Common and specific large-scale brain changes in major depressive disorder, anxiety disorders, and chronic pain: a transdiagnostic multimodal meta-analysis of structural and functional MRI studies

Felix Brandl,Nazia Jassim,Christian Sorg,Daniel Hoffmann Ayala,Teresa Bertram,Satja Mulej Bratec,Benedikt Weise,Markus Ploner

doi:10.1038/s41386-022-01271-y

Felix Brandl, Nazia Jassim + Show 6 more

Open Access

https://doi.org/10.1038/s41386-022-01271-y

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Abstract

Major depressive disorder (MDD), anxiety disorders (ANX), and chronic pain (CP) are closely-related disorders with both high degrees of comorbidity among them and shared risk factors. Considering this multi-level overlap, but also the distinct phenotypes of the disorders, we hypothesized both common and disorder-specific changes of large-scale brain systems, which mediate neural mechanisms and impaired behavioral traits, in MDD, ANX, and CP. To identify such common and disorder-specific brain changes, we conducted a transdiagnostic, multimodal meta-analysis of structural and functional MRI-studies investigating changes of gray matter volume (GMV) and intrinsic functional connectivity (iFC) of large-scale intrinsic brain networks across MDD, ANX, and CP. The study was preregistered at PROSPERO (CRD42019119709). 320 studies comprising 10,931 patients and 11,135 healthy controls were included. Across disorders, common changes focused on GMV-decrease in insular and medial-prefrontal cortices, located mainly within the so-called default-mode and salience networks. Disorder-specific changes comprised hyperconnectivity between default-mode and frontoparietal networks and hypoconnectivity between limbic and salience networks in MDD; limbic network hyperconnectivity and GMV-decrease in insular and medial-temporal cortices in ANX; and hypoconnectivity between salience and default-mode networks and GMV-increase in medial temporal lobes in CP. Common changes suggested a neural correlate for comorbidity and possibly shared neuro-behavioral chronification mechanisms. Disorder-specific changes might underlie distinct phenotypes and possibly additional disorder-specific mechanisms.

Highlights

Major depressive disorder (MDD), anxiety disorders (ANX), and chronic pain (CP) are frequent disorders of brain and behavior [1]
Of its critical points, namely why we restricted our approach to changes overlap [38]. This approach is ‘transdiagnostic’ since it MDD, ANX, and CP, and why we focused on intrinsic brain respects current diagnostic categories of MDD, ANX, and CP, and looks for commonalities
While common and specific gray matter volume (GMV)- and intrinsic functional connectivity (iFC)-changes across MDD, ANX, and CP are reported pairwise contrasts between single disorders and healthy controls as well as across disorder pairs are described in Supplementary Results, Figs

Summary

Introduction

Major depressive disorder (MDD), anxiety disorders (ANX), and chronic pain (CP) are frequent disorders of brain and behavior [1] They are closely related due to overlap of changes at different levels—from genetic to brain and symptom level -, high degrees of comorbidity among them, and shared risk factors [2,3,4,5]. Disorder-specific brain-changes have been reported—for instance, concerning dorsolateral prefrontal cortex (dlPFC) in MDD [15] and distinct amygdala nuclei in ANX [16, 17]. These disorder-specific alterations might reflect specific phenotypes of these three related disorders. We selected a meta-analytic approach since especially for transdiagnostic comparisons, individual studies are often underpowered; meta-analyses can overcome this problem by synthesizing results

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Conclusion