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The volumes of subcortical regions in depressed and healthy individuals are strikingly similar: a reinterpretation of the results by Schmaal et al.

Molecular Psychiatry volume 21, pages 724–725 (2016)Cite this article

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In their recent meta-analysis of magnetic resonance imaging data from 15 research samples worldwide, Schmaal et al.1 examined the structural differences of nine subcortical brain volumes between 1728 patients with major depressive disorder (MDD) and 7199 healthy participants. In the authors’ univariate analyses, none of the nine volumes was associated with depression severity, and only hippocampal volume was significantly decreased in MDD patients compared to controls, with the largest effect being observed in the recurrent MDD group (difference 1.4%, Cohen’s d 0.17). The study is the result of a huge collaborative effort, and we commend the authors on their insightful manuscript. However, as the findings present the best empirical evidence currently available, an accurate interpretation of the results is paramount, especially considering the report’s goal to ‘robustly discriminate MDD patients from healthy controls’ (p. 1). We therefore add two observations and future research directions.

Second, the authors mainly discuss reduced hippocampal volume as a consequence or a precursor of MDD, but we see a number of alternative possibilities: the association could also be the result of a shared underlying cause (e.g., a genetic predisposition) of bidirectional/mutual reinforcement, or spurious due to confounders/mediators (lack of exercise/activity3 and accelerated aging4 have an impact on hippocampal volume and are more prevalent among depressed patients). It is noteworthy that the lack of specificity of reduced hippocampal volume for depression,2 the lack of discriminatory power and also most of the above explanations are inconsistent with reduced hippocampal volume as a biological marker of depression as a clinical state. This also holds for the authors’ primary hypothesis that depression causes structural changes, since—unless volume increases post-MDD—all individuals with previous instances of depression would be indistinguishable (no matter if, at present, healthy or not). In the absence of convincing longitudinal support for a causal role of hippocampal volume for depression, we believe the findings may warrant a more nuanced interpretation than ‘this resolves for good the issue that persistent experiences of depression hurts the brain’.5

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References

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Authors and Affiliations

  1. Faculty of Psychology, University of Leuven, Leuven, Belgium

    E I Fried

  2. Medical Research Council Cognition and Brain Sciences Unit, Cambridge, UK

    R A Kievit

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  1. E I Fried
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  2. R A Kievit
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Correspondence to E I Fried.

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Fried, E., Kievit, R. The volumes of subcortical regions in depressed and healthy individuals are strikingly similar: a reinterpretation of the results by Schmaal et al.. Mol Psychiatry 21, 724–725 (2016). https://doi.org/10.1038/mp.2015.199

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