Association of IL-12p70 and IL-6:IL-10 ratio with autism-related behaviors in 22q11.2 deletion syndrome: A preliminary report

22q11.2 deletion syndrome (22q11DS) is a genetic disorder that conveys a significant risk for the development of social behavior disorders, including autism and schizophrenia. Also known as DiGeorge syndrome, 22q11DS is the second most common genetic disorder and is characterized by an elevated risk for immune dysfunction, up to 77% of individuals have an identifiable immune deficiency. We hypothesize that this immune dysfunction could contribute to the elevated risk of impaired social behavior seen in 22q11DS. The current study begins to elucidate these immune deficits and link them with the behavioral alterations associated with the disorder. Serum concentrations of a series of cytokines were examined, using a multiplex immunoassay, in sixteen individuals with 22q11DS and screened for autism-related behavior using the Autism Diagnostic Interview-Revised (ADI-R). This preliminary study examined correlations between specific immune proteins and each of the ADI-R algorithm scores (social, communication, and repetitive behavior). The inflammatory cytokine IL-1β, as well as the ratio between the inflammatory cytokine IL-6 and the anti-inflammatory cytokine IL-10, were correlated with social scores (r = 0.851, p = 0.004; r = 0.580, p = 0.018). In addition, the inflammatory cytokines interferon gamma and IL-12p70 were correlated with repetitive behaviors (r = 0.795, p = 0.033; r = 0.774, p = 0.002). Interestingly, IL-12 has been reported to be increased in autistic children. These data show a positive association between severity of autism-related behaviors and level of serum concentrations of inflammatory cytokines in individuals with 22q11DS, providing a basis for further inquiry.     

Altered expression of hippocampal dentate granule neuron genes in a mouse model of human 22q11 deletion syndrome

Hemizygous deletion of a 3 Mb region of 22q11.2 is found in 1/4000 humans and produces 22q11 deletion syndrome (22q11DS). Up to 35% of 22q11DS patients develop schizophrenia, making it the second highest risk factor for schizophrenia. A mouse model for 22q11DS, the Df1/+ mouse, carries a hemizygous deletion in a region syntenic with the human deletion. Df1/+ mice are mostly viable but display deficits in prepulse inhibition and learning and memory, two common traits of schizophrenia thought to result, at least in part, from defects in hippocampal neurons. We used oligonucleotide microarrays and QRT-PCR to evaluate gene expression changes in hippocampal dentate granule neurons of Df1/+ mice versus wild-type littermates (n = 12/group). The expression of only 287 genes changed with p value significance below 0.05 by microarray, yet 12 of the 21 Df1 region genes represented on the array showed highly significantly reduced expression compared to wild-type controls (33% on average, p values from 10^− 3 to 10^− 7). Variants in two of these genes, COMT and PRODH, have been linked with schizophrenia. Overlap of the 287 genes with the reportedly reduced expression of mitochondrial, ubiquitin/proteasome, and synaptic plasticity genes in schizophrenia dentate granule neurons, was not significant. However, modest increases in expression of mitochondrial electron transport genes were observed in the Df1/+ mice. This perhaps indicates a compensation for mitochondrial dysfunction caused by the strongly reduced expression of the Df1 region-encoded mitochondrial enzymes proline dehydrogenase (Prodh) and thioredoxin reductase 2 (Txnrd2).     

Duration of untreated psychosis is associated with orbital-frontal grey matter volume reductions in first episode psychosis

BackgroundDelay in treatment of psychosis is associated with poor clinical and social outcome and is measured as the duration of untreated psychosis (DUP) prior to treatment of the first episode. It has been suggested that this may be mediated through toxic effects of psychosis on the structure and function of the brain. Equivocal evidence exists regarding association between longer DUP and neuro-anatomical changes such as, reduced grey matter volume in specific regions in the brain and deficits in neurocognitive functions.ObjectiveTo examine if duration of untreated psychosis (DUP) preceding treatment of a first episode of psychosis is associated with structural brain abnormalities and deficits in neurocognitive functions.MethodWe investigated the relationship between DUP and grey matter volume using voxel-based morphometry techniques and with multiple domains of cognition. Eighty patients with a first episode of psychosis were separated into two equal sized groups based on a median split (18 weeks) of their DUP.ResultsCompared to the short-DUP group (mean DUP 7.9 weeks ± 5.6), the long-DUP group (mean 113.7 weeks ± 170.4) showed significant grey matter volume reductions in orbital–frontal regions (bilateral medial frontal gyrus and bilateral rectal gyrus, BA 11) and parietal regions (postcentral gyrus and superior parietal lobule) as well as a significant reduction in whole brain grey matter volume (p < 0.04). For schizophrenia spectrum cases only these findings were confined to left rectal gyrus. There were no differences in white matter or cerebral spinal fluid volumes or on cognitive functions. Results are controlled for antipsychotic medication exposure.LimitationsThe inherent difficulty in separating slow and insidious onset from long-DUP may limit the interpretation of our results and there may be an overlap between DUP and duration of illness (including the prodrome).ConclusionPatients with a longer delay in treatment of psychosis show a significant reduction in overall grey matter volume with specific reductions in the inferior-orbital region. These results provide some support to a possible neurotoxic effect of prolonged untreated psychosis.     

Cognitive and behavioral trajectories in 22q11DS from childhood into adolescence: A prospective 6-year follow-up study

Patients with 22q11DS are at risk of behavioral problems and cognitive impairment. Recent studies suggest a possible intellectual decline in 22q11DS children. To date it is unknown if cognitive development is related to the behavioral problems in 22q11DS. We studied 53 children with 22q11DS who underwent cognitive and behavioral assessments at 9.5 years (T1) and 15.3 years (T2). In about one third, IQ data obtained at 7.5 years (T0) were also available. Results showed that internalizing behaviors intensified while externalizing behaviors decreased. Simultaneously, in about a third a significant decline in IQ was found, which, surprisingly, was unrelated to the behavioral changes. It can be concluded that children with 22q11DS follow a unique developmental trajectory. Cognitive deterioration is severe in some but does not appear to predict behavioral problems in early adolescence.     

The lack of association between catechol-O-methyltransferase (COMT) Val108/158Met and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms and schizophrenia in a group of Turkish population

IntroductionSchizophrenia is a complex neuropsychiatric disorder with deficits of multiple domains of cognitive functions, volition and emotions. Family and twin studies have provided cumulative evidence for the genetic basis of schizophrenia. The aetiolgy of this disease involves the interplay of multifactiorial inheritance operating on brain maturational processes and polygenic inheritance with some genes showing susceptibility at many genomic locations such as 22q and 11q.The catechol-O-methyltransferase (COMT-22q11) is an extensively studied candidate gene for schizophrenia. COMT acts as an enzymatic detoxicating barrier between the blood and other tissues regulating the amounts of active dopamine and norepinephrine in various parts of the brain and therefore to be associated with schizophrenia.The presence of a common functional single nucleotide polymorphism (SNP) in exon 4 [Guanine (G) Adenine (A); Val108/158Met], alters the enzymatic activity with a trimodal distribution of high-HH, intermediate-HL and low-LL activity alleles which appear to have association with schizophrenia.Brain-derived neurotrophic factor (BDNF-11q13) is a member of the nerve growth factor family working as a molecular regulator of neuronal development and plasticity. Molecules that are critical in the development and survival of neurons such as BDNF play a significant role in the neuropathology of schizophrenia. While upregulation of BDNF increases the neuronal cell size and synaptic plasticity, a functional polymorphism at codon 66 [G→A; Val66Met] down regulates this process and induces schizophrenia.ObjectiveIn the present study, our aim was to investigate the differences in allele frequencies between schizophrenic patients [n = 97 (51 men, 46 women)] and control group [n = 376 (228 men, 148 women)] subjects.ResultsWhen the control and schizophrenia groups were compared for BDNFVal66Met polymorphism, we did not find a significant difference between the study groups either for genotype (χ² = 3.370447, p > 0.05) or Val/Met haplotype analysis (χ² = 2.840264, p > 0.05). When a comparison was revealed for COMT-Val108/158Met polymorphism, no significant difference was detected among schizophrenia and control groups for genotype (χ² = 0.373330, p > 0.05) and Val/Met haplotype analysis (χ² = 0.339073, p > 0.05). When the control and study groups were compared for BDNFVal66Met–COMTVal108/158Met polymorphisms compound genotype and haplotype analyses, there was no significant difference between the two groups (χ² = 11.015; p > 0.05 and χ² = 3.191; p > 0.05), respectively.ConclusionOur results indicate that there is no association between schizophrenia and BDNF–COMT polymorphisms and haplotypes analysis. We also did not find an association between schizophrenia and BDNF–COMT compound genotype and haplotype analyses. Although our study is unique in Turkey as combining BDNF and COMT compound genotype–haplotype analyses, for a generalization of Turkish schizophrenia patient's susceptibility to schizophrenia; we need further studies with an enlarged cohort.     

Regional Brain Abnormalities in 22q11.2 Deletion Syndrome: Association With Cognitive Abilities and Behavioral Symptoms

Children with 22q11.2 microdeletions (Velocardiofacial Syndrome; VCFS) have previously been shown to exhibit learning deficits and elevated rates of psychopathology. The aim of this study was to assess regional brain abnormalities in children with 22q11DS, and to determine the relationship of these measures to neurocognitive and behavioral function. Thirteen children with confirmed deletions and 9 demographically matched comparison subjects were assessed with a neurocognitive battery, behavioral measures, and high-resolution MRI. Twenty-two q11DS children showed a nonsignificant 4.3% global decrease in total brain volume as compared to healthy controls, with differential reduction in white matter, and significantly increased sulcal cerebrospinal fluid (CSF) in temporal and posterior brain regions. In 22q11DS subjects, but not controls, bilateral temporal gray and white matter volumes were significant predictors of overall cognitive performance. Further, reduced temporal gray matter was associated with elevated Thought Problems score on the CBCL. Results indicate that global alterations in brain volume are common in children with 22q deletions, particularly those with low IQ and/or behavioral disturbance. Although preliminary, these findings suggest a possible underlying pathophysiology of the cognitive deficits seen in this syndrome, and provide insight into complex gene-brain-behavior relationships.     

Reduced gray matter volume in psychotic disorder patients with a history of childhood sexual abuse

Childhood trauma is associated with smaller gray matter volume, similar to the pattern seen in psychotic disorders. We explored the relationship between childhood abuse, psychosis, and brain volume in a group of 60 individuals with a psychotic disorder and 26 healthy control subjects. We used voxel-based morphometry (VBM) to quantify gray and white matter volume and the Childhood Trauma Questionnaire (CTQ) to measure childhood abuse. Within the psychotic disorder group, total gray matter volume was inversely correlated with the severity of childhood sexual abuse (r = ? .34, p = .008), but not the other types of abuse. When the 24 patients with sexual abuse were compared with demographically matched samples of 23 patients without sexual abuse and 26 control subjects, only patients with a history of sexual abuse had reduced total gray matter volume (t(48) = 2.3, p = .03; Cohen's d = .63). Voxel-based analysis revealed a cluster in the prefrontal cortex where volume was negatively correlated with sexual abuse severity. Voxel based comparison of the three matched groups revealed a similar pattern of results, with widespread reductions in psychosis patients with sexual abuse relative to controls that were not found in psychosis patients without sexual abuse. These findings indicate that some of the variance of gray matter volume in psychotic disorders can be explained by a history of sexual abuse.     

Prospective control abilities during visuo-manual tracking in children with 22q11.2 Deletion syndrome compared to age- and IQ-matched controls

To examine whether children with a 22q11.2 Deletion syndrome (22q11.2DS) are able to use prospective control, 21 children with 22q11.2DS (mean age = 9.6 ± 1.9; mean FSIQ = 73.05 ± 10.2) and 21 control children (mean age = 9.6 ± 1.9; mean FSIQ = 73.38 ± 12.0) were asked to perform a visuo-manual tracking task in which they had to track a cursor rhythmically between 2 target zones. Children with 22q11.2DS performed worse than the age- and IQ-matched controls (higher absolute time and distance errors) suggesting that the 22q11.2DS group experiences an additional (syndrome specific) processing deficit that cannot be attributed to their lower intellectual abilities. The 22q11.2DS group neither the control group improved their tracking performance throughout five identical full feedback conditions of the tracking task possibly due to a slow visuo-motor adaptation process, a short span of attention and cognitive flexibility impairments. The results showed that both the 22q11.2DS group and the controls had difficulties anticipating the movement of the target (prospective control) and thus are assumed to rely more on feedback instead of on an internal representation of the movement.     

Developmental changes in multivariate neuroanatomical patterns that predict risk for psychosis in 22q11.2 deletion syndrome

The primary objective of the current prospective study was to examine developmental patterns of voxel-by-voxel gray and white matter volumes (GMV, WMV, respectively) that would predict psychosis in adolescents with 22q11.2 deletion syndrome (22q11.2DS), the most common known genetic risk factor for schizophrenia. We performed a longitudinal voxel-based morphometry analysis using structural T1 MRI scans from 19 individuals with 22q11.2DS and 18 typically developing individuals. In 22q11.2DS, univariate analysis showed that greater reduction in left dorsal prefrontal cortical (dPFC) GMV over time predicted greater psychotic symptoms at Time2. This dPFC region also showed significantly reduced volumes in 22q11.2DS compared to typically developing individuals at Time1 and 2, greater reduction over time in 22q11.2DS COMT^Met compared to COMT^Val, and greater reduction in those with greater decline in verbal IQ over time. Leave-one-out Multivariate pattern analysis results (MVPA) on the other hand, showed that patterns of GM and WM morphometric changes over time in regions including but not limited to the dPFC predicted risk for psychotic symptoms (94.7-100% accuracy) significantly better than using univariate analysis (63.1%). Additional predictive brain regions included medial PFC and dorsal cingulum. This longitudinal prospective study shows novel evidence of morphometric spatial patterns predicting the development of psychotic symptoms in 22q11.2DS, and further elucidates the abnormal maturational processes in 22q11.2DS. The use of neuroimaging using MVPA may hold promise to predict outcome in a variety of neuropsychiatric disorders.     

Erratum to “Psychomotor slowing in older patients with major depression: Relationships with blood flow in the caudate nucleus and white matter lesions” [Psychiatry Research: Neuroimaging 155(3)(2007)211–220]

We sought to investigate the link between substance abuse and increased striatal gray matter densities (GMD) in schizophrenia, using voxel-based morphometry (VBM). Increased striatal GMD were found in patients with schizophrenia and substance use disorder (n = 12), but not schizophrenia only patients (n = 11), compared to healthy volunteers (n = 15).     

Grey matter volume reductions in the emotion network of patients with depression and coronary artery disease

Coronary Artery Disease (CAD) and Major Depressive Disorder (MDD) commonly co-occur and may be linked by a network of brain regions involved in emotion regulation, including the orbitofrontal cortex, amygdala/parahippocamal region and insula. We hypothesized structural differences in this emotion network more prominently in CAD + MDD versus CAD and healthy control (CTRL) groups that do not involve depression-related emotion circuitry. In contrast, we hypothesized structural similarities between CAD + MDD and MDD groups, both involving depression-related circuitry. We obtained structural magnetic resonance imaging scans from age-matched consenting subjects (CAD + MDD, n = 12; CAD, n = 12; MDD, n = 19; CTRL, n = 17) and performed a region of interest analysis. We found decreased grey matter volumes in the bilateral orbitofrontal cortex, bilateral amygdala/parahippocampal gyrus and right insula in CAD + MDD versus CTRL subjects and decreased grey matter volumes in the bilateral amygdala/parahippocampal regions in CAD + MDD versus CAD subjects. We found grey matter reductions in the right orbitofrontal cortex of CAD + MDD versus MDD subjects, and reductions in right insula of CAD versus CRTL subjects. Our results support that the network of brain regions involved in emotion regulation may be relevant to the relationship between CAD and MDD.     

Kinematic movement strategies in primary school children with 22q11.2 Deletion Syndrome compared to age- and IQ-matched controls during visuo-manual tracking

The present study focused on the mechanism subserving the production of kinematic patterns in 21 children with 22q11.2DS (mean age = 9.6 ± 1.9; mean FSIQ = 73.05 ± 10.2) and 21 age- and IQ-matched control children (mean age = 9.6 ± 1.9; mean FSIQ = 73.38 ± 12.0) when performing a visuo-manual tracking task in which they had to track a cursor rhythmically between 2 target zones. Children with 22q11.2DS moved faster (overall) and reached their maximum velocity sooner when compared to controls. However, the number of corrective submovements to attain the target did not differ. Children with 22q11.2DS seem to adopt a young ballistic movement strategy, with a fast ballistic first movement phase, followed by a second movement phase with very little online corrections to attain the target. Children with 22q11.2DS are not able to process the incoming feedback during the second movement phase to maximize the accuracy of the ongoing movement and use this phase to prepare the following. The fact that the parietal cortex and cerebellum are involved in action prediction and internal representation and are implicated in children with 22q11.2DS provides a possible neurological basis for their problems with prospective control and tracking behavior.     

Regional brain abnormalities in 22q11.2 deletion syndrome: association with cognitive abilities and behavioral symptoms

Children with 22q11.2 microdeletions (Velocardiofacial Syndrome; VCFS) have previously been shown to exhibit learning deficits and elevated rates of psychopathology. The aim of this study was to assess regional brain abnormalities in children with 22q11DS, and to determine the relationship of these measures to neurocognitive and behavioral function. Thirteen children with confirmed deletions and 9 demographically matched comparison subjects were assessed with a neurocognitive battery, behavioral measures, and high-resolution MRI. Twenty-two qllDS children showed a nonsignificant 4.3% global decrease in total brain volume as compared to healthy controls,with differential reduction in white matter, and significantly increased sulcal cerebrospinal fluid (CSF) in temporal and posterior brain regions. In 22q11 DS subjects, but not controls, bilateral temporal gray and white matter volumes were significant predictors of overall cognitive performance. Further, reduced temporal gray matter was associated with elevated Thought Problems score on the CBCL. Results indicate that global alterations in brain volume are common in children with 22q deletions, particularly those with low IQ and/or behavioral disturbance. Although preliminary,these findings suggest a possible underlying pathophysiology of the cognitive deficits seen in this syndrome,and provide insight into complex gene-brain-behavior relationships.     

Relationship between cognition,clinical and cognitive insight in psychotic disorders: A review and meta-analysis

The neurocognitive theory of insight posits that poor insight in psychotic illnesses is related to cognitive deficits in cognitive self-appraisal mechanisms. In this paper we perform a comprehensive meta-analysis examining relationships between clinical insight and neurocognition in psychotic disorders. We have also completed a meta-analysis of studies examining ‘cognitive insight’, as measured by the Beck Cognitive Insight Scale (BCIS), and its relationship with neurocognitive function in patients with psychosis. The clinical insight analysis included data from 72 studies and a total population of 5429 patients. We found that insight in psychosis was significantly associated with total cognition (r = 0.16, p < 0.001), IQ (r = 0.16, p < 0.001), memory (r = 0.13, p < 0.001) and executive function (r = 0.14, p < 0.001). All of these correlations were stronger when examined in patients with schizophrenia only. In the BCIS analysis we included 7 studies and 466 patients in total. We found that no significant associations were found between the self-reflectiveness sub-component and neurocognition. By contrast there were significant correlations between the self-certainty subcomponent and memory (r = –0.23, p < 0.001), IQ (r = –0.19, p < 0.001) and total cognition (r = –0.14, p = 0.01). We did not find evidence of significant publication bias in any analyses. Overall, our results indicate that there is a small but significant relationship between clinical insight, some aspects of cognitive insight and neurocognition. These findings reflect the complexity of the insight construct and indicate that while the neurocognitive model is important it is likely to be one of many which contribute to the understanding of this phenomenon.     

Distribution of regional gray matter abnormalities in a pediatric population with temporal lobe epilepsy and correlation with neuropsychological performance

ObjectiveThe goals of the work described here were to determine if hippocampal and extrahippocampal atrophy in children with temporal lobe epilepsy (TLE) follows a pattern similar to that in adult patients, and to assess the clinical and neuropsychological relevance of regional brain atrophy in pediatric TLE.MethodsChildren with symptomatic TLE (n = 14: 9 with mesial TLE due to hippocampal atrophy and 5 with TLE due to neocortical lesions), healthy children (n = 14), and 9 adults with mesial temporal lobe epilepsy (MTLE) were compared using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI). The children underwent a comprehensive neuropsychological battery.ResultsChildren with MTLE with unilateral hippocampal atrophy (n = 9) exhibited a significant reduction in gray matter in the hippocampus ipsilateral to the seizure origin and significant atrophy in the ipsilateral cingulate gyrus and contralateral middle frontal lobe. Children with TLE (n = 14) exhibited a significant reduction in the gray matter of the ipsilateral hippocampus and parahippocampal gyrus. There was a correlation between gray matter volume in children with TLE and scores on several neuropsychological tests. Atrophy in pediatric patients with MTLE was less extensive than that in adults, and involved the hippocampi and the frontal cortex.ConclusionsSimilar to adult MTLE, pediatric MTLE is associated with hippocampal and extrahippocampal cell loss. However, children display less intense quantifiable gray matter atrophy, which affects predominantly frontal lobe areas. There was a significant association between volume of gray matter in medial temporal and frontal regions and scores on neuropsychological tests. In childhood, TLE and the concomitant cognitive/behavior disturbances are the result of a damaged neural network.     

A longitudinal study of neurocognitive function in individuals at-risk for psychosis

IntroductionClinically defined prodromal diagnostic criteria identify at-risk individuals with a 35–40% likelihood of developing a psychotic disorder within a year. The time course and predictive value of cognitive deficits in the development of psychosis has not been established.MethodsA comprehensive neurocognitive battery and clinical assessments were administered to 37 subjects meeting Criteria of Prodromal States (COPS) criteria for being at risk for psychosis, and two comparison groups: 59 first episode and 47 healthy subjects. Subjects were also evaluated at 6-month and 1-year follow-up periods. Primary analyses used a neurocognitive composite score derived from individual neurocognitive measures, including measures of vigilance, verbal memory, working memory, and processing speed.ResultsAt-risk subjects performed more poorly than healthy subjects (t = 2.93, P = 0.01), but better than first episode subjects (t = 4.72, p < 0.0001). At-risk subjects were particularly impaired on measures of vigilance and processing speed. Cognitive composite scores were significantly lower in at-risk subjects who progressed to psychosis (N = 11; z = − 1.2), while those at-risk subjects who did not progress to psychosis (N = 17) performed better (z = − 0.5), and not significantly different from controls. Poor CPT performance combined with better WAIS-R digit symbol performance predicted progression to psychosis. Severity of neurocognitive deficits was not related to duration of prodrome or to time to development of psychosis and neurocognitive function improved in all subjects except those who progressed to psychosis.ConclusionNeurocognitive impairment emerges early in the course of psychotic illness. Performance on tests of neurocognition may prove to be an early risk predictor for subsequent development of psychotic disorders.     

White matter abnormalities in adults with 22q11 deletion syndrome with and without schizophrenia

Dysfunction of cerebral white matter (WM) is a potential factor underlying the neurobiology of schizophrenia. People with 22q11 deletion syndrome have altered brain morphology and increased risk for schizophrenia, therefore decreased WM integrity may be related to schizophrenia in 22q11DS. We measured fractional anisotropy (FA) and WM volume in 27 adults with 22q11DS with schizophrenia (n = 12, 22q11DS SCZ+) and without schizophrenia (n = 15, 22q11DS SCZ−), 12 individuals with idiopathic schizophrenia and 31 age-matched healthy controls. We found widespread decreased WM volume in posterior and temporal brain areas and decreased FA in areas of the frontal cortex in the whole 22q11DS group compared to healthy controls. In 22q11DS SCZ+ compromised WM integrity included inferior frontal areas of parietal and occipital lobe. Idiopathic schizophrenia patients showed decreased FA in inferior frontal and insular regions compared to healthy controls. We found no WM alterations in 22q11DS SCZ+ vs. 22q11DS SCZ−. However, there was a negative correlation between FA and PANSS scores (Positive and Negative Symptom Scale) in the whole 22q11DS group in the inferior frontal, cingulate, insular and temporal areas. This is the first study to investigate WM integrity in adults with 22q11DS. Our results suggest that pervasive WM dysfunction is intrinsic to 22q11DS and that psychotic development in adults with 22q11DS involves similar brain areas as seen in schizophrenia in the general population.     

Community based study of sleep bruxism during early childhood

ObjectivesThe aims for this study were to determine the prevalence of sleep-bruxism among young children, explore child behavior problems that may be associated with sleep-bruxism, and identify relations among sleep-bruxism, health problems, and neurocognitive performance.MethodsThe current study was a retrospective analysis of parent report surveys, and behavioral and neurocognitive assessments. Parents of 1953 preschool and 2888 first grade children indicated their child’s frequency of bruxism during sleep. A subsample of preschool children (n = 249) had additional behavioral, as well as neurocognitive assessments. Among the subsample, parents also reported on their child’s health, and completed the Child Behavioral Checklist; children were administered the Differential Ability Scales, and Pre-Reading Abilities subtests of the Developmental Neuropsychological Assessment.Results36.8% of preschoolers and 49.6% of first graders were reported to brux ⩾1 time per week. Among the preschool subsample, bruxing was independently associated with increased internalizing behaviors (β = .17). Bruxism was also associated with increased health problems (β = .19), and increased health problems were associated with decreased neurocognitive performance (β = .22).ConclusionsThe prevalence of sleep-bruxism was high. A dynamic and potentially clinically relevant relation exists among sleep-bruxism, internalizing behaviors, health, and neurocognition. Pediatric sleep-bruxism may serve as a sentinel marker for possible adverse health conditions, and signal a need for early intervention. These results support the need for an interdisciplinary approach to pediatric sleep medicine, dentistry, and psychology.     

Cannabis use and callosal white matter structure and integrity in recent-onset schizophrenia

Adolescent-onset cannabis use, compared with adult-onset use, has been associated with a higher risk for developing symptoms of schizophrenia-like psychotic disorders. To test the hypothesis that onset of cannabis use in early adolescence in male schizophrenia patients is associated with abnormalities in white matter structure and integrity, we used high resolution structural and diffusion tensor brain images to compare three groups of patients: those who started regular use of cannabis (1) before the age of 15 years (early-onset cannabis users, n = 10) or (2) at the age of 17 years or later (late-onset cannabis users, n = 8), and (3) those who were cannabis naïve (n = 8). To verify patient findings, we also compared white matter integrity of the three patient groups with that of a healthy control group (n = 10). Cannabis naïve patients showed reduced white matter density and reduced fractional anisotropy, an indicator for white matter integrity, in the splenium of the corpus callosum compared with patients with early-onset cannabis use. In the same brain area, cannabis naïve patients showed reduced fractional anisotropy compared with healthy controls. Our results suggest that the age of onset of cannabis use is not an identifying characteristic for white matter abnormalities in schizophrenia patients; however, our results might indicate a more vulnerable brain structure in cannabis naïve schizophrenia patients.     

Gender differences of neurocognitive functioning in patients with first-episode schizophrenia in China

AimsTo investigate the gender differences in neurocognitive functioning in patients with first-episode schizophrenia (FES) in China.MethodsA total of 449 Chinese patients with FES (210 males, 239 females) were included in this study. Participants’ psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). Neurocognitive functioning was assessed by 10 neuropsychological tests from a battery. Neurocognitive test scores were converted to scale scores and t-scores using normative data from Chinese populations.ResultsMales were younger and less likely to be married, had an earlier age of illness onset and a longer duration of untreated psychosis (DUP), and scored higher on the PANSS negative, general and total scales than females. After controlling for potential confounders, females performed better than males in the verbal learning and memory domain (p=0.016). While most neurocognitive domains were correlated with PANSS negative scores for male patients with FES, for female patients with FES, negative associations were found between scores on the PANSS general subscales and neurocognitive domains. We also performed a case-control comparison with a group of patients with clinically stable schizophrenia (CSS) (n = 60) who were matched by age, sex and education years with patients with FES (n = 58). After controlling for potential confounders, no significant differences were found between patients with FES and patients with CSS in all neurocognitive domains. Female patients still performed better in the verbal learning and memory domain (t = 2.14, p = 0.034). No interaction effects of gender and disease were found.ConclusionsGender was an independent influence factor for the verbal learning and memory domain. Both female patients with first-episode schizophrenia and female patients with clinically stable schizophrenia performed better than male patients.