Purpose

Electroconvulsive therapy is a safe, rapid acting antidepressant treatment which has been associated with grey matter (GM) volume increase, primarily in the temporal lobe¹, and also the basal ganglia^2,3. How these structural changes relate to ECT’s antidepressant mechanism is currently unclear, with studies finding inconsistent associations between GM increase and clinical improvement^1,2. Here we aim to further localise ECT-induced GM surface area and displacement changes and clarify the role of electrical stimulus placement and dose effects on subcortical grey matter, including the thalamus. Additionally we replicate previous analyses investigating the association between mood improvement and GM increase.

Methods

T1-weighted, MPRAGE data (3T, voxel size = 0.98 x 0.98 x 1.2 mm) from 70 patients with severe late-life depression and high quality longitudinal data pre and one week following the last ECT were included from two sites: the University Psychiatric Center KU Leuven, Belgium (n=35, mean age 72.3 years, 23 female), and GGZinGeest, Amsterdam, the Netherlands (n=35, mean 71.3 years, 20 female)⁴. Longitudinal data at a third time point 6 months post last ECT were included for 23 patients. Patients were treated twice weekly with right unilateral (RUL) constant-current brief-pulse (0.5– 1.0 ms) ECT (Thymatron System IV, Somatics, IL, USA) until remission (MADRS score <10 at two consecutive weekly assessments). Twenty-two non-responders were switched to bitemporal ECT. Measures of shape and surface area for thalamus, striatum, pallidum, hippocampus and amygdala were obtained from the T1-weighted images using an automated segmentation algorithm: Multiple Automatically Generated Templates Brain Segmentation (MAGeT Brain)^5,6. Vertex-wise shape and surface area measures were analyzed using linear mixed models (LMM) testing local shape/displacement by time-point controlling for age, gender and study site. Time-point was modelled as a factor and site was included as a random (grouping) variable in all models. Separate LMMs were used to investigate the effect of electrode placement (RUL v BL), number of ECTs and change in MADRS score (mood improvement) on subcortical and MTL GM. All analyses were corrected for multiple comparisons using false discovery rate (FDR) thresholded at 5%. q-values are reported.

Results

We detected widespread changes in both surface area and displacement one week following the final ECT treatment, characterised primarily by increases in surface area and displacement towards the lateral ventricles. The most pronounced effects were observed in the right hemisphere, ipsilateral to the stimulation side. The hippocampus showed both surface area increases, in the medial head and body, and surface area decreases laterally and inferiorly, but no displacements. The greatest surface area changes were detected in the amygdala, bilaterally, whereas the most pronounced displacement was observed in the basal ganglia and thalamus in the right hemisphere. There was a significant effect of electrode placement on subcortical GM, with bilateral electrode placement associated with greater volume increases in the left hippocampus, the amygdala bilaterally, and the left thalamus. There was also a significant effect of the number of ECTs on subcortical GM, with an increase in the number of treatments being associated with greater surface area increases in the right hippocampus and bilateral amygdalae. There was no significant association between any structural change and change in MADRS score. There were no significant structural changes present in the subsample of 23 patients 6 months post-ECT.

Discussion / Conclusion

This study replicates previous findings suggesting relatively transient GM increases associated with ECT⁷ and that the degree of increase appears related to the ECT stimulus. In contrast to another shape analysis of the basal ganglia², although we found surface area increases in the caudate, this was not associated with mood improvement in our study. Notably, in our previous work including data from the present study³, we found the increase in caudate GM was associated with improvement in psychomotor function, suggesting basal ganglia structural change could underlie a non-antidepressant therapeutic mechanism of ECT. One of the most striking findings was the increase in right thalamus surface area and its pronounced displacement in the stimulated hemisphere. Whilst its proximity to the lateral and third ventricles allows such physical displacement, the origin of the GM increase and its role in ECT neurobiology is unclear. Previous research has reported acute thalamic blood flow changes following ECT⁸, and altered resting-state functional connectivity in thalamic networks has been reported 2-4 weeks after ECT⁹, suggesting the role of the thalamus in ECT neurobiology may be a fruitful avenue of further investigation.

Acknowledgements

No acknowledgement found.

References

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