Higher 5-HT_1A autoreceptor binding as an endophenotype for major depressive disorder identified in high risk...

Higher serotonin-1A (5-HT_1A) receptor binding potential (BP_F) has been found in major depressive disorder (MDD) during and between major depressive episodes. We investigated whether higher 5-HT_1A binding is a biologic trait transmitted to healthy high risk (HR) offspring of MDD probands. Data were collected contemporaneously from: nine HR, 30 depressed not-recently medicated (NRM) MDD, 18 remitted NRM MDD, 51 healthy volunteer (HV) subjects. Subjects underwent positron emission tomography (PET) using [¹¹C]WAY100635 to quantify 5-HT_1A BP_F, estimated using metabolite, free fraction-corrected arterial input function and cerebellar white matter as reference region. Multivoxel pattern analyses (MVPA) of PET data evaluated group status classification of individuals. When tested across 13 regions of interest, an effect of diagnosis is found on BP_F which remains significant after correction for sex, age, injected mass and dose: HR have higher BP_F than HV (84.3% higher in midbrain raphe, 40.8% higher in hippocampus, mean BP_F across all 13 brain regions is 49.9% ± 11.8% higher). Voxel-level BP_F maps distinguish HR vs. HV. Elevated 5-HT_1A BP_F appears to be a familially transmitted trait abnormality. Future studies are needed to replicate this finding in a larger cohort and demonstrate the link to the familial transmission of mood disorders.