INTRODUCCIÓN
Los potenciales relacionados a eventos N200 y P300 son herramientas sensibles para evaluar el funcionamiento sensorial y cognitivo. Debido a que, frecuentemente se reporta una prolongación de la latencia y una disminución de la amplitud de los componentes N200 y P300 en pacientes con esquizofrenia, estos potenciales constituyen marcadores biológicos de vulnerabilidad genética para este trastorno mental.

OBJETIVO
Precisar la asociación de las alteraciones en la latencia, la amplitud y la distribución topográfica de los potenciales N200 y P300 de pacientes con esquizofrenia paranoide y sus familiares sanos de primer grado, pertenecientes a familias con esquizofrenia multiplex.

MÉTODOS
Se utilizó un paradigma “odd-ball” auditivo para evaluar la latencia, la amplitud y la distribución topográfica de los componentes N200 y P300 en 25 pacientes con esquizofrenia paranoide (probandos), 23 familiares sanos de primer grado y 25 sujetos controles, mediante un estudio de asociación familiar en 60 familias afectadas con esquizofrenia multiplex.

RESULTADOS
Los probandos y sus familiares mostraron una prolongación significativa de la latencia y una disminución de amplitud de las ondas N200 y P300 cuando se compararon con los sujetos sanos. De igual forma, la amplitud de los potenciales N200 y P300 resultó significativamente disminuida en regiones temporales del hemisferio izquierdo de los probandos y sus familiares con respecto al grupo control.

CONCLUSIONES
En concordancia con resultados de otros investigadores, este estudio sugiere que, la prolongación de latencia, la disminución de amplitud y las alteraciones en la distribución topográficas detectadas en regiones temporales de los potenciales N200 y P300, pueden constituir por su elevada asociación familiar, marcadores de rasgo para la esquizofrenia paranoide.

Authors: Seidel Guerra López[1,2], Migdyrai Martín Reyes[3], María de los Ángeles Pedroso Rodríguez[4], Adnelys Reyes Berazain[5], Raúl Mendoza Quiñones[5], Tania Martha Bravo Collazo[6], Thais Días de Villarvilla[5], María Julia Machado Cano[7], María Antonieta Bobés León[5]

Affiliation:
[1] Universidad Nacional del Este, Alto Paraná, Paraguay
[2] Universidad de Integración Latinoamericana, Foz de Iguazú, Paraná, Brasil
[3] Clínica de Rehabilitación de Salud Mental, Servicio Navarro de Salud, Pamplona, Navarra, España
[4] Centro de Investigaciones Médicas, Facultad de Ciencias de la Salud, Universidad Nacional del Este, Minga Guazú, Paraguay
[5] Departamento de Neurociencias de Cuba, Centro de Neurociencias de Cuba, La Habana, Cuba
[6] Centros de Investigación y Tratamiento de las Adicciones (CITA) Dosrius, Barcelona, España
[7] Universidad de Ciencias Médicas de Ciego de Ávila, Ciego de Ávila, Cuba

E-mail: seidelguerra@yahoo.es

Author address:
[1] Km. 16 Acaray
Avda. Mcal. López entre Mcal. Estigarribia y Padre Moleón
Minga Guazú
Paraguay

Citation: Guerra López S, Martín Reyes M, Pedroso Rodríguez MA, Reyes Berazain A, Mendoza Quiñones R, Bravo Collazo T, et al. Evoked potentials N200/P300 disorders and clinical phenotype in Cuban families with paranoid schizophrenia: a family-based association study. Medwave 2015 Abr;15(3):e6112 doi: 10.5867/medwave.2015.03.6112

Submission date: 27/11/2014

Acceptance date: 17/3/2015

Publication date: 1/4/2015

Origin: not requested

Type of review: reviewed by five external peer reviewers, double-blind

PubMed record

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1. Amenedo E, Díaz F. Aging-related changes in processing of non-target and target stimuli during an auditory oddball task. Biol Psychol. 1998 Aug;48(3):235-67. | PubMed |
2. American Psychiatric Association. DSM-IV. Diagnostic and statistical manual of mental disorders, 4 ed, Washington, DC: American Psychiatric Association, 1994.
3. Braff DL. Psychophysiological and information processing approaches to schizophrenia. En: Neurobiological foundation of mental illness. New York: Oxford University Press, 1999:258-271.
4. Blackwood DH, Young AH, McQueen JK, Martin MJ, Roxborough HM, Muir WJ, et al. Magnetic resonance imaging in schizophrenia: altered brain morphology associated with P300 abnormalities and eye tracking dysfunction. Biol Psychiatry. 1991 Oct;30(8):753-69. | PubMed |
5. Bharath S, Gangadhar BN, Janakiramaiah N. P300 in family studies of schizophrenia: review and critique. Int J Psychophysiol. 2000 Oct;38(1):43-54. | PubMed |
6. Boutros N, Nasrallah H, Leighty R, Torello M, Tueting P, Olson S. Auditory evoked potentials in schizophrenia. Biol Psychiatry. 1996;39(7):651. | CrossRef |
7. Bramon E, McDonald C, Croft RJ, Landau S, Filbey F, Gruzelier JH, et al. Is the P300 wave an endophenotype for schizophrenia? A meta-analysis and a family study. Neuroimage. 2005 Oct 1;27(4):960-8. | PubMed |
8. Brown KJ, Gonsalvez CJ, Harris AW, Williams LM, Gordon E. Target and non-target ERP disturbances in first episode vs. chronic schizophrenia. Clin Neurophysiol. 2002 Nov;113(11):1754-63. | CrossRef | PubMed |
9. Cohen RA, Sparling-Cohen YA, O’Donnell BF. The Neuropsychology of Attention. New York: Plenum Press, 1993.
10. Donchin E, Coles MGH. Is the P300 component a manifestation of context updating ? Behav Brain Sci. 1988;11(3):357-373. | CrossRef |
11. Debruille JB, Schneider-Schmid A, Dann P, King S, Laporta M, Bicu M. The correlation between positive symptoms and left temporal event-related potentials in the P300 time window is auditory specific and training sensitive. Schizophr Res. 2005 Oct 15;78(2-3):117-25. | CrossRef | PubMed |
12. Egan MF, Duncan CC, Suddath RL, Kirch DG, Mirsky AF, Wyatt RJ. Event-related potential abnormalities correlate with structural brain alterations and clinical features in patients with chronic schizophrenia. Schizophrenia Research. 1994;11(3):259-271. | CrossRef |
13. Fabiani M, Gratton G, Karis D, Donchin E: Definition, identification, and reliability of measurement of the P300 component of the event-related brain potential. En: Advances in Psychophysiology, vol 2. Greenwich, CT: JAI Press, 1987.
14. Ford JM, Mathalon DH, White PM, Pfefferbaum A. Left temporal deficit of P300 in patients with schizophrenia: effects of task. Int J Psychophysiol. 2000 Oct;38(1):71-9. | PubMed |
15. Forte A, Bernardo A, Caputo F, Bucci P, Mucci A, Galderisi S, et al. P300 Brain Microstate in deficit and nondeficit schizophrenia. Eur Psychiatr. 2002;17(1):188. | PubMed |
16. Frodl T, Meisenzahl EM, Müller D, Greiner J, Juckel G, Leinsinger G, et al. Corpus callosum and P300 in schizophrenia. Schizophr Res. 2001 Apr 15;49(1-2):107-19. | CrossRef | PubMed |
17. Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry. 2003 Apr;160(4):636-45. | CrossRef | PubMed |
18. Gonul AS, Suer C, Coburn K, Ozesmi C, Oguz A, Yilmaz A. Effects of olanzapine on auditory P300 in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Feb;27(1):173-7. | PubMed |
19. Grillon C, Courchesne E, Ameli R, Geyer MA, Braff DL. Increased distractibility in schizophrenic patients. Electrophysiologic and behavioral evidence. Arch Gen Psychiatry. 1990 Feb;47(2):171-9. | CrossRef | PubMed |
20. Guerra S, Ibáñez A, Martín M, Bobes MA, Reyes A, Mendoza R, et al. N400 deficits from semantic matching of pictures in probands and first-degree relatives from multiplex schizophrenia families. Brain Cogn. 2009 Jul;70(2):221-30. | CrossRef | PubMed |
21. Higashima M, Kawasaki Y, Urata K, Sakai N, Nagasawa T, Koshino Y, et al. Regional cerebral blood flow in male schizophrenic patients performing an auditory discrimination task. Schizophr Res. 2000 Mar 16;42(1):29-39. | CrossRef | PubMed |
22. Shaikh M, Hall MH, Schulze K, Dutt A, Li K, Williams I, Walshe M, et al. Effect of DISC1 on the P300 waveform in psychosis. Schizophr Bull. 2013 Jan;39(1):161-7. | CrossRef | PubMed |
23. Havermans R, Honig A, Vuurman EF, Krabbendam L, Wilmink J, Lamers T, et al. A controlled study of temporal lobe structure volumes and P300 responses in schizophrenic patients with persistent auditory hallucinations. Schizophr Res. 1999 Aug 17;38(2-3):151-8. | PubMed |
24. Hotchkiss AP, Harvey PD. Effect of concurrent distraction on thought disorder in schizophrenia. American Journal of Psychiatry. 1990;147(2):153-156.
25. Díaz-Anzaldúa A, Velázquez-Pérez J, Berlanga C. Endophenotypes and biomarkers: an approach to molecular genetic studies of mental disorders. Salud Mental 2013;36(3):161-168. | Link |
26. Ogura C, Nageishi Y, Omura F, Fukao K, Ohta H, Kishimoto A, er al. N200 component of event-related potentials in depression. Biol Psychiatry. 1993 May 15;33(10):720-6. | CrossRef | PubMed |
27. Meisenzahl EM, Frodl T, Müller D, Schmitt G, Gallinat J, Zetzsche T, et al. Superior temporal gyrus and P300 in schizophrenia: a combined ERP/structural magnetic resonance imaging investigation. J Psychiatr Res. 2004 Mar-Apr;38(2):153-62. | CrossRef | PubMed |
28. McCarley RW, O’Donnell BF, Niznikiewicz MA, Salisbury DF, Potts GF, Hirayasu Y, et al. Update on electrophysiology in schizophrenia. Int Rev Psychiatry. 1997;9(4):373-386. | CrossRef |
29. Matthysse S, Holzman PS, Lange K. The genetic transmission of schizophrenia: application of Mendelian latent structure analysis to eye tracking dysfunctions in schizophrenia and affective disorder. J Psychiatr Res. 1986;20(1):57-67. | PubMed |
30. Moser RK, Cienfuegos A, Barros J, Javitt D. Auditory distraction and thought disorder in chronic schizophrenic inpatients. Evidence for separate contributions by incapacity and poor allocation and a subsyndrome related to the allocation deficit. Schizophr Res. 2001 Sep 1;51(2-3):163-70. | CrossRef | PubMed |
31. Vázquez- Barquero JL, et al. Report on the Spanish Translation of the SCAN, Schedules and Glossary. Informe a la Organización Mundial de la Salud. Santander, España: Unidad de Investigación en Psiquiatría Social de Cantabria, 1992.
32. Kay SR, Fiszbein A, Vital-Herne M, Fuentes LS. The Positive and Negative Syndrome Scale--Spanish adaptation. J Nerv Ment Dis. 1990 Aug;178(8):510-7. | PubMed |
33. Bunney WE Jr, Hetrick WP, Bunney BG, Patterson JV, Jin Y, Potkin SG, Sandman CA. Structured Interview for Assessing Perceptual Anomalies (SIAPA). Schizophr Bull. 1999;25(3):577-92. | CrossRef | PubMed |
34. Frangou S, Sharma T, Alarcon G, Sigmudsson T, Takei N, Binnie C, Murray RM. The Maudsley Family Study, II: Endogenous event-related potentials in familial schizophrenia. Schizophr Res. 1997 Jan 17;23(1):45-53. | CrossRef | PubMed |
35. Schreiber H, Stolz-Born G, Rothmeier J, Kornhuber A, Kornhuber HH, Born J. Endogenous event-related brain potentials and psychometric performance in children at risk for schizophrenia. Biol Psychiatry. 1991 Jul 15;30(2):177-89. | CrossRef | PubMed |
36. Surwillo WW. Cortical evoked potentials in monozygotic twins and unrelated subjects: comparisons of exogenous and endogenous components. Behav Genet. 1980 Mar;10(2):201-9. | PubMed |
37. Phillips NA, Chertkow H, Leblanc MM, Pim H, Murtha S. Functional and anatomical memory indices in patients with or at risk for Alzheimer's disease. J Int Neuropsychol Soc. 2004 Mar;10(2):200-10. | CrossRef | PubMed |
38. Polich J, Pollock VE, Bloom FE. Meta-analysis of P300 amplitude from males at risk for alcoholism. Psychol Bull. 1994 Jan;115(1):55-73. | CrossRef |
39. Rao KM, Ananthnarayanan CV, Gangadhar BN, Janakiramaiah N. Smaller auditory P300 amplitude in schizophrenics in remission. Neuropsychobiology. 1995;32(3):171-4. | PubMed |
40. Guerra S, Iglesias J, Matín M, Bravo TM, Mendoza R, Reyes A, et al. Redes neurales de la atención en pacientes con esquizofrenia y sus familiares no afectados de primer grado: un endofenotipo potencial. Actas Esp. Psiquiatr. 2011;39(1):32-44. | Link |
41. Martín-Reyes M, Mendoza R, Domínguez M, Caballero A, Bravo TM, Díaz T, et al. Depressive symptoms evaluated by the Calgary Depression Scale for Schizophrenia (CDSS): genetic vulnerability and sex effects. Psychiatry Res. 2011 Aug 30;189(1):55-61. | CrossRef | PubMed |
42. Sponheim SR, McGuire KA, Stanwyck JJ. Neural anomalies during sustained attention in first-degree biological relatives of schizophrenia patients. Biol Psychiatry. 2006 Aug 1;60(3):242-52. | CrossRef | PubMed |
43. Mendoza R, Cabral-Calderin Y, Domínguez M, Garcia A, Borrego M, Caballero A, et al. Impairment of emotional expression recognition in schizophrenia: a Cuban familial association study. Psychiatry Res. 2011 Jan 30;185(1-2):44-8. | CrossRef | PubMed |

Amenedo E, Díaz F. Aging-related changes in processing of non-target and target stimuli during an auditory oddball task. Biol Psychol. 1998 Aug;48(3):235-67. | PubMed |

American Psychiatric Association. DSM-IV. Diagnostic and statistical manual of mental disorders, 4 ed, Washington, DC: American Psychiatric Association, 1994.

Braff DL. Psychophysiological and information processing approaches to schizophrenia. En: Neurobiological foundation of mental illness. New York: Oxford University Press, 1999:258-271.

Blackwood DH, Young AH, McQueen JK, Martin MJ, Roxborough HM, Muir WJ, et al. Magnetic resonance imaging in schizophrenia: altered brain morphology associated with P300 abnormalities and eye tracking dysfunction. Biol Psychiatry. 1991 Oct;30(8):753-69. | PubMed |

Bharath S, Gangadhar BN, Janakiramaiah N. P300 in family studies of schizophrenia: review and critique. Int J Psychophysiol. 2000 Oct;38(1):43-54. | PubMed |

Boutros N, Nasrallah H, Leighty R, Torello M, Tueting P, Olson S. Auditory evoked potentials in schizophrenia. Biol Psychiatry. 1996;39(7):651. | CrossRef |

Bramon E, McDonald C, Croft RJ, Landau S, Filbey F, Gruzelier JH, et al. Is the P300 wave an endophenotype for schizophrenia? A meta-analysis and a family study. Neuroimage. 2005 Oct 1;27(4):960-8. | PubMed |

Brown KJ, Gonsalvez CJ, Harris AW, Williams LM, Gordon E. Target and non-target ERP disturbances in first episode vs. chronic schizophrenia. Clin Neurophysiol. 2002 Nov;113(11):1754-63. | CrossRef | PubMed |

Cohen RA, Sparling-Cohen YA, O’Donnell BF. The Neuropsychology of Attention. New York: Plenum Press, 1993.

Donchin E, Coles MGH. Is the P300 component a manifestation of context updating ? Behav Brain Sci. 1988;11(3):357-373. | CrossRef |

Debruille JB, Schneider-Schmid A, Dann P, King S, Laporta M, Bicu M. The correlation between positive symptoms and left temporal event-related potentials in the P300 time window is auditory specific and training sensitive. Schizophr Res. 2005 Oct 15;78(2-3):117-25. | CrossRef | PubMed |

Egan MF, Duncan CC, Suddath RL, Kirch DG, Mirsky AF, Wyatt RJ. Event-related potential abnormalities correlate with structural brain alterations and clinical features in patients with chronic schizophrenia. Schizophrenia Research. 1994;11(3):259-271. | CrossRef |

Fabiani M, Gratton G, Karis D, Donchin E: Definition, identification, and reliability of measurement of the P300 component of the event-related brain potential. En: Advances in Psychophysiology, vol 2. Greenwich, CT: JAI Press, 1987.

Ford JM, Mathalon DH, White PM, Pfefferbaum A. Left temporal deficit of P300 in patients with schizophrenia: effects of task. Int J Psychophysiol. 2000 Oct;38(1):71-9. | PubMed |

Forte A, Bernardo A, Caputo F, Bucci P, Mucci A, Galderisi S, et al. P300 Brain Microstate in deficit and nondeficit schizophrenia. Eur Psychiatr. 2002;17(1):188. | PubMed |

Frodl T, Meisenzahl EM, Müller D, Greiner J, Juckel G, Leinsinger G, et al. Corpus callosum and P300 in schizophrenia. Schizophr Res. 2001 Apr 15;49(1-2):107-19. | CrossRef | PubMed |

Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry. 2003 Apr;160(4):636-45. | CrossRef | PubMed |

Gonul AS, Suer C, Coburn K, Ozesmi C, Oguz A, Yilmaz A. Effects of olanzapine on auditory P300 in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Feb;27(1):173-7. | PubMed |

Grillon C, Courchesne E, Ameli R, Geyer MA, Braff DL. Increased distractibility in schizophrenic patients. Electrophysiologic and behavioral evidence. Arch Gen Psychiatry. 1990 Feb;47(2):171-9. | CrossRef | PubMed |

Guerra S, Ibáñez A, Martín M, Bobes MA, Reyes A, Mendoza R, et al. N400 deficits from semantic matching of pictures in probands and first-degree relatives from multiplex schizophrenia families. Brain Cogn. 2009 Jul;70(2):221-30. | CrossRef | PubMed |

Higashima M, Kawasaki Y, Urata K, Sakai N, Nagasawa T, Koshino Y, et al. Regional cerebral blood flow in male schizophrenic patients performing an auditory discrimination task. Schizophr Res. 2000 Mar 16;42(1):29-39. | CrossRef | PubMed |

Shaikh M, Hall MH, Schulze K, Dutt A, Li K, Williams I, Walshe M, et al. Effect of DISC1 on the P300 waveform in psychosis. Schizophr Bull. 2013 Jan;39(1):161-7. | CrossRef | PubMed |

Havermans R, Honig A, Vuurman EF, Krabbendam L, Wilmink J, Lamers T, et al. A controlled study of temporal lobe structure volumes and P300 responses in schizophrenic patients with persistent auditory hallucinations. Schizophr Res. 1999 Aug 17;38(2-3):151-8. | PubMed |

Hotchkiss AP, Harvey PD. Effect of concurrent distraction on thought disorder in schizophrenia. American Journal of Psychiatry. 1990;147(2):153-156.

Díaz-Anzaldúa A, Velázquez-Pérez J, Berlanga C. Endophenotypes and biomarkers: an approach to molecular genetic studies of mental disorders. Salud Mental 2013;36(3):161-168. | Link |

Ogura C, Nageishi Y, Omura F, Fukao K, Ohta H, Kishimoto A, er al. N200 component of event-related potentials in depression. Biol Psychiatry. 1993 May 15;33(10):720-6. | CrossRef | PubMed |

Meisenzahl EM, Frodl T, Müller D, Schmitt G, Gallinat J, Zetzsche T, et al. Superior temporal gyrus and P300 in schizophrenia: a combined ERP/structural magnetic resonance imaging investigation. J Psychiatr Res. 2004 Mar-Apr;38(2):153-62. | CrossRef | PubMed |

McCarley RW, O’Donnell BF, Niznikiewicz MA, Salisbury DF, Potts GF, Hirayasu Y, et al. Update on electrophysiology in schizophrenia. Int Rev Psychiatry. 1997;9(4):373-386. | CrossRef |

Matthysse S, Holzman PS, Lange K. The genetic transmission of schizophrenia: application of Mendelian latent structure analysis to eye tracking dysfunctions in schizophrenia and affective disorder. J Psychiatr Res. 1986;20(1):57-67. | PubMed |

Moser RK, Cienfuegos A, Barros J, Javitt D. Auditory distraction and thought disorder in chronic schizophrenic inpatients. Evidence for separate contributions by incapacity and poor allocation and a subsyndrome related to the allocation deficit. Schizophr Res. 2001 Sep 1;51(2-3):163-70. | CrossRef | PubMed |

Vázquez- Barquero JL, et al. Report on the Spanish Translation of the SCAN, Schedules and Glossary. Informe a la Organización Mundial de la Salud. Santander, España: Unidad de Investigación en Psiquiatría Social de Cantabria, 1992.

Kay SR, Fiszbein A, Vital-Herne M, Fuentes LS. The Positive and Negative Syndrome Scale--Spanish adaptation. J Nerv Ment Dis. 1990 Aug;178(8):510-7. | PubMed |

Bunney WE Jr, Hetrick WP, Bunney BG, Patterson JV, Jin Y, Potkin SG, Sandman CA. Structured Interview for Assessing Perceptual Anomalies (SIAPA). Schizophr Bull. 1999;25(3):577-92. | CrossRef | PubMed |

Frangou S, Sharma T, Alarcon G, Sigmudsson T, Takei N, Binnie C, Murray RM. The Maudsley Family Study, II: Endogenous event-related potentials in familial schizophrenia. Schizophr Res. 1997 Jan 17;23(1):45-53. | CrossRef | PubMed |

Schreiber H, Stolz-Born G, Rothmeier J, Kornhuber A, Kornhuber HH, Born J. Endogenous event-related brain potentials and psychometric performance in children at risk for schizophrenia. Biol Psychiatry. 1991 Jul 15;30(2):177-89. | CrossRef | PubMed |

Surwillo WW. Cortical evoked potentials in monozygotic twins and unrelated subjects: comparisons of exogenous and endogenous components. Behav Genet. 1980 Mar;10(2):201-9. | PubMed |

Phillips NA, Chertkow H, Leblanc MM, Pim H, Murtha S. Functional and anatomical memory indices in patients with or at risk for Alzheimer's disease. J Int Neuropsychol Soc. 2004 Mar;10(2):200-10. | CrossRef | PubMed |

Polich J, Pollock VE, Bloom FE. Meta-analysis of P300 amplitude from males at risk for alcoholism. Psychol Bull. 1994 Jan;115(1):55-73. | CrossRef |

Rao KM, Ananthnarayanan CV, Gangadhar BN, Janakiramaiah N. Smaller auditory P300 amplitude in schizophrenics in remission. Neuropsychobiology. 1995;32(3):171-4. | PubMed |

Guerra S, Iglesias J, Matín M, Bravo TM, Mendoza R, Reyes A, et al. Redes neurales de la atención en pacientes con esquizofrenia y sus familiares no afectados de primer grado: un endofenotipo potencial. Actas Esp. Psiquiatr. 2011;39(1):32-44. | Link |

Martín-Reyes M, Mendoza R, Domínguez M, Caballero A, Bravo TM, Díaz T, et al. Depressive symptoms evaluated by the Calgary Depression Scale for Schizophrenia (CDSS): genetic vulnerability and sex effects. Psychiatry Res. 2011 Aug 30;189(1):55-61. | CrossRef | PubMed |

Sponheim SR, McGuire KA, Stanwyck JJ. Neural anomalies during sustained attention in first-degree biological relatives of schizophrenia patients. Biol Psychiatry. 2006 Aug 1;60(3):242-52. | CrossRef | PubMed |

Mendoza R, Cabral-Calderin Y, Domínguez M, Garcia A, Borrego M, Caballero A, et al. Impairment of emotional expression recognition in schizophrenia: a Cuban familial association study. Psychiatry Res. 2011 Jan 30;185(1-2):44-8. | CrossRef | PubMed |