Youth-GEMS: Understanding genetic and environmental interactions in youth mental health

1. Approved 07/02/2024, Comité de Ética de la Investigación con Medicamentos (CEIm) Hospital General Universitario Gregorio Marañón / Ethics Committee in Research with Drugs Gregorio Marañón Hospital (C/ Dr. Esquerdo 46, Pabellón de Gobierno, Madrid, 28007, Spain; +34 (0)91 586 7007 - 91 426 9378; ceim.hgugm@salud.madrid.org), ref: 313/23

2. Approved 14/03/2024, Klinika za neurologiju i psihijatriju za decu i omladinu (Ethics Committee of the Clinic for Child and Adolescent Neurology and Psychiatry in Belgrade) (Dr Subotića starijeg 6, Belgrade, 11000, Serbia; +381 11 2658 355; ana.kesic.npk@gmail.com), ref: 193/3

3. Approved 29/04/2024, Etičko povjerenstvo Medicinskog fakulteta Sveučilišta u Splitu (Ethics Committee of the Faculty of Medicine, University of Split) (Šoltanska ul. 2A, Split, 21000, Croatia; +385 (0)21 557 929; uzz@mefst.hr), ref: 2181-198-03-04-24-0048

4. Approved 14/01/2025, University of Tartu Research Ethics Committee (Raekoja plats 9, Tartu, 51004, Estonia; +372 (0)737 6215; eetikakomitee@ut.ee), ref: 394/T-32

5. Approved 09/12/2024, Regional Medical Research Ethics Committee of the North Ostrobothnia Welfare Region (c/o OYS Tutkimuspalveluyksikkö N5, Research Service Unit N5 PO Box 10, OYS, 90029, Finland; +358 (0)50 448 4955; tutkimuspalvelut@pohde.fi), ref: OTE 11/2024

6. Approved 24/01/2025, Medisch-ethische toetsingscommissie (Medical Ethics Review Committee) (P. Debyelaan 25, Postbus 5800, Maastricht, 6202 AZ, Netherlands; +31 (0)43 387 6009; secretariaat.metc@mumc.nl), ref: METC 24-018

Quality of life, with general wellbeing, daily functioning, relationships with friends, relationships with family and coping as subdomains, measured with the MyLifeTracker outcome measure at baseline, 3, 6, 12, 18 and 24 months follow-up

Current secondary outcomes as of 04/02/2026:
Clinical dimensions:
1. Anxiety and depression measured with the RCADS at baseline, and 3, 6, 12, 18 and 24 months follow-up
2. Distress tolerance measured with the DTS-short at baseline, and 3, 6, 12, 18 and 24 months follow-up
3. Current mania measured with the Altman Self-rating Mania Scale (ASRM) and Rapid Mood Screener (RMS) at baseline, and 3, 6, 12, 18 and 24 months follow-up
4. Psychotic-like symptoms measured with the Psychosis Experiences Inventory (PEI) at baseline, and 3, 6, 12, 18 and 24 months follow-up
5. Dissociative symptoms measured with the Dissociative Experiences Scale (DES) at baseline, and 6, 12, and 24 months follow-up
6. Suicidality measured with the Columbia Suicide Severity Rating scaleat baseline, and 24 months follow-up
7. Non-suicidal self-harm measured at baseline, and 24 months follow-up
8. General psychopathology measured with the Strengths and Difficulties Questionnaire (SDQ) at baseline, and 3, 6, 12, 18 and 24 months follow-up
9. Eating disorders measured with the Eating Disorder Screen for Primary Care at baseline, 12, and 24 months follow-up
10. Obsessions and intrusive thoughts measured with the Children’s Obsessional Compulsive Inventory Revised (ChOCI-R) at baseline, and 3, 6, 12, 18 and 24 months follow-up
11. Stressful life events measured with an ad-hoc questionnaire at baseline, 12, and 24 months follow-up
12. Childhood Trauma measured with the Childhood Trauma Questionnaire - Short version, Juvenile Victimization Questionnaire (JVQ), and Childhood Experience of Care and Abuse (CECA) at baseline
13. Bullying and cyberbullying measured with an ad-hoc questionnaire at baseline.
14. PTSD symptoms measured with the UCLA PTSD Reaction Index for DSM-5 Brief form at baseline.
15. Family and social environment measured with an ad-hoc questionnaire at baseline and 12 and 24-month follow-up.
16. Parental bonding measured with the Relationship Structures (ECR-RS) questionnaire and peer bonding measured with the Community and Youth Collaborative Institute (CAYCI) at baseline and 12 and 24-month follow-up.
17. Alcohol use and abuse measured with the AUDIT at baseline, and 3, 6, 12, 18 and 24 months follow-up
18. Drug use and abuse measured with the DUDIT at baseline, and 3, 6, 12, 18 and 24 months follow-up
19. Loneliness emotion with the Loneliness 3 item scale at baseline, 12 and 24 months follow-up.
20. Emotions and affect with Positive and Negative Affect Schedule (PANAS) at baseline, 3, 6, 12, 18 and 24 months follow-up.
21. Clinical impression measured with the Clinical Global Impressions Scale (CGI) at baseline, and 3, 6, 12, 18 and 24 months follow-up
22. Social and ocuppational measured with the Social and Occupational Functioning Assessment Scale (SOFAS) at baseline, and 3, 6, 12, 18 and 24 months follow-up
23. Mental health symptoms measured with DSM-5 Dimensional Cross-Cutting Symptom Assessment (DSM5-CC) at baseline, and 6, 12, 18 and 24 months.
24. Premorbid Adjustment measured with the Premorbid Adjustment Scale (PAS) at baseline.
25. Pregnancy and early development measured with the APGAR measure and ad hoc questions at baseline
26. Obstetric complications measured with the Scale of Obstetric Complications by Lewis at baseline
27. Development milestones with ad hoc questions at baseline

Lifestyle and behavioural factors:
1. Internet and social media use measured with the Social Media Disorder Scale (SMDS-9) at baseline, and 3, 6, 12, 18 and 24 months follow-up
2. History of crime and violent behaviour measured with an ad hoc questionnaire at baseline, and 3, 6, 12, 18 and 24 months follow-up
3. Reward response measured with Behavioral Inhibition and Behavioral Activation System (BIS/BAS) Scales at baseline, and 3, 6, 12 and 24 months follow-up

Physical health:

1. General health measured with the EQ-5D-Y at baseline, and 3, 6, 12, 18 and 24 months follow up
2. Disability measured using 12-item Self-Report World Health Organization Disability Assessment Schedule (WHODAS) at baseline, and 3, 6, 12, 18 and 24 months follow-up
3. Sleep and circadian alterations measured with the REACH study at baseline, and 3, 6, 12, 18 and 24 months follow-up
4. Physical activity measured with the REACH study at baseline, and 3, 6, 12, 18 and 24 months follow-up

5. Menstrual cycle measured with the Menstrual Distress Questionnaire (MDQ) at baseline, and 3, 6, 12, 18 and 24 months follow-up

Psychological mechanisms, subjective experience and existential dimensions:

1. Coping mechanisms measured with Coping Orientation to Problems Experienced Inventory (Brief-COPE) at baseline, and 3, 6, 12, 18 and 24 months follow-up.
2. Resilience measured with the Brief Resilient Coping Scale (BRCS) at baseline, and 3, 6, 12, 18 and 24 months follow-up
3. Self-esteem measured with the Multidimensional Wellbeing in Youth Scale – self-confidence dimension at baseline, and 3, 6, 12, 18 and 24 months follow-up
4. Well-being measured with the EPOCH measure of adolescent well-being at baseline, and 3, 6, 12, 18 and 24 months follow up
5. Callous/unemotional traits measured with the Inventory of Callous-Unemotional Traits and Antisocial Behavior (INCA) for Young People at baseline, and 3, 6, 12, 18 and 24 months follow-up
6. Reward responsiveness measured with the BAS Reward Responsiveness & Frustrative Nonreward Responsiveness Subscale at baseline, and 3, 6, 12, 18 and 24 months follow-up
7. Irritability measured with the Affective Reactivity Index (ARI) at baseline, and 3, 6, 12, 18 and 24 months follow-up

8. Reflective functioning measured with the Reflective Functioning Questionnaire (RFQ) at baseline, and 3, 6, 12, 18 and 24 months follow-up.

Neurocognitive functioning
1. Estimated IQ, assessed using the Wechsler Intelligence Scales (WAIS and WISC) at baseline.
2. Sustained attention, cognitive flexibility, working memory, visual memory, sensorimotor ability, and motor speed, assessed using an ad hoc neuropsychological battery at baseline.


Previous secondary outcomes:
Clinical dimensions:
1. Anxiety and depression measured with the RCADS at baseline, and 3, 6, 12, 18 and 24 months follow-up
2. Distress tolerance measured with the DTS-short at baseline, and 3, 6, 12, 18 and 24 months follow-up
3. Current mania measured with the Altman Self-rating Mania Scale at baseline, and 3, 6, 12, 18 and 24 months follow-up
4. Psychotic-like symptoms measured with the Prodromal Questionnaire (PQ-16) and the PEI at baseline, and 3, 6, 12, 18 and 24 months follow-up
5. Dissociative symptoms measured with the DES-B at baseline, and 3, 6, 12, 18 and 24 months follow-up
6. Suicidality measured with the Columbia Suicide Severity Rating scaleat baseline, and 3, 6, 12, 18 and 24 months follow-up
7. Non-suicidal self-harm measured at baseline, and 3, 6, 12, 18 and 24 months follow-up
8. General psychopathology measured with the Strenghts and Difficulties Questionnaire (SDQ) at baseline, and 3, 6, 12, 18 and 24 months follow-up
9. Eating disorders measured with the Eating Disorder Screen for Primary Care at baseline, and 3, 6, 12, 18 and 24 months follow-up
10. Obsessions and intrusive thoughts measured with the Obsessional Compulsive Inventory - Child self report at baseline, and 3, 6, 12, 18 and 24 months follow-up
11. Childhood Trauma measured with the Childhood Trauma Questionnaire - brief at baseline
12. Stressful life events measured with an ad-hoc questionnaire at baseline, and 3, 6, 12, 18 and 24 months follow-up
1. Bullying and cyberbullying measured with an ad-hoc questionnaire at baseline and 3, 6, 9 and 12 months follow-up
2. PTSD symptoms measured with the UCLA PTSD Reaction Index for DSM-5 Brief form at baseline and 12 months follow-up
3. Family and social environment measured with an ad-hoc questionnaire at baseline
4. Parental bonding measured with the Relationship Structures (ECR-RS) questionnaire and peer bonding measured with the Attachment Questionnaire for Children (AQC) at baseline and 12 and 24-month follow-up.
5. Alcohol use and abuse measured with the AUDIT at baseline, and 3, 6, 12, 18 and 24 months follow-up
6. Drug use and abuse measured with the DUDIT at baseline, and 3, 6, 12, 18 and 24 months follow-up

Lifestyle and behavioural factors:
1. Internet and social media use measured with the Social Media Disorder Scale at baseline, and 3, 6, 12, 18 and 24 months follow-up
2. Gaming disorder measured with the Nine-Item Internet Gaming Disorder Scale at baseline, and 3, 6, 12, 18 and 24 months follow-up
3. History of crime and violent behaviour measured with an ad hoc questionnaire at baseline, and 3, 6, 12, 18 and 24 months follow-up

Physical health:
1. General health measured with the EQ-5D-Y at baseline, and 3, 6, 12, 18 and 24 months follow up
2. Disability measured using 12-item Self-Report World Health Organization Disability Assessment Schedule (WHODAS) at baseline, and 3, 6, 12, 18 and 24 months follow-up
3. Sleep and circadian alterations measured with the PROMIS Sleep Disturbance and Sleep-Related Impairment in Adolescents at baseline, and 3, 6, 12, 18 and 24 months follow-up

Psychological mechanisms, subjective experience and existential dimensions:
1. Coping mechanisms measured with the Brief COPE at baseline, and 3, 6, 12, 18 and 24 months follow-up
2. Resilience measured with the Brief Resilient Coping Scale at baseline, and 3, 6, 12, 18 and 24 months follow-up
3. Self-esteem measured with the Multidimensional Wellbeing in Youth Scale – self-confidence dimension at baseline, and 3, 6, 12, 18 and 24 months follow-up
4. Well-being measured with the EPOCH measure of adolescent well-being at baseline, and 3, 6, 12, 18 and 24 months follow up
5. Callous/unemotional traits measured with the INventory of Callous-Unemotional Traits and Antisocial Behavior (INCA) for Young People at baseline, and 3, 6, 12, 18 and 24 months follow-up
6. Reward responsiveness measured with the BAS Reward Responsiveness & Frustrative Nonreward Responsiveness Subscale at baseline, and 3, 6, 12, 18 and 24 months follow-up
7. Irritability measured with the Affective Reactivity Index at baseline, and 3, 6, 12, 18 and 24 months follow-up