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 D2/3 receptor (D2/3R) binding has not been investigated in TRD subjects. We used [123I]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.
Highlights
About one third of patients with major depressive disorder (MDD) do not respond to two or more trials with different classes of antidepressants and are considered treatment resistant [1,2]
Hamilton Depression Rating Scale (HAM-D) and Montgomery Asberg Depression Rating Scale (MADRS) scores did not differ between Treatment resistant depression (TRD) and TRD AP patients which indicates no difference in severity of depression between both groups
We included a unique group of severe TRD patients which were eligible for deep brain stimulation, with an illness duration of more than 2 years defined as non-response to at least four adequate treatments of different antidepressants and at least 6 sessions of bilateral electroconvulsive therapy (ECT)
Summary
About one third of patients with major depressive disorder (MDD) do not respond to two or more trials with different classes of antidepressants and are considered treatment resistant [1,2]. Little is known about the pathophysiology of TRD, several studies in TRD subjects demonstrated improvement of depressive symptoms after treatment with dopamine agonists [4,5,6]. These findings suggest that abnormal dopaminergic neurotransmission is implicated in the pathophysiology of TRD [7]. In TRD, anhedonia is often more profound and long-lasting and associated with a deficiency of the reward/motivational systems in the brain. This mesolimbic tract arises from the ventral tegmental area (VTA) and projects to the ventral striatum (including the nucleus accumbens), hippocampus and amygdala
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
