Comparing trajectories of cognitive functioning in treatment-resistant and non-resistant depression: a multicentre linear mixed-effects analysis
Abstract
BACKGROUND: Impaired cognitive functioning is a severe symptom in major depressive disorder (MDD). Recent evidence suggests it may be a central characteristic in its treatment resistant form (TRD), potentially constituting a clinical marker for treatment resistance and a target amenable to intervention. To date, cognitive functioning in TRD remains poorly understood and longitudinal investigations are scarce. METHODS: This observational prospective cohort study, including 320 patients diagnosed with MDD from the multicentre PROMPT study, examined differences in cognitive functioning between 118 TRD and 202 non-TRD patients over a period of twelve weeks in a real-world setting, using linear mixed modelling. Patients that failed to respond to at least two prior antidepressants trials at baseline were classified as TRD. RESULTS: TRD patients showed significantly poorer baseline performances than non-TRD patients in attention/processing speed (β = -0.45; 95%CI[-0.70, -0.19]; FDR-p = 0.003) and verbal memory (β = -0.45; 95%CI[-0.72, -0.18]; FDR-p = 0.003). Significant time × group interactions were observed in motor speed and verbal fluency tasks. Post-hoc-analyses revealed stagnation in TRD patients and significant improvement in non-TRD patients. Across all other tasks improvement was observed in both groups, and random effects showed large heterogeneity between patients, indicating notable individual differences in cognitive performances. CONCLUSIONS: The results suggest distinct recovery patters between non-TRD and TRD patients, and diminished functioning in TRD patients at the domain level. However, intact and diminished performances likely occur in both groups, warranting further investigation of cognitive heterogeneity. These short-term findings highlight the need for more comprehensive longitudinal research on cognition in TRD.
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BibTeX
@article{wahner2026comparing,
title = {{Comparing trajectories of cognitive functioning in treatment-resistant and non-resistant depression: a multicentre linear mixed-effects analysis}},
author = {Viktor T.H. Wahner and Toni Lange and Inga Stonner and Pasquale Paribello and Martina Contu and Marco Pinna and Dobrochna Kopeć and Ewa Ferensztajn-Rochowiak and Filip Rybakowski and Mara Dierssen and Massimo Gennarelli and Mirko Manchia and Alessandra Minelli and Marie-Claude Potier and Claudia Pisanu and Ferran Sanz and Alessio Squassina and Júlia Perera-Bel and Silke Jörgens and Bernhard Baune},
journal = {Journal of Affective Disorders},
year = {2026},
month = oct,
doi = {10.1016/j.jad.2026.122380},
url = {https://hal.science/hal-05844233v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Comparing trajectories of cognitive functioning in treatment-resistant and non-resistant depression: a multicentre linear mixed-effects analysis
AU - Viktor T.H. Wahner
AU - Toni Lange
AU - Inga Stonner
AU - Pasquale Paribello
AU - Martina Contu
AU - Marco Pinna
AU - Dobrochna Kopeć
AU - Ewa Ferensztajn-Rochowiak
AU - Filip Rybakowski
AU - Mara Dierssen
AU - Massimo Gennarelli
AU - Mirko Manchia
AU - Alessandra Minelli
AU - Marie-Claude Potier
AU - Claudia Pisanu
AU - Ferran Sanz
AU - Alessio Squassina
AU - Júlia Perera-Bel
AU - Silke Jörgens
AU - Bernhard Baune
PY - 2026
DA - 2026/10/29
JO - Journal of Affective Disorders
DO - 10.1016/j.jad.2026.122380
UR - https://hal.science/hal-05844233v1
AB - BACKGROUND: Impaired cognitive functioning is a severe symptom in major depressive disorder (MDD). Recent evidence suggests it may be a central characteristic in its treatment resistant form (TRD), potentially constituting a clinical marker for treatment resistance and a target amenable to intervention. To date, cognitive functioning in TRD remains poorly understood and longitudinal investigations are scarce. METHODS: This observational prospective cohort study, including 320 patients diagnosed with MDD from the multicentre PROMPT study, examined differences in cognitive functioning between 118 TRD and 202 non-TRD patients over a period of twelve weeks in a real-world setting, using linear mixed modelling. Patients that failed to respond to at least two prior antidepressants trials at baseline were classified as TRD. RESULTS: TRD patients showed significantly poorer baseline performances than non-TRD patients in attention/processing speed (β = -0.45; 95%CI[-0.70, -0.19]; FDR-p = 0.003) and verbal memory (β = -0.45; 95%CI[-0.72, -0.18]; FDR-p = 0.003). Significant time × group interactions were observed in motor speed and verbal fluency tasks. Post-hoc-analyses revealed stagnation in TRD patients and significant improvement in non-TRD patients. Across all other tasks improvement was observed in both groups, and random effects showed large heterogeneity between patients, indicating notable individual differences in cognitive performances. CONCLUSIONS: The results suggest distinct recovery patters between non-TRD and TRD patients, and diminished functioning in TRD patients at the domain level. However, intact and diminished performances likely occur in both groups, warranting further investigation of cognitive heterogeneity. These short-term findings highlight the need for more comprehensive longitudinal research on cognition in TRD.
SN - 0165-0327
SN - 1573-2517
ER -