The role of platelet/lymphocyte serotonin transporter in depression and beyond

Current Drug Targets

Volumn 14, Issue 5, 2013, Pages 522-530

  Marazziti, Donatella ^a   Landi, Paola ^a   Baroni, Stefano ^a   Vanelli, Federica ^a   Bartolommei, Natalia ^a   Picchetti, Michela ^a   Dell'Osso, Liliana ^a  

^a UNIVERSITY OF PISA   (Italy)

Author keywords

Antidepressants; Depression; Immune system; Lymphocytes; Platelets; Psychological dimensions; Serotonin; Serotonin transporter

Indexed keywords

3, 4 METHYLENEDIOXYMETHAMPHETAMINE; 5 HYDROXYINDOLEACETIC ACID; 5 HYDROXYTRYPTOPHAN; AMINO ACID; CHEMOTACTIC FACTOR; COCAINE; CYCLIC AMP DEPENDENT PROTEIN KINASE; CYTOKINE; FENCLONINE; FENFLURAMINE; GLUCOCORTICOID; IMIPRAMINE; PHORBOL ESTER; PROLACTIN; PROTEIN KINASE C; RECEPTOR SUBTYPE; RESERPINE; SEROTONIN 1A RECEPTOR; SEROTONIN 2 RECEPTOR; SEROTONIN TRANSPORTER; SEROTONIN UPTAKE INHIBITOR; TRICYCLIC ANTIDEPRESSANT AGENT; TRYPTOPHAN; UNCLASSIFIED DRUG;

AGGRESSION; AMYGDALOID NUCLEUS; CEREBELLUM CORTEX; DELAYED HYPERSENSITIVITY; DEPRESSION; DEXAMETHASONE SUPPRESSION TEST; DRUG CEREBROSPINAL FLUID LEVEL; EATING DISORDER; HIPPOCAMPUS; HUMAN; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; INSULA; LYMPHOCYTE; LYMPHOCYTE TRANSFORMATION; NATURAL KILLER CELL; PARKINSON DISEASE; PREFRONTAL CORTEX; PRESYNAPTIC NERVE; PSYCHOSIS; PUTAMEN; REVIEW; SEROTONINERGIC SYSTEM; SIGNAL TRANSDUCTION; T LYMPHOCYTE ACTIVATION; THALAMUS; THROMBOCYTE;

ANIMALS; BLOOD PLATELETS; DEPRESSION; HUMANS; LYMPHOCYTES; PROTEIN CONFORMATION; SEROTONIN; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SEROTONIN UPTAKE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84876702721     PISSN: 13894501     EISSN: 18735592     Source Type: Journal    
DOI: 10.2174/1389450111314050003     Document Type: Review

References (163)

1. Carlsson A. Perspectives on the discovery of central monoaminergic neurotransmission. Annu Rev Neurosci 1987; 10: 19-40.
2. Greengard P. The neurobiology of slow synaptic transmission. Science 2001; 294: 1024-30.
3. Olivier B. Serotonin and aggression. Ann NY Acad Sci 2004; 1036: 382-92.
4. Clark L, Roiser JP, Cools R, Rubinsztein DC, Sahakian BJ, Robbins TW. Stop signal response inhibition is not modulated by tryptophan depletion or the serotonin transporter polymorphism in healthy volunteers: implications for the 5-HT theory of impulsivity. Psychopharmacology 2005; 182: 570-8.
5. Rothman RB, Blough BE, Baumann MH. Dual dopamine/serotonin releasers: potential treatment agents for stimulant addiction. Exp Clin Psychopharmacol 2008; 16(6): 458-74.
6. Davies SJ, Esler M, Nutt DJ. Anxiety--bridging the heart/mind divide. J Psychopharmacol 2010; 24(5): 633-8.
7. Deakin JF. Depression and antisocial personality disorder: two contrasting disorders of 5HT function. J Neural Transm 2003; 64: 79-93.
8. Amara SG, Kuhar MJ. Neurotransmitter transporters: recent progress. Annu Rev Neurosci 1993; 16: 73-93.
9. Blakely RD, Ramamoorthy S, Schroeter S, et al. Regulated phosphorylation and trafficking of antidepressant-sensitive serotonin transporter proteins. Biol Psychiatry 1998; 44: 169-78.
10. Murphy DL, Lesch KP. Targeting the murine serotonin transporter: insights into human neurobiology. Nat Rev Neurosci 2008; 9: 85-96.
11. Marcusson JO, Baeckstroem I, Ross SB. Single-site model of the neuronal 5-hydroxytrypamine uptake and imipramine binding site. Mol Pharmacology 1986; 30: 121-8.
12. Meyerson LR, Ieni JR, Wennogle LP. Allosteric interaction between the site labeled by [3H]imipramine and the serotonin transporter in human platelets. J Neurochem 1987; 48: 560-5.
13. Altamura AC, Montgomery SA, Wernicke JF. The evidence for 20 mg a day of fluoxetine as the optimal dose in the treatment of depression. Br J Psychiatry 1988; 153: 109-12.
14. Bergstrom RF, Lemberger L, Farid NA, Wolen RL. Clinical pharmacology and pharmacokinetics of fluoxetine: a review. Br J Psychiatry 1988; 153: 47-50.
15. Aberg-Wistedt A. The antidepressant effects of 5-HT uptake inhibitors. Br J Psychiatry 1989; 155: 32-40.
16. Van Harten J. Clinical pharmacokinetics of selective serotonin reuptake inhibitors. Clin Pharmacokinet 1993; 24: 203-20.
17. Pigott TA, Seay SM. A review of the efficacy of selective serotonin reuptake inhibitors in obsessive-compulsive disorder. J Clin Psychiatry 1999; 60: 101-6.
18. Chen JG, Liu-Chen S, Rudnick G. Determination of external loop topology in the serotonin transporter by site-directed chemical labeling. J Biol Chem 1998; 273: 12675-81.
19. Rudnick G. Active transport of 5-Hydroxytryptamine by plasma membrane vesicles isolated from human blood platelets. J Biol Chem 1977; 252: 2170-74.
20. Stahl SM. The human platelet. A diagnostic and research tool for the study of biogenic amines in psychiatric and neurologic disorders. Arch Gen Psychiatry 1977; 34: 509-16.
21. Nelson PJ, Rudnick G. Coupling between platelet 5-hydroxytryptamine and potassium transport. J Biol Chem 1979; 254: 10084-89.
22. Langer SZ, Galzin AM, Poirier MF, Loo H, Sechter D, Zarifian E. Association of [3H]-imipramine and [3H]-paroxetine binding with the 5HT transporter in brain and platelets: relevance to studies in depression. J Recept Res 1987; 7: 499-521.
23. Langer SZ, Schoemaker H. Effects of antidepressants on monoamine transporters. Prog Neuropsychopharmacol Biol Psychiatry 1988; 12: 193-216.
24. Andersson A, Marcusson J. Inhibition and dissociation of [3H]-paroxetine binding to human platelets. Neuropsychobiol 1989; 22: 135-40.
25. Marcusson JO, Ross SB. Binding of some antidepressants to the 5-hydroxytryptamine transporter in brain and platelets. Psychopharmacol (Berl) 1990; 102: 145-55.
26. Ramamoorthy S, Blakely RD. Phosphorylation and sequestration of serotonin transporters differentially modulated by psychostimulants. Science 1999; 285: 763-6.
27. Brenner B, Harney JT, Ahmed BA, et al. Plasma serotonin levels and the platelet serotonin transporter. J Neurochem 2007; 102: 206-15.
28. Faraj BA, Olkowski ZL, Jackson RT. Expression of a high-affinity serotonin transporter in human lymphocytes. Int J Immunopharmacol 1994; 16: 561-7.
29. Marazziti D, Rossi A, Giannaccini G, Baroni S, Lucacchini A, Cassano GB. Presence and characterization of the serotonin transporter in human resting lymphocytes. Neuropsychopharmacology 1998; 19: 154-9.
30. Humphreys CJ, Beidler D, Rudnick G. Substrate and inhibitor binding and translocation by the platelet plasma membrane serotonin transporter. Biochem Soc Trans 1991; 19: 95-8.
31. Ramamoorthy S, Bauman AL, Moore KR, et al. Antidepressantand cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci USA 1993; 90: 2542-6.
32. Ramamoorthy S, Leibach FH, Mahesh VB, Ganapathy V. Partial purification and characterization of the human placental serotonin transporter. Placenta 1993; 14: 449-61.
33. Lesch KP, Wolozin BL, Murphy DL, Riederer P. Primary structure of the human platelet serotonin uptake: identity with the brain serotonin transporter. J Neurochem 1993; 60: 2319-22.
34. Qian Y, Melikian HE, Rye DB, Levey AI, Blakely RD. Identification and characterization of antidepressant-sensitive serotonin transporter proteins using site-specific antibodies. J Neurosci 1995; 15: 1261-74.
35. Padbury JF, Tseng YT, McGonnigal B, Penado K, Stephan M, Rudnick G. Placental biogenic amine transporters: cloning and expression. Brain Res Mol Brain Res 1997; 45: 163-8.
36. Marazziti D, Rossi A, Gemignani A, et al. Decreased platelet 3Hparoxetine binding in obsessive-compulsive patients. Neuropsychobiology 1996; 34: 184-7.
37. Serafeim A, Gordon J. The immune system gets nervous. Curr Opin Pharmacol 2001; 1: 398-403.
38. Gordon J, Barnes NM. Lymphocytes transport serotonin and dopamine: agony or ecstasy? Trends Immunol 2003; 24: 438-43.
39. Urbina M, Pineda S, Piñango L, Carreira I, Lima L. [3H]Paroxetine binding to human peripheral lymphocyte membranes of patients with major depression before and after treatment with fluoxetine. Int J Immunopharmacol 1999; 21: 631-46.
40. Hernández E, Lastra S, Urbina M, Carreira I, Lima L. Serotonin, 5-hydroxyindoleacetic acid and serotonin transporter in blood peripheral lymphocytes of patients with generalized anxiety disorder. Int Immunopharmacol 2002; 2: 893-900.
41. Lima L, Urbina M. Serotonin transporter modulation in blood lymphocytes from patients with major depression. Cell Mol Neurobiol 2002; 22: 797-804.
42. Peña S, Baccichet E, Urbina M, Carreira I, Lima L. Effect of mirtazapine treatment on serotonin transporter in blood peripheral lymphocytes of major depression patients. Int Immunopharmacol 2005; 5: 1069-76.
43. Barkan T, Peled A, Modai I, Barak P, Weizman A, Rehavi M. Serotonin transporter characteristics in lymphocytes and platelets of male aggressive schizophrenia patients compared to nonaggressive schizophrenia patients. Eur Neuropsychopharmacol 2006; 16: 572-9.
44. Marazziti D, Dell'Osso B, Baroni S, et al. Common alterations in the serotonin transporter in platelets and lymphocytes of psychotic patients. Pharmacopsychiatry 2006; 39: 35-8.
45. Meltzer HY, Lowy MT. The serotonin hypothesis of depression. In: Psychopharmacology: the third generation of progress; Meltzer HY, Ed. New York: Raven Press 1987; pp 513-26.
46. Maes M, Jacobs MP, Suy E, et al. Suppressant effects of dexamethasone on the availability of plasma L-tryptophan and tyrosine in healthy controls and in depressed patients. Acta Psychiatr Scand 1990; 81: 19-23.
47. Deakin JF, Pennell I, Upadhyaya AJ, Lofthouse R. A neuroendocrine study of 5HT function in depression: evidence for biological mechanisms of endogenous and psychosocial causation. Psychopharmacology 1990; 101: 85-92.
48. Koyama T, Meltzer HY. A biochemical and neuroendocrine study of the serotonergic system in depression. In: New results in depression research, Hippius H, Ed. Berlin-Heidelberg: Springer-Verlag 1986; pp 169-188.
49. Hoes MJAJM, Sijben N. The clinical significance of disordered renal excretion of xanthurenic acid in depressive patients. Psychopharmacology 1981; 75: 346-9.
50. Maes M, De Ruyter M, Suy E. The renal excretion of xanthurenic acid following L-tryptophan loading in depressed patients. Hum Psychopharmacology 1987; 2: 231-5.
51. Oxenkrug GF. Tryptophan kynurenine metabolism as a common mediator of genetic and environmental impacts in major depressive disorder: the serotonin hypothesis revisited 40 years later. Isr J Psychiatry Relat Sci 2010; 47(1): 56-63.
52. Delgado PL, Charney DS, Price LH, Landis H, Heninger GR. Neuroendocrine and behavioral effects of dietary tryptophan restriction in healthy subjects. Life Sci 1990; 45: 2323-32.
53. Heninger GR, Delgado PL, Charney DS, Price LH, Aghajanian GK. Tryptophan-deficient diet and amino acid drink deplete plasma tryptophan and induce a relapse of depression in susceptible patients. J Chem Neuroanatomy 1992; 5: 347-8.
54. Moller SE, Kirk I, Brandrup E, Holnagel M, Kaldan B, Odum K. Tryptophan availability in endogenous depression: relation to efficacy of l-tryptophan treatment. Adv Biol Psychiatry 1983; 10: 30-46.
55. Miller HL, Delgado PL, Salomon RM, Licinio J, Barr LC, Charney DS. Acute tryptophan depletion: a method of studying antidepressant action. J Clin Psychiatry 1992; 53: 28-35.
56. Åsberg M, Traskman L, Theoren P. 5-HIAA in the cerebrospinal fluid: a biochemical suicide predictors? Archives of General Psychiatry 1976; 33: 1193-7.
57. Traskman L, Asberg M, Bertilsson L, Sjostrand L. Monoamine metabolites in CSF and suicidal behavior. Archives of General Psychiatry 1981; 38: 631-6.
58. Linnoila M, Virkunnen M, Scheinin M, Nuutila A, Rimobn R, Goodwin FK. Low cerebrosopinal fluid 5HIAA concentration differentiates impulsive from nonimpulsive violent behaviour. Life Sci 1983; 33: 2609-14.
59. Van Praag HM. Depression, suicide and the metabolism of serotonin in the brain. J Affect Disord 1982; 4: 275-90.
60. Faustman WO, King RJ, Faull KF, et al. MMPI measures of impulsivity and depression correlate with CSF 5-HIAA and HVA in depression but not schizophrenia. J Affect Disord 1991; 22: 235-9.
61. Meltzer HY, Wiita B, Robertson A, Tricou BJ, Lowy M, Perline R. Effect of 5-hydroxytryptophan on serum cortisol levels in major affective disorders: enhanced response in depression and mania. Arch Gen Psychiatry 1984; 41: 366-74.
62. Maes M, Vandevelde R, Suy E. Influences on cortisol and noradrenergic turnover of healthy controls and depressed patients during L-tryptophan loading. J Affect Disord 1989; 17: 173-82.
63. Huether G, Hajak G, Reimer A, et al. The metabolic fate of infused L-tryptophan in men: possible clinical implications of the accumulation of circulating tryptophan and tryptophan metabolites. Psychopharmacology 1992; 109: 422-32.
64. Maes M, Vandervorst C, Suy E, Minner B, Raus J. A multivariate study on the simultaneous urinary free cortisol, plasma cortisol, adrenocorticotropic hormone and beta-endorphin escape from suppression by dexamethasone in melancholic patients. Acta Psychiatr Scand 1991; 83: 480-91.
65. Meltzer HY, Maes M. Effect of pindolol on the L-5-HTP-induced increase in plasma prolactin and cortisol concentrations in man. Psychopharmacology 1994; 114(4): 635-43.
66. Lichtenberg P, Shapira B, Gillon D, et al. Hormone responses to fenfluramine and placebo challenge in endogenous depression. Psychiatr Res 1992; 43: 137-46.
67. Maes M, D'Hondt P, Suy E, Minner B, Vandervorst C, Raus J. HPA-axis hormones and prolactin responses to dextro-fenfluramine in depressed patients and healthy controls. Prog Neuro-Psychopharmacol Biol Psychiatry 1991; 15: 781-90.
68. Lesch KP, Mayer S, Disselkamp-Tietze J, et al. 5-HT1A receptor responsivity in unipolar depression: evaluation of ipsapironeinduced ACTH and cortisol secretion in patients and controls. Biol Psychiatry 1990; 28: 620-8.
69. Stanley M, Stanley B. Postmortem evidence for serotonin's role in suicide. J Clin Psychiatry 1990; 51: 22-30.
70. Reddy PL, Khanna S, Subhash MN, Channabasavanna SM, Rao BS. CSF amine metabolites in depression. Biol Psychiatry 1992; 31: 112-8.
71. Cheetham SC, Crompton MR, Czudek C, Horton RW, Katona CL, Reynolds GP. Serotonin concentrations and turnover in brains of depressed suicides. Brain Res 1989; 502: 332-40.
72. Cheetham SC, Crompton MR, Katona CLE, Horton RW. Brain 5-HT2 receptor binding sites in depressed suicide victims. Brain Res 1988; 443: 272-80.
73. Matsubara S, Rora RC, Meltzer HY. Serotonergic measures in suicide brain: 5-HT1A binding sites in frontal cortex of suicide victims. J Neural Trans 1991; 85: 181-94.
74. Cheetham SC, Crompton MR, Katona CLE, Horton RW. Brain 5-HT1 binding sites in depressed suicides. Psychopharmacology 1990; 102: 544-8.
75. Arango V, Underwood MD, Mann JJ. Alterations in monoamine receptors in the brain of suicide victims. J Clin Psychopharmacology 1992; 12: 8-12.
76. Arora RC, Meltzer HY. Serotonergic measures in brain of suicide victims: 5HT2 binding sites in the frontal cortex of suicide victims and control subjects. Am J Psychiatry 1989; 146: 730-6.
77. Mann JJ, Henteleff RA, Lagattuta TF, Perper JA, Li S, Arango V. Lower 3H-Paroxetine binding in cerebral cortex of suicide victims is partly due to fewer high affinity, non-transporter sites. J Neural Trans 1996; 103(11): 1337-50.
78. Lawrence KM, De Paermentier F, Lowther S, Crompton MR, Katona CL, Horton RW. Brain 5-hydroxytryptamine uptake sites labeled with [3H] Paroxetine in antidepressant drug treated depressed suicide victims and controls. J Psychiatry Neurosci 1997; 22(3): 185-91.
79. Lawrence KM, Kanagasundaram M, Lowther S, Katona CL, Crompton MR, Horton RW. [3H] imipramine binding in brain samples from depressed suicides and controls: 5-HT uptake sites compared with defined by desmethylimipramine. J Affect Dis 1998; 47(1-3): 105-12.
80. Verkes RJ, Fekkes D, Zwinderman AH, et al. Platelet serotonin and [3H] Paroxetine binding correlate with recurrence of suicidal behavior. Psychopharmacology 1997; 132(1): 89-94.
81. Rosel P, Arranz B, Vallejo J, et al. Variations in [3H] imipramine and 5-HT2A but not [3H] Paroxetine binding sites in suicide brains. Psychiatry Research 1998; 82(3): 161-70.
82. Rosel P, Arranz B, Vallejo J, et al. High affinity [3H]-Paroxetine binding sites in suicide brains. J Neural Trans 1997; 104(8-9): 921-9.
83. Perry EK, Marshall EF, Blessed G, Tomlinson BE, Perry RH. Decreased imipramine binding in the brains of patients with depressive illness. Br J Psychiatry 1983; 142: 188-92.
84. Stanley M, Mann JJ. Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet 1983; 349: 214-6.
85. Stockmeier CA, Shapiro LA, Dilley GE, Kolli TN, Friedman L, Rajkowska G. Increase in serotinin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity. J Neurosci 1998; 18(18): 7394-401.
86. Mann JJ, Oquendo M, Underwood MD, Arango V. The neurobiology of suicide risk: a review for the clinician. J Clin Psychiatry 1999; 60: 7-11.
87. Stahl SM. Essential Psychopharmacology. Ed. New York: Cambridge Press, 2008.
88. Drevets WC, Thase ME, Moses-Kolko EL, et al. Serotonin-1A receptor imaging in recurrent depression: replication and literature review. Nucl Med Biol 2007; 34(7): 865-77.
89. Kraus C, Hahn A, Savli M, et al. Serotonin-1A receptor binding is positively associated with gray matter volume-a multimodal neuroimaging study combining PET and structural MRI. Neuroimage 2012; 63(3): 1091-8.
90. Newberg AB, Amsterdam JD, Wintering N, Shults J. Low brain serotonin transporter binding in major depressive disorder. Psychiatry Res 2012; 202(2): 161-7.
91. Shrestha S, Hirvonen J, Hines CS, et al. Serotonin-1A receptors in major depression quantified using PET: controversies, confounds, and recommendations. Neuroimage 2012; 59(4): 3243-51.
92. Hahn A, Nics L, Baldinger P, et al. Application of image-derived and venous input functions in major depression using [carbonyl-(11)C]WAY-100635. Nucl Med Biol 2013; 40(3): 371-7.
93. Lanzenberger R, Baldinger P, Hahn A, et al. Global decrease of serotonin-1A receptor binding after electroconvulsive therapy in major depression measured by PET. Mol Psychiatry 2013; Jan 29. [Epub ahead of print].
94. Amara SG, Kuhar MJ. Neurotransmitter transporter: recent progress. Ann Rev Neurosci 1993; 16: 73-93.
95. Blakely RD, De Felice LJ, Hartzell HC. Molecular physiology of norepinephrine and serotonin transporters. J Exp Biol 1994; 196: 263-81.
96. Lesch KP, Balling U, Gross J, et al. Organization of the human serotonin transporter gene. J Neural Transm Gen Sect 1994; 95: 157-62.
97. Merickel A, Kaback HR, Edwards RH. Charged residues in transmembrane domains II and XI of a vesicular monoamine transporter form a charge pair that promotes high affinity substrate recognition. J Biol Chem 1997; 272: 5403-8.
98. Rudnick G. In: Neurotransmitter Transporters, Structure, Function, and Regulation; Reith M. E. A., Ed. Totowa, New Jersey: Humana Press 2002; 25-52.
99. Nelson N. The family of Na+/Cl-neurotransmitter transporters. J Neurochem 1998; 71: 1785-03.
100. Rudnick G, Clark J. From synapse to vesicle: the reuptake and storage of biogenic amine neurotransmitters. Biochim Biophys Acta 1993; 1144: 249-63.
101. Rotondo A, Giannaccini G, Quattrone K, et al. Solubilization and characterization of 3H-imipramine and 3H-Paroxetine binding sites from rat striatum. Neurochem Res 1994; 19: 1295-300.
102. Gu H, Wall SC, Rudnick G. Stable expression of biogenic amine transporters reveals differences in inhibitor sensitivity, kinetics, and ion dependence. J Biol Chem 1994; 269: 7124-30.
103. Anderson G, Horne WC. Activators of protein kinase C decrease serotonin transport in human platelets. Biochem Biophys Acta 1992; 1137: 331-3.
104. Laruelle M, Vanisberg MA, Maloteaux JM. Regional and subcellular localization in human brain of 3H-Paroxetine binding, a marker of serotonin uptake sites. Biol Psychiatry 1988; 24: 299-309.
105. Briley M, Langer SZ, Raisman R. Specific [3H]-imipramine binding in rat brain [proceedings]. Br J Pharmacol 1979; 67(3): 434P-5P.
106. Willoughby S, Holmes A, Loscalzo J. Platelets and cardiovascular disease. Eur J Cardiovasc Nurs 2002; 1(4): 273-88.
107. Blakely RD, Berson HE. Molecular biology of serotonin receptors and transporters. Clin Neuropharmacol 1992; 15: 351A-352A.
108. Rausch JJ, Hutchinson J, Li X. Correlations of drug action between human platelets and human brain 5HTT. Biol Psychiatry 1995; 137(1): 600.
109. Paul SM, Rehavi M, Skolnick P, Ballenger JC, Goodwin FK. Depressed patients have decreased binding of tritiated imipramine to platelet serotonin "transporter". Arch Gen Psychiatry 1981; 38(12): 1315-7.
110. Marazziti D, Perugi G, Deltito J, et al. High-affinity 3Himipramine binding sites: a possible state-dependent marker for major depression. Psychiatry Res 1988; 23(2): 229-37.
111. Mellerup ET, Plenge P, Engelstoft M. High-affinity binding of 3HParoxetine and 3H-imipramine to human platelet membranes. Eur J Pharmacol 1983; 96: 303-9.
112. Marazziti D, Rotondo A, Placidi GF, Perugi G, Cassano GB, Pacifici GM. Imipramine binding in platelets of patients with panic disorder. Pharmacopsychiatry 1988; 21(1): 47-9.
113. Marazziti D, Macchi E, Rotondo A, Placidi GF, Cassano GB. Involvement of serotonin system in bulimia. Life Sci 1988; 43(25): 2123-6.
114. Marazziti D, Rossi A, Dell'Osso L, et al. Decreased platelet 3HParoxetine binding in untreated panic disorder patients. Life Sci 1999; 65: 2735-42.
115. Van Praag HM, Asnis GM, Kahn RS, et al. Nosological tunnel vision in biological psychiatry. A plea for a functional psychopathology. Ann NY Acad Sci 1990; 600: 501-10.
116. Van Praag HM, Kahn RS, Asnis GM, et al. Denosologization of biological psychiatry or the specificity of 5-HT disturbances in psychiatric disorders. J Affect Disord 1987; 13(1): 1-8.
117. Van Praag HM. Biological psychiatry: still marching forward in a dead end. World Psychiatry 2010; 9(3): 164-5.
118. Van Praag HM. No functional psychopharmacology without functional psychopathology. Acta Psychiatr Scand 2010; 122(6): 438-9.
119. Marazziti D. What came first: dimensions or categories? Br J Psychiatry 2001; 178: 478-9.
120. Lesch KP, Bengel D, Heils A, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996; 274: 1527-31.
121. Coccaro EF, Kavoussi RJ, Sheline YI, Lish JD, Csernansky JC. Impulsive aggression in personality disorder correlates with tritiated Paroxetine binding in the platelet. Arch Gen Psychiatry 1996; 53: 531-6.
122. Mazzanti CM, Lappalainen J, Long JC, et al. Role of the serotonin transporter promoter polymorphism in anxiety-related traits. Arch Gen Psychiatry 1998; 55(10): 936-40.
123. Marazziti D, Akiskal HS, Rossi A, Cassano GB. Alteration of the platelet serotonin transporter in romantic love. Psychol Med. 1999; 29(3): 741-5.
124. Marazziti D, Rucci P, Di Nasso E, et al. Jealousy and subthreshold psychopathology: a serotonergic link. Neuropsychobiology 2003; 47(1): 12-6.
125. Insel TR, Akiskal HS. Obsessive-compulsive disorder with psychotic features: a phenomenologic analysis. Am J Psychiatry 1986; 143(12): 1527-33.
126. O'Dwyer AM, Marks I. Obsessive-compulsive disorder and delusions revisited. Br J Psychiatry 2000; 174: 281-4.
127. Marcusson J, Eriksson K. Dissociation kinetics of [3H]paroxetine binding to rat brain consistent with a single-site model of the antidepressant binding/5-hydroxytryptamine uptake site. J Neurochem 1988; 51: 1477-81.
128. Bäckström I, Bergström M, Marcusson J. High affinity [3H]paroxetine binding to serotonin uptake sites in human brain tissue. Brain Res 1989; 486: 261-8.
129. Rotondo A, Giannaccini G, Betti L, et al. The serotonin transporter from human brain: purification and partial characterization. Neurochem Int 1996; 28: 299-307.
130. Serafeim A, Grafton G, Chamba A, et al. 5-Hydroxytryptamine drives apoptosis in biopsy like Burkitt lymphoma cells: reversal by selective serotonin reuptake inhibitors. Blood 2002; 99: 2545-53.
131. Aune TM, Golden HW, McGrath KM. Inhibitors of serotonin synthesis and antagonists of serotonin 1A receptors inhibit T lymphocyte function in vitro and cell-mediated immunity in vivo. J Immunol 1994; 153: 489-98.
132. Askenase PW, Herzog WR, Millet I, et al. Serotonin initiation of delayed-type hypersensitivity: mediation by a primitive Thy-1+ antigen-specific clone or by specific monoclonal IgE antibody. Skin Pharmacol 1991; 4: 25-42.
133. Matsuda H, Ushio H, Geba GP, Askenase PW. Human platelets can initiate T cell-dependent contact sensitivity through local serotonin release mediated by IgE antibodies. J Immunol 1997; 158: 2891-7.
134. Laberge S, Cruikshank WW, Beer DJ, Center DM. Secretion of IL-16 (lymphocyte chemoattractant factor) from serotonin-stimulated CD8+ T cells in vitro. J Immunol 1996; 156: 310-15.
135. Betten A, Dahlgren C, Hermodsson S, Hellstrand K. Serotonin protects NK cells against oxidatively induced functional inhibition and apoptosis. J Leukoc Biol 2001; 70: 65-72.
136. Iken K, Chheng S, Fargin A, Goulet AC, Kouassi E. Serotonin upregulates mitogen-stimulated B lymphocyte proliferation through 5-HT1A receptors. Cell Immunol 1995; 163: 1-9.
137. Hellstrand K, Hermodsson S. Serotonergic 5-HT1A receptors regulate a cell contact-mediated interaction between natural killer cells and monocytes. Scand J Immunol 1993; 37: 7-18.
138. Eugen-Olsen J, Afzelius P, Andresen L, et al. Serotonin modulates immune function in T cells from HIV-seropositive subjects. Clin Immunol Immunopathol 1997; 84: 115-21.
139. Kut JL, Young MR, Crayton JW, Wright MA, Young ME. Regulation of murine T-lymphocyte function by spleen cell-derived and exogenous serotonin. Immunopharmacol Immunotoxicol 1992; 14: 783-96.
140. Young MR, Kut, JL, Coogan MP, Wright MA, Young ME, Matthews J. Stimulation of splenic T-lymphocyte function by endogenous serotonin and by low-dose exogenous serotonin. Immunology 1993; 80: 395-400.
141. Khan NA, Hichami A. Ionotrophic 5-hydroxytryptamine type 3 receptor activates the protein kinase C-dependent phospholipase D pathway in human T-cells. Biochem J 1999; 34: 199-204.
142. Norregaard L, Gether U. The monoamine neurotransmitter transporters: structure, conformational changes and molecular gating. Curr Opin Drug Discov Dev 2001; 4: 591-601.
143. Torres GE, Gainetdinov RR, Caron MG. Plasma membrane monoamine transporters: structure, regulation and function. Nat Rev Neurosci 2003; 4: 13-25.
144. Rudnick G. Serotonin transporters-structure and function. J Membr Biol 2006; 213: 101-10.
145. Xia Z, DePierre JW, Nässberger L. Modulation of apoptosis induced by tricyclic antidepressants in human peripheral lymphocytes. J Biochem Mol Toxicol 1998; 12: 115-23.
146. Edgar VA, Sterin-Borda L, Cremaschi GA, Genaro AM. Role of protein kinase C and cAMP in fluoxetine effects on human T-cell proliferation. Eur J Pharmacol 1999; 372: 65-73.
147. Genaro AM, Edgar VA, Sterin-Borda L. Differential effects of fluoxetine on murine B-cell proliferation depending on the biochemical pathways triggered by distinct mitogens. Biochem Pharmacol 2000; 60: 1279-83.
148. Frick LR, Rapanelli M, Cremaschi GA, Genaro AM. Fluoxetine directly counteracts the adverse effects of chronic stress on T cell immunity by compensatory and specific mechanisms. Brain Behav Immun 2009; 23: 36-40.
149. Frank MG, Hendricks SE, Johnson DR, Wieseler JL, Burke WJ. Antidepressants augment natural killer cell activity: in vivo and in vitro. Neuropsychobiology 1999; 39: 18-24.
150. Schleifer SJ, Keller SE, Stein M. Brain, behaviour and the immune system. Nature 1984; 310: 456.
151. Schleifer SJ, Keller SE, Bond RN, Cohen J, Stein M. Major depressive disorder and immunity. Role of age, sex, severity, and hospitalization. Arch Gen Psychiatry 1989; 46: 81-7.
152. Ader R, Cohen N. Conditioning of the immune response. Neth J Med 1991; 39: 263-73.
153. Kenis G, Maes M. Effects of antidepressants on the production of cytokines. Int J Neuropsychopharmacol 2002; 5: 401-12.
154. Maes M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuroendocrinol Lett 2008; 29: 287-91.
155. Dinan TG. Inflammatory markers in depression. Curr Opin Psychiatry 2009; 22: 32-6.
156. Lima L, Urbina M. Serotonin transporter modulation in blood lymphocytes from patients with major depression. Cell Mol Neurobiol 2002; 22: 797-804.
157. Fazzino F, Montes C, Urbina M, Carreira I, Lima L. Serotonin transporter is differentially localized in subpopulations of lymphocytes of major depression patients. Effect of fluoxetine on proliferation. J Neuroimmunol 2008; 196(1-2): 173-80.
158. Fazzino F, Urbina M, Cedeño N, Lima L. Fluoxetine treatment to rats modifies serotonin transporter and cAMP in lymphocytes, CD4+ and CD8+ subpopulations and interleukins 2 and 4. Int Immunopharmaco 2009; 9(4): 463-7.
159. Rivera-Baltanas T, Olivares JM, Calado-Otero M, Kalynchuk LE, Martinez-Villamarin JR, Caruncho HJ. Serotonin transporter clustering in blood lymphocytes as a putative biomarker of therapeutic efficacy in major depressive disorder. J Affect Disord 2012; 137(1-3): 46-55.
160. Catena-Dell'Osso M, Bellantuono C, Consoli G, Baroni S, Rotella F, Marazziti D. Inflammatory and neurodegenerative pathways in depression: a new avenue for antidepressant development? Curr Med Chem 2011; 18(2): 245-55.
161. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 2009; 65(9): 732-41.
162. Marazziti D, Conti L. Aggression, hyperactivity and platelet imipramine binding. Acta Psych Scand 1991; 84(3): 209-11.
163. Marazziti D, Rotondo A, Presta S, Panciolli-Guadagnucci ML, Palego L, Conti L. Role of serotonin in human aggressive behaviour. Aggress Behav 1993; 19: 347-53.