Vagally Mediated Heart Rate Variability Is Associated With Executive Function Changes in Patients With Treatment-Resistant Depression Following Magnetic Seizure Therapy

Abstract

Objectives: Magnetic seizure therapy (MST) is a novel investigational brain stimulation modality for patients with treatment-resistant depression (TRD). MST is a potential alternative seizure-based treatment to electroconvulsive therapy (ECT), given that it may offer equivalent antidepressant efficacy, yet with a relative sparing of cognitive functioning. Heart rate variability (HRV) is a marker of central autonomic functioning. We aimed to explore the relationships among baseline HRV, age, clinical outcome, and executive function following MST, in patients with TRD.

Materials and methods: Eighty-eight TRD patients (55 females; 18-70 years) were enrolled and 48 patients completed a course of MST in an open-label study. Patients received MST treatments two to three times per week, using one of three stimulation frequencies (ie, 100 Hz, 50 Hz, or 25 Hz) at 100% stimulator output. Root mean square of the successive R-R differences (RMSSD), an index of HRV, was computed from a baseline electrocardiogram (ECG) recording. Clinical symptoms were assessed using the Hamilton Depression Rating Scale (HAM-D₂₄) and the Quick Inventory of Depressive Symptomatology (QIDS₁₆). Executive function was assessed using the Trail Making Test and the Mazes Test from the MATRICS battery.

Results: Baseline RMSSD was correlated with baseline HAM-D₂₄ (r = -0.340, p = 0.001) and baseline Mazes Test (r = 0.417, p = 0.0007) but not with baseline Trail Making Test. Furthermore, baseline RMSSD was not correlated with changes on the HAM-D₂₄, QIDS₁₆, or total scores on the Trail Making Test. However, there was a significant correlation between baseline RMSSD and improvement on the Mazes Test following MST (r = 0.502, p = 0.0004).

Conclusions: Since this is an open-label trial, the influence of the placebo effect cannot be excluded. However, our results suggest that baseline RMSSD may be a state-biomarker of depression and executive function impairment. Additionally, while baseline vagally mediated resting cardiac activity did not predict the outcome of depression, it may mediate executive function improvements following MST.

Keywords: Executive function; heart rate variability; magnetic seizure therapy; root mean square of the successive R-R differences; treatment-resistant depression.