Will imaging individual raphe nuclei in males with major depressive disorder enhance diagnostic sensitivity and specificity?

Background: Positron emission tomography (PET) studies in major depressive disorder (MDD) have reported higher serotonin 1A (5-HT_1A) autoreceptor binding in the raphe. In males, the difference is so large that it can potentially be used as the first biological marker for MDD. However, the raphe includes several nuclei, which project to different regions of the brain and spinal cord and may be differentially involved in disease. We aimed to identify 5-HT_1A differences in individual raphe nuclei using PET in order to determine whether use of subnuclei would provide greater sensitivity and specificity of diagnosing MDD. Methods: We identified individual nuclei using a hybrid set-level technique on an average [¹¹C]-WAY100635 PET image derived from 52 healthy volunteers (HV). We delineated three nuclei: dorsal raphe nucleus (DRN), median raphe nucleus (MRN), and raphe magnus (RMg). An atlas image of these nuclei was created and nonlinearly warped to each subject (through an associated MRI) in a separate sample of 41 males (25 HV, 16 MDD) who underwent [¹¹C]-WAY100635 PET. Results: 5-HT_1A binding was elevated in DRN in MDD (P <.01), and was not different in the RMg and MRN between groups. Receiver operating characteristic (ROC) curves showed that combining DRN and MRN produces highest sensitivity (94%) and specificity (84%) to identify MDD. Conclusion: In agreement with postmortem studies, we found higher 5-HT_1A autoreceptor binding in MDD selectively in the DRN. 5-HT_1A autoreceptor binding in the combined DRN and MRN is a better biomarker for MDD than in the raphe as a whole.