Is Psychotic Depression a Distinct Entity?: New MRI Findings From GEMRIC

 Neural Substrates of Psychotic Depression: Findings From the Global ECT-MRI Research Collaboration.

Takamiya A, Dols A, Emsell L, Abbott C, Yrondi A, Soriano Mas C, Jorgensen MB, Nordanskog P, Rhebergen D, van Exel E, Oudega ML, Bouckaert F, Vandenbulcke M, Sienaert P, Péran P, Cano M, Cardoner N, Jorgensen A, Paulson OB, Hamilton P, Kampe R, Bruin W, Bartsch H, Ousdal OT, Kessler U, van Wingen G, Oltedal L, Kishimoto T.Schizophr Bull. 2021 Oct 8:sbab122. doi: 10.1093/schbul/sbab122. Online ahead of print.PMID: 34624103

The abstract is copied below:

Psychotic major depression (PMD) is hypothesized to be a distinct clinical entity from nonpsychotic major depression (NPMD). However, neurobiological evidence supporting this notion is scarce. The aim of this study is to identify gray matter volume (GMV) differences between PMD and NPMD and their longitudinal change following electroconvulsive therapy (ECT). Structural magnetic resonance imaging (MRI) data from 8 independent sites in the Global ECT-MRI Research Collaboration (GEMRIC) database (n = 108; 56 PMD and 52 NPMD; mean age 71.7 in PMD and 70.2 in NPMD) were analyzed. All participants underwent MRI before and after ECT. First, cross-sectional whole-brain voxel-wise GMV comparisons between PMD and NPMD were conducted at both time points. Second, in a flexible factorial model, a main effect of time and a group-by-time interaction were examined to identify longitudinal effects of ECT on GMV and longitudinal differential effects of ECT between PMD and NPMD, respectively. Compared with NPMD, PMD showed lower GMV in the prefrontal, temporal and parietal cortex before ECT; PMD showed lower GMV in the medial prefrontal cortex (MPFC) after ECT. Although there was a significant main effect of time on GMV in several brain regions in both PMD and NPMD, there was no significant group-by-time interaction. Lower GMV in the MPFC was consistently identified in PMD, suggesting this may be a trait-like neural substrate of PMD. Longitudinal effect of ECT on GMV may not explain superior ECT response in PMD, and further investigation is needed.

Keywords: depression; gray matter volume; magnetic resonance imaging; medial prefrontal cortex; psychosis.

And from the text:

From a therapeutic point of view, PMD has shown poor response to placebo,15 and antidepressant/antipsychotic monotherapy,16 but favorable response to the combination of antipsychotics and antidepressants,16 and to electroconvulsive therapy (ECT).17–19 Notably, ECT is particularly effective in late life PMD,20 and ECT is considered a first-line treatment for PMD in several clinical guidelines.21 Compared to this clinical and therapeutic evidence that supports the notion of PMD as a distinct clinical entity, little is known about its underlying neurobiology.

Discussion

To the best of our knowledge, this is the first study to investigate GMV differences between PMD and NPMD at two time points. We found that PMD showed lower GMV in the MPFC compared to NPMD both before and after ECT in this largest cohort ever, suggesting that lower GMV in the MPFC is one of the neural substrates of PMD. We also found that ECT increased GMV in widely distributed brain regions in both PMD and NPMD, but the longitudinal effect of ECT on GMV did not differ between PMD and NPMD.

...In conclusion, lower GMV in the MPFC was consistently identified in PMD both before and after ECT, suggesting this may be one of the trait-like neural substrates of PMD. The longitudinal effect of ECT on brain structure did not differ between PMD and NPMD, suggesting GMV changes following ECT may not explain superior ECT response in PMD. Future research should focus on brain functional changes to elucidate the underlying neural mechanisms of ECT action.

This is an important study showing more brain atrophy in psychotic depression at baseline, and no difference in structural response to ECT. While the authors are not shy about touting the importance of their findings, it is possible they may have a point.

On the other hand, despite this paper coming from GEMRIC, the sample size is just moderate (total n=108) and replication will be necessary.

This paper is a must-read for all followers of the neuroimaging ECT literature and the neurotrophic hypothesis of the mechanism of action of ECT, ~25 minutes.