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01-07-2018 | Original Article

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

Authors: Francesca Zanderigo, Spiro Pantazatos, Harry Rubin-Falcone, R. Todd Ogden, Binod Thapa Chhetry, Gregory Sullivan, Maria Oquendo, Jeffrey M. Miller, J. John Mann

Published in: Brain Structure and Function | Issue 6/2018

Abstract

Serotonin 1A (5-HT_1A) receptors mediate serotonin trophic role in brain neurogenesis. Gray matter volume (GMV) loss and 5-HT_1A receptor binding alterations have been identified in major depressive disorder (MDD). Here we investigated the relationship between 5-HT_1A 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-HT_1A binding (expressed as BP_F, 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 BP_F, 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-HT_1A 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-HT_1A autoreceptor binding and anterior cingulate GMV in both groups, and a statistically significant positive correlation between raphe 5-HT_1A binding and temporal GMV in MDD. Analysis of covariance at the voxel-level revealed a trend towards interaction between diagnosis and raphe 5-HT_1A 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-HT_1A binding with postsynaptic GMV. These results suggest that 5-HT_1A receptors contribute to altered neuroplasticity in MDD, possibly via effects predating depression onset.

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 CrossRefPubMed

Ashburner J (2007) A fast diffeomorphic image registration algorithm. NeuroImage. 38:95–113 https://doi.org/10.1016/j.neuroimage.2007.07.007 CrossRefPubMed

Azmitia EC (2001) Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis. Brain Res Bull 56:413–424CrossRefPubMed

Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571CrossRefPubMed

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 CrossRef

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 CrossRef

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 CrossRefPubMed

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 CrossRefPubMed

Braestrup C, Squires RF (1978) Pharmacological characterization of benzodiazepine receptors in the brain European. J Pharmacol 48:263–270

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 CrossRef

Citri A, Malenka RC (2008) Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacol 33:18–41. https://doi.org/10.1038/sj.npp.1301559 CrossRef

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 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

Dayer A (2014) Serotonin-related pathways and developmental plasticity: relevance for psychiatric disorders. Dialog Clin Neurosci 16:29–41

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, FL

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 CrossRef

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 328:467–470CrossRef

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 CrossRefPubMed

Drevets WC et al (1999) PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry 46:1375–1387CrossRefPubMed

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 CrossRef

Duvernoy H (1991) The human brain: surface, three-dimensional sectional anatomy and MRI. New York

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 York

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.

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

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 CrossRef

Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62CrossRefPubMedPubMedCentral

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 11:465–476CrossRefPubMed

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 87:182–194CrossRefPubMed

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 CrossRefPubMed

Jasinska AJ, Lowry CA, Burmeister M (2012a) Corrigendum: serotonin transporter gene, stress, and raphe-raphe interactions: a molecular mechanism of depression. Trends Neurosci 35:454–455CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH (2003) An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage 19:1233–1239CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRef

Meltzer CC et al (2004) Serotonin 1A receptor binding and treatment response in late—life depression. Neuropsychopharmacology 29:2258–2265CrossRefPubMed

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 CrossRef

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMedPubMedCentral

Nautiyal KM, Hen R (2017) Serotonin receptors in depression: from A to B F1000Res 6:123 https://doi.org/10.12688/f1000research.9736.1

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRef

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 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMed

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:R5-7CrossRefPubMed

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 CrossRef

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 301:1144–1150CrossRefPubMed

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 CrossRefPubMed

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 57:174–180CrossRefPubMed

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMed

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 CrossRef

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 CrossRefPubMedPubMedCentral

Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain: three-dimensional proportional system. Thieme Medical, New York

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMed

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 98:185–190CrossRefPubMed

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 CrossRefPubMedPubMedCentral

Title: In vivo relationship between serotonin 1A receptor binding and gray matter volume in the healthy brain and in major depressive disorder
Authors: Francesca Zanderigo
Spiro Pantazatos
Harry Rubin-Falcone
R. Todd Ogden
Binod Thapa Chhetry
Gregory Sullivan
Maria Oquendo
Jeffrey M. Miller
J. John Mann
Publication date: 01-07-2018
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 6/2018
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-018-1649-6

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

Abstract

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Abstract

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