FDG PET could predict treatment response for major depressives

Previous studies have pointed to treatment-specific imaging biomarkers for predicting response to therapy for patients with major depressive disorder (MDD), but brain imaging with FDG PET, particularly of the anterior insula, is going a step further to differentiate response to combined treatments, which could improve management of patients with the mood disorder, according to a study published June 12 in JAMA Psychiatry.

Callie L. McGrath, BA, from the department of psychiatry and behavioral sciences at Emory University in Atlanta, and colleagues analyzed metabolic patterns in PET imaging of different brain regions for their ability to predict differential response to multiple therapies, either pharmacological or cognitive behavioral psychotherapy.

“Major depressive disorder is a highly prevalent, disabling, and costly illness,” wrote McGrath et al. “For a patient presenting with MDD, an antidepressant medication or evidence-based psychotherapy is currently recommended as first-line treatment. However, fewer than 40 percent of patients achieve remission with initial treatment, and choosing the ‘wrong’ initial treatment has significant individual and societal costs due to continued distress, risk of suicide, loss of productivity, and wasted resources associated with two to three months of an ineffective treatment. Given the public health consequences of inadequately treated depression, a clinical or biological marker to guide initial treatment selection for MDD could have major health and economic impact.”

A total of 38 subjects, ages 18 to 60 years, with current and untreated major depressive disorder were included in the analysis. Glucose metabolism of the brain was imaged using FDG PET and a majority of imaging was coregistered with MRI for attenuation correction. Imaging took place before subjects received randomized phase-one treatment for 12 weeks of either cognitive behavior therapy or the selective serotonin reuptake inhibitor (SSRI) escitalopram oxalate. If patients did not achieve remission at the conclusion of the first phase, they entered into a second phase of treatment with an additional 12 weeks of a combination of both cognitive behavioral therapy and escitalopram.

Remission was defined as a score of seven along the 17-item Hamilton Depression Rating Scale and patients were assessed by blinded rating. Of the 38 imaging subjects included in the study, 12 achieved remission with cognitive behavioral therapy and 11 with the SSRI. Nine were unresponsive to cognitive behavior therapy, while six did not respond to escitalopram.

Brain regions of interest included six limbic and cortical areas and the right anterior insula was the strongest indicator of predictive response with an effect size equal to 1.43. Relative to whole-brain mean, poor response to cognitive behavior therapy and remission with escitalopram drug treatment was connected to insula hypermetabolism, whereas insula hypometabolism was correlated with a poor response to escitalopram and successful remission with cognitive behavior therapy.

“If verified with prospective testing, the insula metabolism-based treatment-specific biomarker defined in this study provides the first objective marker, to our knowledge, to guide initial treatment selection for depression,” wrote the authors.