The bidirectional association between sleep problems and autism spectrum disorder

Background: Sleep difficulties are prevalent in children with autism spectrum disorder (ASD). The temporal nature of the association between sleep problems and ASD is unclear because longitudinal studies are lacking. Our aim is to clarify whether sleep problems precede and worsen autistic traits and ASD or occur as a consequence o

Genetic variants for head size share genes and pathways with cancer

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.</p

Predicting persistence of hallucinations from childhood to adolescence

Background Psychotic experiences predict adverse health outcomes, particularly if they are persistent. However, it is unclear what distinguishes persistent from transient psychotic experiences. Aims In a large population-based cohort, we aimed to (a) describe the course of hallucinatory experiences from childhood to adolescence, (b) compare characteristics of youth with persistent and remittent hallucinatory experiences, and (c) examine prediction models for persistence. Method Youth were assessed longitudinally for hallucinatory experiences at mean ages of 10 and 14 years (n = 3473). Multi-informant-rated mental health problems, stressful life events, self-esteem, non-verbal IQ and parental psychopathology were examined in relation to absent, persistent, remittent and incident hallucinatory experiences. We evaluated two prediction models for persistence with logistic regression and assessed discrimination using the area under the curve (AUC). Results The persistence rate of hallucinatory experiences was 20.5%. Adolescents with persistent hallucinatory experiences had higher baseline levels of hallucinatory experiences, emotional and behavioural problems, as well as lower self-esteem and non-verbal IQ scores than youth with remittent hallucinatory experiences. Although the prediction model for persistence versus absence of hallucinatory experiences demonstrated excellent discriminatory power (AUC-corrected = 0.80), the prediction model for persistence versus remittance demonstrated poor accuracy (AUC-corrected = 0.61). Conclusions This study provides support for the dynamic expression of childhood hallucinatory experiences and suggests increased neurodevelopmental vulnerability in youth with persistent hallucinatory experiences. Despite the inclusion of a wide array of psychosocial parameters, a prediction model discriminated poorly between youth with persistent versus remittent hallucinatory experiences, confirming that persistent hallucinatory experiences are a complex multifactorial trait

Hallucinations and Brain Morphology Across Early Adolescence: A Longitudinal Neuroimaging Study

Background: Psychotic disorders have been widely associated with structural brain abnormalities. However, it is unclear whether brain structure predicts psychotic experiences in youth from the general population, owing to an overall paucity of studies and predominantly cross-sectional designs. Here, the authors investigated longitudinal associations between brain morphology and hallucinations from childhood to early adolescence. Methods: This study was embedded in the population-based Generation R Study. Children underwent structural neuroimaging at age 10 years (N = 2042); a subsample received a second scan at age 14 years (n = 964). Hallucinations were assessed at ages 10 and 14 years and studied as a binary variable. Cross-lagged panel models and generalized linear mixed-effects models were fitted to examine longitudinal associations between brain morphology and hallucinations. Results: Smaller total gray and white matter volumes and total cortical surface area at baseline were associated with a higher occurrence of hallucinations between ages 10 and 14 years. The regions associated with hallucinations were widespread, including the frontal, parietal, temporal, and occipital lobes, as well as the insula and cingulate cortex. Analyses of subcortical structures revealed that smaller baseline hippocampal volumes were longitudinally associated with hallucinations, although this association was no longer significant following adjustment for intracranial volume. No evidence for reverse temporality was observed (i.e., hallucinations predicting brain differences). Conclusions: The findings from this longitudinal study suggest that global structural brain differences are associated with the development of hallucinations. These results extend findings from clinical populations and provide evidence for a neurodevelopmental vulnerability across the psychosis continuum

Prevalence and predictors of vitamin D deficiency based on maternal mid-gestation and neonatal cord bloods: the Generation R Study

Background Population-based studies have confirmed that the prevalence of vitamin D deficiency is substantial in many societies, and is of particular concern in pregnant women. Vitamin D deficiency during pregnancy is associated with a wide range of adverse maternal and offspring health outcomes. To date, studies of vitamin D deficiency during pregnancy have focused on measurements at one or two time points in isolation. We examined both midgestation and cord blood 25 hydroxyvitamin D (25OHD) concentration and explored the prevalence and correlates of vitamin D deficiency in a large ethnically diverse cohort of pregnant women and their infants in the Netherlands. Methods This study was embedded in the Generation R Study, a population-based prospective cohort from fetal life onwards in Rotterdam, The Netherlands. Using a highly sensitive tandem mass spectroscopy-based assay, we measured 25OHD in 7256 midgestation samples (mean gestation 20.6 weeks) and 5023 neonatal cord blood samples (mean gestation 40.0 weeks). Using a conservative threshold of less than 25 nmol/L to define vitamin D deficiency, we examined the prevalence and socio-demographic correlates of vitamin D deficiency in mothers and infants. We also derived a measure of vitamin D deficiency based on the two time points in order to explore persistent vitamin D deficiency in mother-infant pairs. Results The prevalence of vitamin D deficiency at midgestation was 26%, while in neonates 46% were deficient. 21% of the mother-infant pairs had persistent vitamin D deficiency (i.e., deficient in maternal and cord samples) and an additional 29% were vitamin D deficient in one of the two samples only. Persistent vitamin D deficiency was strongly associated with non-European ancestry and spring birth. Conclusions A sizeable proportion of women and their neonatal offspring in the Generation R cohort were vitamin D deficient. In light of the large body of evidence linking vitamin D deficiency with adverse health outcomes for pregnant women and their offspring, our findings indicate a large unmet need in this population. In particular, women and infants from non-European ethnic background are at high risk of vitamin D deficiency

Psychotic experiences, suicidality and non-suicidal self-injury in adolescents: Independent findings from two cohorts

Background: Prior studies have shown that psychotic experiences are prospectively associated with an increased risk of suicidality. However, it is unclear whether this association is causal or arises from shared risk factors. Furthermore, little is known about the association between psychotic experiences and non-suicidal self-injury (NSSI). Methods: We used data from two independent samples of young adolescents, which we analyzed separately. In a population-based cohort, data on hallucinatory experiences and suicidality were collected at ages 10 and 14 years (N = 3435). In a cross-sectional study of a population oversampled for elevated psychopathology levels, psychotic experiences, suicidality, and NSSI were assessed at age 15 years (N = 910). Analyses were adjusted for sociodemographic covariates, maternal psychopathology, intelligence, childhood adversity, and mental health problems. Results: Psychotic experiences were prospectively associated with an increased risk of suicidality, even when considering self-harm ideation at baseline. Furthermore, persistent and incident, but not remittent, patterns of psychotic experiences were related to an increased burden of suicidality. Self-harm ideation was also prospectively associated with the risk for psychotic experiences, although of smaller magnitude and only by self-report. Among at-risk adolescents, psychotic experiences were cross-sectionally associated with a greater burden of suicidality and a higher frequency of NSSI events, with more extensive tissue damage. Conclusion: Psychotic experiences are longitudinally associated with suicidality beyond the effects of shared risk factors. We also found modest support for reverse temporality, which warrants further investigation. Overall, our findings highlight the importance of assessing psychotic experiences as an index of risk for suicidality and NSSI

Enhancing studies of the connectome in autism using the autism brain imaging data exchange II

The second iteration of the Autism Brain Imaging Data Exchange (ABIDE II) aims to enhance the scope of brain connectomics research in Autism Spectrum Disorder (ASD). Consistent with the initial ABIDE effort (ABIDE I), that released 1112 datasets in 2012, this new multisite open-data resource is an aggregate of resting state functional magnetic resonance imaging (MRI) and corresponding structural MRI and phenotypic datasets. ABIDE II includes datasets from an additional 487 individuals with ASD and 557 controls previously collected across 16 international institutions. The combination of ABIDE I and ABIDE II provides investigators with 2156 unique cross-sectional datasets allowing selection of samples for discovery and/or replication. This sample size can also facilitate the identification of neurobiological subgroups, as well as preliminary examinations of sex differences in ASD. Additionally, ABIDE II includes a range of psychiatric variables to inform our understanding of the neural correlates of co-occurring psychopathology; 284 diffusion imaging datasets are also included. It is anticipated that these enhancements will contribute to unraveling key sources of ASD heterogeneity.ISSN:2052-446