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Longitudinal brain changes in MDD during emotional encoding: effects of presence and persistence of symptomatology

Published online by Cambridge University Press:  06 June 2019

Hui Ai*
Shenzhen Key Laboratory of Affective and Social Neuroscience, Center for Brain Disorders and Cognitive Sciences, Shenzhen University, Shenzhen, China Cognitive Neuroscience Center, Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, Groningen, The Netherlands
Esther M. Opmeer
Cognitive Neuroscience Center, Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, Groningen, The Netherlands
Jan-Bernard C. Marsman
Cognitive Neuroscience Center, Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, Groningen, The Netherlands
Dick J. Veltman
Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Nic J. A. van der Wee
Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands Leiden University, Leiden Institute for Brain and Cognition, Leiden, The Netherlands
André Aleman
Shenzhen Key Laboratory of Affective and Social Neuroscience, Center for Brain Disorders and Cognitive Sciences, Shenzhen University, Shenzhen, China Cognitive Neuroscience Center, Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, Groningen, The Netherlands
Marie-José van Tol*
Cognitive Neuroscience Center, Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, Groningen, The Netherlands
Author for correspondence: Hui Ai, E-mail: and Marie-José van Tol, E-mail:
Author for correspondence: Hui Ai, E-mail: and Marie-José van Tol, E-mail:



The importance of the hippocampus and amygdala for disrupted emotional memory formation in depression is well-recognized, but it remains unclear whether functional abnormalities are state-dependent and whether they are affected by the persistence of depressive symptoms.


Thirty-nine patients with major depressive disorder and 28 healthy controls were included from the longitudinal functional magnetic resonance imaging (fMRI) sub-study of the Netherlands Study of Depression and Anxiety. Participants performed an emotional word-encoding and -recognition task during fMRI at baseline and 2-year follow-up measurement. At baseline, all patients were in a depressed state. We investigated state-dependency by relating changes in brain activation over time to changes in symptom severity. Furthermore, the effect of time spent with depressive symptoms in the 2-year interval was investigated.


Symptom change was linearly associated with higher activation over time of the left anterior hippocampus extending to the amygdala during positive and negative word-encoding. Especially during positive word encoding, this effect was driven by symptomatic improvement. There was no effect of time spent with depression in the 2-year interval on change in brain activation. Results were independent of medication- and psychotherapy-use.


Using a longitudinal within-subjects design, we showed that hippocampal–amygdalar activation during emotional memory formation is related to depressive symptom severity but not persistence (i.e. time spent with depression or ‘load’), suggesting functional activation patterns in depression are not subject to functional ‘scarring’ although this hypothesis awaits future replication.

Original Articles
Copyright © Cambridge University Press 2019

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