Neural Circuitry and Therapeutic Targeting of Depressive Symptoms in Schizophrenia Spectrum Disorders

Poster Session C - Sunday, April 14, 2024, 5:00 – 7:00 pm EDT, Sheraton Hall ABC

Julia Gallucci^1,2 (julia.gallucci@mail.utoronto.ca), Ju-chi Yu¹, Lindsay Oliver¹, Hajer Nakua^1,2, Peter Zhukovsky¹, Erin Dickie^1,3, Zafiris Daskalakis⁴, George Foussias^1,2,3, Daniel Blumberger^1,2,3,5, Colin Hawco^1,2,3, Aristotle Voineskos^1,2,3; ¹Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada, ²Institute of Medical Science, University of Toronto, Toronto, ON, Canada, ³Department of Psychiatry, University of Toronto, Toronto, ON, Canada, ⁴Department of Psychiatry, University of California San Diego School of Medicine, La Jolla, CA, United States of America, ⁵Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada

Conceptual similarities between depressive and negative symptoms complicate biomarker and intervention development.This study employed a data-driven approach to delineate the neural circuitry underlying depressive and negative symptoms in SSDs.Data from three studies: two neuroimaging studies and a randomized repetitive transcranial magnetic stimulation(rTMS) trial were analyzed(n=157) to assess brain-behavior relationships.Partial Least Squares Correlation(PLSC) investigated associations between resting-state functional connectivity and depressive and negative symptoms.Secondary analysis of rTMS trial data(active n=37,sham n=33) were used to assess relationships between PLSC-derived symptom profiles and treatment outcomes.PLSC identified three latent variables(LVs) relating functional brain circuitry with symptom profiles. LV1 related a general depressive symptom factor with positive associations between and within Default Mode Network(DMN), Frontoparietal Network(FPN), and Cingulo-Opercular Network(CON).LV2 related negative symptoms(no depressive symptoms) via negative associations, especially between FPN and CON, but also between DMN with FPN and CON.LV3 related a guilt and early wakening depression factor via negative rather than positive associations to the DMN, FPN, and CON.The secondary visual network had a positive association with general depressive symptoms and negative associations with guilt and negative symptoms.Active(but not sham) rTMS to the bilateral dorsolateral prefrontal cortex(DLPFC) reduced general depressive but not guilt-related or negative symptoms.Our findings clearly differentiate the neural circuitry underlying depressive and negative symptoms, and even segregated across the two-factor structure of depression in SSDs.These findings support divergent neurobiological pathways of depressive symptoms and negative symptoms in people with SSDs.As treatment options are currently limited,rTMS to the bilateral DLPFC is worth exploring further for general depressive symptoms in people with SSDs.

Topic Area: METHODS: Neuroimaging