TY - JOUR
T1 - Deep phenotyping towards precision psychiatry of first-episode depression — the Brain Drugs-Depression cohort
AU - Jensen, Kristian H. j Reveles
AU - Dam, Vibeke H.
AU - Ganz, Melanie
AU - Fisher, Patrick MacDonald
AU - Ip, Cheng-Teng
AU - Sankar, Anjali
AU - Marstrand-Joergensen, Maja Rou
AU - Ozenne, Brice
AU - Osler, Merete
AU - Penninx, Brenda W. J. H.
AU - Pinborg, Lars H.
AU - Frokjaer, Vibe Gedsø
AU - Knudsen, Gitte Moos
AU - Jørgensen, Martin Balslev
N1 - Funding Information: The Lundbeck Foundation (R279–2018–1145) and the Research Fund of the Mental Health Services—Capital Region of Denmark granted economic support for the study. Publisher Copyright: © 2023, The Author(s).
PY - 2023/12/1
Y1 - 2023/12/1
N2 - Background: Major Depressive Disorder (MDD) is a heterogenous brain disorder, with potentially multiple psychosocial and biological disease mechanisms. This is also a plausible explanation for why patients do not respond equally well to treatment with first- or second-line antidepressants, i.e., one-third to one-half of patients do not remit in response to first- or second-line treatment. To map MDD heterogeneity and markers of treatment response to enable a precision medicine approach, we will acquire several possible predictive markers across several domains, e.g., psychosocial, biochemical, and neuroimaging. Methods: All patients are examined before receiving a standardised treatment package for adults aged 18–65 with first-episode depression in six public outpatient clinics in the Capital Region of Denmark. From this population, we will recruit a cohort of 800 patients for whom we will acquire clinical, cognitive, psychometric, and biological data. A subgroup (subcohort I, n = 600) will additionally provide neuroimaging data, i.e., Magnetic Resonance Imaging, and Electroencephalogram, and a subgroup of patients from subcohort I unmedicated at inclusion (subcohort II, n = 60) will also undergo a brain Positron Emission Tomography with the [11C]-UCB-J tracer binding to the presynaptic glycoprotein-SV2A. Subcohort allocation is based on eligibility and willingness to participate. The treatment package typically lasts six months. Depression severity is assessed with the Quick Inventory of Depressive Symptomatology (QIDS) at baseline, and 6, 12 and 18 months after treatment initiation. The primary outcome is remission (QIDS ≤ 5) and clinical improvement (≥ 50% reduction in QIDS) after 6 months. Secondary endpoints include remission at 12 and 18 months and %-change in QIDS, 10-item Symptom Checklist, 5-item WHO Well-Being Index, and modified Disability Scale from baseline through follow-up. We also assess psychotherapy and medication side-effects. We will use machine learning to determine a combination of characteristics that best predict treatment outcomes and statistical models to investigate the association between individual measures and clinical outcomes. We will assess associations between patient characteristics, treatment choices, and clinical outcomes using path analysis, enabling us to estimate the effect of treatment choices and timing on the clinical outcome. Discussion: The BrainDrugs-Depression study is a real-world deep-phenotyping clinical cohort study of first-episode MDD patients. Trial Registration: Registered at clinicaltrials.gov November 15th, 2022 (NCT05616559).
AB - Background: Major Depressive Disorder (MDD) is a heterogenous brain disorder, with potentially multiple psychosocial and biological disease mechanisms. This is also a plausible explanation for why patients do not respond equally well to treatment with first- or second-line antidepressants, i.e., one-third to one-half of patients do not remit in response to first- or second-line treatment. To map MDD heterogeneity and markers of treatment response to enable a precision medicine approach, we will acquire several possible predictive markers across several domains, e.g., psychosocial, biochemical, and neuroimaging. Methods: All patients are examined before receiving a standardised treatment package for adults aged 18–65 with first-episode depression in six public outpatient clinics in the Capital Region of Denmark. From this population, we will recruit a cohort of 800 patients for whom we will acquire clinical, cognitive, psychometric, and biological data. A subgroup (subcohort I, n = 600) will additionally provide neuroimaging data, i.e., Magnetic Resonance Imaging, and Electroencephalogram, and a subgroup of patients from subcohort I unmedicated at inclusion (subcohort II, n = 60) will also undergo a brain Positron Emission Tomography with the [11C]-UCB-J tracer binding to the presynaptic glycoprotein-SV2A. Subcohort allocation is based on eligibility and willingness to participate. The treatment package typically lasts six months. Depression severity is assessed with the Quick Inventory of Depressive Symptomatology (QIDS) at baseline, and 6, 12 and 18 months after treatment initiation. The primary outcome is remission (QIDS ≤ 5) and clinical improvement (≥ 50% reduction in QIDS) after 6 months. Secondary endpoints include remission at 12 and 18 months and %-change in QIDS, 10-item Symptom Checklist, 5-item WHO Well-Being Index, and modified Disability Scale from baseline through follow-up. We also assess psychotherapy and medication side-effects. We will use machine learning to determine a combination of characteristics that best predict treatment outcomes and statistical models to investigate the association between individual measures and clinical outcomes. We will assess associations between patient characteristics, treatment choices, and clinical outcomes using path analysis, enabling us to estimate the effect of treatment choices and timing on the clinical outcome. Discussion: The BrainDrugs-Depression study is a real-world deep-phenotyping clinical cohort study of first-episode MDD patients. Trial Registration: Registered at clinicaltrials.gov November 15th, 2022 (NCT05616559).
KW - Biomarker
KW - Cognition
KW - EEG
KW - MRI
KW - Major depressive disorder
KW - PET
KW - Precision medicine
KW - Psychotherapy
KW - SSRI
KW - Synaptic density
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85149657955&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/36894940
U2 - https://doi.org/10.1186/s12888-023-04618-x
DO - https://doi.org/10.1186/s12888-023-04618-x
M3 - Article
C2 - 36894940
SN - 1471-244X
VL - 23
JO - BMC psychiatry
JF - BMC psychiatry
IS - 1
M1 - 151
ER -