Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. METHODS: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R2) at the optimal p-value threshold is reported. RESULTS: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R2 = 8.18%, p = .0013), Belgium (R2 = 6.83%, p = .016), and the Netherlands (R2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R2 = 4.42%, p = .0024) and unipolar MDE only (R2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold. CONCLUSIONS: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry

Characterization of left ventricle function by analysis of pressure responses to steps in rotational speed of the Hemopump

Optimizing the procedure of weaning the left ventricle from a left ventricular assist device requires the determination of the momentaneous condition of the left ventricle. In sheep, a method was developed to momentaneously quantify the left ventricular condition. The left ventricular pump condition was quantified by the time-varying parameters elastance and resistance. They were determined from perturbations in the left ventricular pressure of two subsequent beats induced by changes in flow of the assist device. The end-diastolic volume of the ventricle was estimated without directly measuring ventricular volume. Maximum elastance and resistance were 201.3 ± 32.7 [Palmi] and 12.3 ± 1.6 [Pa·s/ml], respectively (mean ± SE). The ventricular time constant, defined by the ratio of resistance to elastance, was 84.6 ± 17.1 [ms] (man ± SE). </jats:p

Dynamic Pumping Characteristics of the Hemopump®

While pumping blood with the Hemopump® in sheep, the ability of predicting the instantaneous pump flow from the pressure difference over the pump system and pump parameters was investigated. For rotational speed n between 300 and 475 revolutions per second (rps), maximum pump flow QO(n) at zero pressure difference, internal pump resistance R(n), and inertia parameter Lc were found to be suitable parameters for Hemopump® characterization. The instantaneous pump flow could be estimated with an accuracy of approximately 1.0 [ml/s]. The values of the pump source parameters (± sd) were: (the figures in parentheses represent earlier reported values found while pumping water) Lc was a constant of 21.4 ± 6.4 [Pa·s2/ml] (in water: 10.8). QO(n) is linearly related to rotational speed n according to: QO(n) = Qo(ncen) + CQ(n - ncen), with QO(ncen) = 49.4 ± 4.5 [ml/s] (in water: 60.3), CQ = 142 ± 22.4 [10−3 ml] (in water: 146), and ncen = 387.5 [rps]. R(n) is linearly related to rotational speed n according to: R(n) = R(ncen) + CR(n - ncen), with R(ncen) = 556 ± 124 [Pa·s/ml] (in water: 502) and CR = 1.47 ± 0.83 [Pa·s2/ml] (in water: 1.67)