Am J Psychiatry 160:709-719, April 2003
© 2003 American Psychiatric Association
Abnormal fMRI Response of the Dorsolateral Prefrontal Cortex in Cognitively Intact Siblings of Patients With Schizophrenia
Joseph H. Callicott, M.D.,
Michael F. Egan, M.D.,
Venkata S. Mattay, M.D.,
Alessandro Bertolino, M.D.,
Ashley D. Bone, B.S.,
Beth Verchinksi, B.S., and
Daniel R. Weinberger, M.D.
OBJECTIVE: The identification of neurobiological intermediate phenotypes may hasten the search for susceptibility genes in complex psychiatric disorders such as schizophrenia. Earlier family studies have suggested that deficits in executive cognition and working memory may be related to genetic susceptibility for schizophrenia, but the biological basis for this behavioral phenotype has not been identified. METHOD: The authors used functional magnetic resonance imaging (fMRI) during performance of the N-back working memory task to assess working memory-related cortical physiology in nonschizophrenic, cognitively intact siblings of patients with schizophrenia. They compared 23 unaffected siblings of schizophrenic patients to 18 matched comparison subjects. As a planned replication, they studied another 25 unaffected siblings and 15 comparison subjects. RESULTS: In both cohorts, there were no group differences in working memory performance. Nevertheless, both groups of siblings showed an exaggerated physiological response in the right dorsolateral prefrontal cortex that was qualitatively similar to results of earlier fMRI studies of patients with schizophrenia. CONCLUSIONS: These fMRI data provide direct evidence of a primary physiological abnormality in dorsolateral prefrontal cortex function in individuals at greater genetic risk for schizophrenia, even in the absence of a manifest cognitive abnormality. This exaggerated fMRI response implicates inefficient processing of memory information at the level of intrinsic prefrontal circuitry, similar to earlier findings in patients with schizophrenia. These data predict that inheritance of alleles that contribute to inefficient prefrontal information processing will increase risk for schizophrenia.
This article has been cited by other articles:
|
|
|
|
 
A. W. MacDonald III, H. W. Thermenos, D. M. Barch, and L. J. Seidman
Imaging Genetic Liability to Schizophrenia: Systematic Review of fMRI Studies of Patients' Nonpsychotic Relatives
Schizophr Bull,
November 1, 2009;
35(6):
1142 - 1162.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. Bassett, E. T. Bullmore, A. Meyer-Lindenberg, J. A. Apud, D. R. Weinberger, and R. Coppola
Cognitive fitness of cost-efficient brain functional networks
PNAS,
July 14, 2009;
106(28):
11747 - 11752.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Goldman, L. Pezawas, V. S. Mattay, B. Fischl, B. A. Verchinski, Q. Chen, D. R. Weinberger, and A. Meyer-Lindenberg
Widespread Reductions of Cortical Thickness in Schizophrenia and Spectrum Disorders and Evidence of Heritability
Arch Gen Psychiatry,
May 1, 2009;
66(5):
467 - 477.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Rasetti, V. S. Mattay, L. M. Wiedholz, B. S. Kolachana, A. R. Hariri, J. H. Callicott, A. Meyer-Lindenberg, and D. R. Weinberger
Evidence That Altered Amygdala Activity in Schizophrenia Is Related to Clinical State and Not Genetic Risk
Am J Psychiatry,
February 1, 2009;
166(2):
216 - 225.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Potkin, J. A. Turner, G. Guffanti, A. Lakatos, J. H. Fallon, D. D. Nguyen, D. Mathalon, J. Ford, J. Lauriello, F. Macciardi, et al.
A Genome-Wide Association Study of Schizophrenia Using Brain Activation as a Quantitative Phenotype
Schizophr Bull,
January 1, 2009;
35(1):
96 - 108.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Potkin, J. A. Turner, G. G. Brown, G. McCarthy, D. N. Greve, G. H. Glover, D. S. Manoach, A. Belger, M. Diaz, C. G. Wible, et al.
Working memory and DLPFC inefficiency in schizophrenia: The FBIRN study
Schizophr Bull,
January 1, 2009;
35(1):
19 - 31.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Broome, P. Matthiasson, P. Fusar-Poli, J. B. Woolley, L. C. Johns, P. Tabraham, E. Bramon, L. Valmaggia, S. C. R. Williams, M. J. Brammer, et al.
Neural correlates of executive function and working memory in the 'at-risk mental state'
The British Journal of Psychiatry,
January 1, 2009;
194(1):
25 - 33.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ikeda, T. Hikita, S. Taya, J. Uraguchi-Asaki, K. Toyo-oka, A. Wynshaw-Boris, H. Ujike, T. Inada, K. Takao, T. Miyakawa, et al.
Identification of YWHAE, a gene encoding 14-3-3epsilon, as a possible susceptibility gene for schizophrenia
Hum. Mol. Genet.,
October 15, 2008;
17(20):
3212 - 3222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. K. Phillips and L. J. Seidman
Emotion Processing in Persons at Risk for Schizophrenia
Schizophr Bull,
September 1, 2008;
34(5):
888 - 903.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Lawrie, A. M. McIntosh, J. Hall, D. G.C. Owens, and E. C. Johnstone
Brain Structure and Function Changes During the Development of Schizophrenia: The Evidence From Studies of Subjects at Increased Genetic Risk
Schizophr Bull,
March 1, 2008;
34(2):
330 - 340.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. Harms, L. Wang, D. Mamah, D. M. Barch, P. A. Thompson, and J. G. Csernansky
Thalamic Shape Abnormalities in Individuals with Schizophrenia and Their Nonpsychotic Siblings
J. Neurosci.,
December 12, 2007;
27(50):
13835 - 13842.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Haenschel, R. A. Bittner, F. Haertling, A. Rotarska-Jagiela, K. Maurer, W. Singer, and D. E. J. Linden
Contribution of Impaired Early-Stage Visual Processing to Working Memory Dysfunction in Adolescents With Schizophrenia: A Study With Event-Related Potentials and Functional Magnetic Resonance Imaging
Arch Gen Psychiatry,
November 1, 2007;
64(11):
1229 - 1240.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-Y. Tan, J. H. Callicott, and D. R. Weinberger
Dysfunctional and Compensatory Prefrontal Cortical Systems, Genes and the Pathogenesis of Schizophrenia
Cereb Cortex,
September 1, 2007;
17(suppl_1):
i171 - i181.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. W. Buckholtz, A. Meyer-Lindenberg, R. A. Honea, R. E. Straub, L. Pezawas, M. F. Egan, R. Vakkalanka, B. Kolachana, B. A. Verchinski, S. Sust, et al.
Allelic Variation in RGS4 Impacts Functional and Structural Connectivity in the Human Brain
J. Neurosci.,
February 14, 2007;
27(7):
1584 - 1593.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. E. Gur, M. E. Calkins, R. C. Gur, W. P. Horan, K. H. Nuechterlein, L. J. Seidman, and W. S. Stone
The Consortium on the Genetics of Schizophrenia: Neurocognitive Endophenotypes
Schizophr Bull,
January 1, 2007;
33(1):
49 - 68.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Prathikanti and D. R. Weinberger
Psychiatric genetics - the new era: genetic research and some clinical implications
Br. Med. Bull.,
December 19, 2005;
73-74(1):
107 - 122.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. SPENCE, R. D. GREEN, I. D. WILKINSON, and M. D. HUNTER
Modafinil modulates anterior cingulate function in chronic schizophrenia
The British Journal of Psychiatry,
July 1, 2005;
187(1):
55 - 61.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. H. Callicott, R. E. Straub, L. Pezawas, M. F. Egan, V. S. Mattay, A. R. Hariri, B. A. Verchinski, A. Meyer-Lindenberg, R. Balkissoon, B. Kolachana, et al.
Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia
PNAS,
June 14, 2005;
102(24):
8627 - 8632.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. C. Whalley, M.-C. Whyte, E. C. Johnstone, and S. M. Lawrie
Neural Correlates of Enhanced Genetic Risk for Schizophrenia
Neuroscientist,
June 1, 2005;
11(3):
238 - 249.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. W. L. Chee, C. S. Soon, H. L. Lee, and C. Pallier
Left insula activation: A marker for language attainment in bilinguals
PNAS,
October 19, 2004;
101(42):
15265 - 15270.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. F. Egan, R. E. Straub, T. E. Goldberg, I. Yakub, J. H. Callicott, A. R. Hariri, V. S. Mattay, A. Bertolino, T. M. Hyde, C. Shannon-Weickert, et al.
Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia
PNAS,
August 24, 2004;
101(34):
12604 - 12609.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. C. Whalley, E. Simonotto, S. Flett, I. Marshall, K. P. Ebmeier, D. G. C. Owens, N. H. Goddard, E. C. Johnstone, and S. M. Lawrie
fMRI correlates of state and trait effects in subjects at genetically enhanced risk of schizophrenia
Brain,
March 1, 2004;
127(3):
478 - 490.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. I. Gottesman and T. D. Gould
The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions
Am J Psychiatry,
April 1, 2003;
160(4):
636 - 645.
[Abstract]
[Full Text]
[PDF]
|
|
|
Get information about faster international access.
Privacy Policy
Copyright © 2003
American Psychiatric Association.
All rights reserved.
Home
| Search
| Current Issue
| Past Issues
| Subscribe
| All APPI Journals
| Help
| Contact Us
|
