Rostral Anterior Cingulate Cortex Oscillatory Power Indexes Treatment-Resistance to Multiple Therapies in Major Depressive Disorder

Introduction: High rostral anterior cingulate cortex (rACC) activity is proposed as a nonspecific prognostic marker for treatment response in major depressive disorder, independent of treatment modality. However, other studies report a negative association between baseline high rACC activation and treatment response. Interestingly, these contradictory findings were also found when focusing on oscillatory markers, specifically rACC-theta power. An explanation could be that rACC-theta activity dynamically changes according to number of previous treatment attempts and thus is mediated by level of treatment-resistance. Methods: Primarily, we analyzed differences in rACC- and frontal-theta activity in large national cross-sectional samples representing various levels of treatment-resistance and resistance to multimodal treatments in depressed patients (psychotherapy [n = 175], antidepressant medication [AD; n = 106], repetitive transcranial magnetic stimulation [rTMS; n = 196], and electroconvulsive therapy [ECT; n = 41]), and the respective difference between remitters and non-remitters. For exploratory purposes, we also investigated other frequency bands (delta, alpha, beta, gamma). Results: rACC-theta activity was higher (p < 0.001) in the more resistant rTMS and ECT patients relative to the less resistant psychotherapy and AD patients (psychotherapy-rTMS: d = 0.315; AD-rTMS: d = 0.320; psychotherapy-ECT: d = 1.031; AD-ECT: d = 1.034), with no difference between psychotherapy and AD patients. This association was even more pronounced after controlling for frontal-theta. Post hoc analyses also yielded effects for delta, beta, and gamma bands. Conclusion: Our findings suggest that by factoring in degree of treatment-resistance during interpretation of the rACC-theta biomarker, its usefulness in treatment selection and prognosis could potentially be improved substantially in future real-world practice. Future research should however also investigate specificity of the theta band.(c) 2023 The Author(s).