Neuroimaging Technique Aids Understanding of Treatment-Resistant Depression 


More than 300 million people worldwide suffer from depression, according to a 2017 report by the World Health Organization.

Of that number, approximately 30 percent have Treatment Resistant Depression (TRD), meaning they do not respond to standard antidepressant medications. Compared to patients with non-Treatment Resistant Depression (non-TRD), TRD patients suffer from lower recover/remission rates, increased recurrences and higher mortality rates.

“As the neuropathophysiology of TRD is unknown, clinical evaluation and treatment planning has been based on the subjective judgment of psychiatrists,” explains Zhiyun Jia, MD, PhD, professor at the Nuclear Medicine & Medical Imaging Center, West China Hospital, Sichuan University, Chengdu. “This prompted us to use the objective imaging method to investigate the possible neuropathology of TRD and its differences from non-TRD.”

Few imaging studies have examined the distinct neuropathology of TRD, which involves various abnormalities in different brain regions.

In new Radiology research, Dr. Jia and colleagues used a sensitive neuroimaging technique, magnetic transfer imaging (MTI), to explore the possible neuropathology of TRD and compare it with that of non-TRD in patients with a major depressive disorder (MDD). MDD is characterized as by at least two weeks of low mood that is present across most situations

“MTI is a unique, sensitive neuroimaging technique that lets us explore structural brain alterations at the macromolecular level,” Dr. Jia said.

The Neurology of Treatment-Resistant Depression

The study comprised 69 patients with MDD and 41 healthy control subjects.

Following the use of standard antidepressant medication, each patient was classified into a TRD or a non-TRD group based on their response to the treatment (30 with TRD; 39 with non-TRD).

Using MTI, the team obtained MT-weighted and non-MT-weighted images from all patients. These images were then used to calculate magnetization transfer ration (MTR) maps. Following data pre-processing, these maps were compared to explore macromolecular differences at the whole brain level among TRD, non-TRD and healthy controls.

The results showed that, relative to non-TRD patients, TRD patients exhibited significantly lower MTR in the task-positive network regions, including the bilateral precentral gyrus and left middle occipital lobe. The TRD patients also showed lower MTR in the default mode network regions, including the left precuneus and left temporal lobe.

“Because MTR reflects macromolecular concentrations in brain tissues, these results indicate that treatment resistance in major depression might be induced by abnormal insufficiency of macromolecular substances in the task-positive network and the default mode network regions,” Dr. Jia said.

“In addition, the left laterality of our results might imply that damage to the left hemisphere is more often associated with depressive symptoms than damage to the right hemisphere,” added fellow researcher Qiyong Gong, MD, PhD, also a radiologist at Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University. “This finding is in line with recent hypotheses on brain asymmetry.”

The finding of different macromolecular manifestations between TRD and non-TRD could prove influential in explaining why some patients respond effectively to antidepressant drugs while others respond poorly, even when there are no signs of brain morphometric changes. The study also provides structural evidence to prior functional MRI studies that showed a disrupted functional relationship between task-positive network and the default mode network in TRD.

This Radiology pilot study will likely spur further research, according to the researchers. They expect these findings to generate hypotheses regarding the macromolecular mechanisms for future investigations.

Research Continues on Treatment-resistant Depression

The research adds to the developing field of psychoradiology, a new frontier in neuroimaging that could play a major role in guiding diagnostic and treatment decisions in patients with psychiatric disorders.

Researchers plan to continue their work in TRD using other imaging modalities such as diffusion imaging and functional imaging in order to further explore the resistant mechanisms.

“We plan to integrate multimodal images to investigate correlations and differences between different imaging modalities,” Dr. Jia said. “We will also try to apply machine learning methods to find critical brain imaging markers that could potentially help identify TRD at the individual level for possible clinical translation.”

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