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

Abstract

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.

Deficits in Predictive Coding Underlie Hallucinations in Schizophrenia

“…This interpretation is consistent with the observation that progressive loss of gray matter in the temporal cortex occurs at relatively early stages of schizophrenia (Vita et al, 2012). Nonetheless, volume loss could possibly reflect abnormalities in cortical feedback contributing to deficient PEs at the onset of clinical psychosis or even at preclinical stages, as structural deficits of the temporal cortex have been identified at those stages (Leung et al, 2011;Cullen et al, 2013).…”

“…Furthermore, in the case of hallucinations, disruptions in such a system for prediction-based attenuation of sensory activity could potentially explain the excess activity of sensory cortex reported in symptom-capturing studies. Recent findings in schizophrenia studies support abnormalities in PE signals for reward (Murray et al, 2008;Gradin et al, 2011) that relate to delusion propensity (Corlett et al, 2007), but mechanistic evidence on how disruptions in predictive coding may produce psychotic symptoms is lacking.…”

Grey matter volume differences associated with gender in children with attention-deficit/hyperactivity disorder: A voxel-based morphometry study

“…Cluster-based statistics were used to locate significant regions based on both their peak value and spatial extent after applying an initial cluster defining threshold of p < .001. Due to structural images displaying local variation in smoothness, a non-stationary cluster extent correction was then applied when calculating family-wise error (FWE-cluster) corrected p values (p < .05) using the NS toolbox (Hayasaka et al, 2004;Meisenzahl et al, 2008;Silver et al, 2011;Cullen et al, 2013). For completeness, we also report the p-value for a family-wise error correction at the voxel level (FWE-voxel) (Bennett et al, 2009).…”

114. Electrophysiological, Cognitive and Clinical Profiles of At-Risk Mental State: The Longitudinal Minds in Transition (MinT) Study

“…Relative to matched controls, the at-risk group had larger duration MMN amplitudes. This similarly unexpected result was speculatively associated with abnormal neuroanatomical findings in an overlapping sample who had larger than expected grey matter and white matter volume in the left-temporal lobe [108], whereas volume reductions are more typically associated with schizophrenia [109]. We are currently undertaking a similar analysis of MRI structural data from the participants in this study.…”