Comparing trajectories of cognitive functioning in treatment-resistant and non-resistant depression: a multicentre linear mixed-effects analysis
Year: 2026
Type: article
Study design: Observational Study
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.
Source: Journal of Affective Disorders
Authors: Viktor T.H. Wahner, Toni Lange, Inga Stonner, Pasquale Paribello, Martina Contu, Marco Pinna, Dobrochna Kopeć, Ewa Ferensztajn-Rochowiak, Filip Rybakowski, Mara Dierssen, Massimo Gennarelli, Mirko Manchia, Alessandra Minelli, Marie-Claude Potier, Claudia Pisanu, Ferran Sanz, Alessio Squassina, Júlia Perera-Bel, Silke Jörgens, Bernhard T. Baune
Institutions: University of Münster, Otto-von-Guericke-Universität Magdeburg, University of Cagliari, Poznan University of Medical Sciences, Barcelona Institute of Science and Technology, Centre for Genomic Regulation, Centro San Giovanni di Dio Fatebenefratelli, University of Brescia, Dalhousie University, Centre National de la Recherche Scientifique, Inserm, Sorbonne Université, Pitié-Salpêtrière Hospital, Institut du Cerveau, Universitat Pompeu Fabra, Hospital del Mar Research Institute, Hamm-Lippstadt University of Applied Sciences, The University of Melbourne, Florey Institute of Neuroscience and Mental Health
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,790
Awards: Toward PrecisiOn Medicine for the Prediction of Treatment response in major depressive disorder through stratification of combined clinical and -omics signatures, G3539968147, Medycyna spersonalizowana w depresji – przewidywanie odpowiedzi na leczenie w oparciu o biomarkery kliniczne i molekularne, G7726834290
OpenAlex ID: W7203557689