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Brain Structure and Function

, Volume 223, Issue 6, pp 2609–2625 | Cite as

In vivo relationship between serotonin 1A receptor binding and gray matter volume in the healthy brain and in major depressive disorder

  • Francesca Zanderigo
  • Spiro Pantazatos
  • Harry Rubin-Falcone
  • R. Todd Ogden
  • Binod Thapa Chhetry
  • Gregory Sullivan
  • Maria Oquendo
  • Jeffrey M. Miller
  • J. John Mann
Original Article
  • 201 Downloads

Abstract

Serotonin 1A (5-HT1A) receptors mediate serotonin trophic role in brain neurogenesis. Gray matter volume (GMV) loss and 5-HT1A receptor binding alterations have been identified in major depressive disorder (MDD). Here we investigated the relationship between 5-HT1A receptor binding and GMV in 40 healthy controls (HCs) and, for the first time, 47 antidepressant-free MDD patients using Voxel-Based Morphometry and [11C]WAY100635 Positron Emission Tomography. Values of GMV and 5-HT1A binding (expressed as BPF, one of the types of binding potentials that refer to displaceable or specific binding that can be quantified in vivo with PET) were obtained in 13 regions of interest, including raphe, and at the voxel level. We used regression analysis within each group to predict GMV from BPF, while covarying for age, sex, total gray matter volume and medication status. In the HCs group, we found overall a positive correlation between terminal field 5-HT1A receptor binding and GMV, which reached statistical significance in regions such as hippocampus, insula, orbital prefrontal cortex, and parietal lobe. We observed a trend towards inverse correlation between raphe 5-HT1A autoreceptor binding and anterior cingulate GMV in both groups, and a statistically significant positive correlation between raphe 5-HT1A binding and temporal GMV in MDD. Analysis of covariance at the voxel-level revealed a trend towards interaction between diagnosis and raphe 5-HT1A binding in predicting GMV in cerebellum and supramarginal gyrus (higher correlation in HCs compared with MDD). Our results replicated previous findings in the normative brain, but did not extend them to the brain in MDD, and indicated a trend towards dissociation between MDD and HCs in the relationship of raphe 5-HT1A binding with postsynaptic GMV. These results suggest that 5-HT1A receptors contribute to altered neuroplasticity in MDD, possibly via effects predating depression onset.

Keywords

Positron emission tomography Magnetic resonance imaging Serotonin 1A receptor Gray matter volume Major depressive disorder 

Notes

Compliance with ethical standards

Conflict of interest

Drs. Zanderigo and Ogden, Mr. Rubin-Falcone and Mr. Binod Thapa Chhetry have no conflicts of interest to declare. Dr. Pantazatos’s contribution to this work was supported by NIMH K01MH108721. Drs. Mann and Oquendo receive royalties for commercial use of the Columbia-Suicide Severity Rating Scales from the Research Foundation for Mental Hygeine and Dr. Oquendo receives an honorarium as President of the American Psychiatric Association. Her family owns stock in Bristol Myers Squibb. Dr. Miller’s family previously owned stock in Johnson & Johnson, unrelated to the current manuscript. Dr. Sullivan is currently employed by Tonix Pharmaceuticals, Inc. and holds stock in the same, unrelated to the current manuscript.

References

  1. Akimova E, Lanzenberger R, Kasper S (2009) The serotonin-1A receptor in anxiety disorders. Biol Psychiatry 66:627–635.  https://doi.org/10.1016/j.biopsych.2009.03.012 CrossRefPubMedGoogle Scholar
  2. Ashburner J (2007) A fast diffeomorphic image registration algorithm. NeuroImage. 38:95–113  https://doi.org/10.1016/j.neuroimage.2007.07.007 CrossRefPubMedGoogle Scholar
  3. Azmitia EC (2001) Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis. Brain Res Bull 56:413–424CrossRefPubMedGoogle Scholar
  4. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571CrossRefPubMedGoogle Scholar
  5. Benninghoff J et al (2010) Serotonin depletion hampers survival and proliferation in neurospheres derived from adult neural stem cells. Neuropsychopharmacol 35:893–903.  https://doi.org/10.1038/npp.2009.181 CrossRefGoogle Scholar
  6. Borroto-Escuela DO et al (2015a) Evidence for the existence of FGFR1-5-HT1A heteroreceptor complexes in the midbrain raphe 5-HT system biochem. Biophys Res Commun 456:489–493.  https://doi.org/10.1016/j.bbrc.2014.11.112 CrossRefGoogle Scholar
  7. Borroto-Escuela DO et al (2015b) Enhancement of the FGFR1 signaling in the FGFR1-5-HT1A heteroreceptor complex in midbrain raphe 5-HT neuron systems. Relevance for neuroplasticity depression. Biochem Biophys Res Commun 463:180–186.  https://doi.org/10.1016/j.bbrc.2015.04.133 CrossRefPubMedGoogle Scholar
  8. Borroto-Escuela DO, Tarakanov AO, Fuxe K (2016) FGFR1-5-HT1A heteroreceptor complexes: implications for understanding and treating major. Depression Trends Neurosci 39:5–15.  https://doi.org/10.1016/j.tins.2015.11.003 CrossRefPubMedGoogle Scholar
  9. Braestrup C, Squires RF (1978) Pharmacological characterization of benzodiazepine receptors in the brain European. J Pharmacol 48:263–270Google Scholar
  10. Casanova R et al (2007) Biological parametric mapping: a statistical toolbox for multimodality brain. Image Anal Neuroimage 34:137–143.  https://doi.org/10.1016/j.neuroimage.2006.09.011 CrossRefGoogle Scholar
  11. Citri A, Malenka RC (2008) Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacol 33:18–41.  https://doi.org/10.1038/sj.npp.1301559 CrossRefGoogle Scholar
  12. Dannlowski U et al (2014) Serotonin transporter gene methylation is associated with hippocampal gray matter volume. Hum Brain Mapp 35:5356–5367.  https://doi.org/10.1002/hbm.22555 CrossRefPubMedGoogle Scholar
  13. Daubert EA, Condron BG (2010) Serotonin: a regulator of neuronal morphology and circuitry. Trends Neurosci 33:424–434.  https://doi.org/10.1016/j.tins.2010.05.005 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Dayer A (2014) Serotonin-related pathways and developmental plasticity: relevance for psychiatric disorders. Dialog Clin Neurosci 16:29–41Google Scholar
  15. DeLorenzo CKA, Mikhno A, Gray N, Zanderigo F, Mann JJ, Parsey RV (2009) A new method for assessing PET-MRI coregistration. In: Medical Imaging 2009: Image Processing; 2009, Lake Buena Vista. SPIE, FLGoogle Scholar
  16. Depping MS, Wolf ND, Vasic N, Sambataro F, Thomann PA, Christian Wolf R (2015) Specificity of abnormal brain volume in major depressive disorder: a comparison with borderline personality disorder. J Affective Disorders 174:650–657.  https://doi.org/10.1016/j.jad.2014.11.059 CrossRefGoogle Scholar
  17. Dompert WU, Glaser T, Traber J (1985) 3H-TVX Q 7821: identification of 5-HT1 binding sites as target for a novel putative anxiolytic Naunyn-Schmiedeberg’s. Arch Pharmacol 328:467–470CrossRefGoogle Scholar
  18. Draganski B, Gaser C, Busch V, Schuierer G, Bogdahn U, May A (2004) Neuroplasticity: changes in grey matter induced. by training. Nature 427:311–312.  https://doi.org/10.1038/427311a CrossRefPubMedGoogle Scholar
  19. Drevets WC et al (1999) PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry 46:1375–1387CrossRefPubMedGoogle Scholar
  20. Drevets WC, Thase ME, Moses-Kolko EL, Price J, Frank E, Kupfer DJ, Mathis C (2007) Serotonin-1A receptor imaging in recurrent depression: replication and literature review. Nuclear Med Biol 34:865–877.  https://doi.org/10.1016/j.nucmedbio.2007.06.008 CrossRefGoogle Scholar
  21. Duvernoy H (1991) The human brain: surface, three-dimensional sectional anatomy and MRI. New YorkGoogle Scholar
  22. First MSR, Gibbon M, Williams J (1995) Structured clinical interview for DSM-IV axis I disorders (SCID-I/P, Version 2.0). Biometrics Research Dept., New York State Psychiatric Institute, New YorkGoogle Scholar
  23. First MB, Spitzer RL, Gibbon M, Williams JB (2012) Structured clinical interview for DSM-IV® Axis I disorders (SCID-I), clinician version,. American Psychiatric Pub.Google Scholar
  24. Gaspar P, Cases O, Maroteaux L (2003) The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci 4:1002–1012.  https://doi.org/10.1038/nrn1256 CrossRefPubMedGoogle Scholar
  25. Geuze E, Vermetten E, Bremner JD (2005) MR-based in vivo hippocampal volumetrics: 1. Review of methodologies currently employed. Mol Psychiatry 10:147–159.  https://doi.org/10.1038/sj.mp.4001580 CrossRefPubMedGoogle Scholar
  26. Goodkind M et al (2015) Identification of a common neurobiological substrate for mental illness. JAMA Psychiatry 72:305–315.  https://doi.org/10.1001/jamapsychiatry.2014.2206 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Gunn RN, Gunn SR, Turkheimer FE, Aston JA, Cunningham VJ (2002) Positron emission tomography compartmental models: a basis pursuit strategy for kinetic modeling. J Cereb Blood Flow Metabol 22:1425–1439.  https://doi.org/10.1097/00004647-200212000-00003 CrossRefGoogle Scholar
  28. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62CrossRefPubMedPubMedCentralGoogle Scholar
  29. Hirvonen J et al (2008) Decreased brain serotonin 5-HT1A receptor availability in medication-naive patients with major depressive disorder: an in-vivo imaging study using PET and [carbonyl-11C]WAY-100635. Int J Neuropsychopharmacol 11:465–476CrossRefPubMedGoogle Scholar
  30. Hsiung SC, Adlersberg M, Arango V, Mann JJ, Tamir H, Liu KP (2003) Attenuated 5-HT1A receptor signaling in brains of suicide victims: involvement of adenylyl cyclase, phosphatidylinositol 3-kinase, Akt and mitogen-activated protein kinase. J Neurochem 87:182–194CrossRefPubMedGoogle Scholar
  31. Innis RB et al (2007) Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 27:1533–1539.  https://doi.org/10.1038/sj.jcbfm.9600493 CrossRefPubMedGoogle Scholar
  32. Jasinska AJ, Lowry CA, Burmeister M (2012a) Corrigendum: serotonin transporter gene, stress, and raphe-raphe interactions: a molecular mechanism of depression. Trends Neurosci 35:454–455CrossRefPubMedGoogle Scholar
  33. Jasinska AJ, Lowry CA, Burmeister M (2012b) Serotonin transporter gene, stress and raphe-raphe interactions: a molecular mechanism of depression. Trends Neurosci 35:395–402.  https://doi.org/10.1016/j.tins.2012.01.001 CrossRefPubMedGoogle Scholar
  34. Kanai R, Rees G (2011) The structural basis of inter-individual differences in human behaviour and cognition. Nat Rev Neurosci 12:231–242.  https://doi.org/10.1038/nrn3000 CrossRefPubMedGoogle Scholar
  35. Kraus C et al (2012) Serotonin-1A receptor binding is positively associated with gray matter volume—a multimodal neuroimaging study combining PET and structural. MRI NeuroImage 63:1091–1098.  https://doi.org/10.1016/j.neuroimage.2012.07.035 CrossRefPubMedGoogle Scholar
  36. Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH (2003) An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage 19:1233–1239CrossRefPubMedGoogle Scholar
  37. Malykhin NV, Coupland NJ (2015) Hippocampal neuroplasticity in major. depressive disorder. Neuroscience 309:200–213.  https://doi.org/10.1016/j.neuroscience.2015.04.047 CrossRefPubMedGoogle Scholar
  38. Matheson GJ et al (2015) Diurnal and seasonal variation of the brain serotonin system in healthy male subjects. NeuroImage. 112:225–231  https://doi.org/10.1016/j.neuroimage.2015.03.007 CrossRefPubMedGoogle Scholar
  39. Maya Vetencourt JF et al (2008) The antidepressant fluoxetine restores plasticity in the adult visual cortex. Science (New York, NY) 320:385–388.  https://doi.org/10.1126/science.1150516 CrossRefGoogle Scholar
  40. Meltzer CC et al (2004) Serotonin 1A receptor binding and treatment response in late—life depression. Neuropsychopharmacology 29:2258–2265CrossRefPubMedGoogle Scholar
  41. Milak MS et al (2010) In vivo quantification of human serotonin 1A receptor using 11C-CUMI-101, an agonist PET radiotracer. J Nuclear Med 51:1892–1900.  https://doi.org/10.2967/jnumed.110.076257 CrossRefGoogle Scholar
  42. Miller JM, Brennan KG, Ogden TR, Oquendo MA, Sullivan GM, Mann JJ, Parsey RV (2009) Elevated serotonin 1A binding in remitted major depressive disorder: evidence for a trait biological abnormality. Neuropsychopharmacology 34:2275–2284.  https://doi.org/10.1038/npp.2009.54 CrossRefPubMedPubMedCentralGoogle Scholar
  43. Miller JM, Hesselgrave N, Ogden RT, Zanderigo F, Oquendo MA, Mann JJ, Parsey RV (2013) Brain serotonin 1A receptor binding as a predictor of treatment outcome in major depressive disorder. Biological psychiatry 74:760–767.  https://doi.org/10.1016/j.biopsych.2013.03.021 CrossRefPubMedPubMedCentralGoogle Scholar
  44. Nautiyal KM, Hen R (2017) Serotonin receptors in depression: from A to B F1000Res 6:123  https://doi.org/10.12688/f1000research.9736.1
  45. Ogren SO et al (2008) The role of 5-HT(1A) receptors in learning and memory. Behav Brain Res 195:54–77.  https://doi.org/10.1016/j.bbr.2008.02.023 CrossRefPubMedGoogle Scholar
  46. Parsey RV et al (2000) Validation and reproducibility of measurement of 5-HT1A receptor parameters with [carbonyl-11C]WAY-100635 in humans: comparison of arterial and reference tisssue input functions. J Cereb Blood Flow Metab 20:1111–1133.  https://doi.org/10.1097/00004647-200007000-00011 CrossRefPubMedGoogle Scholar
  47. Parsey RV, Arango V, Olvet DM, Oquendo MA, Van Heertum RL, John Mann J (2005) Regional heterogeneity of 5-HT1A receptors in human cerebellum as assessed by positron emission tomography. J Cereb Blood Flow Metab 25:785–793.  https://doi.org/10.1038/sj.jcbfm.9600072 CrossRefPubMedGoogle Scholar
  48. Parsey RV, Olvet DM, Oquendo MA, Huang YY, Ogden RT, Mann JJ (2006a) Higher 5-HT1A receptor binding potential during a major depressive episode predicts poor treatment response: preliminary data from a naturalistic study. Neuropsychopharmacol 31:1745–1749.  https://doi.org/10.1038/sj.npp.1300992 CrossRefGoogle Scholar
  49. Parsey RV et al (2006b) Altered serotonin 1A binding in major depression: a [carbonyl-C-11]WAY100635 positron emission tomography study. Biol Psychiatry 59:106–113.  https://doi.org/10.1016/j.biopsych.2005.06.016 CrossRefPubMedGoogle Scholar
  50. Parsey RV et al (2010) Higher serotonin 1A binding in a second major depression cohort: modeling and reference region considerations. Biol Psychiatry 68:170–178.  https://doi.org/10.1016/j.biopsych.2010.03.023 CrossRefPubMedPubMedCentralGoogle Scholar
  51. Persico AM, Di Pino G, Levitt P (2006) Multiple receptors mediate the trophic effects of serotonin on ventroposterior thalamic neurons in vitro. Brain Res 1095:17–25.  https://doi.org/10.1016/j.brainres.2006.04.006 CrossRefPubMedGoogle Scholar
  52. Pike VW et al (1996) Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11 C]WAY-100635. Eur J Pharmacol 301:R5-7CrossRefPubMedGoogle Scholar
  53. Pittenger C, Duman RS (2008) Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacol 33:88–109.  https://doi.org/10.1038/sj.npp.1301574 CrossRefGoogle Scholar
  54. Rabiner EA, Wilkins MR, Turkheimer F, Gunn RN, Udo de Haes J, de Vries M, Grasby PM (2002) 5-Hydroxytryptamine1A receptor occupancy by novel full antagonist 2-[4-[4-(7-chloro-2,3-dihydro-1,4-benzdioxyn-5-yl)-1-piperazinyl]butyl]-1,2-benzi sothiazol-3-(2H)-one-1,1-dioxide: a[11C][O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635) positron emission tomography study in humans. J Pharmacol Exp Ther 301:1144–1150CrossRefPubMedGoogle Scholar
  55. Salvadore G et al (2011) Prefrontal cortical abnormalities in currently depressed versus currently remitted patients with major depressive disorder. NeuroImage 54:2643–2651  https://doi.org/10.1016/j.neuroimage.2010.11.011 CrossRefPubMedGoogle Scholar
  56. Sargent PA et al (2000) Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment. Arch Gen Psychiatry 57:174–180CrossRefPubMedGoogle Scholar
  57. Savitz JB, Drevets WC (2009) Imaging phenotypes of major depressive disorder:. genetic correlates. Neuroscience 164:300–330.  https://doi.org/10.1016/j.neuroscience.2009.03.082 CrossRefPubMedPubMedCentralGoogle Scholar
  58. Savitz J, Lucki I, Drevets WC (2009) 5-HT(1A) receptor function in major depressive. disorder. Prog Neurobiol 88:17–31.  https://doi.org/10.1016/j.pneurobio.2009.01.009 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Schmidt HD, Duman RS (2007) The role of neurotrophic factors in adult hippocampal neurogenesis, antidepressant treatments and animal models of depressive-like behavior. Behav Pharmacol 18:391–418.  https://doi.org/10.1097/FBP.0b013e3282ee2aa8 CrossRefPubMedGoogle Scholar
  60. Smith R, Chen K, Baxter L, Fort C, Lane RD (2013) Antidepressant effects of sertraline associated with volume increases in dorsolateral prefrontal cortex. J Affective Disord 146:414–419.  https://doi.org/10.1016/j.jad.2012.07.029 CrossRefGoogle Scholar
  61. Sullivan GM et al (2015) Positron emission tomography quantification of serotonin(1A) receptor binding in suicide attempters with major depressive disorder. JAMA Psychiatry 72:169–178.  https://doi.org/10.1001/jamapsychiatry.2014.2406 CrossRefPubMedPubMedCentralGoogle Scholar
  62. Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain: three-dimensional proportional system. Thieme Medical, New YorkGoogle Scholar
  63. Tardito D, Perez J, Tiraboschi E, Musazzi L, Racagni G, Popoli M (2006) Signaling pathways regulating gene expression, neuroplasticity, and neurotrophic mechanisms in the action of antidepressants: a critical overview. Pharmacological reviews 58:115–134.  https://doi.org/10.1124/pr.58.1.7 CrossRefPubMedGoogle Scholar
  64. Tost H, Braus DF, Hakimi S, Ruf M, Vollmert C, Hohn F, Meyer-Lindenberg A (2010) Acute D2 receptor blockade induces rapid, reversible remodeling in human cortical-striatal circuits. Nat Neurosci 13:920–922.  https://doi.org/10.1038/nn.2572 CrossRefPubMedGoogle Scholar
  65. van Spronsen M, Hoogenraad CC (2010) Synapse pathology in psychiatric and neurologic disease. Curr Neurol Neurosci Rep 10:207–214.  https://doi.org/10.1007/s11910-010-0104-8 CrossRefPubMedPubMedCentralGoogle Scholar
  66. van Tol MJ et al (2010) Regional brain volume in depression and anxiety disorders. Arch Gen Psychiatry 67:1002–1011.  https://doi.org/10.1001/archgenpsychiatry.2010.121 CrossRefPubMedGoogle Scholar
  67. Woodward ND et al (2009) Cerebral morphology and dopamine D2/D3 receptor distribution in humans: a combined [18F]fallypride and voxel-based morphometry study. NeuroImage. 46:31–38  https://doi.org/10.1016/j.neuroimage.2009.01.049 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Wright IC et al (1995) A voxel-based method for the statistical analysis of gray and white matter density applied to schizophrenia. NeuroImage. 2:244–252  https://doi.org/10.1006/nimg.1995.1032 CrossRefPubMedGoogle Scholar
  69. Yan W, Wilson CC, Haring JH (1997) 5-HT1a receptors mediate the neurotrophic effect of serotonin on developing dentate granule cells. Brain Res Dev Brain Res 98:185–190CrossRefPubMedGoogle Scholar
  70. Zatorre RJ, Fields RD, Johansen-Berg H (2012) Plasticity in gray and white: neuroimaging changes in brain structure during learning. Nat Neurosci 15:528–536.  https://doi.org/10.1038/nn.3045 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Francesca Zanderigo
    • 1
    • 2
  • Spiro Pantazatos
    • 1
    • 2
  • Harry Rubin-Falcone
    • 1
  • R. Todd Ogden
    • 1
    • 2
    • 3
  • Binod Thapa Chhetry
    • 1
  • Gregory Sullivan
    • 1
  • Maria Oquendo
    • 1
    • 2
  • Jeffrey M. Miller
    • 1
    • 2
  • J. John Mann
    • 1
    • 2
    • 4
  1. 1.Molecular Imaging and Neuropathology DivisionNew York State Psychiatric InstituteNew YorkUSA
  2. 2.Department of PsychiatryColumbia UniversityNew YorkUSA
  3. 3.Department of BiostatisticsColumbia University, Mailman School of Public HealthNew YorkUSA
  4. 4.Department of RadiologyColumbia UniversityNew YorkUSA

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