Edythe D London1, Kyoji Okita2, Kaitlin R Kinney3, Andrew C Dean4, Megan N McClintick3, Elizabeth J Rizor3, Maritza C Johnson3, Tarannom Mahmoudie3, Arthur L Brody3, Erika L Nurmi4, Lauren C Seaman4, Judah Farahi5, Nathaniel Ginder4, Mark A Mandelkern6. 1. Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (UCLA), Los Angeles, CA, 90024, USA; Department of Molecular and Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA, 90024, USA; Brain Research Institute, University of California Los Angeles (UCLA), Los Angeles, CA, 90024, USA; Department of Research, Veterans Administration Greater Los Angeles Healthcare System (VAGLAHS), Los Angeles, CA, 90073, USA. Electronic address: elondon@mednet.ucla.edu. 2. Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (UCLA), Los Angeles, CA, 90024, USA; Department of Research, Veterans Administration Greater Los Angeles Healthcare System (VAGLAHS), Los Angeles, CA, 90073, USA; Department of Clinical Neuroimaging, Integrative Brain Imaging Center, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, 187-8551, Japan; Department of Drug Dependence, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, 187-8551, Japan. 3. Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (UCLA), Los Angeles, CA, 90024, USA; Department of Research, Veterans Administration Greater Los Angeles Healthcare System (VAGLAHS), Los Angeles, CA, 90073, USA. 4. Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (UCLA), Los Angeles, CA, 90024, USA. 5. Department of Research, Veterans Administration Greater Los Angeles Healthcare System (VAGLAHS), Los Angeles, CA, 90073, USA. 6. Department of Research, Veterans Administration Greater Los Angeles Healthcare System (VAGLAHS), Los Angeles, CA, 90073, USA; Department of Physics, University of California Irvine, Irvine, CA, 92697, USA.
Abstract
BACKGROUND: Radioligands for the translocator protein (TSPO) 18 kDa have been used with positron emission tomography (PET) to assess neuroinflammation and microglial activation in psychiatric disorders. One study using this approach showed substantial TSPO elevation throughout the brain in chronic methamphetamine users following long-term abstinence (0.5-4 years), but clients typically present for treatment earlier in abstinence. METHODS: We used PET with [11C]DAA1106 to compare standardized uptake values (SUVs) as an index of TSPO binding in the brains of methamphetamine-dependent participants who were abstinent for < 6 months (n = 11) and healthy controls (n = 12). We also assayed other typical correlates of Methamphetamine Dependence (e.g., striatal D2-type dopamine receptor deficits, depressed mood, anxiety and impaired emotion regulation). RESULTS: Methamphetamine users exhibited depression (p < 0.0001), anxiety (p = 0.002), difficulties in emotional regulation (p = 0.01), and lower striatal dopamine D2-type receptor availability vs. controls (p = 0.02). SUVs for [11C]DAA1106 were larger in all brain regions of methamphetamine-dependent participants vs. controls, but the effect size was small to medium and not statistically significant. CONCLUSIONS: The discrepancy between the lack of significant difference in TSPO binding in early-abstinent methamphetamine users vs. controls in this study and a previous report of elevated binding in longer-abstinent methamphetamine users may reflect methodological differences or limitations of TSPO binding as an index of neuroinflammation. It also seems possible that gliosis increases over time during the first 6 months of abstinence; longitudinal studies could clarify this possibility.
BACKGROUND: Radioligands for the translocator protein (TSPO) 18 kDa have been used with positron emission tomography (PET) to assess neuroinflammation and microglial activation in psychiatric disorders. One study using this approach showed substantial TSPO elevation throughout the brain in chronic methamphetamine users following long-term abstinence (0.5-4 years), but clients typically present for treatment earlier in abstinence. METHODS: We used PET with [11C]DAA1106 to compare standardized uptake values (SUVs) as an index of TSPO binding in the brains of methamphetamine-dependent participants who were abstinent for < 6 months (n = 11) and healthy controls (n = 12). We also assayed other typical correlates of Methamphetamine Dependence (e.g., striatal D2-type dopamine receptor deficits, depressed mood, anxiety and impaired emotion regulation). RESULTS: Methamphetamine users exhibited depression (p < 0.0001), anxiety (p = 0.002), difficulties in emotional regulation (p = 0.01), and lower striatal dopamine D2-type receptor availability vs. controls (p = 0.02). SUVs for [11C]DAA1106 were larger in all brain regions of methamphetamine-dependent participants vs. controls, but the effect size was small to medium and not statistically significant. CONCLUSIONS: The discrepancy between the lack of significant difference in TSPO binding in early-abstinent methamphetamine users vs. controls in this study and a previous report of elevated binding in longer-abstinent methamphetamine users may reflect methodological differences or limitations of TSPO binding as an index of neuroinflammation. It also seems possible that gliosis increases over time during the first 6 months of abstinence; longitudinal studies could clarify this possibility.
Authors: Arthur L Brody; Robert Hubert; Ryutaro Enoki; Lizette Y Garcia; Michael S Mamoun; Kyoji Okita; Edythe D London; Erika L Nurmi; Lauren C Seaman; Mark A Mandelkern Journal: Neuropsychopharmacology Date: 2017-03-06 Impact factor: 7.853
Authors: S M Berman; B Voytek; M A Mandelkern; B D Hassid; A Isaacson; J Monterosso; K Miotto; W Ling; E D London Journal: Mol Psychiatry Date: 2007-10-16 Impact factor: 15.992
Authors: Gausiha Rathitharan; Jennifer Truong; Junchao Tong; Tina McCluskey; Jeffrey H Meyer; Romina Mizrahi; Jerry Warsh; Pablo Rusjan; James L Kennedy; Sylvain Houle; Stephen J Kish; Isabelle Boileau Journal: Addict Biol Date: 2020-02-04 Impact factor: 4.280
Authors: David R J Owen; Roger N Gunn; Eugenii A Rabiner; Idriss Bennacef; Masahiro Fujita; William C Kreisl; Robert B Innis; Victor W Pike; Richard Reynolds; Paul M Matthews; Christine A Parker Journal: J Nucl Med Date: 2010-12-13 Impact factor: 10.057
Authors: David R Owen; Astrid J Yeo; Roger N Gunn; Kijoung Song; Graham Wadsworth; Andrew Lewis; Chris Rhodes; David J Pulford; Idriss Bennacef; Christine A Parker; Pamela L StJean; Lon R Cardon; Vincent E Mooser; Paul M Matthews; Eugenii A Rabiner; Justin P Rubio Journal: J Cereb Blood Flow Metab Date: 2011-10-19 Impact factor: 6.200
Authors: Zoe R Guttman; Dara G Ghahremani; Jean-Baptiste Pochon; Andy C Dean; Edythe D London Journal: Front Neurosci Date: 2021-07-12 Impact factor: 4.677