title: Is treatment-resistance in unipolar melancholic depression characterized by decreased serotonin₂A receptors in the dorsal prefrontal - anterior cingulate cortex?
abstract: OBJECTIVE
  Quite a number of patients diagnosed with major depression are resistant to several well carried-out psychopharmacological interventions. It remains unclear as to how the serotonergic system is implicated in the phenomenon of treatment-resistance.
  
  
  METHODS
  We examined the involvement of post-synaptic 5-HT(2A) receptors in the pathophysiology of treatment-resistance in unipolar melancholic major depression with (123)I-5-I-R91150 SPECT. 15 antidepressant-naïve (ADN) first-episode depressed patients, 15 antidepressant-free treatment-resistant depressed (TRD) patients and 15 never-depressed individuals, matched for age and gender were studied.
  
  
  RESULTS
  Compared to ADN patients and healthy controls, TRD patients displayed significantly lower 5-HT(2A) receptor binding index (BI) in the dorsal regions of the prefrontal and the anterior cingulate cortex. No significant 5-HT(2A) receptor BI differences between ADN patients and controls were observed.
  
  
  CONCLUSIONS
  At the cortical level, 5-HT(2A) receptor BI does not significantly differ in first-episode melancholic depressed patients compared to healthy controls. This observation might imply a limited short-term impact on the serotonergic system in first episode depression. Our results also suggest that when encountered with treatment-resistance, the 5-HT(2A) receptors in the DPFC-ACC axis are significantly down-regulated. However, whether this assumed underlying pathophysiological mechanism is due solely to abnormalities in the serotonergic system remains to be answered. This article is part of a Special Issue entitled 'Anxiety and Depression'.
authors.affiliation: Department of Psychiatry, UZ Brussel, Vrije Universiteit Brussel (VUB), Brussels, Belgium. Chris.baeken@uzbrussel.be
authors.forename: Chris
authors.initials: C
authors.lastname: Baeken
authors.forename: Rudi
authors.initials: R
authors.lastname: De Raedt
authors.forename: Axel
authors.initials: A
authors.lastname: Bossuyt
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001931:Brain Mapping; D003866:Depressive Disorder / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000493:pharmacokinetics; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D011336:Probability; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D007456:Iodine Isotopes; D010880:Piperidines; C105020:R 91150; D044402:Receptor, Serotonin, 5-HT2A