2014, Number 3
<< Back Next >>
Rev Biomed 2014; 25 (3)
Plasma levels of tryptophan in Cuban patients with schizophrenia
Robaina-Jiménez Z, Contreras-Roura J, Morales-Rodríguez E, Marcheco- Teruel B, Monzón-Benítez G, Caballero A, de las Nieves-Milián D, Galan G, Llanes Y, Valenti J, Marín-Padrón LC, Fuentes-Smith E, Ventura R, Riverón-Forment G, Mors O
Language: Spanish
References: 31
Page: 111-118
PDF size: 241.15 Kb.
ABSTRACT
Introduction. Schizophrenia is a heterogeneous
psychiatric disorder that affects 1% of the
world's population. The pathophysiology of
this disease has been reported to be involved
with several neurotransmitter systems, such as
serotonin. Because serotonin synthesis depends
on the availability of tryptophan, we studied
plasma tryptophan levels in Cuban patients with
schizophrenia.
Objective. To determine plasma concentrations
of tryptophan in patients with schizophrenia.
Materials and Methods. A descriptive crosssectional
study was performed. The sample
consisted of 400 patients treated at the Psychiatric
Hospital of Havana with clinical diagnoses of
schizophrenia. Patient's psychopathological
assessment were completed using Schedules for
Clinical Assessment in Neuropsychiatry (SCAN)
protocols. The reference population group
comprised 157 apparently healthy individuals
of both sexes. Plasma tryptophan levels were
quantified by HPLC.
Results. A significant decrease in plasma
tryptophan concentrations (p = 0,0001) were
observed as related to the sex of the patient, with
the female patients presenting the lowest values of
tryptophan compared to reference values. It was
observed that patients with concentrations below
370 µM tryptophan, had the most severe degrees
of SCAN as evaluated by clinical variables related
to negative symptoms with schizophreniform
speech abnormalities (64.3%) and negative
syndrome (61.8%).
Conclusion. Patients with schizophrenia with low
concentrations of tryptophan may have alterations
in their serotonergic systems, which could explain
the severity observed in relation to the negative
symptoms of the disease and could also point
to candidates in the search for genes associated
with serotonin pathways. Based on these findings,
it is recommended that the measurement of
plasma tryptophan concentrations should be
considered when selecting therapies for treating
schizophrenia.
Key words: tryptophan, serotonin, schizophrenia,
serotonergic hypothesis, negative symptoms,
metabolite
REFERENCES
Gejman P, Sanders A. La etiología de la esquizofrenia. Medicina (B Aires) 2012;72(3):227-34.
Sullivan PF, Kendler KS, Neale MC. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 2003 Dec;60(12):1187- 92.
Machado A, Luiz A. La disolución de la paradoja etiológica de la esquizofrenia. Alcmeon 2009;15:196- 209.
Fatemi SH, Folsom TD. The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophr Bull 2009 May;35(3):528-48.
Saiz-Ruiz J, de la Vega-Sánchez DC, Sánchez-Páez. Bases Neurobiológicas de la Esquizofrenia. Clin Salud 2010;21(3):235-54.
Fukuda K. 5-HTP hypothesis of schizophrenia. Med Hypotheses 2014 Jan;82(1):20-3.
World Health Organization, SCAN: Schedules for Clinical Assessment in Neuropsychiatry Version 2.1 Geneva, Switzerland Psychiatric Publishers International/American Psychiatric Press Inc1994- 1997.
Zhao J, Chen H, Ni P, Xu B, Luo X, Zhan Y, et al. Simultaneous determination of urinary tryptophan, tryptophan-related metabolites and creatinine by high performance liquid chromatography with ultraviolet and fluorimetric detection. J Chromatogr B Analyt Technol Biomed Life Sci 2011 Sep 15;879(26):2720-5.
Yao JK, Dougherty GG Jr, Reddy RD, Keshavan MS, Montrose DM, Matson WR, et al. Altered interactions of tryptophan metabolites in first episode neuroleptic-naive patients with schizophrenia. Mol Psychiatry 2010 Sep;15(9):938-53.
Freedman DX, Belendiuk K, Belendiuk GW, Crayton JW. Blood Tryptophan Metabolism in Chronic Schizophrenics. Arch Gen Psychiatry 1981 Jun;38(6):655-9.
Manowitz P, Gilmour DG, Racevskis J. Low plasma tryptophan levels in recently hospitalized schizophrenics. Biol Psychiatry 1973 Apr;6(2):109-18.
Jovanovic H, Lundberg J, Karlsson P, Cerin A, Saijo T, Varrone A, et al. Sex differences in the serotonin 1A receptor and serotonin transporter binding in the human brain measured by PET. Neuroimage 2008 Feb 1;39(3):1408-19.
Parsey RV, Oquendo MA, Simpson NR, Ogden RT, Van Heertum R, Arango V, et al. 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 2002 Nov 8;954(2):173-82.
Versijpt J, Van Laere KJ, Dumont F, Decoo D, Vandecapelle M, Santens P, et al. Imaging of the 5-HT2A system: age-, gender-, and Alzheimer's disease-related findings. Neurobiol Aging 2003 Jul- Aug;24(4):553-61.
Moses-Kolko EL, Berga SL, Greer PJ, Smith G, Cidis Meltzer C, Drevets WC. Widespread increases of cortical serotonin type 2A receptor availability after hormone therapy in euthymic postmenopausal women. Fertil Steril 2003 Sep;80(3):554-9.
Kugaya A, Epperson CN, Zoghbi S, van Dyck CH, Hou Y, Fujita M, et al. Increase in prefrontal cortex serotonin 2A receptors following estrogen treatment in postmenopausal women. Am J Psychiatry 2003 Aug;160(8):1522-4.
Moore P, Landolt HP, Seifritz E, Clark C, Bhatti T, Kelsoe J, et al. Clinical and Physiological Consequences of Rapid Tryptophan Depletion. Neuropsychopharmacology 2000 Dec;23(6):601-22.
Crockett MJ, Clark L, Roiser JP, Robinson OJ, Cools R, Chase HW, et al. Converging evidence for central 5-HT effects in acute tryptophan depletion. Mol Psychiatry 2012 Feb;17(2):121-3.
Neumeister A. Tryptophan depletion, serotonin, and depression: where do we stand?. Psychopharmacol Bull 2003;37(4):99-115.
Williams HJ, Owen MJ, O’Donovan MC. New findings from genetic association studies of schizophrenia. J Hum Genet 2009 Jan;54(1):9-14.
Mortensen PB, Pedersen CB, Westergaard T, Robaina-Jiménez et al. Wohlfahrt J, Ewald H, Mors O, et al. Effects of family history and place and season of birth on the risk of schizophrenia. N Engl J Med 1999 Feb 25;340(8):603-8.
Parra I, Crivillés S, Acebillo S, Soto E, Santos J,Peláez T, et al. Esquizofrenia familiar y esporádica: un estudio clínico comparativo. Rev Psiquiatría Fac Med Barna 2005;32(4):174-8.
Yang J, Visscher PM, Wray NR. Sporadic cases are the norm for complex disease. Eur J Hum Genet 2010 Sep;18(9):1039-43.
Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry. 2003 Apr;160(4):636-45.
Haller CS, Padmanabhan JL, Lizano P, Torous J, Keshavan M. Recent advances in understanding schizophrenia. F1000Prime Rep 2014 Jul;8(6):57.
Cornblatt BA, Carrión RE, Addington J, Seidman L, Walker EF, Cannon TD, et al. Risk factors for psychosis: impaired social and role functioning. Schizophr Bull. 2012 Nov;38(6):1247-57.
García-Portilla MP, Bobes J. The new challenge in identifying the negative syndrome of schizophrenia. Rev Psiquiatr Salud Ment 2013 Oct-Dec;6(4):141-3.
Bobes J, Arango C, Garcia-Garcia M, Rejas J; CLAMORS Study Collaborative Group. Prevalence of negative symptoms in outpatients with schizophrenia spectrum disorders treated with antipsychotics in routine clinical practice: findings from the CLAMORS study. J Clin Psychiatry 2010 Mar;71(3):280-6.
Stanghellini G, Rossi R. Pheno-phenotypes: a holistic approach to the psychopathology of schizophrenia. Curr Opin Psychiatry 2014 May;27(3):236-41.
Kałuzyńska O, Rabe-Jabłońska J. Neurological soft signs as a candidate for endophenotype of schizophrenia. Psychiatr Pol 2014 Jan-Feb;48(1):5-18.
Glahn DC, Knowles EE, McKay DR, Sprooten E, Raventós H, Blangero J, et al. Arguments for the sake of endophenotypes: examining common misconceptions about the use of endophenotypes in psychiatric genetics. Am J Med Genet B Neuropsychiatr Genet 2014 Mar;165B(2):122-30.
Full text