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Abstract
Objectives. Treatment-resistant depression is a common clinical occurrence among patients with major depressive disorder (MDD), but its neurobiology is poorly understood. We used data collected as part of routine clinical care to study white matter integrity of the brain's limbic system and its association to treatment response. Methods. Electronic medical records of multiple large New England hospitals were screened for patients with an MDD billing diagnosis, and natural language processing was subsequently applied to find those with concurrent diffusion-weighted images, but without any diagnosed brain pathology. Treatment outcome was determined by review of clinical charts. MDD patients (n = 29 non-remitters, n = 26 partial-remitters, and n = 37 full-remitters), and healthy control subjects (n = 58) were analyzed for fractional anisotropy (FA) of the fornix and cingulum bundle. Results. Failure to achieve remission was associated with lower FA among MDD patients, statistically significant for the medial body of the fornix. Moreover, global and regional-selective age-related FA decline was most pronounced in patients with treatment-refractory, non-remitted depression. Conclusions. These findings suggest that specific brain microstructural white matter abnormalities underlie persistent, treatment-resistant depression. They also demonstrate the feasibility of investigating white matter integrity in psychiatric populations using legacy data.
Acknowledgements
The authors thank Victor Castro, BS, for his assistance in collecting data from the research patient data registry; Sergey Goryachev, MS, for his assistance with natural language processing; Kenneth Nesbitt, for providing access to MRI data from Massachusetts General Hospital's radiology department; and Dr Bouix and Dr Kubicki, for their advice in the development of the imaging study.
Statement of Interest
Dr Iosifescu has received research support from Aspect Medical Systems, Forest Laboratories and Janssen Pharmaceutica; he has been a speaker for Eli Lilly & Co., Forest Laboratories, Pfizer, Inc. and Reed Medical Education. Dr Perlis has received consulting fees from Concordant Rater Systems, Proteus Biomedical, and RIDventures. All other contributors have none to declare.
This research is supported as a Driving Biological Project (PI: Dr Iosifescu) with the i2b2 grant (National Institutes of Health, NIH U54-LM008748; PI: Dr Kohane). Dr Iosifescu is also supported by the National Institutes of Health Career Development Award K23 MH067111. Dr Shenton is supported by grants from the National Institutes of Health (R01 MH 50740), and the Department of Veterans Affairs (VA) (VA Merit Award and VA Schizophrenia Research Center Grant). Dr Perlis is supported by a grant from the National Institute of Mental Health (MH086026).