Molecular connectivity disruptions in males with major depressive disorder.

In most positron emission tomography (PET) molecular brain imaging studies, regions of interest have been defined anatomically and examined in isolation. However, by defining regions based on physiology and examining relationships between them, we may derive more sensitive measures of receptor abnormalities in conditions such as major depressive disorder (MDD). Using an average of 52 normalized binding potential maps, acquired using radiotracer [11C]-WAY100635 and full arterial input analysis, we identified two molecular volumes of interest (VOIs) with contiguously high serotonin 1A receptor (5-HT1A) binding sites: the olfactory sulcus (OLFS) and a band of tissue including piriform, olfactory, and entorhinal cortex (PRF). We applied these VOIs to a separate cohort of 25 healthy control males and 16 males with MDD who received [11C]-WAY100635 imaging. Patients with MDD had significantly higher binding than controls in both VOIs, (p < 0.01). To identify potential homeostatic disruptions in MDD, we examined molecular connectivity, i.e. the correlation between binding of raphe nucleus (RN) 5-HT1A autoreceptors and post-synaptic receptors in molecular VOIs. Molecular connectivity was significant in healthy controls (p < 0.01), but not in patients with MDD. This disruption in molecular connectivity allowed identification of MDD cases with high sensitivity (81%) and specificity (88%).