Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-546b4f848f-fhndm Total loading time: 0 Render date: 2023-06-04T09:31:43.852Z Has data issue: false Feature Flags: { "useRatesEcommerce": true } hasContentIssue false

Chapter 4 - Translational research in mood disorders

using imaging technologies in biomarker research

Published online by Cambridge University Press:  19 October 2021

By
Jul Lea Shamy ,
Adam M. Brickman ,
Chris D. Griesemer ,
Anna Parachikova  and
Mark Day
Edited by
Chad E. Beyer  and
Stephen M. Stahl
Chad E. Beyer
Affiliation:
University of Colorado School of Medicine
Stephen M. Stahl
Affiliation:
University of California, San Diego
Get access

Summary

Dramatic scientific and technological advances in the field of drug discovery have been made over the past decade, without a corresponding improvement in the success rate of compounds in clinical development. In response, translational research was developed as a research discipline with the aim of improving the correspondence between preclinical and clinical success of therapeutic treatments by identifying novel disease biomarkers, drug targets, and mechanisms of action for compounds of interest. Functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have been widely used to reveal the neurobiological underpinnings of human cognition and emotion. The knowledge gained from such studies is currently being employed in the clinical setting to better diagnose and develop treatments for mood disorders. Many of the imaging techniques established in humans are now feasible in animal models (rodents and non-human primates), allowing closer alignment of imaging biomarkers across species and improved congruency between the laboratory and clinical setting. In this review, we explore the use of neuroimaging biomarkers as a translational technique to pave the way to improved clinical success through greater psychiatric disease understanding.

Type
Chapter
Information
Next Generation Antidepressants
Moving Beyond Monoamines to Discover Novel Treatment Strategies for Mood Disorders
 , pp. 45 - 69
Publisher: Cambridge University Press
Print publication year: 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Kessler, R. C., et al., The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA, 2003. 289(23): 3095–105.CrossRefGoogle Scholar
First, B., Frances, M. A., and A. Pincus, H., DSM-IV-TR Handbook of Differential Diagnosis. Arlington, VA, American Psychiatric Publishing, 2002: p. 247.CrossRefGoogle Scholar
Kessler, R. C., et al., Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry, 2005. 62(6): 593–602.CrossRefGoogle ScholarPubMed
Merikangas, K. R., et al., Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry, 2007. 64(5): 543–52.CrossRefGoogle ScholarPubMed
Borsook, D., Becerra, L., and Hargreaves, R., A role for fMRI in optimizing CNS drug development. Nat Rev Drug Discov, 2006. 5(5): 411–25.CrossRefGoogle ScholarPubMed
Wise, R. and Tracey, I., The role of fMRI in drug discovery. J Magn Reson Imaging, 2006. 23(6): 862–76.CrossRefGoogle ScholarPubMed
Wong, D. F., Tauscher, J., and Gründer, G., The role of imaging in proof of concept for CNS drug discovery and development. Neuropsychopharmacology, 2009. 34(1): 187–203.CrossRefGoogle ScholarPubMed
Rudin, M., Noninvasive structural, functional, and molecular imaging in drug development. Curr Opin Chem Biol, 2009. 13(3): 360–71.CrossRefGoogle ScholarPubMed
DiMasi, J. A., Hansen, R. W., and Grabowski, H. G., The price of innovation: new estimates of drug development costs. J Health Econ, 2003. 22(2): 151–85.CrossRefGoogle Scholar
Lesko, L. J. and Atkinson, A. J., Use of biomarkers and surrogate endpoints in drug development and regulatory decision making: criteria, validation, strategies. Annu Rev Pharmacol Toxicol, 2001. 41: 347–66.CrossRefGoogle ScholarPubMed
Boissel, J. P., et al., Surrogate endpoints: a basis for a rational approach. Eur J Clin Pharmacol, 1992. 43(3): 235–44.Google ScholarPubMed
Williams, S. A., et al., A cost-effectiveness approach to the qualification and acceptance of biomarkers. Nat Rev Drug Discov, 2006. 5(11): 897–902.CrossRefGoogle ScholarPubMed
Feuerstein, G. and Chavez, J., Translational medicine for stroke drug discovery: the pharmaceutical industry perspective. Stroke, 2008. 40(3, Supplement 1): S121–25.CrossRefGoogle ScholarPubMed
Feuerstein, G. Z., Rutkowski, J. L. R., Walsh, F. S., Stiles, G. L, Ruffolo, R. R, The role of translational medicine and biomarker research in drug discovery and development. Am Drug Discovery, 2007. 2(1): 23–28.Google Scholar
Stanford, S. C., Depression. In Webster, R. A. (Ed.), Neurotransmitters, Drugs, and Brain Function. Chichester, John Wiley, 2001: p. 534.Google Scholar
Day, M., Rutkowski, J. L., and Feuerstein, G. Z., Translational medicine – a paradigm shift in modern drug discovery and development: the role of biomarkers. Adv Exp Med Biol, 2009. 655: 1–12.CrossRefGoogle ScholarPubMed
Baghai, T. C., Volz, H. P., and Moller, H. J., Drug treatment of depression in the 2000s: An overview of achievements in the last 10 years and future possibilities. World J Biol Psychiatry, 2006. 7(4): 198–222.CrossRefGoogle ScholarPubMed
Little, A., Treatment-resistant depression. Am Fam Physician, 2009. 80(2): 167–72.Google ScholarPubMed
Rosenzweig-Lipson, S., et al., Differentiating antidepressants of the future: efficacy and safety. Pharmacol Ther, 2007. 113(1): 134–53.CrossRefGoogle ScholarPubMed
Capitanio, J. P. and Emborg, M. E., Contributions of non-human primates to neuroscience research. Lancet, 2008. 371(9618): 1126–35.CrossRefGoogle ScholarPubMed
Kinnally, E. L., et al., Effects of early experience and genotype on serotonin transporter regulation in infant rhesus macaques. Genes Brain Behav, 2008. 7(4): 481–86.CrossRefGoogle ScholarPubMed
Shively, C. A., Laber-Laird, K., and Anton, R. F., Behavior and physiology of social stress and depression in female cynomolgus monkeys. Biol Psychiatry, 1997. 41(8): 871–82.CrossRefGoogle ScholarPubMed
Shively, C. A., et al., Social stress, depression, and brain dopamine in female cynomolgus monkeys. Ann NY Acad Sci, 1997. 807: 574–77.CrossRefGoogle ScholarPubMed
Izquierdo, A., et al., Genetic modulation of cognitive flexibility and socioemotional behavior in rhesus monkeys. Proc Natl Acad Sci USA, 2007. 104(35): 14128–33.CrossRefGoogle ScholarPubMed
Barr, C. S., et al., The utility of the non-human primate; model for studying gene by environment interactions in behavioral research. Genes Brain Behav, 2003. 2(6): 336–40.CrossRefGoogle ScholarPubMed
Rupniak, N. M., Animal models of depression: challenges from a drug development perspective. Behav Pharmacol, 2003. 14(5–6): 385–90.Google ScholarPubMed
Porsolt, R. D., et al., Immobility induced by forced swimming in rats: effects of agents which modify central catecholamine and serotonin activity. Eur J Pharmacol, 1979. 57(2–3): 201–10.CrossRefGoogle ScholarPubMed
Sherman, A. D., Sacquitne, J. L., and Petty, F., Specificity of the learned helplessness model of depression. Pharmacol Biochem Behav, 1982. 16(3): 449–54.CrossRefGoogle ScholarPubMed
Willmann, J., et al., Molecular imaging in drug development. Nat Rev Drug Discov, 2008. 7(7): 591–607.CrossRefGoogle ScholarPubMed
Hargreaves, R. J., The role of molecular imaging in drug discovery and development. Clin Pharmacol Ther, 2008. 83(2): 349–53.CrossRefGoogle ScholarPubMed
Rowland, D. J. and Cherry, S. R., Small-animal preclinical nuclear medicine instrumentation and methodology. Semin Nucl Med, 2008. 38(3): 209–22.CrossRefGoogle ScholarPubMed
Townsend, D. W., Multimodality imaging of structure and function. Phys Med Biol, 2008. 53(4): R1–39.CrossRefGoogle ScholarPubMed
Cherry, S. R., Sorenson, J. A., and Phelps, M. E.. Physics in Nuclear Medicine, Philadelphia, PA, Saunders, 2003, p. 523.Google Scholar
Lee, C. M. and Farde, L., Using positron emission tomography to facilitate CNS drug development. Trends Pharmacol Sci, 2006. 27(6): 310–16.CrossRefGoogle ScholarPubMed
Ogawa, S., et al., Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci USA, 1990. 87(24): 9868–72.CrossRefGoogle ScholarPubMed
Ogawa, S., et al., Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc Natl Acad Sci USA, 1992. 89(13): 5951–55.CrossRefGoogle ScholarPubMed
Logothetis, N. K. What we can do and what we cannot do with fMRI. Nature, 2008. 453(7197): 869–78.CrossRefGoogle Scholar
Logothetis, N. K. and Pfeuffer, J. On the nature of the BOLD fMRI contrast mechanism. Magn Reson Imaging, 2004. 22(10): 1517–31.CrossRefGoogle ScholarPubMed
Matthews, P. M., Honey, G., and Bullmore, E., Applications of fMRI in translational medicine and clinical practice. Nat Neurosci, 2006. 7(9): 732–44.Google ScholarPubMed
Barch, D. M., et al., Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression. Biol Psychiatry, 2003. 53(5): 376–84.CrossRefGoogle ScholarPubMed
Greicius, M. D., et al., Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol Psychiatry, 2007. 62(5): 429–37.CrossRefGoogle ScholarPubMed
Lagopoulos, J. and Malhi, G. S, A functional magnetic resonance imaging study of emotional Stroop in euthymic bipolar disorder. Neuroreport, 2007. 18(15): 1583–87.CrossRefGoogle ScholarPubMed
Honey, G. and Bullmore, E., Human pharmacological MRI. Trends Pharmacol Sci, 2004. 25(7): 366–74.CrossRefGoogle ScholarPubMed
Rauch, A., et al., Pharmacological MRI combined with electrophysiology in non-human primates: effects of Lidocaine on primary visual cortex. Neuroimage, 2008. 40(2): 590–600.CrossRefGoogle ScholarPubMed
Anderson, I. M., et al., Assessing human 5-HT function in vivo with pharmacoMRI. Neuropharmacology, 2008. 55(6): 1029–37.CrossRefGoogle ScholarPubMed
Martin, C. and Sibson, N. R., Pharmacological MRI in animal models: a useful tool for 5-HT research? Neuropharmacology, 2008. 55(6): 1038–47.CrossRefGoogle ScholarPubMed
King, J. A., et al., Procedure for minimizing stress for fMRI studies in conscious rats. J Neurosci Methods, 2005. 148(2): 154–60.CrossRefGoogle ScholarPubMed
Gottesman, I. I. and Gould, T. D., The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry, 2003. 160(4): 636–45.CrossRefGoogle ScholarPubMed
Frank, R. and Hargreaves, R., Clinical biomarkers in drug discovery and development. Nat Rev Drug Discov, 2003. 2(7): 566–80.CrossRefGoogle ScholarPubMed
Katz, R., Biomarkers and surrogate markers: an FDA perspective. NeuroRx, 2004. 1(2): 189–95.CrossRefGoogle Scholar
Mukhtar, M., Evolution of biomarkers: drug discovery to personalized medicine. Drug Discov Today, 2005. 10(18): 1216–18.CrossRefGoogle ScholarPubMed
Pien, H. H., et al., Using imaging biomarkers to accelerate drug development and clinical trials. Drug Discov Today, 2005. 10(4): 259–66.CrossRefGoogle ScholarPubMed
Bakhtiar, R., Biomarkers in drug discovery and development. J Pharmacol Toxicol Methods, 2008. 57(2): 85–91.CrossRefGoogle ScholarPubMed
Day, M., et al., Cognitive endpoints as disease biomarkers: optimizing the congruency of preclinical models to the clinic. Curr Opin Investig Drugs, 2008. 9(7): 696–706.Google ScholarPubMed
Chan, S. W., et al., Risk for depression is associated with neural biases in emotional categorisation. Neuropsychologia, 2008. 46(12): 2896–903.CrossRefGoogle ScholarPubMed
Drevets, W. C., Price, J. L., and Furey, M. L., Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Struct Func, 2008. 213(1–2):93–118.CrossRefGoogle ScholarPubMed
Ekman, P. and Friesen, W. V., Constants across cultures in the face and emotion. J Pers Soc Psychol, 1971. 17(2): 124–29.CrossRefGoogle ScholarPubMed
Davidson, R. J., et al., The neural substrates of affective processing in depressed patients treated with venlafaxine. Am J Psychiatry, 2003. 160(1): 64–75.CrossRefGoogle ScholarPubMed
Davidson, R. J., et al., Depression: perspectives from affective neuroscience. Annu Rev Psychol, 2002. 53: 545–74.CrossRefGoogle ScholarPubMed
Hamilton, J. P. and Gotlib, I. H., Neural substrates of increased memory sensitivity for negative stimuli in major depression. Biol Psychiatry, 2008. 63(12): 1155–62.CrossRefGoogle ScholarPubMed
Anand, A., et al. Antidepressant effect on connectivity of the mood-regulating circuit: an FMRI study. Neuropsychopharmacology, 2005. 30(7): 1334–44.CrossRefGoogle ScholarPubMed
Johnstone, T., et al., Stability of amygdala BOLD response to fearful faces over multiple scan sessions. NeuroImage, 2005. 25(4): 1112–23.CrossRefGoogle ScholarPubMed
Fu, C. H., et al., Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. Arch Gen Psychiatry, 2004. 61(9): 877–89.CrossRefGoogle ScholarPubMed
Joormann, J. and Siemer, M., Memory accessibility, mood regulation, and dysphoria: difficulties in repairing sad mood with happy memories? J Abnorm Psychol, 2004. 113(2): 179–88.CrossRefGoogle ScholarPubMed
Gilboa-Schechtman, E., Erhard-Weiss, D., and Jeczemien, P., Interpersonal deficits meet cognitive biases: memory for facial expressions in depressed and anxious men and women. Psychiatry Res, 2002. 113(3): 279–93.CrossRefGoogle ScholarPubMed
Anand, A., et al., Activity and connectivity of brain mood regulating circuit in depression: a functional magnetic resonance study. Biol Psychiatry, 2005. 57(10): 1079–88.CrossRefGoogle ScholarPubMed
Berg, E. A., A simple objective technique for measuring flexibility in thinking. J Gen Psychol, 1948. 39: 15–22.CrossRefGoogle ScholarPubMed
Kirchner, W. K., Age differences in short-term retention of rapidly changing information. J Exp Psychol, 1958. 55(4): 352–58.CrossRefGoogle ScholarPubMed
Kiloh, L. G., Pseudo-dementia. Acta Psychiatr Scand, 1961. 37: 336–51.CrossRefGoogle ScholarPubMed
Zakzanis, K. K., Leach, L., and Kaplan, E., On the nature and pattern of neurocognitive function in major depressive disorder. Neuropsychiatry Neuropsychol Behav Neurol, 1998. 11(3): 111–19.Google ScholarPubMed
van Gorp, W. G., et al., Cognitive impairment in euthymic bipolar patients with and without prior alcohol dependence. A preliminary study. Arch Gen Psychiatry, 1998. 55(1): 41–46.CrossRefGoogle ScholarPubMed
Veiel, H. O., A preliminary profile of neuropsychological deficits associated with major depression. J Clin Exp Neuropsychol, 1997. 19(4): 587–603.CrossRefGoogle ScholarPubMed
Paterniti, S., et al., Anxiety, depression, psychotropic drug use and cognitive impairment. Psychol Med, 1999. 29(2): 421–28.CrossRefGoogle ScholarPubMed
Wadsworth, E. J., et al., SSRIs and cognitive performance in a working sample. Hum Psychopharmacol, 2005. 20(8): 561–72.CrossRefGoogle Scholar
Harlow, H. and Bromer, J., A test apparatus for monkeys. Psychol Rec, 1939. 2: 434–36.Google Scholar
Hoffman, K. L., et al., Facial-expression and gaze-selective responses in the monkey amygdala. Curr Biol, 2007. 17(9): 766–72.CrossRefGoogle ScholarPubMed
Passingham, R., How good is the macaque monkey model of the human brain? Curr Opin Neurobiol, 2009. 19(1): 6–11.CrossRefGoogle ScholarPubMed
Preuss, T. M., Do rats have prefrontal cortex? The Rose–Woolsey–Akert program reconsidered. J Cogn Neurosci, 1995. 7(1): 1–24.CrossRefGoogle ScholarPubMed
Campbell, M., et al., RNAi-mediated reversible opening of the blood–brain barrier. J Gene Med, 2008. 10(8): 930–47.CrossRefGoogle ScholarPubMed
Cho, Z. H., et al., A fusion PET-MRI system with a high-resolution research tomograph-PET and ultra-high field 7.0 T-MRI for the molecular-genetic imaging of the brain. Proteomics, 2008. 8(6): 1302–23.CrossRefGoogle ScholarPubMed
Ruhé, H. G., et al., Serotonin transporter gene promoter polymorphisms modify the association between paroxetine serotonin transporter occupancy and clinical response in major depressive disorder. Pharmacogenet Genomics, 2009. 19(1): 67–76.CrossRefGoogle ScholarPubMed
Smith, D. F. and Jakobsen, S., Molecular tools for assessing human depression by positron emission tomography. Eur Neuropsychopharmacol, 2009. 19(9): 611–28.CrossRefGoogle ScholarPubMed
Ross, J. S., et al., Pharmacogenomics and clinical biomarkers in drug discovery and development. Am J Clin Pathol, 2005. 124 Suppl: S29–41.Google ScholarPubMed
Kato, T., Molecular genetics of bipolar disorder and depression. Psychiatry Clin Neurosci, 2007. 61(1): 3–19.CrossRefGoogle ScholarPubMed
Maier, W., Common risk genes for affective and schizophrenic psychoses. Eur Arch Psychiatry Clin Neurosci, 2008. 258(S2): 37–40.CrossRefGoogle ScholarPubMed
Caspi, A., et al., Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science, 2003. 301(5631): 386–89.CrossRefGoogle ScholarPubMed
Hayden, E. P., et al., Early emerging cognitive vulnerability to depression and the serotonin transporter promoter region polymorphism. J Affect Disord, 2008. 107(1–3): 227–30.CrossRefGoogle ScholarPubMed
Collier, D., et al., A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. Mol Psychiatry, 1996. 1(6): 453–60.Google ScholarPubMed
Willis-Owen, S. A., et al., The serotonin transporter length polymorphism, neuroticism, and depression: a comprehensive assessment of association. Biol Psychiatry, 2005. 58(6): 451–56.CrossRefGoogle ScholarPubMed
Wilson, M. E. and Kinkead, B., Gene–environment interactions, not neonatal growth hormone deficiency, time puberty in female rhesus monkeys. Biol Reprod, 2008. 78(4): 736–43.CrossRefGoogle Scholar
Jarrell, H., et al., Polymorphisms in the serotonin reuptake transporter gene modify the consequences of social status on metabolic health in female rhesus monkeys. Physiol Behav, 2008. 93(4–5): 807–19.CrossRefGoogle ScholarPubMed
Bethea, C. L., et al., Anxious behavior and fenfluramine-induced prolactin secretion in young rhesus macaques with different alleles of the serotonin reuptake transporter polymorphism (5HTTLPR). Behav Genet, 2004. 34(3): 295–307.CrossRefGoogle Scholar
Hariri, A. R., et al., Serotonin transporter genetic variation and the response of the human amygdala. Science, 2002. 297(5580): 400–03.CrossRefGoogle ScholarPubMed
Hariri, A. R., et al., A susceptibility gene for affective disorders and the response of the human amygdala. Arch Gen Psychiatry, 2005. 62(2): 146–52.CrossRefGoogle ScholarPubMed
Pezawas, L., et al., 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci, 2005. 8(6): 828–34.CrossRefGoogle ScholarPubMed
David, S. P., et al., A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans. J Neurosci, 2005. 25(10): 2586–90.CrossRefGoogle ScholarPubMed
Willeit, M., et al. No evidence for in vivo regulations of midbrain serotonin transporter availability by serotonin transporter promoter gene polymorphism. Biol Psychiatry, 2001. 50(1): 8–12.CrossRefGoogle Scholar
Shioe, K., et al. No association between genotype of the promoter region of serotonin transporter gene and serotonin transporter binding in human brain measured by PET. Synapse, 2003. 48(4): 184–88.CrossRefGoogle Scholar
Pezawas, L., et al., Evidence of biologic epistasis between BDNF and SLC6A4 and implications for depression. Mol Psychiatry, 2008. 13(7): 709–16.CrossRefGoogle ScholarPubMed
Frank, R. and Hargreaves, R., Clinical biomarkers in drug discovery and development. Nat Rev Drug Discov, 2003. 2(7): 566–80.CrossRefGoogle ScholarPubMed
Meyerlindenberg, A., et al., False positives in imaging genetics. Neuroimage, 2008. 8(2): 655–61.Google Scholar
Gardier, A. M., Mutant mouse models and antidepressant drug research: focus on serotonin and brain-derived neurotrophic factor. Behav Pharmacol, 2009. 20(1): 18–32.CrossRefGoogle ScholarPubMed
Kato, T., et al., Behavioral and gene expression analyses of Wfs1 knockout mice as a possible animal model of mood disorder. Neurosci Res, 2008. 61(2): 143–58.CrossRefGoogle ScholarPubMed
Bearer, E. L., et al., Reward circuitry is perturbed in the absence of the serotonin transporter. NeuroImage, 2009. 46(4): 1091–104.CrossRefGoogle ScholarPubMed
Willmann, J. K., et al., Molecular imaging in drug development. Nat Rev Drug Discov, 2008. 7(7): 591–607.CrossRefGoogle ScholarPubMed
Hume, S. P., Gunn, R. N., and Jones, T., Pharmacological constraints associated with positron emission tomographic scanning of small laboratory animals. Eur J Nucl Med, 1998. 25(2): 173–76.CrossRefGoogle ScholarPubMed
Sossi, V. and Ruth, T. J., Micropet imaging: in vivo biochemistry in small animals. J Neural Transm, 2005. 112(3): 319–30.CrossRefGoogle ScholarPubMed
Pardridge, W. M., The blood–brain barrier: bottleneck in brain drug development. NeuroRx, 2005. 2(1): 3–14.CrossRefGoogle ScholarPubMed
Pardridge, W. M., Blood–brain barrier drug targeting: the future of brain drug development. Mol Interv, 2003. 3(2): 90–105, 51.CrossRefGoogle ScholarPubMed
Meyer, J. H., Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. J Psychiatry Neurosci, 2007. 32(2) 86–102.Google ScholarPubMed
Andrée, B., et al., Use of PET and the radioligand [carbonyl-(11)C]WAY-100635 in psychotropic drug development. Nucl Med Biol, 2000. 27(5): 515–21.CrossRefGoogle Scholar
Lemaire, C., et al., Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats. J Nucl Med, 1991. 32(12): 2266–72.Google Scholar
Kato, T., Inubushi, T., and Kato, N., Magnetic resonance spectroscopy in affective disorders. J Neuropsychiatry Clin Neurosci, 1998. 10(2): 133–47.CrossRefGoogle ScholarPubMed
Bolo, N. R., et al., Brain pharmacokinetics and tissue distribution in vivo of fluvoxamine and fluoxetine by fluorine magnetic resonance spectroscopy. Neuropsychopharmacology, 2000. 23(4): 428–38.CrossRefGoogle ScholarPubMed
Henry, M. E., et al., A comparison of brain and serum pharmacokinetics of R-fluoxetine and racemic fluoxetine: a 19-F MRS study. Neuropsychopharmacology, 2005. 30(8): 1576–83.CrossRefGoogle ScholarPubMed
Chen, C. H., et al., Brain imaging correlates of depressive symptom severity and predictors of symptom improvement after antidepressant treatment. Biol Psychiatry, 2007. 62(5): 407–14.CrossRefGoogle ScholarPubMed
Frankel, R. J., Jenkins, J. S., and Wright, J. J., Pituitary–adrenal response to stimulation of the limbic system and lateral hypothalamus in the rhesus monkey (Macacca mulatta). Acta Endocrinol, 1978. 88(2): 209–16.CrossRefGoogle Scholar
Kalin, N. H., Shelton, S., and Davidson, R. J., The role of the central nucleus of the amygdala in mediating fear and anxiety in the primate. J Neurosci, 2004. 24(24): 5506–15.CrossRefGoogle ScholarPubMed
Machado, C. J. and Bachevalier, J., Behavioral and hormonal reactivity to threat: effects of selective amygdala, hippocampal or orbital frontal lesions in monkeys. Psychoneuroendocrinology, 2008. 33(7): 926–41.CrossRefGoogle ScholarPubMed
Sapolsky, R. M., Krey, L. C., and McEwen, B. S., Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response. Proc Natl Acad Sci USA, 1984. 81(19): 6174–77.CrossRefGoogle ScholarPubMed
Feldman, S. and Weidenfeld, J., Electrical stimulation of the dorsal hippocampus caused a long lasting inhibition of ACTH and adrenocortical responses to photic stimuli in freely moving rats. Brain Res, 2001. 911(1): 22–26.CrossRefGoogle ScholarPubMed
Goursaud, A. P., Mendoza, S. P., and Capitanio, J. P., Do neonatal bilateral ibotenic acid lesions of the hippocampal formation or of the amygdala impair HPA axis responsiveness and regulation in infant rhesus macaques (Macaca mulatta)? Brain Res, 2006. 1071(1): 97–104.CrossRefGoogle ScholarPubMed
Halbreich, U., et al., Cortisol secretion in endogenous depression. I. Basal plasma levels. Arch Gen Psychiatry, 1985. 42(9): 904–08.Google ScholarPubMed
Stokes, P. E., et al., Pretreatment DST and hypothalamic–pituitary–adrenocortical function in depressed patients and comparison groups. A multicenter study. Arch Gen Psychiatry, 1984. 41(3): 257–67.CrossRefGoogle ScholarPubMed
Heuser, I., Yassouridis, A., and Holsboer, F., The combined dexamethasone/CRH test: a refined laboratory test for psychiatric disorders. J Psychiatr Res, 1994. 28(4): 341–56.CrossRefGoogle ScholarPubMed
Holsboer, F., et al., Stimulation response to corticotropin-releasing hormone (CRH) in patients with depression, alcoholism and panic disorder. Horm Metab Res Suppl, 1987. 16: 80–88.Google ScholarPubMed
Kitamura, Y., Araki, H., and Gomita, Y., Influence of ACTH on the effects of imipramine, desipramine and lithium on duration of immobility of rats in the forced swim test. Pharmacol Biochem Behav, 2002. 71(1–2): 63–69.CrossRefGoogle ScholarPubMed
Kitamura, Y., et al., Effects of imipramine and bupropion on the duration of immobility of ACTH-treated rats in the forced swim test: involvement of the expression of 5-HT2A receptor mRNA. Biol Pharm Bull, 2008. 31(2): 246–49.CrossRefGoogle ScholarPubMed
Kaufman, I. C. and Rosenblum, L. A., Depression in infant monkeys separated from their mothers. Science, 1967. 155(765): 1030–31.CrossRefGoogle ScholarPubMed
Kaufman, I. C. and Rosenblum, L. A., The reaction to separation in infant monkeys: anaclitic depression and conservation-withdrawal. Psychosom Med, 1967. 29(6): 648–75.CrossRefGoogle ScholarPubMed
Harlow, H. F., Plubell, P. E., and Baysinger, C. M., Induction of psychological death in rhesus monkeys. J Autism Child Schizophr, 1973. 3(4): 299–307.CrossRefGoogle ScholarPubMed
Young, L. D., et al., Early stress and later response to separation in rhesus monkeys. Am J Psychiatry, 1973. 130(4): 400–05.Google ScholarPubMed
Harlow, H. F. and Suomi, S. J., Induced depression in monkeys. Behav Biol, 1974. 12(3): 273–96.CrossRefGoogle ScholarPubMed
Suomi, S. J., et al., Depressive behavior in adult monkeys following separation from family environment. J Abnorm Psychol, 1975. 84(5): 576–78.CrossRefGoogle ScholarPubMed
Kalin, N. H., et al., Brain regions associated with the expression and contextual regulation of anxiety in primates. Biol Psychiatry, 2005. 58(10): 796–804.CrossRefGoogle ScholarPubMed
Bennett, A. J., et al., Early experience and serotonin transporter gene variation interact to influence primate CNS function. Mol Psychiatry, 2002. 7(1): 118–22.CrossRefGoogle ScholarPubMed
Suomi, S. J., Risk, resilience, and gene × environment interactions in rhesus monkeys. Ann NY Acad Sci, 2006. 1094: 52–62.CrossRefGoogle Scholar
Kalin, N. H., et al., The serotonin transporter genotype is associated with intermediate brain phenotypes that depend on the context of eliciting stressor. Mol Psychiatry, 2008. 13(11): 1021–27.CrossRefGoogle ScholarPubMed
Mackay, T. F. and Anholt, R. R., Ain’t misbehavin’ ? Genotype-environment interactions and the genetics of behavior. Trends Genet, 2007. 23(7): 311–14.CrossRefGoogle ScholarPubMed
Gotlib, I. H., et al., HPA axis reactivity: a mechanism underlying the associations among 5-HTTLPR, stress, and depression. Biol Psychiatry, 2008. 63(9): 847–51.CrossRefGoogle ScholarPubMed
Malberg, J. E. and Blendy, J. A., Antidepressant action: to the nucleus and beyond. Trends Pharmacol Sci, 2005. 26(12): 631–38.CrossRefGoogle ScholarPubMed
Krishnan, V. and Nestler, E., The molecular neurobiology of depression. Nature, 2008. 455(7215): 894–902.CrossRefGoogle ScholarPubMed
Roffman, J. L., et al., Neuroimaging-genetic paradigms: a new approach to investigate the pathophysiology and treatment of cognitive deficits in schizophrenia. Harvard Rev Psychiatry, 2006. 14(2): 78–91.CrossRefGoogle Scholar
Savitz, J. B. and Drevets, W. C., Imaging phenotypes of major depressive disorder: genetic correlates. Neuroscience, 2009. 164(1): 300–30.CrossRefGoogle ScholarPubMed
Sklar, P., et al., Family based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor. Mol Psychiatry, 2002. 7(6): 579–93.CrossRefGoogle ScholarPubMed
Neves-Pereira, M., et al., The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family based association study. Am J Hum Genet, 2002. 71(3): 651–55.CrossRefGoogle ScholarPubMed
Green, E. K., et al., Genetic variation of brain-derived neurotrophic factor (BDNF) in bipolar disorder: case-control study of over 3000 individuals from the UK. Br J Psychiatry, 2006. 188: 21–25.CrossRefGoogle ScholarPubMed
Hariri, A. R., et al., Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. J Neurosci, 2003. 23(17): 6690–94.CrossRefGoogle ScholarPubMed
Egan, M. F., et al., The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell, 2003. 112(2): 257–69.CrossRefGoogle ScholarPubMed
Frey, B. N., et al., Brain-derived neurotrophic factor val66met polymorphism affects prefrontal energy metabolism in bipolar disorder. Neuroreport, 2007. 18(15): 1567–70.CrossRefGoogle ScholarPubMed
Rybakowski, J. K., et al., Polymorphism of the brain-derived neurotrophic factor gene and performance on a cognitive prefrontal test in bipolar patients. Bipolar Disord, 2003. 5(6): 468–72.CrossRefGoogle ScholarPubMed
Fukumoto, T., et al., Chronic lithium treatment increases the expression of brain-derived neurotrophic factor in the rat brain. Psychopharmacology, 2001. 158(1): 100–06.CrossRefGoogle ScholarPubMed
Alme, M. N., et al., Chronic fluoxetine treatment induces brain region-specific upregulation of genes associated with BDNF-induced long-term potentiation. Neural Plast, 2007. 2007: 26496.CrossRefGoogle ScholarPubMed
Gratacòs, M., et al., Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biol Psychiatry, 2007. 61(7): 911–22.CrossRefGoogle Scholar
Rybakowski, J. K., et al., Prophylactic lithium response and polymorphism of the brain-derived neurotrophic factor gene. Pharmacopsychiatry, 2005. 38(4): 166–70.CrossRefGoogle ScholarPubMed
Yoshida, K., et al., The G196A polymorphism of the brain-derived neurotrophic factor gene and the antidepressant effect of milnacipran and fluvoxamine. J Psychopharmacol (Oxford), 2007. 21(6): 650–56.CrossRefGoogle ScholarPubMed
Tsai, S. J., et al., Association study of a brain-derived neurotrophic-factor genetic polymorphism and major depressive disorders, symptomatology, and antidepressant response. Am J Med Genet B Neuropsychiatr Genet, 2003. 123B(1): 19–22.CrossRefGoogle ScholarPubMed
Choi, M. J., et al., Brain-derived neurotrophic factor gene polymorphism (Val66Met) and citalopram response in major depressive disorder. Brain Res, 2006. 1118(1): 176–82.CrossRefGoogle ScholarPubMed
Rybakowski, J. K., et al., Response to lithium prophylaxis: interaction between serotonin transporter and BDNF genes. Am J Med Genet B Neuropsychiatr Genet, 2007. 144B(6): 820–23.CrossRefGoogle ScholarPubMed
Capuron, L. and Dantzer, R., Cytokines and depression: the need for a new paradigm. Brain Behav Immun, 2003. 17 Suppl 1: S119–24.CrossRefGoogle ScholarPubMed
Miller, A. H., Maletic, V., and Raison, C. L., Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry, 2009. 65(9): 732–41.CrossRefGoogle ScholarPubMed
Hickie, I. and Lloyd, A., Are cytokines associated with neuropsychiatric syndromes in humans? Int J Immunopharmacol, 1995. 17(8): 677–83.CrossRefGoogle ScholarPubMed
Hickie, I., et al., Biochemical correlates of in vivo cell-mediated immune dysfunction in patients with depression: a preliminary report. Int J Immunopharmacol, 1995. 17(8): 685–90.CrossRefGoogle ScholarPubMed
Capuron, L., et al., Treatment of cytokine-induced depression. Brain Behav Immun, 2002. 16(5): 575–80.CrossRefGoogle ScholarPubMed
Felger, J. C., et al., Effects of interferon-alpha on rhesus monkeys: a nonhuman primate model of cytokine-induced depression. Biol Psychiatry, 2007. 62(11): 1324–33.CrossRefGoogle ScholarPubMed
Larson, S. J., et al., Effects of interleukin-1beta on food-maintained behavior in the mouse. Brain Behav Immun, 2002. 16(4): 398–410.CrossRefGoogle ScholarPubMed
Mendlewicz, J., et al., Shortened onset of action of antidepressants in major depression using acetylsalicylic acid augmentation: a pilot open-label study. Int Clin Psychopharmacol, 2006. 21(4): 227–31.CrossRefGoogle ScholarPubMed
Muller, N., et al., The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry, 2006. 11(7): 680–84.CrossRefGoogle ScholarPubMed
Harrison, N. A., et al., Neural origins of human sickness in interoceptive responses to inflammation. Biol Psychiatry, 2009. 66(5): 415–22.CrossRefGoogle ScholarPubMed
Harrison, N. A., et al., Inflammation causes mood changes through alterations in subgenual cingulate activity, and mesolimbic connectivity. Biol Psychiatry, 2009. 66(5): 407–14.CrossRefGoogle ScholarPubMed
Brydon, L., et al., Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans. Biol Psychiatry, 2008. 63(11): 1022–29.CrossRefGoogle ScholarPubMed
Mayberg, H. S., et al., Reciprocal limbic–cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry, 1999. 156(5): 675–82.Google ScholarPubMed
Alexopoulos, G. S., et al., ‘Vascular depression’ hypothesis. Arch Gen Psychiatry, 1997. 54(10): 915–22.CrossRefGoogle ScholarPubMed
Steffens, D. C. and Krishnan, K. R., Structural neuroimaging and mood disorders: recent findings, implications for classification, and future directions. Biol Psychiatry, 1998. 43(10): 705–12.CrossRefGoogle ScholarPubMed
Alexopoulos, G. S., Frontostriatal and limbic dysfunction in late-life depression. Am J Geriatr Psychiatry, 2002. 10(6): 687–95.Google ScholarPubMed
Alexopoulos, G. S., et al., Clinical presentation of the “depression–executive dysfunction syndrome” of late life. Am J Geriatr Psychiatry, 2002. 10(1): 98–106.Google ScholarPubMed
Alexopoulos, G. S., The vascular depression hypothesis: 10 years later. Biol Psychiatry, 2006. 60(12): 1304–05.CrossRefGoogle ScholarPubMed
Simpson, S., et al., Is subcortical disease associated with a poor response to antidepressants? Neurological, neuropsychological and neuroradiological findings in late-life depression. Psychol Med, 1998. 28(5): 1015–26.CrossRefGoogle ScholarPubMed
Hickie, I., et al., Subcortical hyperintensities on magnetic resonance imaging: clinical correlates and prognostic significance in patients with severe depression. Biol Psychiatry, 1995. 37(3): 151–60.CrossRefGoogle ScholarPubMed
Simpson, S., et al., Subcortical vascular disease in elderly patients with treatment resistant depression. J Neurol, Neurosurg Psychiatry, 1997. 62(2): 196–97.CrossRefGoogle ScholarPubMed
Potter, G. G., et al., Prefrontal neuropsychological predictors of treatment remission in late-life depression. Neuropsychopharmacology, 2004. 29(12): 2266–71.CrossRefGoogle ScholarPubMed
Ernst, E., Placebo: new insights into an old enigma. Drug Discov Today, 2007. 12(9–10): 413–18.CrossRefGoogle ScholarPubMed
Walsh, B. T., et al., Placebo response in studies of major depression: variable, substantial, and growing. JAMA, 2002. 287(14): 1840–47.CrossRefGoogle ScholarPubMed
Kirsch, I., Challenging received wisdom: antidepressants and the placebo effect. Mcgill J Med, 2008. 11(2): 219–22.Google ScholarPubMed
Brunoni, A. R., et al., Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis. PLoS ONE, 2009. 4(3): e4824.CrossRefGoogle ScholarPubMed
Lidstone, S. C. and Stoessl, A. J., Understanding the placebo effect: contributions from neuroimaging. Molec Imaging Biol, 2007. 9(4): 176–85.CrossRefGoogle ScholarPubMed
Mayberg, H. S., et al., The functional neuroanatomy of the placebo effect. Am J Psychiatry, 2002. 159(5): 728–37.CrossRefGoogle ScholarPubMed
Mayberg, H. S., et al., Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry, 2000. 48(8): 830–43.CrossRefGoogle ScholarPubMed
Leuchter, A. F., et al., Changes in brain function of depressed subjects during treatment with placebo. Am J Psychiatry, 2002. 159(1): 122–29.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×