Background
Prospective studies of young individuals at high risk of schizophrenia allow the investigation
of whether neural abnormalities predate development of illness and, if present, have
the potential to identify those who may become ill.
Methods
We studied young individuals with at least two relatives with the disorder. At baseline
functional magnetic resonance imaging (fMRI) scan, none met criteria for any psychiatric
disorder, but four subjects subsequently developed schizophrenia. We report the baseline
functional imaging findings in these subjects performing a sentence completion task
compared with normal control subjects (n = 21) and those at high risk with (n = 21) and without (n = 41) psychotic symptoms who have not developed the disorder.
Results
High-risk subjects who became ill demonstrated increased activation of the parietal
lobe, decreased activation of the anterior cingulate, and smaller increases in activation
with increasing task difficulty in the right lingual gyrus and bilateral temporal
regions. The hypothesized predictive power of parietal activation was supported only
in combination with lingual gyrus activity, which gave a positive predictive value
in this sample of .80.
Conclusions
Although these findings should be considered cautiously, as only four subjects who
had an fMRI scan subsequently became ill, they suggest functional abnormalities are
present in high-risk subjects who later became ill, which distinguish them not only
from normal control subjects but also those at high risk who had not developed the
disorder. These differences are detectable with fMRI and may have clinical utility.
Key Words
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References
- A comment on the functional localization of the phonological storage subsystem of working memory.Brain Cogn. 1999; 41: 27-38
- Altered cerebral perfusion measured by SPECT in relatives of patients with schizophrenia.Br J Psychiatry. 1999; 175: 357-366
- Completion norms for 329 sentence contexts.Mem Cognit. 1980; 8: 631-642
- How good is good enough in path analysis of fMRI data?.Neuroimage. 2000; 11: 289-301
- The Hayling and Brixton Tests. Thames Valley Test Company Limited, Bury St. Edmunds, UK1997
- Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia.Am J Psychiatry. 2003; 160: 709-719
- The early symptoms of schizophrenia.Br J Psychiatry. 1966; 112: 225-251
- The functional anatomy of inhibition processes investigated with the Hayling task.Neuroimage. 2001; 14: 258-267
- Modern molecular genetic approaches to psychiatric disease.Br Med Bull. 1996; 52: 434-452
- Neuroimaging of cognitive functions in human parietal cortex.Curr Opin Neurobiol. 2001; 11: 157-163
- Attenutated frontal activation during a verbal fluency task in patients with schizophrenia.Am J Psychiatry. 1998; 155: 1056-1063
- Attention, memory, and motor skills as childhood predictors of schizophrenia-related psychoses.Am J Psychiatry. 2000; 157: 1416-1422
- Functional neuroimaging of schizophrenia.Brain. 2004; 127: 457-459
- Brain activations in schizophrenia during a graded memory task studied with functional neuroimaging.Arch Gen Psychiatry. 1998; 55: 1001-1008
- Cerebral blood flow changes associated with Schneiderian first-rank symptoms in schizophrenia.J Neuropsychiatry Clin Neurosci. 2002; 14: 277-282
- Regional brain activity in chronic schizophrenic patients during the performance of a verbal fluency task.Br J Psychiatry. 1995; 167: 343-349
- Subjective and objective neuropsychological abnormalities in a psychosis prodrome clinic.Br J Psychiatry Suppl. 2002; 43: s30-s37
- People at risk of schizophrenia. Sample characteristics of the first 100 cases in the Edinburgh high-risk study.Br J Psychiatry. 1999; 174: 547-553
- Edinburgh high risk study–findings after four years.Schizophr Res. 2000; 46: 1-15
- Phenomenology of organic and functional psychoses and the overlap between them.Br J Psychiatry. 1988; 153: 770-776
- Predicting schizophrenia–findings from the Edinburgh High Risk Study.Br J Psychiatry. 2005; 186: 18-25
- What does the Edinburgh High-Risk Study tell us about schizophrenia.Am J Med Genet. 2002; 114: 906-912
- A preliminary functional magnetic resonance imaging study in offspring of schizophrenic parents.Prog Neuropsychopharmacol Biol Psychiatry. 2002; 26: 1143-1149
- Differential activation of temporal cortex during sentence completion in schizophrenic patients with and without formal thought disorder.Schizophr Res. 2001; 50: 27-40
- Diagnosing schizopohrenia in the initial prodromal phase.Arch Gen Psychiatry. 2001; 58: 158-164
- Early self-experienced neuropsychological deficits and subsequent schizophrenic diseases.Acta Psychiatr Scand. 1997; 95: 396-404
- Brain abnormality in schizophrenia. A systematic and quantitative review of volumetric magnetic resonance imaging studies.Br J Psychiatry. 1998; 172: 110-120
- Reduced frontotemporal functional connectivity in schizophrenia associated with auditory hallucinations.Biol Psychiatry. 2002; 51: 1008-1011
- Distributed disturbances in brain structure and function in schizophrenia.Am J Psychiatry. 2000; 157: 1-2
- Basic principles of ROC analysis.Semin Nucl Med. 1978; 8: 283-298
- The functional anatomy of verbal initiation and suppression using the Hayling Test.Neuropsychologia. 1997; 35: 559-566
- The role of the dorsolateral prefrontal cortex.Neuroimage. 2002; 16: 1094-1102
- Neural correlates of eye tracking deficits in first-degree relatives of schizophrenic patients.Arch Gen Psychiatry. 1999; 56: 1127-1134
- Pathogenesis of schizophrenia.Br J Psychiatry. 2005; 186: 386-393
- Activation of extrastriate and frontal cortical areas by visual words and word-like stimuli.Science. 1990; 249: 1041-1044
- A review of MRI findings in schizophrenia.Schizophr Res. 2001; 49: 1-52
- Language activation in monozygotic twins discordant for schizophrenia.Br J Psychiatry. 2004; 184: 128-135
- A PET study of voluntary movement in schizophrenic patients experiencing passivity phenomena (delusions of alien control).Brain. 1997; 120: 1997-2011
- Functional anatomy of verbal fluency in people with schizophrenia and those at genetic risk. Focal dysfunction and distributed disconnectivity reappraised.Br J Psychiatry. 2000; 176: 52-60
- Functional magnetic resonance imaging during auditory verbal working memory in nonpsychotic relatives of persons with schizophrenia.Biol Psychiatry. 2004; 55: 490-500
- Neural correlates of outcome after stroke.Brain. 2003; 126: 1430-1448
- fMRI correlates of state and trait effects in subjects at genetically enhanced risk of schizophrenia.Brain. 2004; 127: 478-490
- The Description and Classification of Psychiatric Symptoms. An Instruction Manual for the PSE and Catego Systems. Cambridge University Press, Cambridge, UK1974
- ICD-10: The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. World Health Organisation, Geneva1993
- Receiver-operating characteristic (ROC) plots.Clin Chem. 1993; 39: 561-577
Article info
Publication history
Published online: February 06, 2006
Accepted:
November 3,
2005
Received in revised form:
October 19,
2005
Received:
April 12,
2005
Identification
Copyright
© 2006 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
