Evaluation of functional and structural connectivity as predictors of clinical response to Transcranial Direct Current Stimulation use in the treatment of unipolar Major Depressive Disorder and Obsessive Compulsive Disorder

• Grant number: 20/03235-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2020
• End date: August 08, 2024
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Andre Russowsky Brunoni
• Grantee: Tamires Araujo Zanão Mariano
• Host Institution: Instituto de Psiquiatria Doutor Antonio Carlos Pacheco e Silva (IPq). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated scholarship(s): 22/09688-4 - FSL analysis of structural, diffusion and functional connectivity as predictors of clinical response to transcranial direct current stimulation use in the treatment of unipolar major depressive disorder, BE.EP.PD

Abstract

The Major Depressive Disorder (MDD) and the Obsessive-Compulsive Disorder (OCD) cause important disabilities. The most frequent treatments for these disorders are antidepressant drugs and psychotherapy, but an expressive percentage of patients don't show significant improvement after the traditional therapies and other interventions are necessary. The transcranial direct current stimulation (tDCS) is a non-invasive stimulation technique that injects low-intensity electrical current via electrodes located on the scalp, acting to facilitate or inhibit synaptic transmission and Magnetic Resonance Imaging (MRI) studies aid to stablish stimulation targets with greater precision. The first study of biomarkers analysis based on MRI and antidepressant effects of tDCS (Bulubas et al., 2019) was carried out in a sample of the ELECT-TDCS study, granted by FAPESP (JP 12 / 20911-5), and compared tDCS with escitalopram (20mg / day) and placebo, establishing a correlation between gray matter volume of the left dorsal prefrontal cortex (DPFC) with improvement of depressive symptoms compared to the active tDCS and sham group. Dr. Roseli Shavitt, in collaboration with this project supervisor, coordinated another study of tDCS with OCD patients in which they acquired neuroimaging data that will be analyzed for relationships between the effect of tDCS, volumetry of regions related to OCD, and the integrity of white matter of these regions of interest. The images acquired at ELECT-TDCS and by Dr. Shavitt's group include structural, functional and diffusion images (3T Phillips Scanner, HC-FMUSP). The tDCS (Soterix Medical, USA; electrodes = 25 cm2; sessions = 30 minutes of tDCS, with automatic shutdown after 30 seconds in the sham groups) was applied to areas involved in the physiopathology of the disorders, with anode on the left DPFC and cathode on right DPFC for MDD and, cathode in supplementary motor area and anode at extra cephalic for OCD. The ELECT-TDCS (total n = 243, 52 with MRI) held 22 sessions and the group of Dr. Shavitt (n = 43) 20 sessions. For both studies, using the SimNibs software, current density that effectively reached gray matter will be analyzed. Based on the preliminary results of Bulubas et al and images acquired by Shavitt's group, our hypotheses are: (1) association between antidepressant response and density of the electric field in the prefrontal regions for MDD, (2) association between decreased symptoms of OCD and density of the electric field in the supplementary motor area, (3) positive correlations between gray matter volume of the left DPFC associated with improvement of depressive symptoms in the active tDCS group for MDD, (4) Default Mode Network (DMN) will be more hyper connected in individuals with more severe depressive symptoms; (5) DMN will be more hypo connected in individuals with more disabling symptoms of OCD, (6) fractional anisotropy of the prefrontal cortex will be associated with the antidepressant response of tDCS, (7) the brain volume of left Brodmann's areas 9, 10 and 46 and right Brodmann's area 9, not investigated in Bulubas et al., 2019, will be directly associated with tDCS antidepressant effects for MDD, (8) the brain volume of the thalamus and striatum will be directly associated with tDCS effects for OCD, (9) fractional anisotropy of the cingulate and corpus callosum will be negatively correlated with severity of symptoms for OCD.