A study by Jodie Gray, Ph.D., a recent graduate of UT Health San Antonio’s Radiological Sciences Program has found select brain areas which are reliably impacted by major depressive disorder (MDD).

The study, Multi-Modal Abnormalities of Brain Structure and Function in Major Depressive Disorder: A Meta-Analysis of Neuroimaging Studies, published in the May 2020 issue of the American Journal of Psychiatry, is the largest meta-analysis of brain imaging studies in depression to date and is the first to assess unified structural and functional brain imaging findings at this scale.

“Considering the problems that arise when analyzing brain imaging findings, we sought to cast a very wide net over the available data in depression,” Dr. Gray said.

The study analyzed findings from 92 previously published brain imaging studies of MDD spanning data from 2,928 human subjects. The study examined the effects of different imaging modalities (MRI, PET, SPECT) on observed brain changes as well as the potential role of varying clinical presentation of MDD on brain imaging findings.

Replication problem in brain imaging

These findings arise from large-scale analysis of brain imaging findings in human subjects and are unique in that previous attempts at finding an MDD-specific brain signature from big-data analysis have been unsuccessful.

Meta-analysis of brain imaging literature aims to identify brain areas that are reliably impacted by disease at a highly robust statistical level. Several recent such studies in psychiatric disorders indicate shared pathology across multiple diseases and a weak neurobiological “signal” of depression alone. These findings could be due to the preponderance of false positives in brain imaging literature, variability in clinical presentation of MDD, or a combination of both.

Nonetheless, clinical trials testing new therapies, and indeed the mental health care system as a whole, continue to evaluate depression as a unique disorder distinct from other mental health conditions. For these reasons, determining if MDD exhibits disease-specific brain changes – detectable through brain imaging studies – is of importance to the field.

The research team adopted a comprehensive approach to assess widespread MDD-specific brain abnormalities across imaging modalities. The breadth of data acquired for this study also allowed researchers to assess the effects of varied clinical aspects of MDD on brain imaging results – something that hasn’t been possible before due to limitations of available data.

Concordance of brain structure and function

The trans-imaging modality approach utilized in this study also enabled the assessment of convergent structural (gray matter atrophy) and functional (metabolism, neural activation and blood flow) brain abnormalities associated with MDD. This study is the first to largely assess effects across multiple brain imaging modalities in this manner and is the first to use the term “voxel-based pathophysiology” to define the union of such datasets.

As a result of these findings, the BrainMap database, housed at the Research Imaging Institute, plans to expand into the realm of voxel-based pathophysiology data to make such analyses available to researchers in future studies of other neuropsychiatric diseases.

Future directions    

These findings support longstanding theories of the role of the subgenual cingulate in depression, and indicate that MDD-specific structural and functional changes target the same areas within the brain.

Identification of the subgenual cingulate in the present study is of great importance to ongoing research in depression. The subgenual cingulate cortex  has long been hypothesized as a crucial brain area implicated in MDD and is a downstream target for experimental treatments such as transcranial magnetic stimulation.

“This endorses the selection of subgenual cingulate cortex as a “downstream target” for neuromodulatory treatments including transcranial magnetic stimulation and deep-brain stimulation” said Peter T. Fox, M.D., Professor of Neurology, Psychiatry and Radiology and director of the Research Imaging Institute.

Future studies stemming from this project will include brain connectivity analyses with the goal of improving targeting methods for network-based treatments such as transcranial magnetic stimulation.

Research collaborators Veronika Müller, Ph.D., and Simon Eickoff, M.D., of Research Center Jüelich and Heinrich Heine University Düsseldorf (Germany) contributed to study design and interpretation of findings for this study.

News coverage

This study was recently covered by the American Journal of Psychiatry Editor’s Spotlight:

https://www.youtube.com/watch?v=Y4b8JxNmi9E

Interested in connecting with Jodie? Find her on gsbsalumni.com. In Press is a section in The Pipette Gazette that highlights publications by students. To read more In Press articles, click here.