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Cognitive Trajectories in the Nine Months following Recent-Onset Major Depressive Disorder

Stainton, A.; Gao, C. X.; Thomas, G. D.; Hester, R.; Bryce, S.; Chisholm, K.; Griffiths, S. L.; Kambeitz-Ilankovic, L.; Wenzel, J.; Bonivento, C.; Brambilla, P.; Iqbal, M.; Lichtenstein, T. K.; Rosen, M.; Antonucci, L. A.; Maggioni, E.; Kambeitz, J.; Borgwardt, S.; Reicher-Rössler, A.; Andreou, C.; Schmidt, A.; Schultze-Lutter, F.; Meisenzahl, E.; Ruhrmann, S.; Salokangas, R. K. R.; Pantelis, C.; Lencer, R.; Bienek, O.; Romer, G.; Dannlowski, U.; Bertolino, A.; Upthegrove, R.; Dwyer, D. B.; Koutsouleris, N.; Wood, S. J.; Allott, K.

2025-05-09 psychiatry and clinical psychology
10.1101/2025.05.08.25327188 medRxiv
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BACKGROUNDSpecific cognitive impairments are common in major depressive disorder, impacting functioning and quality of life. However, the longitudinal course of cognitive functioning in depression is unclear. AIMSThis study aimed to determine the longitudinal course of cognitive functioning following a recent onset of depression, as compared to healthy controls. METHODSHealthy controls and individuals experiencing a recent onset of depression (within two years) were recruited across ten European sites, completing the baseline and nine-month follow-up clinical, demographic, and cognitive assessment for the "PRONIA" study. RESULTSThe sample comprised 421 participants (depression, N=152; healthy controls, N=269) aged 15-40 years (M = 25.4, SD = 6.1; 55% female). Linear mixed effects models demonstrated baseline cognitive deficits in the depression group across most domains, except for visual memory, visuospatial working memory, and emotion recognition. Deficits in verbal learning and memory, attention, processing speed, mental flexibility, phonetic and semantic verbal fluency remained stable. Auditory verbal working memory showed a lag trajectory, with healthy controls improving at a greater rate than the depression group. Finally, sustained attention followed a catch-up trajectory, with baseline deficits normalising over time relative to healthy controls. In the depression group, most cognitive improvements were associated with reductions in depression symptomatology, except for verbal learning and memory, and verbal fluency. The catch-up trajectory of sustained attention was associated with reductions in depression. CONCLUSIONSSpecific cognitive impairments can already be evident at the first episode of depression, but cognitive functions show differential longitudinal trajectories irrespective of depressive course. Tailored treatment addressing cognition should be provided early to promote cognitive health and functional recovery.

Published in Journal of Affective Disorders (predicted rank #3) · training set

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