Deficits in Regional Cerebral Blood Flow on Brain SPECT Predict Treatment Resistant Depression

Background: Depression remains an important risk factor for Alzheimer's disease, yet few neuroimaging biomarkers are available to identify treatment response in depression. Objective: To analyze and compare functional perfusion neuroimaging in persons with treatment resistant depression (TRD) compared to those experiencing full remission. Methods: A total of 951 subjects from a community psychiatry cohort were scanned with perfusion single photon emission computed tomography (SPECT) of the brain in both resting and task related settings. Of these, 78% experienced either full remission (n=506) or partial remission (n=237) and 11% were minimally responsive (n=103) or non-responsive (11%. n=106). Severity of depression symptoms were used to define these groups with changes in the Beck Depression Inventory prior to and following treatment. Voxel-based analyses of brain SPECT images from full remission compared to the worsening group was conducted with the statistical parametric mapping software, version 8 (SPM 8). Multiple comparisons were accounted for with a false discovery rate (p<0.001). Results: Persons with depression that worsened following treatment had reduced cerebral perfusion compared to full remission in the multiple regions including the bilateral frontal lobes, right hippocampus, left precuneus, and cerebellar vermis. Such differences were observed on both resting and concentration SPECT scans. Conclusion: Our findings identify imaging-based biomarkers in persons with depression related to treatment response. These findings have implications in understanding both depression to prognosis and its role as a risk factor for dementia.