Serotonin 1A receptor density measured by F18-Mefway PET/CT in mesiotemporal cortex and raphe does not discriminate therapeutic response in patients with major depressive episode.

Background: More than 50% of patients with major depressive episode (MDE) fail to respond to initial treatment with first line pharmacological therapy. Altered receptor and serotonin transporter function are considered to be associated with mental disorders. Our investigation aimed on the density of the HT1A receptor in mesiotemporal cortex (MTC) and raphe measured by F18-Mefway in patients with MDD.

Methods: Patients with untreated clinically suspected major depressive episode were recruited from June 2012 to May 2014. 49 patients were included into the study: 36 patients (73%) were identified as responders, whereas 13 (27%) were non-responders. Gender distribution was 26 men (56%) and 23 women (44%). For treatment, only a standard medication of a selective serotonin reuptake inhibitor (SSRI) with escitalopram in a range of 10-20 mg/day was permitted. Responders were defined by improvement of the MADRS>50%. Visually MTC had the highest uptake of F18-Mefway among all brain regions, an asymmetry could not be observed in any patient. An elliptical region was drawn over the amygdala and hippocampus area and a small circular region was drawn over the raphe nuclei. All data were calculated related to (unspecific) cerebellar uptake.

Results: The quotient of the right MTC was 5.00 [4.33; 5.50] in all patients, in responders 5.00 [4.00; 5.75] and in non-responders 5.00 [4.50; 5.50] (P=0.56). The quotient of the left MTC presented with a median level of 4.50 [4.50; 5.50] in all persons. The responders had 4.50 [4.50; 5.75] which was not statistically significant to the data of the non-responders with 5.00 [4.50; 5.50] at P=0.64. The raphe had a median quotient of 2.50 [2.00; 3.00] in all and the cohort of responders, whereas non-responders had 2.50 [2.00; 2.50] (P=0.61). Also the absolute values of SUV in the three brain regions were not statistically different between the cohorts. Additionally, we did not find any sex-related differences in our patient group.

Conclusions: Serotonin 1A receptor density can be assessed efficiently by F18-Mefway and PET-CT in patients with MDE. The method can be estimated as a possible tool for clinical and academic investigation, marked tracer uptake can constantly be observed at MTC and the raphe. Anyhow, under conditions of real life in patient care, it is not possible to distinguish patients with a good prognosis who will respond to standard SSRI therapy from non-responders who would benefit from a different therapeutic approach starting earlier.