The Role of Educational Attainment and Brain Morphology in Major Depressive Disorder: Findings From the ENIGMA Major Depressive Disorder Consortium

Brain structural abnormalities and low educational attainment are consistently associated with major depressive disorder (MDD), yet there has been little research investigating the complex interaction of these factors. Brain structural alterations may represent a vulnerability or differential suscep...

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Published in:Journal of psychopathology and clinical science 2022-08, Vol.131 (6), p.664-673
Main Authors: Whittle, Sarah, Rakesh, Divyangana, Schmaal, Lianne, Veltman, Dick J., Thompson, Paul M., Singh, Aditya, Gonul, Ali Saffet, Aleman, Andre, Uyar Demir, Aslıhan, Krug, Axel, Mwangi, Benson, Krämer, Bernd, Baune, Bernhard T., Stein, Dan J., Grotegerd, Dominik, Pomarol-Clotet, Edith, Rodríguez-Cano, Elena, Melloni, Elisa, Benedetti, Francesco, Stein, Frederike, Grabe, Hans J., Völzke, Henry, Gotlib, Ian H., Nenadić, Igor, Soares, Jair C., Repple, Jonathan, Sim, Kang, Brosch, Katharina, Wittfeld, Katharina, Berger, Klaus, Hermesdorf, Marco, Portella, Maria J., Sacchet, Matthew D., Wu, Mon-Ju, Opel, Nils, Groenewold, Nynke A., Gruber, Oliver, Fuentes-Claramonte, Paola, Salvador, Raymond, Goya-Maldonado, Roberto, Sarró, Salvador, Poletti, Sara, Meinert, Susanne L., Kircher, Tilo, Dannlowski, Udo, Pozzi, Elena
Format: Article
Language:English
Subjects:
Adult
Brain - diagnostic imaging
Brain Size
Brain structure
Cognitive functioning
Cortex
Depressive Disorder, Major - diagnostic imaging
Depressive personality disorders
Educational attainment
Educational Attainment Level
Educational Status
Female
Frontal Lobe
Human
Humans
Magnetic Resonance Imaging
Major Depression
Male
Mental depression
Moderation
Morphology
Neuroanatomy
Socioeconomic Status
Susceptibility
Susceptibility (Disorders)
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Summary:Brain structural abnormalities and low educational attainment are consistently associated with major depressive disorder (MDD), yet there has been little research investigating the complex interaction of these factors. Brain structural alterations may represent a vulnerability or differential susceptibility marker, and in the context of low educational attainment, predict MDD. We tested this moderation model in a large multisite sample of 1958 adults with MDD and 2921 controls (aged 18 to 86) from the ENIGMA MDD working group. Using generalized linear mixed models and within-sample split-half replication, we tested whether brain structure interacted with educational attainment to predict MDD status. Analyses revealed that cortical thickness in a number of occipital, parietal, and frontal regions significantly interacted with education to predict MDD. For the majority of regions, models suggested a differential susceptibility effect, whereby thicker cortex was more likely to predict MDD in individuals with low educational attainment, but less likely to predict MDD in individuals with high educational attainment. Findings suggest that greater thickness of brain regions subserving visuomotor and social-cognitive functions confers susceptibility to MDD, dependent on level of educational attainment. Longitudinal work, however, is ultimately needed to establish whether cortical thickness represents a preexisting susceptibility marker. General Scientific SummaryFindings from this study provide support for a complex interplay of biological and environmental factors being important in predicting major depressive disorder. Findings suggest that alterations in brain structure may not predict depression in all individuals; rather, such alterations may only predict depression in the context of adverse environmental experiences. Conversely, these same alterations may protect against depression in the context of positive environmental experiences.
ISSN:2769-7541
2769-755X
DOI:10.1037/abn0000738