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Oculomotor Delayed Response Abnormalities in Young Offspring and Siblings at Risk for Schizophrenia

Published online by Cambridge University Press:  07 November 2014

Vaibhav A. Diwadkar ,
John A. Sweeney ,
Dawn Boarts ,
Debra M. Montrose  and
Matcheri S. Keshavan
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Abstract

Individuals with schizophrenia are known to demonstrate cognitive and behavioral difficulties, particularly alterations in executive functions, including working memory. It is unclear whether these deficits reflect trait-related vulnerability to schizophrenia indicators and can be assessed by studying nonpsychotic relatives of patients with schizophrenia. In this study, we used an oculomotor delayed response (ODR) paradigm to examine spatial working memory in 37 “high-risk” child and adolescent offspring and siblings (age range=6–25 years) of patients with schizophrenia or schizoaffective disorder. Compared with 37 age- and sex-matched healthy controls (age range=6–23 years), high-risk subjects showed nonsignificantly greater errors in the ODR task at longer delay intervals. Statistical analyses suggested that performance improved with age in healthy control subjects, whereas it worsened with age in high-risk subjects. In both groups, the ODR errors were generally associated with poorer sustained attention (Continuous Performance Test: visuospatial d prime), some-what poorer executive function (Wisconsin Card Sorting Test), and elevated Heinrichs-Buchanan neurological soft signs scores. These findings indicate the presence of spatial working memory abnormalities in individuals at risk for schizophrenia. Furthermore, these abnormalities may be progressive in nature. The ODR task is a valuable indicator of prefrontal cortical function and spatial working memory and may be a potentially valuable marker for familial risk of schizophrenia.

Type
Original Research
Information
CNS Spectrums , Volume 6 , Issue 11: Investigating and Treating Psychosis , November 2001 , pp. 899 - 903
Copyright
Copyright © Cambridge University Press 2001

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References

REFERENCES

1. Schultz, SK, Andreasen, NC. Schizophrenia. Lancet. 1999;353:1425–1430.CrossRefGoogle ScholarPubMed
2. Pearlson, GD, Marsh, L. Structural brain imaging in schizophrenia: a selective review. Biol Psychiatry. 1999;46:627–649.CrossRefGoogle ScholarPubMed
3. McCarley, RW, Wible, CG, Frumin, M, et al. MRI anatomy of schizophrenia. Biol Psychiatry. 1999;45:1099–1119.CrossRefGoogle ScholarPubMed
4. Weinberger, DR, Berman, KF, Zec, RF. Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia, I: regional cerebral blood flow (rCBF) evidence. Arch Gen Psychiatry. 1986;43:114–124.CrossRefGoogle ScholarPubMed
5. Andreasen, NC, O'Leary, DS, Flaum, M, et al. Hypofrontality in schizophrenia: distributed dysfunctional circuits in neuroleptic-naive patients. Lancet. 1997;349:1730–1734.CrossRefGoogle ScholarPubMed
6. Jonides, J, Smith, EE, Koeppe, RA, et al. Spatial working memory in humans as revealed by PET. Nature. 1993;363:623–625.CrossRefGoogle ScholarPubMed
7. Diwadkar, VA, Carpenter, PA, Just, MA. Collaborative activity between parietal and dorso-lateral prefrontal cortex in dynamic spatial working memory revealed by fMRI. Neuroimage. 2000;12:85–99.CrossRefGoogle ScholarPubMed
8. Luna, B, Thulborn, KR, Strojwas, MH, et al. Dorsal cortical regions subserving visually guided saccades in humans: an fMRI study. Cereb Cortex. 1998;8:40–47.CrossRefGoogle ScholarPubMed
9. Fuster, JM. The Prefrontal Cortex: Anatomy, Physiology, and Neuropsychology of the Frontal Lobe. 2nd ed. New York, NY: Raven Press; 1989.Google Scholar
10. Shallice, T. Specific impairments of planning. Philos Trans R Soc Land B Biol Sci. 1982;298:199–209.Google ScholarPubMed
11. Selemon, LD, Goldman-Rakic, PS. Common cortical and sub-cortical targets of the dorsolateral prefrontal and posterior parietal cortices in the rhesus monkey: evidence for a distributed neural network subserving spatially guided behavior. J Neurosci. 1988;8:4049–4068.CrossRefGoogle Scholar
12. Park, S, Holzman, PS. Schizophrenics show spatial working memory deficits. Arch Gen Psychiatry. 1992;49:975–982.CrossRefGoogle ScholarPubMed
13. Sweeney, J, Luna, B, Srinivasagam, N, et al. Eye tracking abnormalities in schizophrenia: evidence for dysfunction in the frontal eye fields. Biol Psychiatry. 1998;44:698–708.CrossRefGoogle ScholarPubMed
14. Gottesman, II, Shields, J. Schizophrenia: The Epigenetic Puzzle. New York, NY: Cambridge University Press; 1982.Google Scholar
15. Parnas, J, Cannon, TD, Jacobsen, B, et al. Lifetime DSM-III-R diagnostic outcomes in the offspring of schizophrenic mothers, results from the Copenhagen high-risk study. Arch Gen Psychiatry. 1993;50:707–714.CrossRefGoogle ScholarPubMed
16. Erlenmeyer-Kimling, L, Squires-Wheeler, E, Hilldoff-Adamo, UH, et al. The New York High-Risk Project. Psychoses and cluster A personality disorders in offspring of schizophrenic parents at 23 years of follow-up. Arch Gen Psychiatry. 1995;52:857–865.CrossRefGoogle Scholar
17. Amminger, GP, Pape, S, Rock, D, et al. Relationship between childhood behavioral disturbance and later schizophrenia in the New York High-Risk Project. Am J Psychiatry. 1999;156:525–530.CrossRefGoogle ScholarPubMed
18. Weinberger, DR. From neuropathology to neurodevelopment. Lancet. 1995;346:552–557.CrossRefGoogle ScholarPubMed
19. Murray, RM, Lewis, SW. Is schizophrenia a neurodevelopmental disorder? Br Med J (Clin Res Ed). 1987;295:681–682.CrossRefGoogle ScholarPubMed
20. Weinberger, DR. Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry. 1987;44:660–669.CrossRefGoogle ScholarPubMed
21. Cannon, TD, Marco, E. Structural brain abnormalities as indicators of vulnerability to schizophrenia [review]. Schizophr Bull. 1994;20:89–102.CrossRefGoogle ScholarPubMed
22. Murray, RM, Fearon, P. The developmental ‘risk factor’ model of schizophrenia. J Psychiatr Res. 1999;33:497–499.CrossRefGoogle ScholarPubMed
23. Cornblatt, B, Obuchowski, M, Roberts, S, Pollack, S, Erlenmeyer-Kimling, L. Cognitive and behavioral precursors of schizophrenia. Deo Psychopathol. 1999;11:487–508.CrossRefGoogle ScholarPubMed
24. Park, S, Holzman, PS, Goldman-Rakic, PS. Spatial working memory deficits in the relatives of schizophrenic patients. Arch Gen Psychiatry. 1995;52:821–828.CrossRefGoogle ScholarPubMed
25. Keshavan, MS, Anderson, S, Pettegrew, JW. Is schizophrenia due to excessive synaptic pruning in the prefrontal cortex? J Psychiatr Res. 1994;28:239–265.CrossRefGoogle ScholarPubMed
26. Funahashi, S, Bruce, CJ, Goldman-Rakic, PS. Dorsolateral prefrontal lesions and oculomotor delayed-response performance: evidence for mnemonic “scotomas”. J Neurosci. 1993;13:1479–1497.CrossRefGoogle ScholarPubMed
27. Sweeney, JA, Mintun, MA, Kwee, S, et al. Positron emission tomography study of voluntary saccadic eye movements and spatial working memory. J Neurophysiol. 1996;75:454–468.CrossRefGoogle ScholarPubMed
28. Sweeney, JA, Strojwas, MH, Mann, JJ, Thase, ME. Prefrontal and cerebellar abnormalities in major depression: evidence from oculomotor studies. Biol Psychiatry. 1998;43:584–594.CrossRefGoogle ScholarPubMed
29. Cornblatt, BA, Keilp, JG. Impaired attention, genetics, and the pathophysiology of schizophrenia. Schizophr Bull. 1994;20:31–46.CrossRefGoogle ScholarPubMed
30. Milner, B. Effects of different brain lesions on card sorting. Arch Neurol. 1963;9:90–100.CrossRefGoogle Scholar
31. Gooding, DC, Kwapil, TR, Tallent, KA. Wisconsin Card Sorting Test deficits in schizotypic individuals. Schizophr Res. 1999;40:201–209.CrossRefGoogle ScholarPubMed
32. Buchanan, RW, Heinrichs, DW. The Neurological Evaluation Scale (NES): a structured instrument for the assessment of neurological signs in schizophrenia. Psychiatry Res. 1989;27:335–350.CrossRefGoogle Scholar
33. Cohen, J, Cohen, P. Applied Multiple Regression/Correlation analysis for the Behavioral Sciences. 2nd ed. Hillsdale, NJ: Lawrence Erlbaum Associates; 1983.Google Scholar
34. Kraemer, HC, Yesavage, JA, Taylor, JL, Kupfer, D. How can we learn about developmental processes from cross-sectional studies, or can we? Am J Psychiatry. 2000;157:163–171.CrossRefGoogle ScholarPubMed
35. Keshavan, MS, Montrose, DM, Pierri, JN, et al. Magnetic resonance imaging and spectroscopy in offspring at risk for schizophrenia: preliminary studies. Prog Neuropsychopharmacol Biol Psychiatry. 1997;21:1285–1295.CrossRefGoogle ScholarPubMed