A predictive dimensional and circuit-based analysis of thought distortion and suicide ideation in treatment-resistant depression patients following neuromodulation therapies

• Grant number: 25/04835-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: October 20, 2025
• End date: October 19, 2026
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Ricardo Alberto Moreno
• Grantee: Adriana Carneiro
• Supervisor: Joan Camprodon
• Host Institution: Instituto de Psiquiatria Doutor Antonio Carlos Pacheco e Silva (IPq). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP)
• Institution abroad: Harvard University, Boston, United States
• Associated to the scholarship: 24/06902-0 - Hot and cold cognition in patients with depressive episode during magnetic and electro convulsive therapies: data from a randomized clinical study, BP.PD

Abstract

Introduction: Despite significant research, treating depression and bipolar disorder remains a challenge. For those patients, neuromodulation treatments, such as electroconvulsive therapy (ECT) and Transcranial Magnetic Stimulation (TMS) constitutes one of the most effective non-pharmacological interventions, with important antidepressant and anti-suicidal effects, however, their mechanisms are still only partially understood. To solve this issue, recent studies suggested that mapping brain activity might not only inform pathophysiological models of disease but also inform biomarker discovery in a way that supports the development of more effective therapies in a bottom-up biomarker-informed experimental medicine framework. Moreover, given the extreme clinical heterogeneity of depressive episodes (and most other psychiatric syndromes) there is a growing push to move beyond strict syndromal formulation and dissect the clinical phenomenology into core dimensional behavioral, affective, cognitive, and autonomic constructs. In this sense, understanding thought distortion, a hallmark of depression, and how some of our most effective treatments impact its severity and neurobiological substrates offers a relevant and promising strategy to both understand disease mechanism and develop translational innovations (e.g., biomarkers and personalized precision treatment strategies) by helping to identify patient subgroups best suited for these specific therapies. Aims: The present study aims to investigate behavioral and circuit-based predictors of response and mechanisms of action of the two most commonly used neuromodulation therapies: ECT and TMS. Aim 1: To understand the behavioral (dimensional) and neurobiological (circuit dynamics) signatures of thought distortion that predict or moderate the therapeutic response to ECT and TMS. Aim 2: To understand the overlapping and differential behavioral (dimensional) and neurobiological (circuit dynamics) signatures of thought distortion that longitudinally change in response to ECT and TMS. Method: Our sample will be composed of patients diagnosed with a major depressive episode (unipolar or bipolar) receiving ECT or rTMS. Before and after the acute course of treatment, demographic, clinical (syndromic severity), behavioral (dimensional assessments, both questionnaires and tasks), and multimodal MRI data were collected. We will analyze (1) behavioral and neurobiological predictors and moderators of response and (2) the overlapping and differential mechanisms of action of ECT and TMS impact on rumination and negative thought distortion, measured by a set of items from different severity scales (MADRS, HAMD, SHAPS), suicide ideation scales (CSSRS, CHRT) and ruminative patterns (RSS, RRQ). Conclusion: We hope that this project might benefit a better comprehension of signatures of thought distortion in TRD patients, to enhance personalized /targeted treatments. (AU)