Neural Correlates of Eye Tracking Deficits in First-degree Relatives of Schizophrenic Patients

O’Driscoll, Gillian A.; Benkelfat, Chawki; Florencio, Patrik S.; Wolff, Anne-Lise V. G.; Joober, Ridha; Lal, Samarthji; Evans, Alan C.

doi:10.1001/archpsyc.56.12.1127

Cited by 69 publications

(35 citation statements)

References 66 publications

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“…However, it has been reported that smooth pursuit quality (measured by pursuit gain or catch-up saccade rate) is significantly associated with measures of frontal structural integrity (Bagary et al, 2004) and frontal activation in schizophrenic patients (Ross et al, 1995;Hong et al, 2005;Keedy et al, 2006) and unaffected relatives (O'Driscoll et al, 1999). Although the PhysAn group did tend towards poorer pursuit gain, the small number of subjects made these results insignificant here.…”

Section: Discussionmentioning

confidence: 58%

“…Eye movements were monitored using an Eyelink infrared video-based tracking system (SR Research, Mississauga, Canada) and data were analyzed with custom software (Holahan and O'Driscoll, 2005). The dependent measure was peak pursuit gain, a measure previously found to be correlated with frontal activation (O'Driscoll et al, 1999) and frontal structural integrity (Bagary et al, 2004). Pursuit gain was compared across groups with a one-way ANOVA.…”

Section: Psychological and Physiological Measuresmentioning

confidence: 99%

“…We hypothesized that schizotypal individuals would show greater striatal DA responses than control subjects. Finally, because theoretical models have linked DA release with frontal lobe dysfunction in schizophrenia (Davis et al, 1991), smooth pursuit eye movements were measured as an index of frontal lobe function (O'Driscoll et al, 1999;Bagary et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Stress-Induced Dopamine Release in Humans at Risk of Psychosis: a [11C]Raclopride PET Study

Soliman

O’Driscoll

Pruessner

et al. 2007

Neuropsychopharmacol

133

109

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Drugs that increase dopamine levels in the brain can cause psychotic symptoms in healthy individuals and worsen them in schizophrenic patients. Psychological stress also increases dopamine release and is thought to play a role in susceptibility to psychotic illness. We hypothesized that healthy individuals at elevated risk of developing psychosis would show greater striatal dopamine release than controls in response to stress. Using positron emission tomography and [ 11 C]raclopride, we measured changes in synaptic dopamine concentrations in 10 controls and 16 psychometric schizotypes; 9 with perceptual aberrations (PerAb, ie positive schizotypy) and 7 with physical anhedonia (PhysAn, ie negative schizotypy). [ 11 C]Raclopride binding potential was measured during a psychological stress task and a sensory-motor control. All three groups showed significant increases in self-reported stress and cortisol levels between the stress and control conditions. However, only the PhysAn group showed significant stress-induced dopamine release. Dopamine release in the entire sample was significantly negatively correlated with smooth pursuit gain, an endophenotype linked to frontal lobe function. Our findings suggest the presence of abnormalities in the dopamine response to stress in negative symptom schizotypy, and provide indirect evidence of a link to frontal function.

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Section: Discussionmentioning

confidence: 58%

Section: Psychological and Physiological Measuresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Stress-Induced Dopamine Release in Humans at Risk of Psychosis: a [11C]Raclopride PET Study

Soliman

O’Driscoll

Pruessner

et al. 2007

Neuropsychopharmacol

133

109

View full text Add to dashboard Cite

show abstract

“…While eye-tracking deficits may involve frontal lobe function, 43 other measures of prefrontal function (eg working memory subscales of the WISC, eg digit span) did not show association. While most of the SNPs tested revealed a positive association with increased frontal gray matter volume loss on MRI over time, one SNP, M03, also showed a positive association with eye-tracking dysfunction and a measure of premorbid functioning, which covers areas such as school, social, speech, and motor delays and difficulties.…”

Section: Discussionmentioning

confidence: 71%

GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss

Addington¹,

Gornick²,

et al. 2004

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Postmortem brain studies have shown deficits in the cortical c-aminobutyric acid (GABA) system in schizophrenic individuals. Expression studies have shown a decrease in the major GABA-synthesizing enzyme (glutamic acid decarboxylase (GAD 67 ) mRNA levels in neurons in dorsolateral prefrontal cortex in schizophrenics relative to controls. In the present study, SNPs in and around the GAD1 gene, which encodes the protein GAD 67 , were tested on a rare, severely ill group of children and adolescents with childhood-onset schizophrenia (COS) (n ¼ 72), in a family-based association analysis. Compared to adult-onset samples, the COS sample has evidence for more salient familial, and perhaps genetic, risk factors for schizophrenia, as well as evidence for frontal cortical hypofunction, and greater decline in cortical gray matter volume on anatomic brain MRI scans during adolescence. We performed family-based TDT and haplotype association analyses of the clinical phenotype, as well as association analyses with endophenotypes using the QTDT program. Three adjacent SNPs in the 5 0 upstream region of GAD1 showed a positive pairwise association with illness in these families (P ¼ 0.022-0.057). Significant transmission distortion of 4-SNP haplotypes was also observed (P ¼ 0.003-0.008). Quantitative trait TDT analyses showed an intriguing association between several SNPs and increased rate of frontal gray matter loss. These observations, when taken together with the positive results reported recently in two independent adult-onset schizophrenia pedigree samples, suggest that the gene encoding GAD 67 may be a common risk factor for schizophrenia. Molecular Psychiatry (2005) 10, 581-588.

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“…In a preliminary study, the authors have observed reduced activation in prefrontal brain regions in HR adolescents during a spatial working memory task [50]. Preliminary fMRI studies have shown that performance on these tasks of eye-movement control and working memory in these subjects result in aberrant fMRI-measured activation in the frontal and parietal regions of the brain [51] and the frontal eye fields, which are thought to regulate eye movement control [52]. Studies have shown that the response of the prefrontal cortex in adult relatives is similarly inefficient to increases in working memory demands [49], providing a measure of convergence with fMRI results of child and adolescent relatives.…”

Section: Functional Magnetic Resonance Imaging Studiesmentioning

confidence: 96%

Approaches for adolescents with an affected family member with schizophrenia

Diwadkar

Prasad²,

Keshavan

2004

Curr Psychiatry Rep

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Prospective studies of adolescents at risk for schizophrenia (high-risk studies) can shed light on the possible premorbid precursors of schizophrenia. Recent studies have provided evidence of neurobehavioral, brain structural, physiologic, and neurochemical deficits in adolescent nonpsychotic high-risk relatives that may date back to childhood or earlier. These results are collectively providing a critical window into the inter-relationships between genetic predisposition, neurodevelopment, and premorbid indicators of risk in schizophrenia. Convergent approaches are inherently powerful in mutually informing each other in enriching the knowledge of the risk factors that predict the eventual onset of schizophrenia. Defining such reliable predictors of the onset of schizophrenia may provide us with the tools to better understand the etiology and pathophysiology of the illness, and may pave the way for innovative methods of treatment and possibly prevention. The authors review the relevant literature in this promising field of inquiry and summarize recent findings from high-risk studies.

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Neural Correlates of Eye Tracking Deficits in First-degree Relatives of Schizophrenic Patients

Abstract: Subtle frontal dysfunction seems to be a pathophysiological substrate of ETD in relatives of schizophrenic patients, and may be one aspect of genetically mediated differences in brain function relevant to schizophrenia.

Cited by 69 publications

References 66 publications

Stress-Induced Dopamine Release in Humans at Risk of Psychosis: a [11C]Raclopride PET Study

Stress-Induced Dopamine Release in Humans at Risk of Psychosis: a [11C]Raclopride PET Study

GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss

Approaches for adolescents with an affected family member with schizophrenia

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