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Dopamine Release in Antidepressant-Naive Major Depressive Disorder: A Multimodal [11C]-(+)-PHNO Positron Emission Tomography and Functional Magnetic Resonance Imaging Study.
Biol Psychiatry. 2018 10 15; 84(8):563-573.BP

Abstract

BACKGROUND

Mesolimbic dopamine system dysfunction is believed to contribute to major depressive disorder (MDD), but molecular neuroimaging of striatal dopamine neurotransmission has yielded mixed results, possibly owing to limited sensitivity of antagonist radioligands used with positron emission tomography to assess dopamine release capacity. This study used an agonist radioligand with agonist challenge to assess dopamine release capacity and D2/D3 receptor availability in MDD.

METHODS

Twenty-six treatment-naive adults with MDD and 26 healthy comparison participants underwent functional magnetic resonance imaging during a probabilistic reinforcement task, and positron emission tomography with the D3-preferring ligand [11C]-(+)-PHNO, before and after oral dextroamphetamine. MDD participants then received pramipexole treatment for 6 weeks.

RESULTS

MDD participants had trend-level greater dopamine release capacity in the ventral striatum, as measured by percent change in baseline binding potential relative to nondisplaceable compartment (ΔBPND) (-34% vs. -30%; p = .072, d = 0.58) but no difference in D2/D3 receptor availability (BPND). Striatal and extrastriatal BPND and percent change in baseline BPND were not significantly associated with blood oxygen level-dependent response to reward prediction error in the ventral striatum, severity of depression and anhedonia, or antidepressant response to pramipexole (response rate = 72.7%).

CONCLUSIONS

[11C]-(+)-PHNO demonstrated high sensitivity to displacement by amphetamine-induced dopamine release, but dopamine release capacity and D2/D3 availability were not associated with ventral striatal activation to reward prediction error or clinical features, in this study powered to detect large effects. While a preponderance of indirect evidence implicates dopaminergic dysfunction in MDD, these findings suggest that presynaptic dopamine dysregulation may not be a feature of MDD or a prerequisite for treatment response to dopamine agonists.

Authors+Show Affiliations

Division of Clinical Therapeutics, New York State Psychiatric Institute, Columbia University Medical Center, New York, New York; Department of Psychiatry, Columbia University Medical Center, New York, New York. Electronic address: fschneier@nyspi.columbia.edu.Division of Translational Imaging, New York State Psychiatric Institute, Columbia University Medical Center, New York, New York; Department of Psychiatry, Columbia University Medical Center, New York, New York.Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont; Department of Psychiatry, Harvard Medical School, Cambridge, Massachusetts.Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont; Department of Psychiatry, Harvard Medical School, Cambridge, Massachusetts.Department of Psychology, Columbia University Medical Center, New York, New York; Department of Psychology, Yale University, New Haven, Connecticut.Division of Clinical Therapeutics, New York State Psychiatric Institute, Columbia University Medical Center, New York, New York; Department of Psychiatry, Columbia University Medical Center, New York, New York.Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.Division of Translational Imaging, New York State Psychiatric Institute, Columbia University Medical Center, New York, New York; Department of Psychiatry, Columbia University Medical Center, New York, New York.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

30041971

Citation

Schneier, Franklin R., et al. "Dopamine Release in Antidepressant-Naive Major Depressive Disorder: a Multimodal [11C]-(+)-PHNO Positron Emission Tomography and Functional Magnetic Resonance Imaging Study." Biological Psychiatry, vol. 84, no. 8, 2018, pp. 563-573.
Schneier FR, Slifstein M, Whitton AE, et al. Dopamine Release in Antidepressant-Naive Major Depressive Disorder: A Multimodal [11C]-(+)-PHNO Positron Emission Tomography and Functional Magnetic Resonance Imaging Study. Biol Psychiatry. 2018;84(8):563-573.
Schneier, F. R., Slifstein, M., Whitton, A. E., Pizzagalli, D. A., Reinen, J., McGrath, P. J., Iosifescu, D. V., & Abi-Dargham, A. (2018). Dopamine Release in Antidepressant-Naive Major Depressive Disorder: A Multimodal [11C]-(+)-PHNO Positron Emission Tomography and Functional Magnetic Resonance Imaging Study. Biological Psychiatry, 84(8), 563-573. https://doi.org/10.1016/j.biopsych.2018.05.014
Schneier FR, et al. Dopamine Release in Antidepressant-Naive Major Depressive Disorder: a Multimodal [11C]-(+)-PHNO Positron Emission Tomography and Functional Magnetic Resonance Imaging Study. Biol Psychiatry. 2018 10 15;84(8):563-573. PubMed PMID: 30041971.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dopamine Release in Antidepressant-Naive Major Depressive Disorder: A Multimodal [11C]-(+)-PHNO Positron Emission Tomography and Functional Magnetic Resonance Imaging Study. AU - Schneier,Franklin R, AU - Slifstein,Mark, AU - Whitton,Alexis E, AU - Pizzagalli,Diego A, AU - Reinen,Jenna, AU - McGrath,Patrick J, AU - Iosifescu,Dan V, AU - Abi-Dargham,Anissa, Y1 - 2018/05/25/ PY - 2018/03/14/received PY - 2018/05/02/revised PY - 2018/05/15/accepted PY - 2018/7/26/pubmed PY - 2019/10/16/medline PY - 2018/7/26/entrez KW - Dopamine KW - Functional magnetic resonance imaging KW - Major depressive disorder KW - Positron emission tomography KW - Pramipexole KW - [(11)C]-(+)-PHNO SP - 563 EP - 573 JF - Biological psychiatry JO - Biol Psychiatry VL - 84 IS - 8 N2 - BACKGROUND: Mesolimbic dopamine system dysfunction is believed to contribute to major depressive disorder (MDD), but molecular neuroimaging of striatal dopamine neurotransmission has yielded mixed results, possibly owing to limited sensitivity of antagonist radioligands used with positron emission tomography to assess dopamine release capacity. This study used an agonist radioligand with agonist challenge to assess dopamine release capacity and D2/D3 receptor availability in MDD. METHODS: Twenty-six treatment-naive adults with MDD and 26 healthy comparison participants underwent functional magnetic resonance imaging during a probabilistic reinforcement task, and positron emission tomography with the D3-preferring ligand [11C]-(+)-PHNO, before and after oral dextroamphetamine. MDD participants then received pramipexole treatment for 6 weeks. RESULTS: MDD participants had trend-level greater dopamine release capacity in the ventral striatum, as measured by percent change in baseline binding potential relative to nondisplaceable compartment (ΔBPND) (-34% vs. -30%; p = .072, d = 0.58) but no difference in D2/D3 receptor availability (BPND). Striatal and extrastriatal BPND and percent change in baseline BPND were not significantly associated with blood oxygen level-dependent response to reward prediction error in the ventral striatum, severity of depression and anhedonia, or antidepressant response to pramipexole (response rate = 72.7%). CONCLUSIONS: [11C]-(+)-PHNO demonstrated high sensitivity to displacement by amphetamine-induced dopamine release, but dopamine release capacity and D2/D3 availability were not associated with ventral striatal activation to reward prediction error or clinical features, in this study powered to detect large effects. While a preponderance of indirect evidence implicates dopaminergic dysfunction in MDD, these findings suggest that presynaptic dopamine dysregulation may not be a feature of MDD or a prerequisite for treatment response to dopamine agonists. SN - 1873-2402 UR - https://www.unboundmedicine.com/medline/citation/30041971/Dopamine_Release_in_Antidepressant_Naive_Major_Depressive_Disorder:_A_Multimodal_[11C]__+__PHNO_Positron_Emission_Tomography_and_Functional_Magnetic_Resonance_Imaging_Study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-3223(18)31531-2 DB - PRIME DP - Unbound Medicine ER -