Serotonin 1A receptor distribution in treatment-resistant depression during psychopharmacotherapy compared to healthy controls

Major depressive disorder (MDD) is associated with a high lifetime prevalence and is a major cause of disability. An additional burden on patients is that up to 60% of the first antidepressant (AD) trials do not provide adequate symptom relief and after two subsequent AD trials, a patient is referred to as treatment-resistant. The serotonin 1A receptor subtype (5-HT1A) has commonly been used to study pathophysiological alteration in MDD. However, PET data on treatment-resistant depression (TRD) populations is still limited. In this cross-sectional study, 5-HT1A receptor binding was assessed in 20 TRD patients (9 female, mean age {+/-} SD, 29.0 {+/-} 5.2) and 20 healthy controls (HC) (10 female, mean age {+/-} SD, 33.2 {+/-} 8.2). Positron emission tomography (PET) scans with the radiotracer [carbonyl-11C]WAY-100635 were acquired and 5-HT1A non-displaceable binding potential (BPND) was quantified using the multilinear reference tissue model 2, with the cerebellar white matter as reference region. Mean regional BPND in five regions of interest (amygdala, anterior cingulate cortex, hippocampus, insula and orbitofrontal cortex) was compared in a repeated measures analysis of covariance (rmANCOVA) with age, sex and group as covariates. Estimated marginal means showed slightly lower BPND in TRD group (mean {+/-} SD = 5.464 {+/-} 0.247) than in the HC group (mean {+/-} SD = 5.938 {+/-} 0.245). However, the rmANCOVA showed no significant group difference (p = 0.659). Studies on 5-HT1A binding in MDD show heterogeneous results, where the directionality of difference as well as the significance of findings strongly depend on specific outcome measures (BPND, BPF or BPP), reference region or quantification method. Here we showed no significant effect of TRD on BPND, similar to other studies applying the same methodology for MDD cohorts.