Preventing Suicide With Digital Phenotyping and Pharmacogenetics-Based Interventions (SMARTomicS-R)

Prevention of Suicidal Behavior Through Therapeutic Interventions Guided by Digital Phenotype and Pharmacogenetics: The SMARTomicS Study Protocol

The goal of this protocol for an observational retrospective multi-site cohort study is to develop a predictive algorithm for suicidal behavior integrating genetic risk markers, digital phenotypes, and exposomic data in people with a lifetime history of suicide attempt. Participants will be aged from 12 onwards (requiring parental consent if under 18) and only be excluded if they are unable to provide a genetic sample or do not consent to the study. The main question[s] it aims to answer is:

- Can genotyping/omics analysis of individuals with a history of suicidal behaviuor reveal potential genetic factors associated with suicide risk?

Secondary questions include:

1. Can behavioral factors associated with suicide risk be explored through data obtained from Google Takeout?
2. Is there an association between medication changes and suicidal behavior, as identified through the Unified Prescription Module and the Digital Health Record?
3. Do different suicidal phenotypes differ based on the collected variables?
4. Can the investigators construct an exposome using geolocated and time-stamped data from Google Takeout, combined anonymously with data from the National Statistics and Meteorology Institutes?

The investigators hypothesize that:

1. Individuals with a history of suicidal behavior will show significant genotypic differences compared to the general population (based on Spanish Genome Project data).
2. Suicidal phenotypes-especially between single and multiple attempters-will differ across collected variables, including genotype, omics, and exposome data.

participants will complete genetic assessments, digital phenotypes, clinical questionnaires and exposomic data

Study Overview

• Status: Recruiting
• Conditions: Suicide Attempt
• Intervention / Treatment: Genetic: No Intervention: Observational Cohort

Detailed Description

Participant recruitment will occur in person at outpatient mental health clinics, emergency departments, and short-stay hospital units. Mental health professionals (psychiatrists, psychologists, and nurses) will assess eligibility during clinical encounters, provide study information, and obtain informed consent. Data will be entered into the MeMind environment for data monitoring, and patient validation, ensuring eligibility criteria and noting any missing information.

Prior to recruitment, training sessions and standardized guidelines are provided to healthcare professionals to ensure adherence to the study protocol.

Data will be verified against INE statistics and hospital records to assess the representativeness and completeness of the data.

The primary outcome is suicidal behavior risk, assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS), the Brugha scale, documented suicidal events, healthcare utilization, behavioral patterns, digital phenotyping, and pharmacological treatment modifications. Secondary outcomes include evaluating the efficacy of pharmacological treatments and the cost-effectiveness of genetic markers in guiding antidepressant selection.

Baseline data collection includes:

1. Genetic sampling for genomic and metabolic profiling.
2. A sociodemographic and clinical assessment.
3. Consent-based extraction of digital behavioral data via Google Takeout.

To enrich participant health profiles, retrospective data from electronic health records (EHRs), prescription registries, and sociodemographic indicators from the Spanish National Institute of Statistics (INE) will be integrated. EHR data will include the Basic Minimum Set of Data (BMSD), a standardized clinical-administrative dataset. Blood samples will allow for DNA/RNA extraction and metabolomic analyses. Genetic findings will be compared with GWAS summary statistics from the Psychiatric Genomics Consortium (PGC) on suicide attempts and validated against control samples from the Banco Nacional de ADN and the Madrid Manic Group cohort.

Google Takeout data will be used to construct digital phenotypes. Patients will choose which data to share, supported by a research assistant. The selected data will be pseudonymized via a secure script before being stored on servers at Universidad Carlos III. Prescription histories from various autonomous regions will be analyzed to monitor treatment trajectories over time.

This study is part of a national consortium targeting a sample of at least 5,000 participants. Power calculations, informed by a recent meta-analysis (Li, 2023), indicate that this sample size would yield 93.5% power at a genome-wide significance level (p < 5×10-⁸), assuming a minor allele frequency of 0.2 and an odds ratio of 1.3, accounting for gender, diagnosis, and treatment response variability.

Statistical analyses will be conducted using SPSS software version 29.0. Logistic regression models will be used to examine factors associated with the primary outcomes, and a multivariate regression model will be developed to assess independent associations. All tests will be two-tailed, with statistical significance defined as p < 0.05 and 95% confidence intervals reported.

To identify digital behavioral biomarkers, advanced statistical and machine learning techniques will be applied. Individualized suicide-related profiles will be generated and compared using integrated data from genetic, metabolic, medical, and digital phenotyping sources. Additionally, a personalized and anonymized exposome will be constructed by combining geo-temporal data from Google Takeout with contextual information from public sociodemographic datasets (e.g., INE).

• Study Type: Observational
• Enrollment (Estimated): 5000

Contacts and Locations

• Study Contact: Name: Enrique Baca Garcia, Psychiatrist; Phone Number: +34 626932936; Email: ebaca@fjd.es

Study Locations

• Spain
  • Madrid
    • Madrid, Madrid, Spain, 28040
      • Recruiting
      • Instituto Fundación Jiménez Díaz
      • Contact: Enrique Baca-García Chief of the psychiatry department; Phone Number: +34 915 50 48 00; Email: ebaca@fjd.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Outpatients with a lifetime history of suicide attempt

Description

Inclusion Criteria:

1. At least one suicide attempt in their lifetime.
2. The attempt must have occurred when the participant was older than 12 years old.
3. Participants must be at least 18 years old or have parental consent if aged 12-17.

Exclusion Criteria:

• medical contraindication prevents blood sample collection
• unable to provide informed consent to participate in the study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; Our only group consists of people with a lifetime history of suicide attempt	Genetic: No Intervention: Observational Cohort; Genetic analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Suicide attempt	Aim to explore associated factors to suicide attempt	Baseline assessment; lifetime suicide attempts occurring from age 12 until enrollment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pharmacological treatment efficacy	Efficacy of different pharmacological treatments for suicide prevention	Assessed at baseline; retrospective evaluation of pharmacological treatments received prior to enrollment.
cost-effectiveness of genetic markers	retrospective cost-effectiveness analysis of genetic markers to guide antidepressant treatments based on treatments received prior to enrollment	Baseline assessment

Collaborators and Investigators

• Sponsor: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
• Collaborators: Hospital General Universitario Gregorio Marañon; Fundació d'investigació Sanitària de les Illes Balears; University of Alcala; Universidad Complutense de Madrid; Centre Hospitalier Universitaire de Nīmes; Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal; Hospital Universitario Ramon y Cajal; University of Valencia; Universitat Autonoma de Barcelona; Corporacion Parc Tauli; Universidad Autonoma de Madrid; Universidad de Zaragoza; University of Seville; Hospital Universitario 12 de Octubre; Hospital Universitario La Fe; The University of New South Wales; University of Santiago de Compostela; Hospitales Universitarios Virgen del Rocío; Universidad Rey Juan Carlos; Hospital Universitario Fundación Jiménez Díaz; Hospital San Carlos, Madrid; Hospital Universitario La Paz; University of Barcelona; University of Castilla-La Mancha; Universidad de Extremadura; Hospital Provincial de Castellon; Hospital Miguel Servet; Universitat Pompeu Fabra; Centro de Investigación Biomédica en Red de Salud Mental; Institut de Recerca Biomèdica de Lleida; Hospital Universitario Infanta Elena; Hospital Universitario Araba; Hospital del Mar Research Institute (IMIM); Hospital de Aviles; Centro de Investigación en Red de Enfermedades Raras (CIBERER); Universidad Católica del Maule; Universidad de Oviedo; Hospital Clínico Universitario de Valencia; Bioaraba; Hospital Universitario Rey Juan Carlos; Hospital Universitario de Móstoles; Instituto de Investigación Sanitaria Gregorio Marañón; Neuroscience Research Australia; Fundación General CSIC; Centro de Biología Molecular Severo Ochoa, Spain (CBMSO); Servicio Gallego de Salud; Universidad Carlos III de Madrid; Servicio de Salud del Principado de Asturias. Área Sanitaria III; Centro de Investigación Médica Aplicada (CIMA); Instituto de Investigación Sanitaria de Navarra (IdiSNA); Hospital Clinic de Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.; Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz-ISCIII; Instituto de Investigación Sanitaria del Principado de Asturias - ISPA; Euskal Herriko Universitatea - Universidad del País Vasco. Qualiker.

Publications and helpful links

General Publications

• DiBlasi E, Kang J, Docherty AR. Genetic contributions to suicidal thoughts and behaviors. Psychol Med. 2021 Oct;51(13):2148-2155. doi: 10.1017/S0033291721001720. Epub 2021 May 25.
• Rejek M, Misiak B. The Associations of Exposome Score with Various Domains of Psychopathology: A Network Analysis in a Non-Clinical Sample. Brain Sci. 2024 Feb 29;14(3):242. doi: 10.3390/brainsci14030242.
• Visoki E, Moore TM, Zhang X, Tran KT, Ly C, Gatavins MM, DiDomenico GE, Brogan L, Fein JA, Warrier V, Guloksuz S, Barzilay R. Classification of Suicide Attempt Risk Using Environmental and Lifestyle Factors in 3 Large Youth Cohorts. JAMA Psychiatry. 2024 Oct 1;81(10):1020-1029. doi: 10.1001/jamapsychiatry.2024.1887.
• Vineis P, Chadeau-Hyam M, Gmuender H, Gulliver J, Herceg Z, Kleinjans J, Kogevinas M, Kyrtopoulos S, Nieuwenhuijsen M, Phillips DH, Probst-Hensch N, Scalbert A, Vermeulen R, Wild CP; EXPOsOMICS Consortium. The exposome in practice: Design of the EXPOsOMICS project. Int J Hyg Environ Health. 2017 Mar;220(2 Pt A):142-151. doi: 10.1016/j.ijheh.2016.08.001. Epub 2016 Aug 19.
• Abascal-Peiro S, Penuelas-Calvo I, Alacreu-Crespo A, Saiz PA, De la Torre-Luque A, Ruiz-Veguilla M, Barrigon ML, Courtet P, Lopez-Castroman J, Baca-Garcia E, Porras-Segovia A. Digital Platform for the Prevention of Suicidal Behaviour and Non-Suicidal Self-Injuries in Adolescents: The SmartCrisis-Teen Study Protocol. Behav Sci (Basel). 2024 Aug 25;14(9):740. doi: 10.3390/bs14090740.
• Porras-Segovia A, Diaz-Olivan I, Barrigon ML, Moreno M, Artes-Rodriguez A, Perez-Rodriguez MM, Baca-Garcia E. Real-world feasibility and acceptability of real-time suicide risk monitoring via smartphones: A 6-month follow-up cohort. J Psychiatr Res. 2022 May;149:145-154. doi: 10.1016/j.jpsychires.2022.02.026. Epub 2022 Mar 3.
• Barrigon ML, Romero-Medrano L, Moreno-Munoz P, Porras-Segovia A, Lopez-Castroman J, Courtet P, Artes-Rodriguez A, Baca-Garcia E. One-Week Suicide Risk Prediction Using Real-Time Smartphone Monitoring: Prospective Cohort Study. J Med Internet Res. 2023 Sep 1;25:e43719. doi: 10.2196/43719.
• de la Torre-Luque A, Pemau A, Ayad-Ahmed W, Borges G, Fernandez-Sevillano J, Garrido-Torres N, Garrido-Sanchez L, Garriga M, Gonzalez-Ortega I, Gonzalez-Pinto A, Grande I, Guinovart M, Hernandez-Calle D, Jimenez-Trevino L, Lopez-Sola C, Mediavilla R, Perez-Aranda A, Ruiz-Veguilla M, Seijo-Zazo E, Toll A, Perez-Sola V, Ayuso-Mateos JL; SURVIVE Consortium. Risk of suicide attempt repetition after an index attempt: A systematic review and meta-analysis. Gen Hosp Psychiatry. 2023 Mar-Apr;81:51-56. doi: 10.1016/j.genhosppsych.2023.01.007. Epub 2023 Jan 23.
• Martinez-Ales G, Cruz Rodriguez JB, Lazaro P, Domingo-Relloso A, Barrigon ML, Angora R, Rodriguez-Vega B, Jimenez-Sola E, Sanchez-Castro P, Roman-Mazuecos E, Villoria L, Ortega AJ, Navio M, Stanley B, Rosenheck R, Baca-Garcia E, Bravo-Ortiz MF. Cost-effectiveness of a Contact Intervention and a Psychotherapeutic Program for Post-discharge Suicide Prevention. Can J Psychiatry. 2021 Aug;66(8):737-746. doi: 10.1177/0706743720980135. Epub 2020 Dec 15.

Helpful Links

• Global information about suicide, suicide risk, prevention, challenges and statistics
• Spanish National Statistics Institute, with statistic data divided by categories

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: February 18, 2026
• First Posted (Actual): February 19, 2026

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: genetic; suicide; suicide attempt; eHealth; suicidal ideation; phenotyping; digital medicine; exposome
• Additional Relevant MeSH Terms: Behavioral Symptoms; Self-Injurious Behavior; Behavior; Suicide; Suicidal Ideation; Suicide, Attempted
• Other Study ID Numbers: PIC301-24_FJD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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