Serotonin-1A receptors in major depression quantified using PET: Controversies, confounds, and recommendations

► PET imaging of 5-HT1A receptor density in MDD patients has yielded mixed results. ► 'Methodological' rather than 'clinical' factors likely explain these discrepancies. ► One methodological confound is the use of the cerebellum as a reference region. ► Measuring parent radioligand concentrations in arterial plasma is imprecise. ► Other confounds are efflux transporter, radiometabolites, & 5-HT1A affinity states.