Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression.

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this causal depression network (CDN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis Principal Component Analysis (PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CDN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CDN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes (t = -2.35, p = 0.019). This evidence further supports that treatment interventions converge on a CDN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.

MDMA for the Treatment of Negative Symptoms in Schizophrenia.

The profound economic burden of schizophrenia is due, in part, to the negative symptoms of the disease, which can severely limit daily functioning. There is much debate in the field regarding their measurement and classification and there are no FDA-approved treatments for negative symptoms despite an abundance of research. 3,4-Methylenedioxy methamphetamine (MDMA) is a schedule I substance that has emerged as a novel therapeutic given its ability to enhance social interactions, generate empathy, and induce a state of metaplasticity in the brain. This review provides a rationale for the use of MDMA in the treatment of negative symptoms by reviewing the literature on negative symptoms, their treatment, MDMA, and MDMA-assisted therapy. It reviews recent evidence that supports the safe and potentially effective use of MDMA to treat negative symptoms and concludes with considerations regarding safety and possible mechanisms of action.