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  • Print publication year: 2010
  • Online publication date: January 2011

11 - Molecular imaging of major depression

from Section II - Mood Disorders

Summary

The primary focus of radiochemistry development for positron emission tomography (PET) and single photon emission computed tomography (SPECT) has been dopamine and serotonin neurotransmission. This chapter reviews the PET and SPECT neurochemical brain imaging studies to understand the neurochemical mechanisms underling depression and the response to treatment. It examines the clinical and methodological aspects involved in the design, analysis and interpretation of neurochemical imaging studies. The chapter overviews the studies on neurochemical imaging in depressive illness. While the majority of studies have focused on unipolar depression, the chapter discusses the available data on other depression subtypes. The serotonin and dopamine systems have been the major focus of in-vivo neurochemical imaging studies in depression, as well as other conditions including schizophrenia and anxiety disorders. The chapter also reviews the available neurochemical imaging data for other neurotransmitter systems, and highlights active areas of radiotracer development for other potentially important neurochemical targets.

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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.
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.
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.
Agren, H and Reibring, L. 1994. PET studies of presynaptic monoamine metabolism in depressed patients and healthy volunteers. Pharmacopsychiatry 27, 2–6.
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.
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.
Alexopoulos, G S, Vrontou, C, Kakuma, T, et al. 1996. Disability in geriatric depression. Am J Psychiatry 153, 877–85.
Allard, P and Norlen, M. 2001. Caudate nucleus dopamine D(2) receptors in depressed suicide victims. Neuropsychobiology 44, 70–3.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Brown, A S and Gershon, S. 1993. Dopamine and depression. J Neural Transm 91, 75–109.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Castren, E. 2004. Neurotrophins as mediators of drug effects on mood, addiction, and neuroprotection. Mol Neurobiol 29, 289–302.
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.
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.
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.
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.
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.
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.
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.
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.
Cowen, P J. 1996. Advances in psychopharmacology: Mood disorders and dementia. Br Med Bull 52, 539–55.
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.
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.
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.
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.
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.
Dilsaver, S C. 1986. Cholinergic mechanisms in depression. Brain Res 396, 285–316.
Ding, Y S, Lin, K S and Logan, J. 2006. PET imaging of norepinephrine transporters. Curr Pharm Des 12, 3831–45.
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.
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.
Duman, R S, Heninger, G R and Nestler, E J. 1997. A molecular and cellular theory of depression. Arch Gen Psychiatry 54, 597–606.
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.
Eckelman, W C. 2001. Radiolabeled muscarinic radioligands for in vivo studies. Nucl Med Biol 28, 485–91.
Eckelman, W C, Reba, R C, Rzeszotarski, W J, et al. 1984. External imaging of cerebral muscarinic acetylcholine receptors. Science 223, 291–3.
Efange, S M. 2000. In vivo imaging of the vesicular acetylcholine transporter and the vesicular monoamine transporter. Faseb J 14, 2401–13.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Frost, J J. 2001. PET imaging of the opioid receptor: The early years. Nucl Med Biol 28, 509–13.
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.
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.
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.
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.
Garnett, E S, Firnau, G and Nahmias, C. 1983. Dopamine visualized in the basal ganglia of living man. Nature 305, 137–8.
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.
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.
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.
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.
Hall, H, Halldin, C, Farde, L and Sedvall, G. 1998. Whole hemisphere autoradiography of the postmortem human brain. Nucl Med Biol 25, 715–9.
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.
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.
Hargreaves, R. 2002. Imaging substance P receptors (NK1) in the living human brain using positron emission tomography. J Clin Psychiatry 63, 18–24.
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.
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.
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.
Heiss, W D. 2009. The potential of PET/MR for brain imaging. Eur J Nucl Med Mol Imaging 36(Suppl 1), S105–12.
Heiss, W D and Herholz, K. 2006. Brain receptor imaging. J Nucl Med 47, 302–12.
Henriksson, M M, Marttunen, M J, Isometsa, E T, et al. 1995. Mental disorders in elderly suicide. Int Psychogeriatr 7, 275–86.
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.
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.
Holsboer, F. 2000. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 23, 477–501.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Kapur, S and Mann, J J. 1992. Role of the dopaminergic system in depression. Biol Psychiatry 32, 1–17.
Kato, M and Serretti, A. 2010. Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Mol Psychiatry 15, 473–500.
Keller, J, Schatzberg, A F and Maj, M. 2007. Current issues in the classification of psychotic major depression. Schizophr Bull 33, 877–85.
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.
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.
Kilts, C D. 1994. Recent pharmacologic advances in antidepressant therapy. Am J Med 97, 3S–12S.
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.
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.
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.
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.
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.
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.
Krishnan, V and Nestler, E J. 2008. The molecular neurobiology of depression. Nature 455, 894–902.
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.
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.
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.
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.
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.
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.
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.
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.
Leysen, J E. 1990. Gaps and peculiarities in 5-HT2 receptor studies. Neuropsychopharmacology 3, 361–9.
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.
Lu, B and Gottschalk, W. 2000. Modulation of hippocampal synaptic transmission and plasticity by neurotrophins. Progr Brain Res 128, 231–41.
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.
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.
Mann, J J. 1999. Role of the serotonergic system in the pathogenesis of major depression and suicidal behavior. Neuropsychopharmacology 21, 99S–105S.
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.
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.
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.
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.
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.
Mathew, S J, Manji, H K and Charney, D S. 2008. Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology 33, 2080–92.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Meyer, J H. 2007. Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. J Psychiatry Neurosci 32, 86–102.
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.
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.
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.
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.
Meyer, J H, Kruger, S, Wilson, A A, et al. 2001a. Lower dopamine transporter binding potential in striatum during depression. Neuroreport 12, 4121–5.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Nestler, E J and Carlezon, W A 2006. The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59, 1151–9.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Pappata, S, Tavitian, B, Traykov, L, et al. 1996. In vivo imaging of human cerebral acetylcholinesterase. J Neurochem 67, 876–9.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Peroutka, S J. 1995. 5-HT receptors: Past, present and future. Trends Neurosci 18, 68–9.
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.
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.
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.
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.
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.
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.
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.
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.
,Psychiatric GWAS Consortium Steering Committee. 2009. A framework for interpreting genome-wide association studies of psychiatric disorders. Mol Psychiatry 14, 10–7.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Rowland, D J and Cherry, S R. 2008. Small-animal preclinical nuclear medicine instrumentation and methodology. Semin Nucl Med 38, 209–22.
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.
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.
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.
Saudou, F and Hen, R. 1994. 5-Hydroxytryptamine receptor subtypes in vertebrates and invertebrates. Neurochem Int 25, 503–32.
Schatzberg, A F. 2002. Brain imaging in affective disorders: More questions about causes versus effects. Am J Psychiatry 159, 1807–8.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Smith, G, Kahn, A, Hanratty, K, et al. 2008. Serotonin transporter occupancy by citalopram treatment in geriatric depression. Neuroimage 41, T168.
Smith, G, Kramer, E, Hermann, C, et al. 2009a. Serotonin modulation of cerebral glucose metabolism in geriatric depression. Biol Psychiatry 66, 259–66.
Smith, G, Kramer, E, Hermann, C, et al. 2009b. The functional neuroanatomy of geriatric depression. Int J Geriatric Psychiatry 24, 798–808.
Smith, G, Lotrich, F, Malhotra, A, et al. 2004. The effect of serotonin transporter polymorphisms on serotonin function. Neuropsychopharmacology 29, 2226–34.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Suhara, T, Higuchi, M and Miyoshi, M. 2008. Neuroimaging in dementia: In vivo amyloid imaging. Tohoku J Exp Med 215, 119–24.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.