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  • Exploratory genome-wide analyses of cortical inhibition, facilitation, and plasticity in late-life depression. Translational psychiatry Wathra, R. A., Men, X., Elsheikh, S. S., Marshe, V. S., Rajji, T. K., Lissemore, J. I., Mulsant, B. H., Karp, J. F., Reynolds, C. F., Lenze, E. J., Daskalakis, Z. J., Müller, D. J., Blumberger, D. M. 2023; 13 (1): 234

    Abstract

    Late-life depression (LLD) is a heterogenous mood disorder influenced by genetic factors. Cortical physiological processes such as cortical inhibition, facilitation, and plasticity may be markers of illness that are more strongly associated with genetic factors than the clinical phenotype. Thus, exploring the relationship between genetic factors and these physiological processes may help to characterize the biological mechanisms underlying LLD and improve diagnosis and treatment selection. Transcranial magnetic stimulation (TMS) combined with electromyography was used to measure short interval intracortical inhibition (SICI), cortical silent period (CSP), intracortical facilitation (ICF), and paired associative stimulation (PAS) in 79 participants with LLD. We used exploratory genome-wide association and gene-based analyses to assess for genetic correlations of these TMS measures. MARK4 (which encodes microtubule affinity-regulating kinase 4) and PPP1R37 (which encodes protein phosphatase 1 regulatory subunit 37) showed genome-wide significant association with SICI. EGFLAM (which encodes EGF-like fibronectin type III and laminin G domain) showed genome-wide significant association with CSP. No genes met genome-wide significant association with ICF or PAS. We observed genetic influences on cortical inhibition in older adults with LLD. Replication with larger sample sizes, exploration of clinical phenotype subgroups, and functional analysis of relevant genotypes is warranted to better characterize genetic influences on cortical physiology in LLD. This work is needed to determine whether cortical inhibition may serve as a biomarker to improve diagnostic precision and guide treatment selection in LLD.

    View details for DOI 10.1038/s41398-023-02532-0

    View details for PubMedID 37391420

    View details for PubMedCentralID 6135847

  • Identifying Neurophysiological Markers of Intermittent Theta-Burst Stimulation in Treatment-Resistant Depression using Transcranial Magnetic Stimulation- Electroencephalography. Biological psychiatry Strafella, R., Momi, D., Zomorrodi, R., Lissemore, J., Noda, Y., Chen, R., Rajji, T. K., Griffiths, J. D., Vila-Rodriguez, F., Downar, J., Daskalakis, Z. J., Blumberger, D. M., Voineskos, D. 2023

    Abstract

    Intermittent theta-burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (L-DLPFC) is effective for treatment-resistant depression (TRD), but iTBS' effects on neurophysiological markers remains unclear. Here, we indexed transcranial magnetic stimulation-electroencephalography (TMS-EEG) markers, specifically, the N45 and N100 amplitudes, at baseline and post-iTBS, comparing separated and contiguous iTBS schedules. TMS-EEG markers were also compared between iTBS responders and non-responders.TMS-EEG was analyzed from a triple-blind 1:1 randomized trial for TRD, comparing a separated (54 min interval) and contiguous (0 min interval) schedule of 2x600 pulse iTBS for 30 treatments. Participants underwent TMS-EEG over the L-DLPFC at baseline and post-treatment. 114 participants had usable TMS-EEG at baseline, and 98 at post-treatment. TMS-evoked potential (TEP) components (N45, N100) were examined via global mean-field analysis.The N100 amplitude decreased from baseline to post-treatment regardless of treatment group (F(1, 106) = 5.20, p = 0.02). There were no changes in N45 amplitude in either treatment group. In responders, the N100 amplitude decreased after iTBS (F(1,102) = 11.30, p = 0.001, pcorrected= 0.0004). Responders showed higher post-treatment N45 amplitude than non-responders (F(1, 94) = 4.11, p = 0.045, pcorrected= 0.016). Higher baseline N100 amplitude predicted lower post-iTBS depression scores (F(4, 106) = 6.28, p = 0.00014).These results further the evidence for an association between neurophysiological effects of iTBS and treatment efficacy in TRD. Future studies are needed to test the predictive potential for clinical applications of TMS-EEG markers.

    View details for DOI 10.1016/j.biopsych.2023.04.011

    View details for PubMedID 37084864

  • Lather, Rinse, Repeat? Breaking Repetitive Behaviors With Repetitive Stimulation. The American journal of psychiatry Lissemore, J. I., Williams, N. R. 2021; 178 (5): 378–80

    View details for DOI 10.1176/appi.ajp.2020.21030265

    View details for PubMedID 33979540