What insights can we gain from studying early-onset schizophrenia? The neurodevelopmental pathway and beyond

Vyas, Nora S.; Kumra, Sanjiv; Puri, Basant K.

doi:10.1586/ern.10.109

Cited by 22 publications

(21 citation statements)

References 78 publications

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“…Our failure to identify GM volume differences in other regions that have been shown to be abnormal in individuals at UHR may also reflect illness stage and participant age. Based on early neurodevelopmental theories of schizophrenia, 54,55 and updated theories that draw evidence from studies of childhood-onset schizophrenia, 50,56 we anticipate that, as ASz children enter adolescence, neuroanatomical abnormalities may become more pronounced and extend into the prefrontal cortex. Indeed, more widespread GM abnormalities have Fig.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Unlike other genetic neurodevelopmental disorders that occur early after birth, schizophrenia is especially rare in children under the ages of 7–8 years old. While about 4% of schizophrenia cases occur before eighteen years old (early-onset schizophrenia, EOS), most individuals manifest psychotic symptoms in late adolescence or early adulthood (adult-onset schizophrenia, AOS) [35]. To examine the emergent time of the schizophrenia-like symptoms in GAT1 KO mice, we performed open field, nesting behavior and Y-maze spontaneous alternation tests on young (4–5 weeks old) mice, which mimics the early adolescence in human [36].…”

Section: Resultsmentioning

confidence: 99%

GABA Transporter-1 Deficiency Confers Schizophrenia-Like Behavioral Phenotypes

Fang

Xiao

et al. 2013

PLoS ONE

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The mechanism underlying the pathogenesis of schizophrenia remains poorly understood. The hyper-dopamine and hypo-NMDA receptor hypotheses have been the most enduring ideas. Recently, emerging evidence implicates alterations of the major inhibitory system, GABAergic neurotransmission in the schizophrenic patients. However, the pathophysiological role of GABAergic system in schizophrenia still remains dubious. In this study, we took advantage of GABA transporter 1 (GAT1) knockout (KO) mouse, a unique animal model with elevated ambient GABA, to study the schizophrenia-related behavioral abnormalities. We found that GAT1 KO mice displayed multiple behavioral abnormalities related to schizophrenic positive, negative and cognitive symptoms. Moreover, GAT1 deficiency did not change the striatal dopamine levels, but significantly enhanced the tonic GABA currents in prefrontal cortex. The GABAA receptor antagonist picrotoxin could effectively ameliorate several behavioral defects of GAT1 KO mice. These results identified a novel function of GAT1, and indicated that the elevated ambient GABA contributed critically to the pathogenesis of schizophrenia. Furthermore, several commonly used antipsychotic drugs were effective in treating the locomotor hyperactivity in GAT1 KO mice, suggesting the utility of GAT1 KO mice as an alternative animal model for studying schizophrenia pathogenesis and developing new antipsychotic drugs.

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“…Furthermore, patients with EOS demonstrate significant cognitive impairments in specific domains, mainly general intellectual ability [36][37][38][39][40][41][42], memory [43][44][45][46][47], attention [43,48,49], and executive function [46,48,50,51]. Studying early-onset cases may provide important insights into the etiopathogenesis of the disorder [50][51].…”

Section: Children and Adolescents With Schizophreniamentioning

confidence: 99%

Theory of Mind in the Early Course of Schizophrenia

Vyas

et al. 2017

CPSR

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Theory of mind deficit is a core feature of schizophrenia and is considered a vulnerability marker of the disorder. The majority of studies measuring theory of mind in schizophrenia involve multiple-episode or chronic schizophrenia patients, and therefore it is important to delineate whether these deficits occur before or following illness-onset by assessing high-risk subjects (clinical high risk and ultra-high risk), early-onset psychosis, and first-degree relatives. We address the question of whether theory of mind impairment is specific or a facet of general cognitive impairment in these clinical populations, and incorporate genetic and neuroimaging studies on theory of mind. The review provides a succinct evaluation of the literature, discusses current limitations and proposes future directions.

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What insights can we gain from studying early-onset schizophrenia? The neurodevelopmental pathway and beyond

Cited by 22 publications

References 78 publications

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

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

GABA Transporter-1 Deficiency Confers Schizophrenia-Like Behavioral Phenotypes

Theory of Mind in the Early Course of Schizophrenia

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