Advancing Personalized Antidepressant Treatment Using PET/MRI

Summary

Despite current medications, morbidity and mortality of Major Depressive Disorder (MDD) remain high. According to the World Health Organization, MDD affects 121 million people worldwide, and is projected to be the second leading cause of global disability by 2020. Monotherapy with selective serotonin reuptake inhibitors (SSRIs) is the most widely used treatment for MDD. However, on average, SSRIs require six weeks for onset of action, and two-thirds of those on SSRIs fail to achieve remission. Compounding this problem, patients with residual symptoms are significantly more likely to discontinue treatment or relapse, be hospitalized for medical and psychiatric conditions, or die of suicide and other causes. Although eliminating ineffective treatment trials would significantly reduce patient suffering and healthcare costs,clinicians currently do not have the tools to objectively select treatment based on an individual's likelihood of remission. Therefore, there is an urgent need to identify markers predictive of an individual's SSRI treatment outcome. Developing this personalized treatment requires increased understanding of the relationship between pretreatment neurobiology, SSRI-induced biological changes, and the corresponding symptom improvements.

Timeline

Start

2015-05

Primary completion

2020-03

Completion

2020-03

Publications

• Dai F, Wengler K, He X, Wang J, Yang J, Parsey RV, DeLorenzo C. Lack of association between pretreatment glutamate/GABA and major depressive disorder treatment response. Transl Psychiatry. 2025 Mar 2;15(1):71. doi: 10.1038/s41398-025-03292-9.
• Narayan GA, Hill KR, Wengler K, He X, Wang J, Yang J, Parsey RV, DeLorenzo C. Does the change in glutamate to GABA ratio correlate with change in depression severity? A randomized, double-blind clinical trial. Mol Psychiatry. 2022 Sep;27(9):3833-3841. doi: 10.1038/s41380-022-01730-4. Epub 2022 Aug 18.

Drugs

Indications