From molecules to neural morphology: understanding neuroinflammation in autism spectrum condition

Growing evidence points toward a critical role for early (prenatal) atypical neurodevelopmental processes in the aetiology of autism spectrum condition (ASC). One such process that could impact early neural development is inflammation. We review the evidence for atypical expression of molecular markers in the amniotic fluid, serum, cerebrospinal fluid (CSF), and the brain parenchyma that suggest a role for inflammation in the emergence of ASC. This is complemented with a number of neuroimaging and neuropathological studies describing microglial activation. Implications for treatment are discussed.

A comprehensive meta-analysis of common genetic variants in autism spectrum conditions

Background Autism spectrum conditions (ASC) are a group of neurodevelopmental conditions characterized by difficulties in social interaction and communication alongside repetitive and stereotyped behaviours. ASC are heritable, and common genetic variants contribute substantial phenotypic variability. More than 600 genes have been implicated in ASC to date. However, a comprehensive investigation of candidate gene association studies in ASC is lacking. Methods In this study, we systematically reviewed the literature for association studies for 552 genes associated with ASC. We identified 58 common genetic variants in 27 genes that have been investigated in three or more independent cohorts and conducted a meta-analysis for 55 of these variants. We investigated publication bias and sensitivity and performed stratified analyses for a subset of these variants. Results We identified 15 variants nominally significant for the mean effect size, 8 of which had P values below a threshold of significance of 0.01. Of these 15 variants, 11 were re-investigated for effect sizes and significance in the larger Psychiatric Genomics Consortium dataset, and none of them were significant. Effect direction for 8 of the 11 variants were concordant between both the datasets, although the correlation between the effect sizes from the two datasets was poor and non-significant. Conclusions This is the first study to comprehensively examine common variants in candidate genes for ASC through meta-analysis. While for majority of the variants, the total sample size was above 500 cases and 500 controls, the total sample size was not large enough to accurately identify common variants that contribute to the aetiology of ASC.

Self-concept clarity and compulsive Internet use: the role of preference for virtual interactions and employment status in British and North-American samples

Background and Aims Compulsive Internet Use (CIU) describes a maladaptive relationship with the Internet characterised by loss of control and conflict. Although also affecting adults, most studies use teenage samples, and theoretical development on risk factors is scarce. According to Davis (2001), the social connectivity function of the Internet is key in identifying traits associated with CIU. Since Self-Concept Clarity (SCC) is strongly related to social anxiety, and virtual interactions allow “self-edition”, we hypothesized that individuals low in SCC could choose virtual interactions as safer alternative to satisfy their social needs. This could in turn increase the risk of CIU. Building on a previous study, we also expected CIU to be more harmful in the unemployed. Methods We collected samples from the UK (N = 532) and US (N = 502) with equal distribution of employed and unemployed individuals. We ran Measurement Invariance tests to confirm that the constructs were equivalent across countries. Subsequently, we conducted mediation and moderation analysis to test our hypothesis with Multigroup Confirmatory Factor Analysis. Results Measurement Invariance was confirmed. The relationship between SCC and CIU was partially mediated by preference of virtual interactions in both countries. This preference was significantly related to lower social support. Short term unemployment seemed to accentuate the negative impact of CIU on life satisfaction in both countries, although only marginally significantly in the US. The unemployed reported significantly lower levels of life satisfaction. Conclusion We demonstrated that SCC is a key vulnerability factor to CIU in adults, and confirmed the additional risks for the unemployed.

Frontal networks in adults with autism spectrum disorder

It has been postulated that autism spectrum disorder is underpinned by an ‘atypical connectivity’ involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a ‘whole brain’ non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate—predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life.

The interface of syntax with pragmatics and prosody in children with Autism Spectrum Disorders

In order to study problems of individuals with Autism Spectrum Disorders (ASD) with morphosyntax, we investigated twenty high-functioning Greek-speaking children (mean age:6;11) and twenty age- and language-matched typically developing children on environments that allow or forbid object clitics or their corresponding noun phrase. Children with ASD fell behind typically developing in comprehending and producing simple clitics and producing noun phrases in focus structures. The two groups performed similarly in comprehending and producing clitics in clitic left dislocation and in producing noun phrases in non-focus structures. We argue that children with ASD have difficulties at the interface of(morpho)syntax with pragmatics and prosody, namely, distinguishing a discourse prominent element, and considering intonation relevant for a particular interpretation that excludes clitics.