Abstract
We investigated if sleep deprivation (SD) and electroconvulsive therapy (ECT) affect striatal dopamine transporter (DAT) availability assessed by single-photon emission computed tomography (SPECT) and 123I-FP-CIT, if dopamine transporter gene (SLC6A3; DAT) variation modifies aforementioned parameters, and if SD response or SD-induced DAT changes correlate with ECT response. Sixteen patients with major depression (MDD) referred for ECT and 12 matched controls were prospectively recruited for imaging and SLC6A3 VNTR genotyping. After withdrawal from any psychiatric medication, 123I-FP-CIT-SPECT was acquired at baseline, after SD and after ECT series. Striatal DAT availability was assessed by volume-of-interest analysis of SPECT data. Eleven patients underwent combined treatment with SD and ECT (five ECT responders and six non-responders). Per-protocol analyses yielded no significant effect of SD or ECT on striatal DAT availability using repeated-measures ANOVA. However, intention-to-treat analysis indicated a significant decrease of striatal DAT availability due to SD (paired t test, p < 0.01). Stratification by SLC6A3 VNTR genotype suggested the 9R allele to drive this effect. In an exploratory analysis, SD-induced change in DAT availability of the left caudate nucleus predicted ECT response. This study revealed a treatment effect of SD on striatal DAT availability—possibly depending on SLC6A3 VNTR genotype. This and the observed association between SD-induced change of striatal DAT availability and response to ECT may help to identify treatment mechanisms and response predictors useful for precision medicine approaches in the treatment of MDD.
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We thank Jean C. Walter and Caspar Geißler for the assistance with data analyses.
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Financial support by GE Healthcare (Munich, Germany). Internal funding.
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SH received research support from GE Healthcare Buchler GmbH & Co. KG. WV received funding for travel and speaker honoria from Deutsche Krankenhausgesellschaft and serves as a consultant for the Nordic Institute for Chiropractice and Clinical Biomechanics, Odense, Denmark, and Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark. PTM, ongoing research support from GE Healthcare, Novartis, Piramal Imaging; LF, AM, CN, and KD report no conflicts.
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Hellwig, S., Frings, L., Masuch, A. et al. Antidepressant treatment effects on dopamine transporter availability in patients with major depression: a prospective 123I-FP-CIT SPECT imaging genetic study. J Neural Transm 125, 995–1005 (2018). https://doi.org/10.1007/s00702-018-1863-7
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DOI: https://doi.org/10.1007/s00702-018-1863-7