GABAA Receptor Availability in Relation to Cortical Excitability in Depressed and Healthy: A Positron Emission Tomography and Transcranial Magnetic Stimulation Study.

INTRODUCTION: Gamma-aminobutyric acid (GABA) deficiency is suggested in depressive disorders, along with alterations in cortical excitability. However, whether these excitability changes are related to GABAA receptor availability is largely unknown. Our aim was to assess the correlation between these measures in depressed patients and healthy controls. METHODS: Twenty-eight patients with a major depressive episode, measured before and after participating in a clinical trial with repetitive transcranial magnetic stimulation (TMS), and 15 controls underwent [11C]flumazenil positron emission tomography to assess GABAA receptor availability and paired pulse TMS (ppTMS) to evaluate cortical excitability. Both whole-brain voxel-wise GABAA receptor availability and mean values from left hand motor cortex and left paracentral lobule were correlated to the ppTMS outcomes: short-interval intracortical inhibition reflecting GABAA receptor activity, long-interval intracortical inhibition representing GABAB receptor activity, intracortical facilitation reflecting glutamate N-methyl-D-aspartate-receptor activity, as well as the resting motor threshold (rMT), considered a global measure of corticospinal excitability. RESULTS: No significant differences in baseline GABAA receptor availability or cortical excitability were found between patients and controls. Additionally, no correlations were observed between baseline measurements of GABAA receptor availability and TMS outcomes. Changes in GABAA receptor availability in the hand motor cortex, between pre- and post-assessments, were inversely related to pre-post changes in hand rMT. CONCLUSION: We found that a change in GABAA receptor availability was inversely related to a change in rMT, suggesting a link between GABA deficiency and increased rMT previously observed in depressive episodes. The results highlight the complex mechanisms governing cortical excitability measures and offer new insight into their properties during the depressive state.

Intercorrelation of physiological seizure parameters and hormonal changes in electroconvulsive therapy.

OBJECTIVE: Physiological parameters that predict electroconvulsive therapy (ECT) effectiveness may reflect propagation of the induced epileptic seizure. As an indication of seizure propagation to the diencephalon, we here examined the correlation between prolactin increase after ECT and clinical seizure evaluation parameters, focusing on peak heart rate. As a proxy for peripheral endocrine stress response, we examined the correlation to postictal cortisol increase. METHODS: Participants were consecutively recruited from clinical ECT patients (n = 131, age 18-85 years). The first ECT session in a series was examined. For each participant, blood serum concentrations of prolactin and cortisol were measured immediately before and within 30 min after the seizure. Physiological parameters were extracted from clinical records: peak heart rate (HR) during seizure, electroencephalography (EEG) seizure duration, and motor seizure duration. Correlations were calculated using non-parametric tests. RESULTS: Serum prolactin increased after ECT and correlated with peak HR, EEG seizure duration, and motor seizure duration. Peak HR during seizure also correlated positively with both EEG seizure duration and motor seizure duration. Correlations were unaffected by age, sex, baseline prolactin levels, antipsychotics, or beta-blocking agents. Serum cortisol increased after ECT but did not correlate with the seizure evaluation parameters, nor with prolactin concentrations. CONCLUSIONS: Our findings of a positive correlation between peak HR and prolactin that was independent from the peripheral endocrine stress response might be in line with the idea that tachycardia during ECT seizures reflects seizure propagation to the diencephalon. This supports the practice of monitoring cardiovascular response for ECT seizure evaluation.

Response rate and subjective memory after electroconvulsive therapy in depressive disorders with psychiatric comorbidity.

BACKGROUND: Response rates after and tolerability of electroconvulsive therapy (ECT) in depressive disorders with psychiatric comorbidity are uncertain. METHODS: Data on patients with a depressive episode and a first course of ECT were collected from the Swedish National Quality Register for ECT. Logistic regression analyses, adjusted for gender, age, and depressive episode severity, were used to compare patients with and without comorbidity. The clinical response assessment Clinical Global Impression - Improvement Scale was used in 4413 patients and the memory item from the Comprehensive Psychiatric Rating Scale was used for subjective memory impairment rating after ECT in 3497 patients. RESULTS: In patients with depressive disorder and comorbid personality disorder or anxiety disorder, 62.7% and 73.5%, respectively, responded after ECT compared with 84.9% in patients without comorbidity [adjusted odds ratio (aOR) 0.43, 95% confidence interval (CI) 0.34-0.55, and aOR 0.61, 95% CI 0.51-0.73, respectively]. The proportion of responding patients with comorbid alcohol use disorder was 77.1%, which was not significantly different from that in patients without comorbidity (aOR 0.75, 95% CI 0.57-1.01). The impact of comorbidity decreased with higher age and depressive episode severity. Subjective ratings of memory impairment did not differ between patients with and without comorbidity. LIMITATIONS: Observational non-validated clinical data. CONCLUSIONS: The response rate after ECT in depression may be lower with concurrent personality disorder and anxiety disorder; however, the majority still respond to ECT. This implies that psychiatric comorbidity should not exclude patients from ECT.