Striatal dopamine D2/3 receptor-mediated neurotransmission in major depression: Implications for anhedonia, anxiety and treatment response
| Autor: | Erich T. Avery, Brian J. Mickey, Marta Peciña, Susana Peciña, Joseph Heffernan, Jon Kar Zubieta, Magdalena Sikora |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Anhedonia Anxiety Synaptic Transmission 0302 clinical medicine Pharmacology (medical) Raclopride Brain Mapping Cross-Over Studies Putamen Middle Aged Antidepressive Agents Fentanyl Psychiatry and Mental health Treatment Outcome medicine.anatomical_structure Neurology Female medicine.symptom Psychology medicine.drug Clinical psychology Adult medicine.medical_specialty Adolescent Nucleus accumbens Article Ventral pallidum Young Adult 03 medical and health sciences Dopamine Internal medicine medicine Humans Biological Psychiatry Pharmacology Depressive Disorder Major Motivation Receptors Dopamine D2 Ventral striatum Receptors Dopamine D3 030227 psychiatry Endocrinology Positron-Emission Tomography Ventral Striatum Neurology (clinical) Radiopharmaceuticals 030217 neurology & neurosurgery |
| Zdroj: | European Neuropsychopharmacology. 27:977-986 |
| ISSN: | 0924-977X |
| Popis: | Dopamine (DA) neurotransmission within the brain’s reward circuit has been implicated in the pathophysiology of depression and in both, cognitive and pharmacological mechanisms of treatment response. Still, a direct relationship between measures of DA neurotransmission and reward-related deficits in patients with depression has not been demonstrated. To gain insight into the symptom-specific alterations in the DA system in patients with depression, we used positron emission tomography (PET) and the D2/3 receptor-selective radiotracer [11C]raclopride in twenty-three non-smoking un-medicated Major Depressive Disorder (MDD) patients and sixteen healthy controls (HC). We investigated the relationship between D2/3 receptor availability and baseline measures of depression severity, anxiety, anhedonia, and cognitive and pharmacological mechanisms of treatment response. We found that, compared to controls, patients with depression showed greater D2/3 receptor availability in several striatal regions, including the bilateral ventral pallidum/nucleus accumbens (vPAL/NAc), and the right ventral caudate and putamen. In the depressed sample, D2/3 receptor availability in the caudal portion of the ventral striatum (NAc/vPAL) correlated with higher anxiety symptoms, whereas D2/3 receptor availability in the rostral area of the ventral striatum correlated negatively with the severity of motivational anhedonia. Finally, MDD non-remitters showed greater baseline anxiety, greater D2/3 availability in the NAc/vPAL, and greater placebo-induced DA release in the bilateral NAc. Our results demonstrate abnormally high D2/3 receptor availability in the ventral striatum of patients with MDD, which seem to be associated with comorbid anxiety symptoms and lack of response to antidepressants. |
| Databáze: | OpenAIRE |
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