Unraveling robust brain-behavior links of depressive complaints through granular network models for understanding heterogeneity

René Freichel; Agatha Lenartowicz; Linda Douw; Johann D Kruschwitz; Tobias Banaschewski; Gareth J Barker; Arun L W Bokde; Sylvane Desrivières; Herta Flor; Antoine Grigis; Hugh Garavan; Andreas Heinz; Rüdiger Brühl; Jean-Luc Martinot; Marie-Laure Paillère Martinot; Eric Artiges; Frauke Nees; Dimitri Papadopoulos Orfanos; Tomáš Paus; Luise Poustka; Nathalie Holz; Christian Baeuchl; Michael N Smolka; Nilakshi Vaidya; Robert Whelan; Vincent Frouin; Gunter Schumann; IMAGEN Consortium; Henrik Walter; Tessa F Blanken

doi:10.1016/j.jad.2024.05.060

Unraveling robust brain-behavior links of depressive complaints through granular network models for understanding heterogeneity

J Affect Disord. 2024 May 14:359:140-144. doi: 10.1016/j.jad.2024.05.060. Online ahead of print.

Authors

René Freichel¹, Agatha Lenartowicz², Linda Douw³, Johann D Kruschwitz⁴, Tobias Banaschewski⁵, Gareth J Barker⁶, Arun L W Bokde⁷, Sylvane Desrivières⁸, Herta Flor⁹, Antoine Grigis¹⁰, Hugh Garavan¹¹, Andreas Heinz⁴, Rüdiger Brühl¹², Jean-Luc Martinot¹³, Marie-Laure Paillère Martinot¹⁴, Eric Artiges¹⁵, Frauke Nees¹⁶, Dimitri Papadopoulos Orfanos¹⁰, Tomáš Paus¹⁷, Luise Poustka¹⁸, Nathalie Holz⁵, Christian Baeuchl¹⁹, Michael N Smolka²⁰, Nilakshi Vaidya²¹, Robert Whelan²², Vincent Frouin¹⁰, Gunter Schumann²³; IMAGEN Consortium; Henrik Walter⁴, Tessa F Blanken²⁴

Affiliations

¹ Department of Psychology, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: r.freichel@uva.nl.
² Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, United States.
³ Department of Anatomy and Neurosciences, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
⁴ Department of Psychiatry and Psychotherapy CCM, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
⁵ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁶ Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, United Kingdom.
⁷ Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
⁸ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, SGDP Centre, King's College London, UK.
⁹ Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany.
¹⁰ NeuroSpin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.
¹¹ Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.
¹² Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany.
¹³ Institut National de la Santé et de la Recherche Médicale, INSERM U A10 'Trajectoires développementales en psychiatrie', Université Paris-Saclay, Ecole Normale supérieure Paris-Saclay, CNRS, Centre Borelli, Gif-sur-Yvette, France.
¹⁴ Institut National de la Santé et de la Recherche Médicale, INSERM U A10 'Trajectoires développementales en psychiatrie', Université Paris-Saclay, Ecole Normale supérieure Paris-Saclay, CNRS, Centre Borelli, Gif-sur-Yvette, France; AP-HP, Sorbonne Université, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris, France.
¹⁵ Institut National de la Santé et de la Recherche Médicale, INSERM U A10 'Trajectoires développementales en psychiatrie', Université Paris-Saclay, Ecole Normale supérieure Paris-Saclay, CNRS, Centre Borelli, Gif-sur-Yvette, France; Psychiatry Department, EPS Barthélémy Durand, Etampes, France.
¹⁶ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Institute of Medical Psychology and Medical Sociology, Kiel University, Kiel, Germany.
¹⁷ Departments of Psychiatry and Psychology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, Faculty of Medicine and Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada.
¹⁸ Department of Child and Adolescent Psychiatry, Center for Psychosocial Medicine, University Hospital Heidelberg, Heidelberg, Germany.
¹⁹ Faculty of Psychology, Technische Universität Dresden, Dresden, Germany.
²⁰ Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
²¹ Centre for Population Neuroscience and Stratified Medicine (PONS), Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Germany.
²² School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.
²³ Centre for Population Neuroscience and Stratified Medicine (PONS), Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Germany; Centre for Population Neuroscience and Precision Medicine (PONS), Institute for Science and Technology of Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, China.
²⁴ Department of Psychology, University of Amsterdam, Amsterdam, the Netherlands.

PMID: 38754596
DOI: 10.1016/j.jad.2024.05.060

Abstract

Background: Depressive symptoms are highly prevalent, present in heterogeneous symptom patterns, and share diverse neurobiological underpinnings. Understanding the links between psychopathological symptoms and biological factors is critical in elucidating its etiology and persistence. We aimed to evaluate the utility of using symptom-brain network models to parse the heterogeneity of depressive complaints in a large adolescent sample.

Methods: We used data from the third wave of the IMAGEN study, a multi-center panel cohort study involving 1317 adolescents (52.49 % female, mean ± SD age = 18.5 ± 0.7). Two network models were estimated: one including an overall depressive symptom severity sum score based on the Adolescent Depression Rating Scale (ADRS), and one incorporating individual ADRS item scores. Both networks included measures of cortical thickness in several regions (insula, cingulate, mOFC, fusiform gyrus) and hippocampal volume derived from neuroimaging.

Results: The network based on individual item scores revealed associations between cortical thickness measures and specific depressive complaints, obscured when using an aggregate depression severity score. Notably, the insula's cortical thickness showed negative associations with cognitive dysfunction (partial cor. = -0.15); the cingulate's cortical thickness showed negative associations with feelings of worthlessness (partial cor. = -0.10), and mOFC was negatively associated with anhedonia (partial cor. = -0.05).

Limitations: This cross-sectional study relied on the self-reported assessment of depression complaints and used a non-clinical sample with predominantly healthy participants (19 % with depression or sub-threshold depression).

Conclusions: This study showcases the utility of network models in parsing heterogeneity in depressive complaints, linking individual complaints to specific neural substrates. We outline the next steps to integrate neurobiological and cognitive markers to unravel MDD's phenotypic heterogeneity.

Keywords: Depression symptoms; Heterogeneity; Network analysis; Neural markers.