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  • Systematic Review
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Effects of deep brain stimulation on cognitive functioning in treatment-resistant depression: a systematic review and meta-analysis

Abstract

Deep brain stimulation (DBS) is a promising intervention for treatment-resistant depression (TRD). Effects on cognitive functioning are unclear since they have been studied in small samples. We aim to estimate the impact of DBS on cognitive functioning in TRD with a systematic review and meta-analyses. After systematically searching PubMed we included 10 studies which compared standardized neuropsychological tests before and after DBS or between active and sham DBS in TRD. Different random-effects meta-analyses were done for different cognitive (sub-)domains and for different follow-up time windows (<6 months, 6–18 months, and >18 months). We found no significant differences in cognitive functioning up to 6 months of DBS. After 6–18 months of DBS small to moderate improvements were found in verbal memory (Hedge’s g = 0.22, 95% CI = [0.01–0.43], p = 0.04), visual memory (Hedge’s g = 0.37, 95% CI = [0.03–0.71], p = 0.04), attention/psychomotor speed (Hedge’s g = 0.26, 95% CI = [0.02–0.50], p = 0.04) and executive functioning (Hedge’s g = 0.37, 95% CI = [0.15–0.59], p = 0.001). Not enough studies could be retrieved for a meta-analysis of effects after >18 months of DBS or for the comparison of active and sham DBS. Qualitatively, generally no differences in cognitive functioning between active and sham DBS were found. No cognitive decline was found in this meta-analysis up to 18 months of DBS in patients with TRD. Results even suggest small positive effects of DBS on cognitive functioning in TRD, although this should be interpreted with caution due to lack of controlled data.

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Fig. 1: Flowchart of study selection process.
Fig. 2: Meta-analysis forest plot depicting changes in cognitive domain Verbal Memory after 6–18 months of DBS.
Fig. 3: Meta-analysis forest plot depicting changes in cognitive domain Visual Memory after 6–18 months of DBS.
Fig. 4: Meta-analysis forest plot depicting changes in cognitive domain Executive Functioning after 6–18 months of DBS.

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Contributions

NR, GM, and TH: these authors contributed equally to this work. Conceptualization: TH and IB. Investigation: NR, GM, TH, ZH, and IB. Project administration: IB. Methodology: NR, GM, TH, and IB. Formal analysis: NR and TH. Writing—original draft and visualization: NR, GM, and TH. Supervision: DD and IB. Writing—review & editing: all authors.

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Correspondence to N. Runia.

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Competing interests

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NR, GM, IB, and DD currently execute an investigator-initiated clinical trial on deep brain stimulation for depression, which is funded by Boston Scientific (24 DBS systems in kind) and a grant of ZonMw (nr. 636310016). All other authors do not declare any conflicts of interest.

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Runia, N., Mol, G.J.J., Hillenius, T. et al. Effects of deep brain stimulation on cognitive functioning in treatment-resistant depression: a systematic review and meta-analysis. Mol Psychiatry 28, 4585–4593 (2023). https://doi.org/10.1038/s41380-023-02262-1

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