title: Striatal dopamine D2/3 receptor availability in treatment resistant depression.
abstract: Several studies demonstrated improvement of depressive symptoms in treatment resistant depression (TRD) after administering dopamine agonists which suggest abnormal dopaminergic neurotransmission in TRD. However, the role of dopaminergic signaling through measurement of striatal dopamine D(2/3) receptor (D2/3R) binding has not been investigated in TRD subjects. We used [(123)I]IBZM single photon emission computed tomography (SPECT) to investigate striatal D2/3R binding in TRD. We included 6 severe TRD patients, 11 severe TRD patients on antipsychotics (TRD AP group) and 15 matched healthy controls. Results showed no significant difference (p = 0.75) in striatal D2/3R availability was found between TRD patients and healthy controls. In the TRD AP group D2/3R availability was significantly decreased (reflecting occupancy of D2/3Rs by antipsychotics) relative to TRD patients and healthy controls (p<0.001) but there were no differences in clinical symptoms between TRD AP and TRD patients. This preliminary study therefore does not provide evidence for large differences in D2/3 availability in severe TRD patients and suggests this TRD subgroup is not characterized by altered dopaminergic transmission. Atypical antipsychotics appear to have no clinical benefit in severe TRD patients who remain depressed, despite their strong occupancy of D2/3Rs.
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, the Netherlands; Brain Imaging Center, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Bart P
authors.initials: BP
authors.lastname: de Kwaasteniet
authors.affiliation: Department of Psychiatry, MC groep, Lelystad, the Netherlands.
authors.forename: Chedwa
authors.initials: C
authors.lastname: Pinto
authors.forename: Henricus G
authors.initials: HG
authors.lastname: Ruhé
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, the Netherlands; Brain Imaging Center, Academic Medical Center, Amsterdam, the Netherlands; University of Groningen, University Medical Center Groningen, Mood and Anxiety Disorders, Department of Psychiatry, Groningen, the Netherlands.
authors.forename: Eric H G
authors.initials: EH
authors.lastname: Ruhé
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, the Netherlands; Brain Imaging Center, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Guido A
authors.initials: GA
authors.lastname: van Wingen
authors.affiliation: Brain Imaging Center, Academic Medical Center, Amsterdam, the Netherlands; Department of Nuclear Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Booij
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, the Netherlands; Brain Imaging Center, Academic Medical Center, Amsterdam, the Netherlands; The Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands.
authors.forename: Damiaan
authors.initials: D
authors.lastname: Denys
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy / Q000473:pathology; D065127:Dopamine D2 Receptor Antagonists / Q000737:chemistry; D005260:Female; D006801:Humans; D007462:Iodobenzenes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D019275:Radiopharmaceuticals / Q000737:chemistry; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000737:chemistry / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D007462:Iodobenzenes; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C426805:idobenzamide