Structural and functional brain correlates of subclinical psychotic symptoms in 11–13 year old schoolchildren

Jacobson, Sarah; Kelleher, Ian; Harley, Michelle; Murtagh, Aileen; Clarke, Mary; Blanchard, Mathieu; Connolly, Colm G.; O’Hanlon, Erik; Garavan, Hugh; Cannon, Mary

doi:10.1016/j.neuroimage.2009.09.015

Cited by 131 publications

(139 citation statements)

References 74 publications

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“…[26][27][28] However, several studies have reported cortical thickness abnormalities among healthy individuals with high levels of schizotypy compared with low levels 29,30 that are broadly consistent with findings in SZ patient samples. 31 Additionally, diffusion tensor imaging (DTI) studies have provided complementary evidence for white matter alterations in psychometrically defined schizotypy similar to those observed in SZ, but these findings have also been inconsistent.…”

Section: Introductionsupporting

confidence: 64%

Evidence From Structural and Diffusion Tensor Imaging for Frontotemporal Deficits in Psychometric Schizotypy

DeRosse

Nitzburg

Ikuta

et al. 2014

Schizophrenia Bulletin

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Background: Previous studies of nonclinical samples exhibiting schizotypal traits have provided support for the existence of a continuous distribution of psychotic symptoms in the general population. Few studies, however, have examined the neural correlates of psychometric schizotypy using structural and diffusion tensor imaging (DTI). Methods: Healthy volunteers between the ages of 18 and 68 were recruited from the community and assessed using the Schizotypal Personality Questionnaire and received structural and DTI exams. Participants with high (N = 67) and low (N = 71) psychometric schizotypy were compared on gray and white matter volume, and cortical thickness in frontal and temporal lobe regions and on fractional anisotropy (FA) within 5 association tracts traversing the frontal and temporal lobes. Results: Higher levels of schizotypy were associated with lower overall volumes of gray matter in both the frontal and temporal lobes and lower gray matter thickness in the temporal lobe. Regionally specific effects were evident in both white matter and gray matter volume of the rostral middle frontal cortex and gray matter volume in the pars orbitalis. Moreover, relative to individuals who scored low, those who scored high in schizotypy had lower FA in the inferior fronto-occipital fasciculus as well as greater asymmetry (right > left) in the uncinate fasciculus. Conclusions: These findings are broadly consistent with recent data on the neurobiological correlates of psychometric schizotypy as well as findings in schizotypal personality disorder and schizophrenia and suggest that frontotemporal lobe dysfunction may represent a core component of the psychosis phenotype.

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Section: Introductionsupporting

confidence: 64%

Evidence From Structural and Diffusion Tensor Imaging for Frontotemporal Deficits in Psychometric Schizotypy

DeRosse

Nitzburg

Ikuta

et al. 2014

Schizophrenia Bulletin

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“…42 Our findings are consistent with those from a cross-sectional study of UHR youth who later transitioned to psychosis that reported reduced GM volume in the right STG relative to healthy controls but increased GM volume in the posterior portions of the left STG and MTG. 43 GM volume increases were also reported in the left STG and MTG in children aged 11-13 years presenting subclinical psychotic symptoms, 17 the only previous VBM study of children in a putative early at-risk phase.…”

Section: Discussionmentioning

confidence: 71%

“…43 In contrast, volume abnormalities in the right MTG were not observed in the study of children presenting subclinical psychotic symptoms. 17 ASz children were additionally characterized by increased WM volume in a cluster encompassing the left parietal, temporal, and occipital lobes, corresponding to parts of the superior longitudinal fasciculus, inferior longitudinal fasciculus, and optic radiation. Reduced WM volume in the inferior longitudinal fasciculus has been reported in first-episode patients, 4 while increased WM within this tract was observed in a study of patients with chronic schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

“…13,15,16 A study that examined brain structure in 11 putatively at-risk children aged 11-13 years who presented subclinical psychotic symptoms on clinical interview showed increased GM volume in the left STG and in the left middle temporal, left angular, and right orbitofrontal gyri relative to healthy children (n = 14) and GM decreases in the left inferior temporal gyrus. 17 WM abnormalities in the parietal and temporal lobes, including the inferior longitudinal fasciculus, were detected by diffusion tensor imaging. We have employed an alternative early identification strategy that might more specifically and sensitively identify putatively atrisk children by requiring the presence of multiple antecedents of schizophrenia (ASz) rather than a single risk factor.…”

Section: Introductionmentioning

confidence: 99%

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Temporal Lobe Volume Abnormalities Precede the Prodrome: A Study of Children Presenting Antecedents of Schizophrenia

Cullen¹,

Brito²,

Gregory³

et al. 2012

Schizophrenia Bulletin

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Distributed abnormalities of gray matter (GM) and white matter (WM) volume characterize individuals experiencing their first episode of schizophrenia. Regions of abnormality are present already, albeit less extensively, during the prodromal phase of illness. This study aimed to determine whether putatively at-risk children, aged 9-12 years, who present multiple antecedents of schizophrenia (ASz), display GM and WM volume abnormalities relative to typically developing (TD) children presenting no antecedents. Structural magnetic resonance images were acquired for 20 ASz children and 20 TD children matched on age, sex, and IQ. Whole-brain differences in GM and WM volume were determined using voxel-based morphometry. Relative to the TD group, ASz children showed significantly decreased GM volume in the right middle temporal gyrus (MTG) and increased GM volume in the left superior-middle temporal gyri (P < 0.05, cluster correction). WM volume was significantly increased in ASz children relative to TD children in a cluster encompassing the left inferior parietal lobe, occipital lobe, and superior temporal gyrus. Post-hoc analyses indicated that these abnormalities were not limited to ASz children who selfreported auditory hallucinations on questionnaire. Our findings suggest that children aged 9-12 years who present multiple ASz are characterized by abnormalities of GM and WM volume in the temporal lobes, comprising a subset of the regions affected in first-episode schizophrenia and in the prodromal phase of illness. These preliminary findings indicate that structural brain abnormalities associated with schizophrenia may be detected in putatively at-risk, preprodromal children. Prospective studies following the brain development of at-risk children are needed.

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“…Several lines of evidence suggest that deficient error processing is not merely a side-effect of treatment. Functional and structural ACC abnormalities, which predict the onset of psychosis (Fornito et al, 2008), are seen in never-medicated high-risk youth (Whalley et al, 2006), and in never-medicated children experiencing psychotic symptoms (Jacobson et al, 2010). In addition, a blunted ERN, similar to that observed in schizophrenia, is seen in syndromally-unaffected siblings (Simmonite et al, 2012), in never-medicated children with putative antecedents to schizophrenia (Laurens et al, 2010) and in antipsychotic naïve patients at high clinical risk for psychosis .…”

Section: Schizophreniamentioning

confidence: 99%

Neural Markers of Errors as Endophenotypes in Neuropsychiatric Disorders

Manoach¹,

Agam²

2016

Innovations in Cognitive Neuroscience

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Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromallyunaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach.

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Structural and functional brain correlates of subclinical psychotic symptoms in 11–13 year old schoolchildren

Cited by 131 publications

References 74 publications

Evidence From Structural and Diffusion Tensor Imaging for Frontotemporal Deficits in Psychometric Schizotypy

Evidence From Structural and Diffusion Tensor Imaging for Frontotemporal Deficits in Psychometric Schizotypy

Temporal Lobe Volume Abnormalities Precede the Prodrome: A Study of Children Presenting Antecedents of Schizophrenia

Neural Markers of Errors as Endophenotypes in Neuropsychiatric Disorders

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