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11 - Molecular imaging of major depression

from Section II - Mood Disorders

Published online by Cambridge University Press:  10 January 2011

By
Julia Sacher  and
Gwenn S. Smith
Edited by
Martha E. Shenton  and
Bruce I. Turetsky
Julia Sacher
Affiliation:
PET Centre Centre for Addiction and Mental Health Toronto, ON, Canada
Gwenn S. Smith
Affiliation:
Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine Baltimore, MD, USA
Martha E. Shenton
Affiliation:
VA Boston Healthcare System and Brigham and Women's Hospital, Harvard Medical School
Bruce I. Turetsky
Affiliation:
University of Pennsylvania
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Summary

Introduction

The initial publications of monoamine receptor binding in the living human brain in the mid 1980s and the progress in neurochemical brain imaging since that time have had a profound influence on our ability to test hypotheses generated from clinical observations, preclinical and post-mortem data regarding the neurochemistry of neuropsychiatric disorders in the living human brain (Wagner et al.,1983; Wong et al., 1984; Arnett et al., 1986). Progress in radiotracer chemistry and instrumentation over the past 20 years has enabled us to test mechanistic hypotheses about pathophysiology, as well as to understand the mechanism of action of psychotropic medications.

The primary focus of radiochemistry development for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) has been dopamine and serotonin neurotransmission (including imaging of neurotransmitter metabolism/synthesis, transporters and receptors). Major advances have been made in areas including cholinergic (muscarinic and nicotinic), glutamatergic (Brown et al., 2008), and opiate systems (Hashimoto et al., 2008; Hirvonen et al., 2009; Reid et al., 2008; Sorger et al., 2008). More recently, the focus of radiotracer development has broadened to include molecular targets such as signal transduction, inflammation and aspects of neuropathology such as amyloid deposition (Vasdev et al., 2008; Fujita et al., 2008; Suhara et al., 2008). Other more challenging targets of interest for which radiotracers continue to be in development include receptors and transporters for norepinephrine, corticotrophin-releasing factor and the hypothalamo-pituitary–adrenal (HPA) axis and neurogenesis (Schou et al., 2007; Steiniger et al., 2008; Sullivan et al., 2007).

Keywords

depressiondepressive illnessdopaminesingle photon emission computed tomographyserotoninpositron emission tomographyneurochemical brain imagingneurotransmitter system
Type
Chapter
Information
Understanding Neuropsychiatric Disorders
Insights from Neuroimaging
 , pp. 170 - 196
Publisher: Cambridge University Press
Print publication year: 2010

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References

Abas, M A, Sahakian, B J and Levy, R. 1990. Neuropsychological deficits and CT scan changes in elderly depressives. Psychol Med 20, 507–20.Google Scholar
Abi-Dargham, A, Laruelle, M, Lipska, B, et al. 1993. Serotonin 5-HT3 receptors in schizophrenia: A postmortem study of the amygdala. Brain Res 616, 53–7.Google Scholar
Agid, Y, Buzsáki, G, Diamond, D M, et al. 2007. How can drug discovery for psychiatric disorders be improved? Nat Rev Drug Discov 6, 189–201.Google Scholar
Agren, H and Reibring, L. 1994. PET studies of presynaptic monoamine metabolism in depressed patients and healthy volunteers. Pharmacopsychiatry 27, 2–6.Google Scholar
Agren, H, Reibring, L, Hartvig, P, et al. 1991. Low brain uptake of L-[11C]5-hydroxytryptophan in major depression: A positron emission tomography study on patients and healthy volunteers. Acta Psychiatr Scand 83, 449–55.Google Scholar
Alexopoulos, G S, Meyers, B S, Young, R C, et al. 2000. Executive dysfunction and long-term outcomes of geriatric depression. Arch Gen Psychiatry 57, 285–90.Google Scholar
Alexopoulos, G S, Vrontou, C, Kakuma, T, et al. 1996. Disability in geriatric depression. Am J Psychiatry 153, 877–85.Google Scholar
Allard, P and Norlen, M. 2001. Caudate nucleus dopamine D(2) receptors in depressed suicide victims. Neuropsychobiology 44, 70–3.Google Scholar
Anand, A, Verhoeff, P, Seneca, N, et al. 2000. Brain SPECT imaging of amphetamine-induced dopamine release in euthymic bipolar disorder patients. Am J Psychiatry 157, 1108–14.Google Scholar
Arango, V, Underwood, M D, Gubbi, A V and Mann, J J. 1995. Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims. Brain Res 688, 121–33.Google Scholar
Arango, V, Underwood, M D and Mann, J J. 2002. Serotonin brain circuits involved in major depression and suicide. Progr Brain Res 136, 443–53.Google Scholar
Arango, V, Underwood, M D and Mann, J J. 1997. Postmortem findings in suicide victims. Implications for in vivo imaging studies. Ann N Y Acad Sci 836, 269–87.Google Scholar
Arnett, C D, Wolf, A P, Shiue, C Y, et al. 1986. Improved delineation of human dopamine receptors using [18F]-N-methylspiroperidol and PET. J Nucl Med 27, 1878–82.Google Scholar
Beekman, A T, Copeland, J R and Prince, M J. 1999. Review of community prevalence of depression in later life. Br J Psychiatry 174, 307–11.Google Scholar
Beekman, A T, Geerlings, S W, Deeg, D J, et al. 2002. The natural history of late-life depression: A 6-year prospective study in the community. Arch Gen Psychiatry 59, 605–11.Google Scholar
Bergstrom, M, Westerberg, G, Kihlberg, T and Langstrom, B. 1997a. Synthesis of some 11C-labelled MAO-A inhibitors and their in vivo uptake kinetics in rhesus monkey brain. Nucl Med Biol 24, 381–8.Google Scholar
Bergstrom, M, Westerberg, G and Langstrom, B. 1997b. 11C-harmine as a tracer for monoamine oxidase A (MAO-A): In vitro and in vivo studies. Nucl Med Biol 24, 287–93.Google Scholar
Bhagwagar, Z, Hinz, R, Taylor, M, Fancy, S, Cowen, P and Grasby, P. 2006. Increased 5-HT(2A) receptor binding in euthymic, medication-free patients recovered from depression: A positron emission study with [(11)C]MDL 100,907. Am J Psychiatry 163, 1580–7.Google Scholar
Bhagwagar, Z, Murthy, N, Selvaraj, S, et al. 2007. 5-HTT binding in recovered depressed patients and healthy volunteers: A positron emission tomography study with [11C]DASB. Am J Psychiatry 164, 1858–65.Google Scholar
Biegon, A, Kargman, S, Snyder, L and McEwen, B S. 1986. Characterization and localization ofserotonin receptors in human brain postmortem. Brain Res 363, 91–8.Google Scholar
Biver, F, Wikler, D, Lotstra, F, Damhaut, P, Goldman, S and Mendlewicz, J. 1997. Serotonin 5-HT2 receptor imaging in major depression: Focal changes in orbito-insular cortex. Br J Psychiatry 171, 444–8.Google Scholar
Blakely, R D, Ramamoorthy, S, Schroeter, S, et al. 1998. Regulated phosphorylation and trafficking of antidepressant-sensitive serotonin transporter proteins. Biol Psychiatry 44, 169–78.Google Scholar
Blier, P, Montigny, C and Chaput, Y. 1990. A role for the serotonin system in the mechanism of action of antidepressant treatments: Preclinical evidence. J Clin Psychiatry 51 (Suppl), 14–20; discussion 21.Google Scholar
Blin, J, Denis, A, Yamaguchi, T, Crouzel, C, MacKenzie, E T and Baron, J C. 1991. PET studies of [18F]methyl-MK-801, a potential NMDA receptor complex radioligand. Neurosci Lett 121, 183–6.Google Scholar
Blin, J, Sette, G, Fiorelli, M, et al. 1990. A method for the in vivo investigation of the serotonergic 5-HT2 receptors in the human cerebral cortex using positron emission tomography and 18F-labeled setoperone. J Neurochem 54, 1744–54.Google Scholar
Bowden, C, Theodorou, A E, Cheetham, S C, et al. 1997. Dopamine D1 and D2 receptor binding sites in brain samples from depressed suicides and controls. Brain Res 752, 227–33.Google Scholar
Bowden, C L, Seleshi, E and Javors, M A. 1989. Mania associated with high percentage of inhibition of monoamine oxidase. Am J Psychiatry 146, 121.Google Scholar
Brown, A K, Kimura, Y, Zoghbi, S S, et al. 2008. Metabotropic glutamate subtype 5 receptors are quantified in the human brain with a novel radioligand for PET. J Nucl Med 49, 2042–8.Google Scholar
Brown, A S and Gershon, S. 1993. Dopamine and depression. J Neural Transm 91, 75–109.Google Scholar
Bruce, M L and Leaf, P J. 1989. Psychiatric disorders and 15-month mortality in a community sample of older adults. Am J Public Hlth 79, 727–30.Google Scholar
Brücke, T, Kornhuber, J, Angelberger, P, Asenbaum, S, Frassine, H, and Podreka, I. 1993. SPECT imaging of dopamine and serotosin transporters with [123I]beta-CIT. Binding kinetics in the human brain. J Neurol Transm Gen Sect 94, 137–46.Google Scholar
Buck, A, Gucker, P M, Schonbachler, R D, et al. 2000. Evaluation of serotonergic transporters using PET and [11C](+)McN-5652: Assessment of methods. J Cerebr Blood Flow Metab 20, 253–62.Google Scholar
Camps, M, Cortés, R, Gueye, B, Probst, A and Palacios, J M. 1989. Dopamine receptors in human brain: Autoradiographic distribution of D2 sites. Neuroscience 28, 275–90.Google Scholar
Cannon, D M, Ichise, M, Fromm, S J, et al. 2006. Serotonin transporter binding in bipolar disorder assessed using [11C]DASB and positron emission tomography. Biol Psychiatry 60, 207–17.Google Scholar
Cannon, D M, Ichise, M, Rollis, D, et al. 2007. Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorder. Biol Psychiatry 62, 870–7.Google Scholar
Cannon, D M, Klaver, J M, Peck, S A, Rallis-Voak, D, Erickson, K and Drevets, W C. 2009. Dopamine type-1 receptor binding in major depressive disorder assessed using positron emission tomography and [11C]NNC-112. Neuropsychopharmacology, 5, 1277–87.Google Scholar
Carson, R E, Kiesewetter, D O, Jagoda, E, Der, M G, Herscovitch, P and Eckelman, W C. 1998. Muscarinic cholinergic receptor measurements with [18F]FP-TZTP: Control and competition studies. J Cereb Blood Flow Metab 18, 1130–42.Google Scholar
Caspi, A, Sugden, K, Moffitt, T E, et al. 2003. Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science 301, 386–9.Google Scholar
Castren, E. 2004. Neurotrophins as mediators of drug effects on mood, addiction, and neuroprotection. Mol Neurobiol 29, 289–302.Google Scholar
Catafau, A M, Perez, V, Plaza, P, et al. 2006. Serotonin transporter occupancy induced by paroxetine in patients with major depression disorder: A 123I-ADAM SPECT study. Psychopharmacology (Berl) 189, 145–53.Google Scholar
Chaly, T, Dhawan, V, Kazumata, K, et al. 1996. Radiosynthesis of [18F] N-3-fluoropropyl-2-beta-carbomethoxy-3-beta-(4-iodophenyl) nortropane and the first human study with positron emission tomography. Nucl Med Biol 23, 999–1004.Google Scholar
Chauveau, F, Boutin, H, Camp, N, Dollé, F and Tavitian, B. 2008. Nuclear imaging of neuroinflammation: A comprehensive review of [(11)C]PK11195 challengers. Eur J Nucl Med Mol Imaging 35, 2304–19.Google Scholar
Ciliax, B J, Drash, G W, Staley, J K, et al. 1999. Immunocytochemical localization of the dopamine transporter in human brain. J Comp Neurol 409, 38–56.Google Scholar
Cole, M G, Bellavance, F and Mansour, A. 1999. Prognosis of depression in elderly community and primary care populations: A systematic review and meta-analysis. Am J Psychiatry 156, 1182–9.Google Scholar
Comley, R, Parker, C, Wishart, M, Martarello, L, Jakobsen, S and Gunn, R. 2006. In vivo evaluation and quantification of the 5-HT4 receptor PET ligand [11C]SB-207145. Neuroimage 31, T23.Google Scholar
Conwell, Y, Duberstein, P R, Cox, C, Herrmann, J H, Forbes, N T and Caine, E D. 1996. Relationships of age and axis I diagnoses in victims of completed suicide: A psychological autopsy study. Am J Psychiatry 153, 1001–08.Google Scholar
Cortes, R, Soriano, E, Pazos, A, Probst, A and Palacios, J M. 1988. Autoradiography of antidepressant binding sites in the human brain: Localization using [3H]imipramine and [3H]paroxetine. Neuroscience 27, 473–96.Google Scholar
Cowen, P J. 1996. Advances in psychopharmacology: Mood disorders and dementia. Br Med Bull 52, 539–55.Google Scholar
DaSilva, J N, Lourenco, C M, Meyer, J H, Hussey, D, Potter, W Z and Houle, S. 2002. Imaging cAMP-specific phosphodiesterase-4 in human brain with R-[(11)C]rolipram and positron emission tomography. Eur J Nucl Med Mol Imag 29, 1680–3.Google Scholar
David, S P, Murthy, N V, Rabiner, E A, et al. 2005. A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans. J Neurosci 25, 2586–90.Google Scholar
Davis, M R, Votaw, J R, Bremner, J D, et al. 2003. Initial human PET imaging studies with the dopamine transporter ligand 18F-FECNT. J Nucl Med 44, 855–61.Google Scholar
Dewey, S L, MacGregor, R R, Brodie, J D, et al. 1990. Mapping muscarinic receptors in human and baboon brain using [N-11C-methyl]-benztropine. Synapse 5, 213–23.Google Scholar
Dewey, S L, Smith, G, Logan, J, Brodie, J D, Fowler, J S and Wolf, A P. 1993. Striatal binding of the PET ligand 11C-raclopride is altered by drugs that modify synaptic dopamine levels. Synapse 13, 350–6.Google Scholar
Dilsaver, S C. 1986. Cholinergic mechanisms in depression. Brain Res 396, 285–316.Google Scholar
Ding, Y S, Lin, K S and Logan, J. 2006. PET imaging of norepinephrine transporters. Curr Pharm Des 12, 3831–45.Google Scholar
Drevets, W C, Frank, E, Price, J C, et al. 1999. PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry 46, 1375–87.Google Scholar
Drevets, W C, Frank, E, Price, J C, Kupfer, D J, Greer, P J and Mathis, C. 2000. Serotonin type-1A receptor imaging in depression. Nucl Med Biol 27, 499–507.Google Scholar
Duman, R S, Heninger, G R and Nestler, E J. 1997. A molecular and cellular theory of depression. Arch Gen Psychiatry 54, 597–606.Google Scholar
Ebert, D, Feistel, H, Kaschka, W, Barocka, A and Pirner, A. 1994. Single photon emission computerized tomography assessment of cerebral dopamine D2 receptor blockade in depression before and after sleep deprivation – Preliminary results. Biol Psychiatry 35, 880–5.Google Scholar
Eckelman, W C. 2001. Radiolabeled muscarinic radioligands for in vivo studies. Nucl Med Biol 28, 485–91.Google Scholar
Eckelman, W C, Reba, R C, Rzeszotarski, W J, et al. 1984. External imaging of cerebral muscarinic acetylcholine receptors. Science 223, 291–3.Google Scholar
Efange, S M. 2000. In vivo imaging of the vesicular acetylcholine transporter and the vesicular monoamine transporter. Faseb J 14, 2401–13.Google Scholar
Erlandsson, K, Sivananthan, T, Lui, D, et al. 2005. Measuring SSRI occupancy of SERT using the novel tracer [123I]ADAM: A SPECT validation study. Eur J Nucl Med Mol Imaging 32, 1329–36.Google Scholar
Farde, L, Ehrin, E, Eriksson, L, et al. 1985. Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography. Proc Natl Acad Sci USA 82, 3863–7.Google Scholar
Farde, L, Ito, H, Swahn, C G, Pike, V W and Halldin, C. 1998. Quantitative analyses of carbonyl-carbon-11-WAY-100635 binding to central 5-hydroxytryptamine-1A receptors in man. J Nucl Med 39, 1965–71.Google Scholar
Ferrarese, C, Guidotti, A, Costa, E, et al. 1991. In vivo study of NMDA-sensitive glutamate receptor by fluorothienylcyclohexylpiperidine, a possible ligand for positron emission tomography. Neuropharmacology 30, 899–905.Google Scholar
First, M, Spitzer, R, Williams, J and Gibbon, M. 1995. Structured Clinical Interview for DSM-IV-Non-Patient Edition (SCID-NP, Version 1.0)., Washington, D.C.: American Psychiatric Press.
Fowler, J S, MacGregor, R R, Wolf, A P, et al. 1987. Mapping human brain monoamine oxidase A and B with 11C-labeled suicide inactivators and PET. Science 235, 481–5.Google Scholar
Francis, P T, Pangalos, M N, Stephens, P H, et al. 1993. Antemortem measurements of neurotransmission: Possible implications for pharmacotherapy of Alzheimer's disease and depression. J Neurol Neurosurg Psychiatry 56, 80–4.Google Scholar
Frankle, W G, Lombardo, I, New, A S, et al. 2005. Brain serotonin transporter distribution in subjects with impulsive aggressivity: A positron emission study with [11C]McN 5652. Am J Psychiatry 162, 915–23.Google Scholar
Frankle, W G, Slifstein, M, Gunn, R N, et al. 2006. Estimation of serotonin transporter parameters with 11C-DASB in healthy humans: Reproducibility and comparison of methods. J Nucl Med 47, 815–26.Google Scholar
Frey, K A, Koeppe, R A, Kilbourn, M R, et al. 1996. Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging. Ann Neurol 40, 873–84.Google Scholar
Frokjaer, V G, Mortensen, E L, Nielsen, F A, et al. 2008. Frontolimbic serotonin 2A receptor binding in healthy subjects is associated with personality risk factors for affective disorder. Biol Psychiatry 63, 569–76.Google Scholar
Frost, J J. 2001. PET imaging of the opioid receptor: The early years. Nucl Med Biol 28, 509–13.Google Scholar
Frost, J J, Rosier, A J, Reich, S G, et al. 1993. Positron emission tomographic imaging of the dopamine transporter with 11C-WIN 35,428 reveals marked declines in mild Parkinson's disease. Ann Neurol 34, 423–31.Google Scholar
Frost, J J, Wagner, H N, Dannals, R F, et al. 1985. Imaging opiate receptors in the human brain by positron tomography. J Comp Assist Tomog 9, 231–6.Google Scholar
Fujita, M, Imaizumi, M, Zoghbi, S S, et al. 2008. Kinetic analysis in healthy humans of a novel positron emission tomography radioligand to image the peripheral benzodiazepine receptor, a potential biomarker for inflammation. Neuroimage 40, 43–52.Google Scholar
Furey, M L and Drevets, W C. 2006. Antidepressant efficacy of the antimuscarinic drug scopolamine: A randomized, placebo-controlled clinical trial. Arch Gen Psychiatry 63, 1121–9.Google Scholar
Garnett, E S, Firnau, G and Nahmias, C. 1983. Dopamine visualized in the basal ganglia of living man. Nature 305, 137–8.Google Scholar
George, T P, Sacco, K A, Vessicchio, J C, Weinberger, A H and Shytle, R D. 2008. Nicotinic antagonist augmentation of selective serotonin reuptake inhibitor-refractory major depressive disorder: A preliminary study. J Clin Psychopharmacol 28, 340–4.Google Scholar
Ginovart, N, Meyer, J H, Boovariwala, A et al. 2006. Positron emission tomography quantification of [11C]-harmine binding to monoamine oxidase-A in the human brain. J Cereb Blood Flow Metab 26, 330–44.Google Scholar
Ginovart, N, Wilson, A A, Meyer, J H, Hussey, D and Houle, S. 2001. Positron emission tomography quantification of [(11)C]-DASB binding to the human serotonin transporter: Modeling strategies. J Cereb Blood Flow Metab 21, 1342–53.Google Scholar
Giovacchini, G, Chang, M C, Channing, M A, et al. 2002. Brain incorporation of [11C]arachidonic acid in young healthy humans measured with positron emission tomography. J Cereb Blood Flow Metab 22, 1453–62.Google Scholar
Hall, H, Halldin, C, Farde, L and Sedvall, G. 1998. Whole hemisphere autoradiography of the postmortem human brain. Nucl Med Biol 25, 715–9.Google Scholar
Halldin, C, Farde, L, Hogberg, T, et al. 1995. Carbon-11-FLB 457: A radioligand for extrastriatal D2 dopamine receptors. J Nucl Med 36, 1275–81.Google Scholar
Halldin, C, Foged, C, Chou, Y H, et al. 1998. Carbon-11-NNC 112: A radioligand for PET examination of striatal and neocortical D1-dopamine receptors. J Nucl Med 39, 2061–8.Google Scholar
Hargreaves, R. 2002. Imaging substance P receptors (NK1) in the living human brain using positron emission tomography. J Clin Psychiatry 63, 18–24.Google Scholar
Hariri, A R, Mattay, V S, Tessitore, A, et al. 2002. Serotonin in transporter genetic variation and the response of the human amygdala. Science 297, 400–3.Google Scholar
Hartvig, P, Agren, H, Reibring, L, et al. 1991. Brain kinetics of L-[beta-11C]dopa in humans studied by positron emission tomography. J Neural Transm Gen Sect 86, 25–41.Google Scholar
Hashimoto, K, Nishiyama, S, Ohba, H, et al. 2008. [11C]CHIBA-1001 as a novel PET ligand for alpha7 nicotinic receptors in the brain: A PET study in conscious monkeys. PLoS ONE 3, e3231.Google Scholar
Heiss, W D. 2009. The potential of PET/MR for brain imaging. Eur J Nucl Med Mol Imaging 36(Suppl 1), S105–12.Google Scholar
Heiss, W D and Herholz, K. 2006. Brain receptor imaging. J Nucl Med 47, 302–12.Google Scholar
Henriksson, M M, Marttunen, M J, Isometsa, E T, et al. 1995. Mental disorders in elderly suicide. Int Psychogeriatr 7, 275–86.Google Scholar
Hirvonen, J, Aalto, S, Hagelberg, N, et al. 2009. Measurement of central micro-opioid receptor binding in vivo with PET and [(11)C]carfentanil: A test–retest study in healthy subjects. Eur J Nucl Med Mol Imaging 36, 275–86.Google Scholar
Hirvonen, J, Karlsson, H, Kajander, J, et al. 2008. Striatal dopamine D2 receptors in medication-naïve patients with major depressive disorder as assessed with [11C]raclopride PET. Psychopharmacology (Berl) 197, 581–90.Google Scholar
Holsboer, F. 2000. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 23, 477–501.Google Scholar
Horti, A G, Chefer, S I, Mukhin, A G, et al. 2000. 6-[18F]fluoro-A-85380, a novel radioligand for in vivo imaging of central nicotinic acetylcholine receptors. Life Sci 67, 463–9.Google Scholar
Houle, S, Ginovart, N, Hussey, D, Meyer, J H and Wilson, A A. 2000. Imaging the serotonin transporter with positron emission tomography: Initial human studies with [11C]DAPP and [11C]DASB. Eur J Nucl Med 27, 1719–22.Google Scholar
Hoyer, D, Pazos, A, Probst, A and Palacios, J M. 1986a. Serotonin receptors in the human brain. I. Characterization and autoradiographic localization of 5-HT1A recognition sites. Apparent absence of 5-HT1B recognition sites. Brain Res 376, 85–96.Google Scholar
Hoyer, D, Pazos, A, Probst, A and Palacios, J M. 1986b. Serotonin receptors in the human brain. II. Characterization and autoradiographic localization of 5-HT1C and 5-HT2 recognition sites. Brain Res 376, 97–107.Google Scholar
Huang, Y, Kegeles, L S, Bae, S, et al. 2001. Synthesis of potent and selective dopamine D(4) antagonists as candidate radioligands. Bioorg Med Chem Lett 11, 1375–7.Google Scholar
Hwang, D R, Kegeles, L S and Laruelle, M. 2000. (–)-N-[(11)C]propyl-norapomorphine: A positron-labeled dopamine agonist for PET imaging of D(2) receptors. Nucl Med Biol 27, 533–9.Google Scholar
Ichimiya, T, Suhara, T, Sudo, Y, et al. 2002. Serotonin transporter binding in patients with mood disorders: A PET study with [11C](+)McN5652. Biol Psychiatry 51, 715–22.Google Scholar
Ikoma, Y, Suhara, T, Toyama, H, et al. 2002. Quantitative analysis for estimating binding potential of the brain serotonin transporter with [11 C]McN5652. J Cereb Blood Flow Metab 22, 490–501.Google Scholar
Ito, H, Nyberg, S, Halldin, C, Lundkvist, C and Farde, L. 1998. PET imaging of central 5-HT2A receptors with carbon-11-MDL 100,907. J Nucl Med 39, 208–14.Google Scholar
Junck, L, Olson, J M, Ciliax, B J, et al. 1989. PET imaging of human gliomas with ligands for the peripheral benzodiazepine binding site. Ann Neurol 26, 752–8.Google Scholar
Kapur, S and Mann, J J. 1992. Role of the dopaminergic system in depression. Biol Psychiatry 32, 1–17.Google Scholar
Kato, M and Serretti, A. 2010. Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Mol Psychiatry 15, 473–500.Google Scholar
Keller, J, Schatzberg, A F and Maj, M. 2007. Current issues in the classification of psychotic major depression. Schizophr Bull 33, 877–85.Google Scholar
Kessler, R C, Chiu, W T, Demler, O, Merikangas, K R and Walters, E E. 2005. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the national comorbidity survey replication. Arch Gen Psychiatry 62, 617–27.Google Scholar
Kessler, R M, Mason, N S, Votaw, J R, et al. 1992. Visualization of extrastriatal dopamine D2 receptors in the human brain. Eur J Pharmacol 223, 105–7.Google Scholar
Kilts, C D. 1994. Recent pharmacologic advances in antidepressant therapy. Am J Med 97, 3S–12S.Google Scholar
Klein, N, Sacher, J, Geiss-Granadia, T, et al. 2006. In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram. Psychopharmacology (Berl) 188, 263–72.Google Scholar
Klein, N, Sacher, J, Geiss-Granadia, T, et al. 2007. Higher serotonin transporter occupancy after multiple dose administration of escitalopram compared to citalopram: An [123I]ADAM SPECT study. Psychopharmacology (Berl) 191, 333–9.Google Scholar
Klimek, V, Schenck, J E, Han, H, Stockmeier, C A and Ordway, G A. 2002. Dopaminergic abnormalities in amygdaloid nuclei in major depression: A postmortem study. Biol Psychiatry 52, 740–8.Google Scholar
Klimke, A, Larisch, R, Janz, A, Vosberg, H, Muller-Gartner, H W and Gaebel, W. 1999. Dopamine D2 receptor binding before and after treatment of major depression measured by [123I]IBZM SPECT. Psychiatry Res 90, 91–101.Google Scholar
Koeppe, R A, Frey, K A, Snyder, S E, Meyer, P, Kilbourn, M R and Kuhl, D E. 1999. Kinetic modeling of N-[11C]methylpiperidin-4-yl propionate: Alternatives for analysis of an irreversible positron emission tomography trace for measurement of acetylcholinesterase activity in human brain. J Cereb Blood Flow Metab 19, 1150–63.Google Scholar
Koeppe, R A, Holthoff, V A, Frey, K A, Kilbourn, M R and Kuhl, D E. 1991. Compartmental analysis of [11C]flumazenil kinetics for the estimation of ligand transport rate and receptor distribution using positron emission tomography. J Cereb Blood Flow Metab 11, 735–44.Google Scholar
Krishnan, V and Nestler, E J. 2008. The molecular neurobiology of depression. Nature 455, 894–902.Google Scholar
Kugaya, A, Sanacora, G, Staley, J K, et al. 2004. Brain serotonin transporter availability predicts treatment response to selective serotonin reuptake inhibitors. Biol Psychiatry 56, 497–502.Google Scholar
Kugaya, A, Seneca, N M, Snyder, P J, et al. 2003. Changes in human in vivo serotonin and dopamine transporter availabilities during chronic antidepressant administration. Neuropsychopharmacology 28, 413–20.Google Scholar
Kuhl, D E, Koeppe, R A, Fessler, J A, et al. 1994. In vivo mapping of cholinergic neurons in the human brain using SPECT and IBVM. J Nucl Med 35, 405–10.Google Scholar
Kung, H F, Alavi, A, Chang, W, et al. 1990. In vivo SPECT imaging of CNS D-2 dopamine receptors: Initial studies with iodine-123-IBZM in humans. J Nucl Med 31, 573–9.Google Scholar
Kung, M P, Hou, C, Oya, S, Mu, M, Acton, P D and Kung, H F. 1999. Characterization of [(123)I]IDAM as a novel single-photon emission tomography tracer for serotonin transporters. Eur J Nucl Med 26, 844–53.Google Scholar
Laruelle, M, Dyck, C, Abi-Dargham, A, et al. 1994. Compartmental modeling of iodine-123-iodobenzofuran binding to dopamine D2 receptors in healthy subjects. J Nucl Med 35, 743–54.Google Scholar
Leopoldo, M, Berardi, F, Colabufo, N A, et al. 2002. Structure–affinity relationship study on N-[4-(4-arylpiperazin-1-yl)butyl]arylcarboxamides as potent and selective dopamine D(3) receptor ligands. J Med Chem 45, 5727–35.Google Scholar
Lesch, K P, Bengel, D, Heils, A, et al. 1996. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527–31.Google Scholar
Leysen, J E. 1990. Gaps and peculiarities in 5-HT2 receptor studies. Neuropsychopharmacology 3, 361–9.Google Scholar
Lopez, J F, Chalmers, D T, Little, K Y and Watson, S J. 1998. A.E. Bennett research award. Regulation of serotonin1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: Implications for the neurobiology of depression. Biol Psychiatry 43, 547–73.Google Scholar
Lu, B and Gottschalk, W. 2000. Modulation of hippocampal synaptic transmission and plasticity by neurotrophins. Progr Brain Res 128, 231–41.Google Scholar
Lundkvist, C, Halldin, C, Ginovart, N, et al. 1996. [11C]MDL 100907, a radioligland for selective imaging of 5-HT(2A) receptors with positron emission tomography. Life Sci 58, PL 187–92.Google Scholar
Maes, M and Meltzer, H. 1995. The serotonin hypothesis of major depression. In Bloom Kupfer, F (ed.) Psychopharmacology: The Fourth Generation of Progress. New York, NY: Raven Press, pp. 933–44.
Malison, R T, Price, L H, Berman, R, et al. 1998. Reduced brain serotonin transporter availability in major depression as measured by [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography. Biol Psychiatry 44, 1090–8.Google Scholar
Mann, J J. 1999. Role of the serotonergic system in the pathogenesis of major depression and suicidal behavior. Neuropsychopharmacology 21, 99S–105S.Google Scholar
Mann, J J, Huang, Y Y, Underwood, M D, et al. 2000. A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide. Arch Gen Psychiatry 57, 729–38.Google Scholar
Marek, G J and Aghajanian, G K. 1998. The electrophysiology of prefrontal serotonin systems: Therapeutic implications for mood and psychosis. Biol Psychiatry 44, 1118–27.Google Scholar
Marner, L, Gillings, N, Gunn, R, et al. 2007. Quantification of 11C-SB207145-PET for 5-HT4 receptors in the human brain: Preliminary results. J Nucl Med Meeting Abstracts 48, 159P.Google Scholar
Martarello, L, Kilts, C D, Ely, T, et al. 2001. Synthesis and characterization of fluorinated and iodinated pyrrolopyrimidines as PET/SPECT ligands for the CRF1 receptor. Nucl Med Biol 28, 187–95.Google Scholar
Massou, J M, Trichard, C, Attar-Levy, D, et al. 1997. Frontal 5-HT2A receptors studied in depressive patients during chronic treatment by selective serotonin reuptake inhibitors. Psychopharmacology 133, 99–101.Google Scholar
Mathew, S J, Manji, H K and Charney, D S. 2008. Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology 33, 2080–92.Google Scholar
Mathis, C A, Wang, Y, Holt, D P, Huang, G F, Debnath, M L and Klunk, W E. 2003. Synthesis and evaluation of (11)C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. J Med Chem 46, 2740–54.Google Scholar
Mayberg, H S. 2003. Modulating dysfunctional limbic-cortical circuits in depression: Towards development of brain-based algorithms for diagnosis and optimised treatment. Br Med Bull 65, 193–207.Google Scholar
Meador-Woodruff, J H, Mansour, A, Bunzow, J R, Tol, H H, Watson, S J and Civelli, O. 1989. Distribution of D2 dopamine receptor mRNA in rat brain. Proc Natl Acad Sci USA 86, 7625–8.Google Scholar
Meltzer, C C, Price, J C, Mathis, C A, et al. 1999. PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders. Am J Psychiatry 156, 1871–8.Google Scholar
Meltzer, C C, Price, J C, Mathis, C A, et al. 2004. Serotonin 1A receptor binding and treatment response in late-life depression. Neuropsychopharmacology 29, 2258–65.Google Scholar
Meltzer, C C, Smith, G, DeKosky, S T, et al. 1998. Serotonin in aging, late-life depression, and alzheimer's disease: The emerging role of functional imaging. Neuropsychopharmacology 18, 407–30.Google Scholar
Mengod, G, Pompeiano, M, Martínez-Mir, M I and Palacios, J M. 1990. Localization of the mRNA for the 5-HT2 receptor by in situ hybridization histochemistry. Correlation with the distribution of receptor sites. Brain Res 524, 139–43.Google Scholar
Merikangas, K R, Akiskal, H S, Angst, J, et al. 2007. Lifetime and 12-month prevalence of bipolar spectrum disorder in the national comorbidity survey replication. Arch Gen Psychiatry 64, 543–52.Google Scholar
Mervaala, E, Könönen, M, Föhr, J, et al. 2001. SPECT and neuropsychological performance in severe depression treated with ECT. J Affect Disord 66, 47–58.Google Scholar
Messa, C, Colombo, C, Moresco, R M, et al. 2003. 5-HT(2A) receptor binding is reduced in drug-naive and unchanged in SSRI-responder depressed patients compared to healthy controls: A PET study. Psychopharmacology 167, 72–8.Google Scholar
Meyer, J H. 2007. Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. J Psychiatry Neurosci 32, 86–102.Google Scholar
Meyer, J H, Cho, R, Kennedy, S and Kapur, S. 1999a. The effects of single dose nefazodone and paroxetine upon 5-HT2A binding potential in humans using [18F]-setoperone PET. Psychopharmacology 144, 279–81.Google Scholar
Meyer, J H, Ginovart, N, Boovariwala, A, et al. 2006. Elevated monoamine oxidase a levels in the brain: An explanation for the monoamine imbalance of major depression. Arch Gen Psychiatry 63, 1209–16.Google Scholar
Meyer, J H, Houle, S, Sagrati, S, et al. 2004. Brain serotonin transporter binding potential measured with carbon 11-labeled DASB positron emission tomography: Effects of major depressive episodes and severity of dysfunctional attitudes. Arch Gen Psychiatry 61, 1271–9.Google Scholar
Meyer, J H, Kapur, S, Houle, S, et al. 1999b. Prefrontal cortex 5-HT2 receptors in depression: An [18F]setoperone PET imaging study. Am J Psychiatry 156, 1029–34.Google Scholar
Meyer, J H, Kruger, S, Wilson, A A, et al. 2001a. Lower dopamine transporter binding potential in striatum during depression. Neuroreport 12, 4121–5.Google Scholar
Meyer, J H, McMain, S, Kennedy, S H, et al. 2003. Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm. Am J Psychiatry 160, 90–9.Google Scholar
Meyer, J H, Wilson, A A, Ginovart, N, et al. 2001b. Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: A [(11)C]DASB PET imaging study. Am J Psychiatry 158, 1843–9.Google Scholar
Milak, M S, Severance, A J, Ogden, R T, et al. 2008. Modeling considerations for 11C-CUMI-101, an agonist radiotracer for imaging serotonin 1A receptor in vivo with PET. J Nucl Med 49, 587–96.Google Scholar
Miller, J M, Oquendo, M A, Ogden, R T, Mann, J J and Parsey, R V. 2008. Serotonin transporter binding as a possible predictor of one-year remission in major depressive disorder. J Psychiatric Res 42, 1137–44.Google Scholar
Montgomery, A J, Thielemans, K, Mehta, M A, Turkheimer, F, Mustafovic, S and Grasby, P M. 2006. Correction of head movement on PET studies: Comparison of methods. J Nucl Med 47, 1936–44.Google Scholar
Moresco, R M, Colombo, C, Fazio, F, et al. 2000. Effects of fluvoxamine treatment on the in vivo binding of [F-18]FESP in drug naive depressed patients: A PET study. Neuroimage 12, 452–65.Google Scholar
Moses-Kolko, E L, Wisner, K L, Price, J C, et al. 2008. Serotonin 1A receptor reductions in postpartum depression: A positron emission tomography study. Fertil Steril 89, 685–92.Google Scholar
Mukherjee, J, Christian, B T, Dunigan, K A, et al. 2002. Brain imaging of 18F-fallypride in normal volunteers: Blood analysis, distribution, test–retest studies, and preliminary assessment of sensitivity to aging effects on dopamine D-2/D-3 receptors. Synapse 46, 170–88.Google Scholar
Muller-Gartner, H W, Wilson, A A, Dannals, R F, Wagner, H N and Frost, J J. 1992. Imaging muscarinic cholinergic receptors in human brain in vivo with Spect, [123I]4-iododexetimide, and [123I]4-iodolevetimide. J Cereb Blood Flow Metab 12, 562–70.Google Scholar
Mullins, D, Adham, N, Hesk, D, et al. 2008. Identification and characterization of pseudoirreversible nonpeptide antagonists of the neuropeptide Y Y(5) receptor and development of a novel Y(5)-selective radioligand. Eur J Pharmacol 601, 1–7.Google Scholar
Murray, C. 1996. Rethinking DALYs. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020. Boston, MA: Harvard School of Public Health.
Myers, R and Hume, S. 2002. Small animal PET. Eur Neuropsychopharmacol 12, 545–55.Google Scholar
Nestler, E J and Carlezon, W A 2006. The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59, 1151–9.Google Scholar
Newberg, A B, Amsterdam, J D, Wintering, N, et al. 2005. 123I-ADAM binding to serotonin transporters in patients with major depression and healthy controls: A preliminary study. J Nucl Med 46, 973–7.Google Scholar
Nobler, M S, Mann, J J and Sackeim, H A. 1999a. Serotonin, cerebral blood flow, and cerebral metabolic rate in geriatric major depression and normal aging. Brain Res 30, 250–63.Google Scholar
Nobler, M S, Pelton, G H and Sackeim, H A. 1999b. Cerebral blood flow and metabolism in late-life depression and dementia. J Geriatric Psychiatry Neurol 12, 118–27.Google Scholar
Nomura, M and Nomura, Y. 2006. Psychological, neuroimaging, and biochemical studies on functional association between impulsive behavior and the 5-HT2A receptor gene polymorphism in humans. Ann N Y Acad Sci 1086, 134–43.Google Scholar
Nordberg, A, Lundqvist, H, Hartvig, P, Lilja, A and Langstrom, B. 1995. Kinetic analysis of regional (S) (–)11C-nicotine binding in normal and Alzheimer brains – in vivo assessment using positron emission tomography. Alzheimer Dis Assoc Disord 9, 21–7.Google Scholar
Ohayon, M M and Schatzberg, A F. 2002. Prevalence of depressive episodes with psychotic features in the general population. Am J Psychiatry 159, 1855–61.Google Scholar
Okazawa, H, Leyton, M, Benkelfat, C, Mzengeza, S and Diksic, M. 2000. Statistical mapping analysis of serotonin synthesis images generated in healthy volunteers using positron-emission tomography and alpha-[11C]methyl-L-tryptophan. J Psychiatry Neurosci 5, 359–70.Google Scholar
Oquendo, M A, Hastings, R S, Huang, Y Y, et al. 2007. Brain serotonin transporter binding in depressed patients with bipolar disorder using positron emission tomography. Arch Gen Psychiatry 64, 201–08.Google Scholar
Owens, M J and Nemeroff, C B. 1994. Role of serotonin in the pathophysiology of depression: Focus on the serotonin transporter. Clin Chem 40, 288–95.Google Scholar
Pappata, S, Tavitian, B, Traykov, L, et al. 1996. In vivo imaging of human cerebral acetylcholinesterase. J Neurochem 67, 876–9.Google Scholar
Parker, C A, Cunningham, V J, Martarello, L, et al. 2008. Evaluation of the novel 5-HT6 receptor radioligand, [11C]GSK-215083 in human. Neuroimage 41, T20.Google Scholar
Parsey, R V, Hastings, R S, Oquendo, M A, et al. 2006a. Lower serotonin transporter binding potential in the human brain during major depressive episodes. Am J Psychiatry 163, 52–8.Google Scholar
Parsey, R V, Kegeles, L S, Hwang, D R, et al. 2000. In vivo quantification of brain serotonin transporters in humans using [11C]McN 5652. J Nucl Med 41, 1465–77.Google Scholar
Parsey, R V, Kent, J M, Oquendo, M A, et al. 2006b. Acute occupancy of brain serotonin transporter by sertraline as measured by [11C]DASB and positron emission tomography. Biol Psychiatry 59, 821–8.Google Scholar
Parsey, R V, Oquendo, M A, Ogden, R T, et al. 2006c. Altered serotonin 1A binding in major depression: A [carbonyl-C-11]WAY100635 positron emission tomography study. Biol Psychiatry 59, 106–13.Google Scholar
Parsey, R V, Oquendo, M A, Simpson, N R, et al. 2002. Effects of sex, age, and aggressive traits in man on brain serotonin 5-HT1A receptor binding potential measured by PET using [C-11]WAY-100635. Brain Res 954, 173–82.Google Scholar
Parsey, R V, Oquendo, M A, Zea-Ponce, Y, et al. 2001. Dopamine D(2) receptor availability and amphetamine-induced dopamine release in unipolar depression. Biol Psychiatry 50, 313–22.Google Scholar
Pazos, A, Probst, A and Palacios, J M. 1987. Serotonin receptors in the human brain – III. Autoradiographic mapping of serotonin-1 receptors. Neuroscience 21, 97–122.Google Scholar
Pearlson, G D, Wong, D F, Tune, L E, et al. 1995. In vivo D2 dopamine receptor density in psychotic and nonpsychotic patients with bipolar disorder. Arch Gen Psychiatry 52, 471–7.Google Scholar
Peroutka, S J. 1995. 5-HT receptors: Past, present and future. Trends Neurosci 18, 68–9.Google Scholar
Pierson, M E, Andersson, J, Nyberg, S, et al. 2008. [11C]AZ10419369: A selective 5-HT1B receptor radioligand suitable for positron emission tomography (PET). Characterization in the primate brain. Neuroimage 41, 1075–85.Google Scholar
Pifferi, F, Tremblay, S, Plourde, M, Tremblay-Mercier, J, Bentourkia, M and Cunnane, S C. 2008. Ketones and brain function: Possible link to polyunsaturated fatty acids and availability of a new brain PET tracer, 11C-acetoacetate. Epilepsia 49 (Suppl 8), 76–9.Google Scholar
Pike, V W, Halldin, C, Nobuhara, K, et al. 2003. Radioiodinated SB 207710 as a radioligand in vivo: Imaging of brain 5-HT4 receptors with SPET. Eur J Nucl Med Mol Imaging 30, 1520–8.Google Scholar
Pike, V W, McCarron, J A, Lammertsma, A A, et al. 1996. Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11 C]WAY-100635. Eur J Pharmacol 301, R5–7.Google Scholar
Pirker, W, Asenbaum, S, Hauk, M, et al. 2000. Imaging serotonin and dopamine transporters with 123I-beta-CIT SPECT: Binding kinetics and effects of normal aging. J Nucl Med 41, 36–44.Google Scholar
Podruchny, T A, Connolly, C, Bokde, A, et al. 2003. In vivo muscarinic 2 receptor imaging in cognitively normal young and older volunteers. Synapse 48, 39–44.Google Scholar
Pogarell, O, Koch, W, Pöpperl, G, et al. 2007. Acute prefrontal rTMS increases striatal dopamine to a similar degree as D-amphetamine. Psychiatry Res 156, 251–5.Google Scholar
Price, J C, Kelley, D E, Ryan, C M, et al. 2002. Evidence of increased serotonin-1A receptor binding in type 2 diabetes: A positron emission tomography study. Brain Res 927, 97–103.Google Scholar
,Psychiatric GWAS Consortium Steering Committee. 2009. A framework for interpreting genome-wide association studies of psychiatric disorders. Mol Psychiatry 14, 10–7.Google Scholar
Rahmim, A, Dinelle, K, Cheng, J C, et al. 2008. Accurate event-driven motion compensation in high-resolution PET incorporating scattered and random events. IEEE Trans Med Imaging 27, 1018–33.Google Scholar
Raison, C L, Capuron, L and Miller, A H. 2006. Cytokines sing the blues: Inflammation and the pathogenesis of depression. Trends Immunol 27, 24–31.Google Scholar
Rapoport, S I. 2008. Brain arachidonic and docosahexaenoic acid cascades are selectively altered by drugs, diet and disease. Prostagland Leukot Essen Fatty Acids 79, 153–6.Google Scholar
Rausch, J L, Stahl, S M and Hauger, R L. 1990. Cortisol and growth hormone responses to the 5-HT1A agonist gepirone in depressed patients. Biol Psychiatry 28, 73–8.Google Scholar
Reid, A E, Ding, Y S, Eckelman, W C, et al. 2008. Comparison of the pharmacokinetics of different analogs of 11C-labeled TZTP for imaging muscarinic M2 receptors with PET. Nucl Med Biol 35, 287–98.Google Scholar
Reimold, M, Batra, A, Knobel, A, et al. 2008. Anxiety is associated with reduced central serotonin transporter availability in unmedicated patients with unipolar major depression: A [11C]DASB PET study. Mol Psychiatry 13, 606–13, 557.Google Scholar
Ressler, K J and Mayberg, H S. 2007. Targeting abnormal neural circuits in mood and anxiety disorders: From the laboratory to the clinic. Nature Neurosci 10, 1116–24.Google Scholar
Riccardi, P, Li, R, Ansari, M S, et al. 2006. Amphetamine-induced displacement of [18F] fallypride in striatum and extrastriatal regions in humans. Neuropsychopharmacology 31, 1016–26.Google Scholar
Riemann, B, Schafers, K P, Schober, O and Schafers, M. 2008. Small animal PET in preclinical studies: Opportunities and challenges. Q J Nucl Med Mol Imaging 52, 215–21.Google Scholar
Rosa-Neto, P, Diksic, M, Okazawa, H, et al. 2004. Measurement of brain regional alpha-[11C]methyl-L-tryptophan trapping as a measure of serotonin synthesis in medication-free patients with major depression. Arch Gen Psychiatry 61, 556–63.Google Scholar
Rousset, O G, Collins, D L, Rahmim, A and Wong, D F. 2008. Design and implementation of an automated partial volume correction in PET: Application to dopamine receptor quantification in the normal human striatum. J Nucl Med 49, 1097–106.Google Scholar
Rowland, D J and Cherry, S R. 2008. Small-animal preclinical nuclear medicine instrumentation and methodology. Semin Nucl Med 38, 209–22.Google Scholar
Sacher, J, Asenbaum, S, Klein, N, et al. 2007. Binding kinetics of 123I[ADAM] in healthy controls: A selective SERT radioligand. Int J Neuropsychopharmacol 10, 211–8.Google Scholar
Sargent, P A, Kjaer, K H, Bench, C J, 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, 174–80.Google Scholar
Satyamurthy, N, Barrio, J R, Bida, G T, Huang, S C, Mazziotta, J C and Phelps, M E. 1990. 3-(2'-[18F]fluoroethyl)spiperone, a potent dopamine antagonist: synthesis, structural analysis and in-vivo utilization in humans. Int J Radiat App Instrument – Part A, Appl Radiat Isotopes 41, 113–29.Google Scholar
Saudou, F and Hen, R. 1994. 5-Hydroxytryptamine receptor subtypes in vertebrates and invertebrates. Neurochem Int 25, 503–32.Google Scholar
Schatzberg, A F. 2002. Brain imaging in affective disorders: More questions about causes versus effects. Am J Psychiatry 159, 1807–8.Google Scholar
Schotte, A, Maloteaux, J M and Laduron, P M. 1983. Characterization and regional distribution of serotonin S2-receptors in human brain. Brain Res 276, 231–5.Google Scholar
Schou, M, Pike, V W and Halldin, C. 2007. Development of radioligands for imaging of brain norepinephrine transporters in vivo with positron emission tomography. Curr Top Med Chem 7, 1806–16.Google Scholar
Sen, S, Nesse, R M, Stoltenberg, S F, et al. 2003. A BDNF coding variant is associated with the NEO personality inventory domain neuroticism, a risk factor for depression. Neuropsychopharmacology 28, 397–401.Google Scholar
Shank, R P, Vaught, J L, Pelley, K A, Setler, P E, McComsey, D F and Maryanoff, B E. 1988. McN-5652: A highly potent inhibitor of serotonin uptake. J Pharmacol Exp Therap 247, 1032–8.Google Scholar
Shidahara, M, Tsoumpas, C, Hammers, A, et al. 2009. Functional and structural synergy for resolution recovery and partial volume correction in brain PET. Neuroimage 44, 340–8.Google Scholar
Shioe, K, Ichimiya, T, Suhara, T, et al. 2003. No association between genotype of the promoter region of serotonin transporter gene and serotonin transporter binding in human brain measured by PET. Synapse 48, 184–8.Google Scholar
Shiue, C Y, Shiue, G G, Mozley, P D, et al. 1997a. P-[18F]-MPPF: A potential radioligand for PET studies of 5-HT1A receptors in humans. Synapse 25, 147–54.Google Scholar
Shiue, C Y, Vallabhahosula, S, Wolf, A P, et al. 1997b. Carbon-11 labelled ketamine-synthesis, distribution in mice and PET studies in baboons. Nucl Med Biol 24, 145–50.Google Scholar
Shoghi-Jadid, K, Small, G W, Agdeppa, E D, et al. 2002. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriat Psychiatry 10, 24–35.Google Scholar
Simpson, S, Talbot, P R, Snowden, J S and Neary, D. 1997. Subcortical vascular disease in elderly patients with treatment resistant depression. J Neurol Neurosurg Psychiatry 62, 196–7.Google Scholar
Smith, G, Dewey, S L, Brodie, J D, et al. 1997. Serotonergic modulation of dopamine measured with [11C]raclopride and PET in normal human subjects. Am J Psychiatry 154, 490–6.Google Scholar
Smith, G, Kahn, A, Hanratty, K, et al. 2008. Serotonin transporter occupancy by citalopram treatment in geriatric depression. Neuroimage 41, T168.Google Scholar
Smith, G, Kramer, E, Hermann, C, et al. 2009a. Serotonin modulation of cerebral glucose metabolism in geriatric depression. Biol Psychiatry 66, 259–66.Google Scholar
Smith, G, Kramer, E, Hermann, C, et al. 2009b. The functional neuroanatomy of geriatric depression. Int J Geriatric Psychiatry 24, 798–808.Google Scholar
Smith, G, Lotrich, F, Malhotra, A, et al. 2004. The effect of serotonin transporter polymorphisms on serotonin function. Neuropsychopharmacology 29, 2226–34.Google Scholar
Smith, G, Price, J C, Lopresti, B J, et al. 1998. Test–retest variability of serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain. Synapse 30, 380–92.Google Scholar
Smith, G S, Gunning-Dixon, F M, Lotrich, F E, Taylor, W D and Evans, J D. 2007. Translational research in late-life mood disorders: implications for future intervention and prevention research. Neuropsychopharmacology 32, 1857–75.Google Scholar
Smith, G S, Ma, Y, Dhawan, V, Chaly, T and Eidelberg, D. 2009. Selective serotonin reuptake inhibitor (SSRI) modulation of striatal dopamine measured with [11C]-raclopride and positron emission tomography. Synapse 63, 1–6.Google Scholar
Smith, J S, Zubieta, J K, Price, J C, et al. 1999. Quantification of delta-opioid receptors in human brain with N1'-([11C]methyl) naltrindole and positron emission tomography. J Cereb Blood Flow Metab 19, 956–66.Google Scholar
Smolka, M N, Schumann, G, Wrase, J, et al. 2005. Catechol-O-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex. J Neurosci 25, 836–42.Google Scholar
Sokoloff, P, Giros, B, Martres, M P, Bouthenet, M L and Schwartz, J C. 1990. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 347, 146–51.Google Scholar
Sorger, D, Scheunemann, M, Grossmann, U, et al. 2008. A new 18F-labeled fluoroacetylmorpholino derivative of vesamicol for neuroimaging of the vesicular acetylcholine transporter. Nucl Med Biol 35, 185–95.Google Scholar
Sotelo, C, Cholley, B, El Mestikawy, S, Gozlan, H and Hamon, M. 1990. Direct immunohistochemical evidence of the existence of 5-HT1A autoreceptors on serotoninergic neurons in the midbrain raphe nuclei. Eur J Neurosci 2, 1144–54.Google Scholar
Staley, J K, Dyck, C H, Weinzimmer, D, et al. 2005. 123I-5-IA-85380 SPECT measurement of nicotinic acetylcholine receptors in human brain by the constant infusion paradigm: Feasibility and reproducibility. J Nucl Med 46, 1466–72.Google Scholar
Steiniger, B, Kniess, T, Bergmann, R, Pietzsch, J and Wuest, F R. 2008. Radiolabeled glucocorticoids as molecular probes for imaging brain glucocorticoid receptors by means of positron emission tomography (PET). Mini Rev Med Chem 8, 728–39.Google Scholar
Stephenson, K A, Oosten, E M, Wilson, A A, Meyer, J H, Houle, S and Vasdev, N. 2008. Synthesis and preliminary evaluation of [(18)F]-fluoro-(2S)-exaprolol for imaging cerebral beta-adrenergic receptors with PET. Neurochem Int 53, 173–9.Google Scholar
Stockmeier, C A. 2003. Involvement of serotonin in depression: Evidence from postmortem and imaging studies of serotonin receptors and the serotonin transporter. J Psychiatric Res 37, 357–73.Google Scholar
Stockmeier, C A, Shapiro, L A, Haycock, J W, Thompson, P A and Lowy, M T. 1996. Quantitative subregional distribution of serotonin1A receptors and serotonin transporters in the human dorsal raphe. Brain Res 727, 1–12.Google Scholar
Strafella, A P, Paus, T, Fraraccio, M and Dagher, A. 2003. Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Brain 126, 2609–15.Google Scholar
Strome, E M, Clark, C M, Zis, A P and Doudet, D J. 2005. Electroconvulsive shock decreases binding to 5-HT2 receptors in nonhuman primates: An in vivo positron emission tomography study with [18F]setoperone. Biol Psychiatry 57, 1004–10.Google Scholar
Suehiro, M, Scheffel, U, Dannals, R F, Ravert, H T, Ricaurte, G A and Wagner, N H 1993. A PET radiotracer for studying serotonin uptake sites: Carbon-11-McN-5652Z. J Nucl Med 34, 120–7.Google Scholar
Suhara, T, Fukuda, H, Inoue, O, et al. 1991. Age-related changes in human D1 dopamine receptors measured by positron emission tomography. Psychopharmacology 103, 41–5.Google Scholar
Suhara, T, Higuchi, M and Miyoshi, M. 2008. Neuroimaging in dementia: In vivo amyloid imaging. Tohoku J Exp Med 215, 119–24.Google Scholar
Suhara, T, Inoue, O, Kobayashi, K, Suzuki, K and Tateno, Y. 1993. Age-related changes in human muscarinic acetylcholine receptors measured by positron emission tomography. Neurosci Lett 149, 225–8.Google Scholar
Suhara, T, Nakayama, K, Inoue, O, et al. 1992. D1 dopamine receptor binding in mood disorders measured by positron emission tomography. Psychopharmacology 106, 14–8.Google Scholar
Sullivan, G M, Parsey, R V, Kumar, J S, et al. 2007. PET imaging of CRF1 with [11C]R121920 and [11C]DMP696: Is the target of sufficient density? Nucl Med Biol 34, 353–61.Google Scholar
Syvanen, S, Eriksson, J, Genchel, T, Lindhe, O, Antoni, G and Langstrom, B. 2007. Synthesis of two potential NK1-receptor ligands using [1–11C]ethyl iodide and [1–11C]propyl iodide and initial PET-imaging. BMC Med Imaging 7, 6.Google Scholar
Szabo, Z, Kao, P F, Scheffel, U, et al. 1995. Positron emission tomography imaging of serotonin transporters in the human brain using [11C](+)McN5652. Synapse 20, 37–43.Google Scholar
Szabo, Z, McCann, U D, Wilson, A A, et al. 2002. Comparison of (+)-(11)C-McN5652 and (11)C-DASB as serotonin transporter radioligands under various experimental conditions. J Nucl Med 43, 678–92.Google Scholar
Takano, A, Arakawa, R, Hayashi, M, Takahashi, H, Ito, H and Suhara, T. 2007. Relationship between neuroticism personality trait and serotonin transporter binding. Biol Psychiatry 62, 588–92.Google Scholar
Takano, A, Gulyas, B, Varrone, A, et al. 2008. Imaging the norepinephrine transporter with positron emission tomography: Initial human studies with (S,S)-[(18)F]FMeNER-D (2). Eur J Nucl Med Mol Imaging 35, 153–7.Google Scholar
Tauscher, J, Bagby, R M, Javanmard, M, Christensen, B K, Kasper, S and Kapur, S. 2001. Inverse relationship between serotonin 5-HT(1A) receptor binding and anxiety: A [(11)C]WAY-100635 PET investigation in healthy volunteers. Am J Psychiatry 158, 1326–8.Google Scholar
Tiihonen, J, Kuoppamäki, M, Någren, K, et al. 1996. Serotonergic modulation of striatal D2 dopamine receptor binding in humans measured with positron emission tomography. Psychopharmacology (Berl) 126, 277–80.Google Scholar
Tweedie, D J and Burke, M D. 1987. Metabolism of the beta-carbolines, harmine and harmol, by liver microsomes from phenobarbitone- or 3-methylcholanthrene-treated mice. Identification and quantitation of two novel harmine metabolites. Drug Metab Disposition: Biol Fate Chem 15, 74–81.Google Scholar
Heeringen, C, Audenaert, K, Laere, K, et al. 2003. Prefrontal 5-HT2a receptor binding index, hopelessness and personality characteristics in attempted suicide. J Affect Disord 74, 149–58.Google Scholar
Tol, H H, Bunzow, J R, Guan, H C, et al. 1991. Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature 350, 610–4.Google Scholar
Varnas, K, Halldin, C and Hall, H. 2004. Autoradiographic distribution of serotonin transporters and receptor subtypes in human brain. Human Brain Mapp 22, 246–60.Google Scholar
Vasdev, N, LaRonde, F J, Woodgett, J R, et al. 2008. Rationally designed PKA inhibitors for positron emission tomography: Synthesis and cerebral biodistribution of N-(2-(4-bromocinnamylamino)ethyl)-N-[11C]methyl-isoquinoline-5-sulfonamide. Bioorg Med Chem 16, 5277–84.Google Scholar
Verhoeff, N P, Wilson, A A, Takeshita, S, et al. 2004. In-vivo imaging of alzheimer disease beta-amyloid with [11C]SB-13 PET. Am J Geriatr Psychiatry 12, 584–95.Google Scholar
Villemagne, V L, Horti, A, Scheffel, U, et al. 1997. Imaging nicotinic acetylcholine receptors with fluorine-18-FPH, an epibatidine analog. J Nucl Med 38, 1737–41.Google Scholar
Volkow, N D, Ding, Y S, Fowler, J S, et al. 1995. A new PET ligand for the dopamine transporter: Studies in the human brain. J Nucl Med 36, 2162–8.Google Scholar
Volkow, N D, Fowler, J S, Gatley, S J, et al. 1996. PET evaluation of the dopamine system of the human brain. J Nucl Med 37, 1242–56.Google Scholar
Volkow, N D, Wang, G J, Fowler, J S, et al. 1994. Imaging endogenous dopamine competition with [11C]raclopride in the human brain. Synapse 16, 255–62.Google Scholar
Wagner, N H, Burns, H D, Dannals, R F, et al. 1983. Imaging dopamine receptors in the human brain by positron tomography. Science 221, 1264–6.Google Scholar
Weissman, M M, Bland, R C, Canino, G J, et al. 1996. Cross-national epidemiology of major depression and bipolar disorder. JAMA 276, 293–9.Google Scholar
Willeit, M, Ginovart, N, Kapur, S, et al. 2006. High-affinity states of human brain dopamine D2/3 receptors imaged by the agonist [11C]-(+)-PHNO. Biol Psychiatry 59, 389–94.Google Scholar
Willeit, M, Praschak-Rieder, N, Neumeister, A, et al. 2000. [123I]-beta-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder. Biol Psychiatry 47, 482–9.Google Scholar
Willeit, M, Stastny, J, Pirker, W, et al. 2001. No evidence for in vivo regulation of midbrain serotonin transporter availability by serotonin transporter promoter gene polymorphism. Biol Psychiatry 50, 8–12.Google Scholar
Wilson, A A, Garcia, A, Parkes, J, et al. 2008. Radiosynthesis and initial evaluation of [18F]-FEPPA for PET imaging of peripheral benzodiazepine receptors. Nucl Med Biol 35, 305–14.Google Scholar
Wilson, A A, Ginovart, N, Hussey, D, Meyer, J and Houle, S. 2002. In vitro and in vivo characterisation of [11C]-DASB: A probe for in vivo measurements of the serotonin transporter by positron emission tomography. Nucl Med Biol 29, 509–15.Google Scholar
Wong, D F, Tauscher, J and Grunder, G. 2009. The role of imaging in proof of concept for CNS drug discovery and development. Neuropsychopharmacology 34, 187–203.Google Scholar
Wong, D F, Wagner, N H, Dannals, R F, et al. 1984. Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain. Science 226, 1393–6.Google Scholar
Xiang, L, Szebeni, K, Szebeni, A, et al. 2008. Dopamine receptor gene expression in human amygdaloid nuclei: Elevated D4 receptor mRNA in major depression. Brain Res 1207, 214–24.Google Scholar
Yasuno, F, Ota, M, Kosaka, J, et al. 2008. Increased binding of peripheral benzodiazepine receptor in Alzheimer's disease measured by positron emission tomography with [11C]DAA1106. Biol Psychiatry 64, 835–41.Google Scholar
Yasuno, F, Sanabria, S M, Burns, D, et al. 2007. PET imaging of neurokinin-1 receptors with [(18)F]SPA-RQ in human subjects: Assessment of reference tissue models and their test–retest reproducibility. Synapse 61, 242–51.Google Scholar
Yatham, L N, Liddle, P F, Dennie, J, et al. 1999. Decrease in brain serotonin 2 receptor binding in patients with major depression following desipramine treatment: A positron emission tomography study with fluorine-18-labeled setoperone. Arch Gen Psychiatry 56, 705–11.Google Scholar
Yatham, L N, Liddle, P F, Lam, R W, et al. 2002b. PET study of the effects of valproate on dopamine D(2) receptors in neuroleptic- and mood-stabilizer-naive patients with nonpsychotic mania. Am J Psychiatry 159, 1718–23.Google Scholar
Yatham, L N, Liddle, P F, Shiah, I S, et al. 2000. Brain serotonin 2 receptors in major depression: A positron emission tomography study. Arch Gen Psychiatry 57, 850–8.Google Scholar
Yatham, L N, Liddle, P F, Shiah, I S, et al. 2002a. PET study of [(18)F]6-fluoro-L-dopa uptake in neuroleptic- and mood-stabilizer-naive first-episode nonpsychotic mania: Effects of treatment with divalproex sodium. Am J Psychiatry 159, 768–74.Google Scholar
Yu, Y W, Tsai, S J, Chen, T J, Lin, C H and Hong, C J. 2002. Association study of the serotonin transporter promoter polymorphism and symptomatology and antidepressant response in major depressive disorders. Mol Psychiatry 7, 1115–9.Google Scholar
Zarate, C A Jr, Singh, J and Manji, H K. 2006. Cellular plasticity cascades: Targets for the development of novel therapeutics for bipolar disorder. Biol Psychiatry 59, 1006–20.Google Scholar
Zoghbi, S S, Baldwin, R M, Seibyl, J P, et al. 1992. Pharmacokinetics of the SPECT benzodiazepine receptor radioligand [123I]iomazenil in human and non-human primates. Int J Radiat Applic Instrum – Part B, Nucl Med Biol 19, 881–8.Google Scholar
Zubieta, J K, Ketter, T A, Bueller, J A, et al. 2003. Regulation of human affective responses by anterior cingulate and limbic mu-opioid neurotransmission. Arch Gen Psychiatry 60, 1145–53.Google Scholar
Zubieta, J K, Smith, Y R, Bueller, J A, et al. 2001a. Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science (New York, NY) 293, 311–5.Google Scholar
Zubieta, J K, Taylor, S F, Huguelet, P, Koeppe, R A, Kilbourn, M R and Frey, K A. 2001b. Vesicular monoamine transporter concentrations in bipolar disorder type I, schizophrenia, and healthy subjects. Biol Psychiatry 49, 110–6.Google Scholar

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