Comparative Study

. 2025 Jun;34(6):1873-1882.

doi: 10.1007/s00787-024-02599-0. Epub 2024 Nov 6.

Neurocognitive dysfunction in adolescents with recent onset major depressive disorder: a cross-sectional comparative study

Olga Bienek¹, Kelly Allott², Linda Antonucci³, Alessandro Bertolino⁴, Carolina Bonivento⁵, Stephan Borgwardt^{6

7}, Paolo Brambilla^{8

9}, Katharine Chisholm¹⁰, Udo Dannlowski¹¹, Theresa K Lichtenstein¹², Joseph Kambeitz¹², Lana Kambeitz-Ilankovic^{12

13}, Nikolaos Koutsouleris^{13

14

15}, Rebekka Lencer^{11

6}, Siân Lowri Griffiths¹⁶, Eleonora Maggioni¹⁷, Eva Meisenzahl¹⁸, Christos Pantelis¹⁹, Marlene Rosen¹², Stephan Ruhrmann¹², Raimo K R Salokangas²⁰, Alexandra Stainton², Marian Surmann¹¹, Rachel Upthegrove^{16

21}, Julian Wenzel¹², Stephen J Wood^{2

22

23}, Georg Romer^#²⁴, Jörg Michael Müller^#²⁴; PRONIA Consortium

Collaborators, Affiliations

Collaborators

PRONIA Consortium:
Shalaila Haas, Alkomiet Hasan, Claudius Hoff, Ifrah Khanyaree, Aylin Melo, Susanna Muckenhuber-Sternbauer, Yanis Köhler, Ömer Öztürk, Nora Penzel, David Popovic, Adrian Rangnick, Sebastian Saldern, Rachele Sanfelici, Moritz Spangemacher, Ana Tupac, Maria Fernanda Urquijo-Castro, Johanna Weiske, Antonia Wosgien, Camilla Krämer, Karsten Blume, Dennis Hedderich, Dominika Julkowski, Nathalie Kaiser, Thorsten Lichtenstein, Ruth Milz, Alexandra Nikolaides, Tanja Pilgram, Mauro Seves, Martina Wassen, Christina Andreou, Laura Egloff, Fabienne Harrisberger, Ulrike Heitz, Claudia Lenz, Letizia Leanza, Amatya Mackintosh, Renata Smieskova, Erich Studerus, Anna Walter, Sonja Widmayer, Chris Day, Sian Lowri Griffiths, Mariam Iqbal, Mirabel Pelton, Pavan Mallikarjun, Ashleigh Lin, Alexander Denissoff, Anu Ellilä, Tiina From, Markus Heinimaa, Tuula Ilonen, Päivi Jalo, Heikki Laurikainen, Antti Luutonen, Akseli Mäkela, Janina Paju, Henri Pesonen, Reetta-Liina Säilä, Anna Toivonen, Otto Turtonen, Sonja Botterweck, Norman Kluthausen, Gerald Antoch, Julian Caspers, Hans-Jörg Wittsack, Giuseppe Blasi, Giulio Pergola, Grazia Caforio, Leonardo Fazio, Tiziana Quarto, Barbara Gelao, Raffaella Romano, Ileana Andriola, Andrea Falsetti, Marina Barone, Roberta Passiatore, Marina Sangiuliano, Ana Beatriz Solana, Manuela Abraham, Timo Schirmer, Carlo Altamura, Marika Belleri, Francesca Bottinelli, Adele Ferro, Marta Re, Emiliano Monzani, Maurizio Sberna, Giampaolo Perna, Maria Nobile, Alessandra Alciati, Armando D'Agostino, Lorenzo Del Fabro, Matteo Balestrieri, Giuseppe Cabras, Franco Fabbro, Marco Garzitto, Sara Piccin

Affiliations

¹ Clinic for Child and Adolescent Psychiatry, Psychotherapy and Psychosomatic Medicine, University Hospital Muenster, Schmeddingstrasse 50, 48149, Muenster, Germany. Olga.bienek@web.de.
² Centre for Youth Mental Health, University of Melbourne, Parkville, Australia.
³ Department of Education, Psychology, and Communication, University of Bari Aldo Moro, Bari, Italy.
⁴ Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
⁵ Pasian Di Prato (UD), Scientific Institute IRCCS 'Eugenio Medea', Polo FVG, 33037, Udine, Italy.
⁶ Clinic for Psychiatry and Psychotherapy, University Hospital Luebeck, Lübeck, Germany.
⁷ Department of Psychiatry, Psychiatric University Hospital, University of Basel, Basel, Switzerland.
⁸ Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
⁹ Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
¹⁰ School of Psychology, Sussex University, Brighton, UK.
¹¹ Institute for Translational Psychiatry, University Hospital Muenster, Münster, Germany.
¹² Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.
¹³ Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
¹⁴ Max-Planck Institute of Psychiatry, Munich, Germany.
¹⁵ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹⁶ Institute for Mental Health, University of Birmingham, Birmingham, UK.
¹⁷ Department of Electronics, Information and Bioengineering, Politecnico Di Milano, Milan, Italy.
¹⁸ Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
¹⁹ Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Melbourne, Australia.
²⁰ Department of Psychiatry, University of Turku, Turku, Finland.
²¹ University of Oxford, Oxford, UK.
²² Orygen, Melbourne, Australia.
²³ School of Psychology, University of Birmingham, Birmingham, UK.
²⁴ Clinic for Child and Adolescent Psychiatry, Psychotherapy and Psychosomatic Medicine, University Hospital Muenster, Schmeddingstrasse 50, 48149, Muenster, Germany.

^# Contributed equally.

PMID: 39503777
PMCID: PMC12198262
DOI: 10.1007/s00787-024-02599-0

Comparative Study

Neurocognitive dysfunction in adolescents with recent onset major depressive disorder: a cross-sectional comparative study

Olga Bienek et al. Eur Child Adolesc Psychiatry. 2025 Jun.

. 2025 Jun;34(6):1873-1882.

doi: 10.1007/s00787-024-02599-0. Epub 2024 Nov 6.

Authors

Collaborators

PRONIA Consortium:
Shalaila Haas, Alkomiet Hasan, Claudius Hoff, Ifrah Khanyaree, Aylin Melo, Susanna Muckenhuber-Sternbauer, Yanis Köhler, Ömer Öztürk, Nora Penzel, David Popovic, Adrian Rangnick, Sebastian Saldern, Rachele Sanfelici, Moritz Spangemacher, Ana Tupac, Maria Fernanda Urquijo-Castro, Johanna Weiske, Antonia Wosgien, Camilla Krämer, Karsten Blume, Dennis Hedderich, Dominika Julkowski, Nathalie Kaiser, Thorsten Lichtenstein, Ruth Milz, Alexandra Nikolaides, Tanja Pilgram, Mauro Seves, Martina Wassen, Christina Andreou, Laura Egloff, Fabienne Harrisberger, Ulrike Heitz, Claudia Lenz, Letizia Leanza, Amatya Mackintosh, Renata Smieskova, Erich Studerus, Anna Walter, Sonja Widmayer, Chris Day, Sian Lowri Griffiths, Mariam Iqbal, Mirabel Pelton, Pavan Mallikarjun, Ashleigh Lin, Alexander Denissoff, Anu Ellilä, Tiina From, Markus Heinimaa, Tuula Ilonen, Päivi Jalo, Heikki Laurikainen, Antti Luutonen, Akseli Mäkela, Janina Paju, Henri Pesonen, Reetta-Liina Säilä, Anna Toivonen, Otto Turtonen, Sonja Botterweck, Norman Kluthausen, Gerald Antoch, Julian Caspers, Hans-Jörg Wittsack, Giuseppe Blasi, Giulio Pergola, Grazia Caforio, Leonardo Fazio, Tiziana Quarto, Barbara Gelao, Raffaella Romano, Ileana Andriola, Andrea Falsetti, Marina Barone, Roberta Passiatore, Marina Sangiuliano, Ana Beatriz Solana, Manuela Abraham, Timo Schirmer, Carlo Altamura, Marika Belleri, Francesca Bottinelli, Adele Ferro, Marta Re, Emiliano Monzani, Maurizio Sberna, Giampaolo Perna, Maria Nobile, Alessandra Alciati, Armando D'Agostino, Lorenzo Del Fabro, Matteo Balestrieri, Giuseppe Cabras, Franco Fabbro, Marco Garzitto, Sara Piccin

Affiliations

¹ Clinic for Child and Adolescent Psychiatry, Psychotherapy and Psychosomatic Medicine, University Hospital Muenster, Schmeddingstrasse 50, 48149, Muenster, Germany. Olga.bienek@web.de.
² Centre for Youth Mental Health, University of Melbourne, Parkville, Australia.
³ Department of Education, Psychology, and Communication, University of Bari Aldo Moro, Bari, Italy.
⁴ Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
⁵ Pasian Di Prato (UD), Scientific Institute IRCCS 'Eugenio Medea', Polo FVG, 33037, Udine, Italy.
⁶ Clinic for Psychiatry and Psychotherapy, University Hospital Luebeck, Lübeck, Germany.
⁷ Department of Psychiatry, Psychiatric University Hospital, University of Basel, Basel, Switzerland.
⁸ Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
⁹ Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
¹⁰ School of Psychology, Sussex University, Brighton, UK.
¹¹ Institute for Translational Psychiatry, University Hospital Muenster, Münster, Germany.
¹² Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.
¹³ Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
¹⁴ Max-Planck Institute of Psychiatry, Munich, Germany.
¹⁵ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹⁶ Institute for Mental Health, University of Birmingham, Birmingham, UK.
¹⁷ Department of Electronics, Information and Bioengineering, Politecnico Di Milano, Milan, Italy.
¹⁸ Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
¹⁹ Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Melbourne, Australia.
²⁰ Department of Psychiatry, University of Turku, Turku, Finland.
²¹ University of Oxford, Oxford, UK.
²² Orygen, Melbourne, Australia.
²³ School of Psychology, University of Birmingham, Birmingham, UK.
²⁴ Clinic for Child and Adolescent Psychiatry, Psychotherapy and Psychosomatic Medicine, University Hospital Muenster, Schmeddingstrasse 50, 48149, Muenster, Germany.

^# Contributed equally.

PMID: 39503777
PMCID: PMC12198262
DOI: 10.1007/s00787-024-02599-0

Abstract

The aim of this study was to examine the neurocognitive deficits associated with the first episode of major depressive disorder (recent onset depression, ROD) in adolescents as compared to adult patients. Cross-sectional neurocognitive data from the baseline assessments of the PRONIA study with N = 650 (55.31% females) were analyzed. Based on a principal component analysis of eleven neurocognitive tests, we constructed an overall neurocognitive performance (NP) score. We examined mean score differences in NP between the groups of healthy controls (HC) and ROD and between adolescents (15-21 years) and adults (22-40 years) within a GLM approach. This accounts for unbalanced data with focus on interaction effects while controlling for effects of medication and educational years. Our results show lower NP for the ROD as compared to the HC group (d = - 0.29, p = .046) and lower NP for the adolescent group as compared to the adult group (d = - 0.29; p < .039). There was no interaction between these two group effects (F = 1.11; p = .29). Our findings suggest that the detrimental effect of ROD on neurocognitive functioning is comparable in adolescent and adult patients, since lower scores in adolescent patients are explained by effects of age and education. Neurocognitive impairment is an under addressed issue in clinical treatment guidelines for adolescent MDD. We suggest efficient monitoring in clinical practice by using an aggregate of the Digit Symbol Substitution Test and the Trail Making Test B, which highly correlated with the overall score of NP (r = 0.82).

Keywords: Adolescent; Major depressive disorder; Neurocognitive dysfunction; PRONIA; Recent onset.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.

Figures

**Fig. 1**
Z-standardized marginal means based on GLM estimates for the main effects of age and health status for overall NP and neurocognitive domains (CHC model) [37]. NP neurocognitive performance

See this image and copyright information in PMC

References

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Neurocognitive dysfunction in adolescents with recent onset major depressive disorder: a cross-sectional comparative study

Collaborators

Affiliations

Neurocognitive dysfunction in adolescents with recent onset major depressive disorder: a cross-sectional comparative study

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous