outcome: adherence to daily study product consumption.[Proportion of allocated daily study product serves consumed, based on daily participant reports in the WeGuide application. Assessed daily from Intervention Day 1 through Day 56 and summarised at Week 8.] Primary feasibility outcome: completion of required study data collection.[Proportion of required study data collection activities completed determined from WeGuide, REDCap, and sample inventory logs. Assessed at each scheduled study assessment from baseline through Week 8 and summarised at Week 8.] Primary feasibility outcome: protocol compliance.[Frequency of protocol deviations recorded in the protocol deviation and breach logs. Assessed throughout study participation and cumulatively at completion of the final participant follow‐up.] Primary feasibility outcome: study product safety and tolerability.[Occurrence of adverse events judged possibly, probably, or definitely related to the study product, determined from participant health check‐ins, study contacts, clinical review, and safety records. Assessed throughout the eight‐week intervention and at the Week 10 post‐intervention follow‐up.] INCLUSION CRITERIA: Participants must meet all of the following criteria to be eligible for enrolment into the ZenZone trial: • Assigned female at birth. • Aged 14 years at the time of consent. • Experiencing elevated depressive symptoms defined as a PHQ‐A score equal to or greater than 10 at the time of consent. • Willing and able to give informed consent prior to study enrolment. • Able to comply with all study procedures, including attending the study site for in‐person study appointments or dairy collection (where required). • A parent or legal guardian willing and able to provide informed consent for the participant’s involvement and to comply with study procedures, including attendance at in‐person study visits where required. • Access to a compatible device (smartphone, tablet, or computer) capable of downloading and using the WeGuide application, with reliable internet access.