Processing Speed as an Endophenotypic Marker of Paranoid Schizophrenia

Ivanka I. Veleva 1 , Maya J. Stoimenova 1 , Petranka G. Chumpalova 1 , Kaloyan R. Stoychev 1 , Lyudmil Z. Tumbev 1 , and Mirena P. Valkova 2 , 3
  • 1 Department of Psychiatry and Medical Psychology, Medical University, Pleven, Bulgaria
  • 2 Clinic of Neurology, Softamed University Hospital, Softa, Bulgaria
  • 3 Department of Psychology, St. St Cyril and Methodius University, Veliko Tarnovo, Bulgaria


Schizophrenia is associated with basic neurocognitive deficit- ineffective space-time information assessment, leading to ineffective judgment and planning of behaviour. Our study aimed to examine and compare the psychomotor speed and number of errors in patients with paranoid schizophrenia (PS), first-degree relatives (FDR) and healthy controls (HC). One-hundred-eight patients with PS, 58 with FDR and 60 HCs were examined via Trail Making Tests (TMT) A and B. The influence of other additional factors as The Positive and Negative Syndrome Scale (PANSS), demographics and education were additionally assessed for PS. Statistical analysis was done using Excel 2010, Statgraphics 5.0+ and SPSS 20. All results were interpreted at 95% confidential level. PS showed most unsatisfactory performances on TMT A and B, as compared to others (p=0.0001). However, FDR differed from HC only in TMTB performance (p=0.0241). The most significant impact in PS group included ageing, education, PANSS and negative syndromes, and syndromes of disorganization. PS showed a significant decline of psychomotor speed and executive functioning, although FDR had average results in TMTB, compared to PS and HC. The above results determined both detentions as endophenotype markers for PS. Additional risk factors for decline include ageing, low education and high PANSS results.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Faustman WO, Ficek SF. Symptom Clusters in Schizophrenia. In: Csernansky JG, editor. Schizophrenia. A New Guide for Clinicians. New York: Marcel Dekker; 2001. p. 29-52.

  • 2. Hoff A. Cognitive assessment in schizophrenia patients. In: Csernansky JG, editor. Schizophrenia. A New Guide for Clinicians. New York: Marcel Dekker; 2001. p. 69-88.

  • 3. Talreja BT, Shah S, Kataria L. Cognitive function in schizophrenia and its association with socio-demographic factors. Ind Psychiatry J. 2013;22(1):47-53

  • 4. Lebedeva GG, Isaeva ER.[Profiles of cognitive deficits in paranoid schizophrenia and schizotypal disorder]. Clinical Psychology and Special Education 2017;6(1):79-94. [Russian].

  • 5. Dickinson D. Digit symbol coding and general cognitive ability in schizophrenia: worth another look? Br. J. Psychiatry. 2008;193(5):354-6.

  • 6. Keefe RS, Fenton WS. How should DSM-V criteria for schizophrenia include cognitive impairment? Schizophr Bull. 2007;33(4):912-20.

  • 7. Cuesta M, Moreno-Izco L, Ribeiro M, López- Ilundain J, Lecumberri P, Cabada T, et al. Motor abnormalities and cognitive impairment in first- episode psychosis patients, their unaffected siblings and healthy controls. Schizophr Res. 2018;200:50-5.

  • 8. Erlenmeyer-Kimling L. Neurobehavioral deficits in offspring of schizophrenic parents: liability indicators and predictors of illness. Am J Med Genet. 2000;97(1):65-71.

  • 9. Martins I, Vieira R, Loureiro C, Santos M. Speech rate and fluency in children and adolescents. Child Neuropsychol. 2007;13(4): 319-32.

  • 10. Green M. Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. J Clin Psychiatry. 2006;67(9):3-8;36-42

  • 11. Keefe RS., Harvey PD. Cognitive impairment in schizophrenia. Handb Exp Pharmacol. 2012;(213):11-37.

  • 12. Kalkstein S, Hurford I., Gur R. C. Neurocognition in schizophrenia. Curr Top Behav Neurosci. 2010;(4):373-90.

  • 13. Lezak M, Howieson D, Loring D, Hannay H, Fischer J: Neuropsychological assessment. 4thed. Oxford: Oxford University Press; 2004.

  • 14. Oldfield R. The assessment and analysis of handedness: The Edinburgh inventory. Neuropsychologia.1971;9(1):97-113.

  • 15. Kay S, Fiszbein A, Opler L. Positive and negative syndrome scale (PANSS). MHS, 2012. [cited . . . ]. Available from:

  • 16. Guy W. The Clinical Global Impression Scale. In: Guy W. ECDEU Assessment Manual for Psychopharmacology. Revised ed. Rockville, MD: US Dept. of Health, Education and Welfare, ADAMHA, MIMH Psychopharmacology Research Branch;1976. p. 218-22

  • 17. Keefe RS, Silverman JM, Roitman SE, Harvey PD, Duncan MA, Alroy D, et al. Performance of nonpsychotic relatives of schizophrenic patients on cognitive tests. Psychiatry Res. 1994;53:1-12.

  • 18. Bhatia T, Garg K, Pogue-Geile M, Nimgaonkar VL, Deshpande SN. Executive functions and cognitive deficits in schizophrenia: Comparisons between probands, parents and controls in India. J Postgrad Med. 2009;55:3-7.

  • 19. Klemm S, Schmidt B, Knappe S, Blanz B. Impaired working speed and frontal lobe dysfunctions in young first-degree relatives of schizophrenic patients. Eur Child Adolesc Psychiatry. 2006;15(7):400-8.

  • 20. Ashendorf L, Jefferson A, O’Connor MK, Chaisson Ch, Green R, Stern RA. Trail Making Test errors in healthy ageing, mild cognitive impairment, and dementia. Arch Clin Neuropsychol. 2008;23(2):29-37.

  • 21. Giovagnoli AR, Del Pesce M, Mascheroni S, Simoncelli M, Laiacona M, Capitani E. Trail making test: Normative values from 287 normal adult controls. Ital J Neurol Sci 1996;17:305-9.

  • 22. Kaneko K. Negative Symptoms and Cognitive Impairments in Schizophrenia: Two Key Symptoms Negatively Influencing Social Functioning; Yonago Acta Med. 2018;61(2):91-100.

  • 23. Rosso M, Murray R., Reichenberg A. Cognitive impairment in schizophrenia and symptom dimensions in psychosis. In: Harvey P, ed. Cognitive impairment in schizophrenia : characteristics, assessment, and treatment. Cambridge :Cambridge University Press; 2013. p. 9-78.

  • 24. Mahurin RK, Velligan DI, Hazleton B, Davis JM, Eckert S, Miller AL. Trail Making Test errors and executive function in schizophrenia and depression. Clin Neuropsychol. 2006;20(2): 71-88.

  • 25. Kopp B, Rösser N, Tabeling S, Sturenburg HJ, Haan de B, Karnath H-O, et al. Errors on the trail making test are associated with right hemispheric frontal lobe damage in stroke patients. Behav Neurol. 2015;2015: Article ID 309235. [cited .]. Available from:

  • 26. Stuss, DT, Levine B. Adult clinical neuropsychology: lessons from studies of the frontal lobes. Annu Rev Psychol. 2002;53(1):401-33.

  • 27. Fujiki R, Morita K, Sato M, Kamada Y. Reduced prefrontal cortex activation using the Trail Making Test in schizophrenia. Neuropsychiatr Dis Treat. 2013;9:675-85.

  • 28. Walter H, Wunderlich AP, Blankenhorn M, Schäfer S, Tomczak R, Spitzer M, et al. No hypofrontality, but the absence of prefrontal lateralization comparing verbal and spatial working memory in schizophrenia. Schizophr Res. 2003;61(2-3):175-84.

  • 29. Carter CS, Perlstein W, Ganguli R, Brar J, Mintun M, Cohen JD. Functional hypofrontality and working memory dysfunction in schizophrenia. Am J Psychiatry. 1998;155(9):1285-1287.

  • 30. Manoach DS. Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophr Res. 2003;60(2-3):285-98.

  • 31. Horacek J, Dockery C, Kopecek M, Spaniel F, Novak T, Tislerova B, et al. Regional brain metabolism as the predictor of performance on the Trail Making Test in schizophrenia. An 18 FDG PET covariation study. Neuro Endocrinol Lett. 2006;27(5):587-94.

  • 32. Müller LD, Guhn A, Zeller JB, Biehl SC, Dresler T, Hahn T. Neural correlates of a standardized versionofthetrailmakingtestinyoungandelderly adults: a functional near-infrared spectroscopy study. Neuropsychologia.2014;56:271-9.

  • 33. Laurent A, Biloa-Tang M, Bougerol T, Duly D, Anchisi AM, Bosson JL, et al. Executive/attentional performance and measures of schizotypy in patients with schizophrenia and in their nonpsychotic first-degree relatives. Schizophr Res. 2000;46(2-3):269-83.

  • 34. Wolwer W, Gabel W. Impaired Trail- Making Test-B performance in patients with acute schizophrenia is related to inefficient sequencing of planning and acting. J Psychiatr Res. 2002;36(6):407.

  • 35. Dollfus S, Lombardo C, B nali K, Halbecq I, Abadie P, Mari RM, et al. Executive/attentional cognitive functions in schizophrenic patients and their parents: Apreliminary study. Schizophr Res. 2002;53:93-9.

  • 36. Gur RE, Nimgaonkar VL, Almasy L, Calkins ME, Ragland JD, Pogue-Geile MF, et al. Neurocognitive endophenotypes in a multiplex multigenerational family study of schizophrenia. Am J Psychiatry 2007;164:813-9.

  • 37. Keefe RS, Silverman JM, Mohs RC, Siever LJ, Harvey PD, Friedman L, et al. Eye tracking, attention, and schizotypal symptoms in nonpsychotic relatives of patients with schizophrenia. Arch Gen Psychiatry 1997;54:169-76.

  • 38. Egan MF, Goldberg TE, Gscheidle T, Weirich M, Rawlings R, Hyde TM Relative risk for cognitive impairments in siblings of 11patients with schizophrenia. Biol Psychiatry 2000;50:98-100.

  • 39. Zalla T, Joyce C, Szöke A, Schürhoff F, Pillon B, Komano O et al. Dysfunctions as potential markers of familial vulnerability to bipolar disorder and schizophrenia. Psychiatry Res. 2004;121(3):207-17.

  • 40. Rybakowski JK, Borkowska A. Eye movement and neuropsychological studies in first-degree relatives of schizophrenic patients. Schizophr Res. 2002;54:105-10.

  • 41. Drane DL, Yuspeh, RL, Huthwaite JS, Klingler LK. Demographic characteristics and normative observations for derived-trail making test indices. Neuropsychiatry Neuropsychol Behav Neurol. 2002;15:39-43.

  • 42. Tombaugh TN. Trail Making Test A and B: Normative data stratified by age and education. Arch Clin Neuropsychol. 2004;19:203-14.

  • 43. Hashimoto R, Meguro K, Lee E, Kasai M, Ishii, H, Yamaguchi S Effect of age and education on the Trail Making Test and determination of normative data for Japanese elderly people: The Tajiri Project. Psychiatry Clin Neurosci. 2006;60:422-8.

  • 44. Hester RL, Kinsella GJ, Ong B, McGregor J. Demographic influences on the baseline and derived scores from the trail making test in healthy older Australian adults. Clin Neuropsychol. 2005;19:45-54.

  • 45. Perianez -JA, Rıos-Lago M, Rodrıguez- Sanchez JM, Adrover-Roig D, Sanchez- Cubillo I, Crespo-Facorro BE Trail Making Test in traumatic brain injury, schizophrenia, and normal ageing: Sample comparisons and normative data. Arch Clin Neuropsychol. 2007;22(4):433-47.

  • 46. Bilder RM, Goldman RS, Robinson D, Reiter G, Bell L, Bates J et al. Neuropsychology of first- episode schizophrenia: initial characterization and clinical correlates. Am. J. Psychiatry. 2000;157(4):549-59.


Journal + Issues