Determinants of brain SPECT perfusion and connectivity in treatment-resistant depression

• Functional neuroimaging could determine brain abnormalities related to TRD.
• Brain SPECT perfusion of 127 TRD patients was compared to healthy subjects.
• A shared SPECT pattern was found whatever the profile of TRD involving fronto-temporal regions and the cerebellum.

This study aims to characterize and compare functional brain single photon emission tomography (SPECT) perfusion and connectivity in treatment-resistant depression (TRD) according to distinct demographic or clinical profiles (male vs. female; old vs. young; unipolar vs. bipolar) and to study their relationship to the severity and the duration of episode/illness. We retrospectively included 127 consecutive patients who met DSM-IV criteria for a nonpsychotic major TRD episode. All patients were studied using 99mTc-ethyl cysteinate dimer SPECT. Whole-brain, voxel-based, between-groups analyses were performed according to demographic and clinical data and in comparison to 37 healthy subjects. Voxel-wise interregional correlation was also performed to compare functional SPECT connectivity. Finally, relationships were searched for regarding severity and duration of episode/illness. The whole group of patients exhibited significant hypoperfusion within bilateral fronto-temporal, insular, and anterior cingulate cortices, as well as within the left caudate. Functional connectivity between left frontal and left cerebellar regions was higher in patients than in healthy subjects. Gender, age, and type of mood disorder did not influence these SPECT patterns. A significant relationship was found between brain SPECT perfusion and either duration or global severity of illness in particular frontal areas. Our data support the hypothesis of a shared SPECT pattern, whatever the profile of TRD, involving fronto-temporal regions and the cerebellum.