Differences in White Matter Associated with Relapse in Patients with Major Depressive Disorder

669 

Abstract Submission 

Jack Gomberg¹, Jungho Cha¹, Boadie Dunlop², Edward Craighead², Helen Mayberg¹, Ki Sueng Choi¹

¹Icahn School of Medicine at Mount Sinai, New York, NY, ²Emory University, Atlanta, GA

Jack Gomberg  
Icahn School of Medicine at Mount Sinai
New York, NY

Jungho Cha  
Icahn School of Medicine at Mount Sinai
New York, NY

Boadie Dunlop, MD  
Emory University
Atlanta, GA

Edward Craighead, MD  
Emory University
Atlanta, GA

Helen Mayberg  
Icahn School of Medicine at Mount Sinai
New York, NY

Ki Sueng Choi  
Icahn School of Medicine at Mount Sinai
New York, NY

Episodes of recurrence in major depressive disorder (MDD) are common.1 However, predictors of recurrence are not well established. Previous studies have found that differential functional connectivity (FC) in the salience and affective networks show promise for predicting symptom recurrence in previously remitted MDD patients.2 Structural changes underlying these functional differences are unknown and may offer further predictors for recurrence.3 Using diffusion-weighted imaging (DWI) and clinical data from the 21-month follow-up phase for remitters in the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) trial, we evaluated if differences in white matter (WM) could identify patients who would experience recurrence.4 We hypothesized that abnormal WM integrity would be found in the tracts between the right SCC and insula, given previous FC findings.

Of the 344 patients randomized to 12 weeks of CBT, SSRI, or SNRI in PReDICT, 60 patients had usable DWI imaging at both baseline and 12 weeks and achieved remission. Of these 60 patients, 14 were assigned to cognitive behavioral therapy (CBT), 22 to duloxetine, and 24 to citalopram. 8 experienced recurrences during the follow-up phase 24 months from the study baseline. Of these 8 patients, 2 had been assigned to CBT, 4 to duloxetine, and 2 to citalopram. MRI scans were obtained during the week prior to treatment randomization and 1-5 days prior to the week 12 visit. A Whole brain fractional anisotropy (FA) map was calculated for each subject using the Fdt FMRIB toolbox. Tract-Based Spatial Statistics (TBSS) analysis was performed for statistical comparison across outcome groups. A two-sample t-test with 5000 permutations was performed using a randomise toolbox in the FA maps of week 12 and the FA changes between baseline and 12 weeks of treatment. We used a significance threshold of family-wise error (FWE) corrected α < 0.05.

In the FWE corrected t-test, there was a significant difference in the change in FA in regions along the right corticospinal tract, superior longitudinal, and frontal-occipital fasciculi. Relapsed patients show significant FA reduction between baseline and week 12 (mean=-0.0259, SE 0.0144, p=0.002) in these white matter tracts, while non-relapse show no changes. There was no significant difference between relapsed and non-relapsed patients in week 12 alone.

These findings suggest that WM changes during treatment are important for relapse, not white matter integrity at the point of remission. This provides insight for the role of white matter in MDD treatment and relapse.

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ¹

Classification and Predictive Modeling

Diffusion MRI Modeling and Analysis ²

Diffusion MRI

Behavioral Therapy

FUNCTIONAL MRI

MRI

Pharmacotherapy

Psychiatric

Psychiatric Disorders

Treatment

White Matter

WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC

Other - depression