White Matter Abnormalities and Differential Treatment Outcomes to CBT or Antidepressant Medication
Poster No:
551
Submission Type:
Abstract Submission
Authors:
Jack Gomberg1, Jungho Cha1, Juna Khang1, Boadie Dunlop2, Edward Craighead2, Helen Mayberg1, Ki Sueng Choi1
Institutions:
1Icahn School of Medicine at Mount Sinai, New York, NY, 2Emory University, Atlanta, GA
First Author:
Co-Author(s):
Introduction:
First-line treatment for major depressive disorder (MDD) includes cognitive behavioral therapy (CBT) and/or antidepressant medications (ADM).1 However, these treatments can be highly effective in one patient but ineffective in another with similar MDD symptom presentations.2–4 Previous treatment selection biomarker studies using resting state fMRI (rsfMRI) implicate differential functional connectivity (FC) from the subcallosal cingulate (SCC) to the left anterior insula, left ventromedial prefrontal, and left periaqueductal gray in CBT and medication remitters.5 Structural white matter (WM) abnormalities that might mediate these functional connectivity patterns are unknown. Therefore, we evaluated pretreatment WM integrity in treatment naïve MDD patients as a function of differential 3-month clinical outcome to monotherapy with CBT or ADM.
Methods:
Diffusion-weighted imaging (DWI) was collected in 167 treatment naïve MDD patients randomized to 12 weeks of CBT or ADM. Subjects were grouped into CBT or ADM remitters (HDRS17 score <7 at 10 and 12 weeks) and CBT or ADM failure (HDRS score improvement <30%). A Whole brain fractional anisotropy (FA) map was calculated for each subject using the Fdt toolbox in FMRIB, and standard Tract-Based Spatial Statistics (TBSS) analysis was performed for preprocessing. A voxel-wise 2 x 2 ANOVA: treatment (CBT/ADM) by outcome (remitter/nonresponder) was performed using the AFNI 3dMVM toolbox. Furthermore, FA values from significant regions in 2 x 2 ANOVA were extracted and analyzed post hoc for treatment group-specific correlations with HDRS17 scores and previously published SCC functional connectivity.
Results:
A significant treatment by outcome interaction was identified, affecting WM tracts adjacent to the left anterior insula, left supplementary motor area, and left anterior/posterior hippocampus (p < 0.001). ADM remitters and CBT nonresponders show higher FA values in the left insula and SMA compared to both ADM nonresponders and CBT remitters, similar to the pattern of functional connectivity biomarkers. In contrast, ADM remitters and CBT nonresponders show lower FA in the left anterior and posterior hippocampus than ADM nonresponders and CBT remitters. In post hoc analysis, the left anterior insula showed significant anticorrelation between HDRS17 score improvement and FA value (r=-0.364, p=0.008) in the CBT treatment group but no significant correlation in the ADM group. The hippocampal findings showed significant anticorrelation for HDRS17 score improvement and FA value in the ADM group in both anterior (r=-0.244, p=0.009) and posterior (r=-0.202, p=0.031) subregions. The SMA revealed no significant correlation in either treatment groups. Finally, the insula and anterior hippocampus showed no significant correlation with past rsfMRI SCC FC biomarkers. The posterior hippocampus FA finding significantly correlated with FC findings in the SCC FC with the PAG (r=0.311, p=0.002), insula (r=0.294, p=0.003), and ventromedial prefrontal cortex (r=0.241, p=0.016). The SMA showed significant anticorrelation with the insular FC finding (r=-0.253, p=0.011).
Conclusions:
These findings identify differential WM integrity in WM tracts adjacent to the insula, SMA, and hippocampus in remitters and failures to CBT and ADM. As with functional connectivity findings, WM integrity may define imaging biotypes that impact the capacity to respond to first-line MDD treatments and guide optimal treatment selection. Furthermore, the differential outcomes between treatment groups for the FA correlations suggest differences in the underlying treatment mechanisms within depression circuit pathophysiology. Finally, the correlation of posterior hippocampal and SMA FA findings with past SCC FC biomarkers suggests a relationship between functional and structural findings in MDD.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Classification and Predictive Modeling 2
Diffusion MRI Modeling and Analysis
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity
Keywords:
Behavioral Therapy
MRI
Pharmacotherapy
Psychiatric
Psychiatric Disorders
Therapy
Treatment
White Matter
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - Depression
1|2Indicates the priority used for review
Provide references using author date format
2. Dunlop BW. Evidence-Based Applications of Combination Psychotherapy and Pharmacotherapy for Depression. Focus J Life Long Learn Psychiatry. 2016;14(2):156-173. doi:10.1176/appi.focus.20150042
3. Gelenberg AJ, Freeman MP, Markowitz JC, et al. WORK GROUP ON MAJOR DEPRESSIVE DISORDER. Published online 2010.
4. Collins FS, Varmus H. A New Initiative on Precision Medicine. N Engl J Med. 2015;372(9):793-795. doi:10.1056/NEJMp1500523
5. Dunlop BW, Rajendra JK, Craighead WE, et al. Functional Connectivity of the Subcallosal Cingulate Cortex And Differential Outcomes to Treatment With Cognitive-Behavioral Therapy or Antidepressant Medication for Major Depressive Disorder. Am J Psychiatry. 2017;174(6):533-545. doi:10.1176/appi.ajp.2016.16050518
6. Guo Q, Duan J, Cai S, Zhang J, Chen T, Yang H. Desynchronized white matter function and structure in drug-naive first-episode major depressive disorder patients. Front Psychiatry. 2023;13:1082052. doi:10.3389/fpsyt.2022.1082052