Background: Impaired executive function (EF) is suggested to be one of the core features in individuals with autism spectrum disorders (ASD); however, little is known about whether the extent of worse EF in ASD than typically developing (TD) controls is age-dependent. We used age-stratified analysis to reveal this issue.Method: We assessed 111 youths with ASD (aged 12.5 ± 2.8 years, male 94.6%) and 114 age-, and sex-matched TD controls with Digit Span and four EF tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Spatial Span (SSP), Spatial Working Memory (SWM), Stockings of Cambridge (SOC), and Intradimensional/Extradimensional Shift Test (I/ED).Results: Compared to TD controls, youths with ASD performed poorer on the Digit Span, SWM, SOC, and I/ED tasks. The performance of all the tasks improved with age for both groups. Age-stratified analyses were conducted due to significant age × group interactions in visuospatial planning (SOC) and set-shifting (I/ED) and showed that poorer performance on these two tasks in ASD than TD controls was found only in the child (aged 8–12 years) rather than the adolescent (aged 13–18 years) group. By contrast, youths with ASD had impaired working memory, regardless of age. The increased magnitude of group difference in visuospatial planning (SOC) with increased task demands differed between the two age groups but no age moderating effect on spatial working memory.Conclusions: Our findings support deficits in visuospatial working memory and planning in youths with ASD; however, worse performance in set-shifting may only be demonstrated in children with ASD.

Background: An uneven neurocognitive profile is a hallmark of autism spectrum disorder (ASD). Studies focusing on the visual memory performance in ASD have shown controversial results. We investigated visual memory and sustained attention in youths with ASD and typically developing (TD) youths.Method: We recruited 143 pairs of youths with ASD (males 93.7%; mean age 13.1, s.d. 3.5 years) and age- and sex-matched TD youths. The ASD group consisted of 67 youths with autistic disorder (autism) and 76 with Asperger's disorder (AS) based on the DSM-IV criteria. They were assessed using the Cambridge Neuropsychological Test Automated Battery involving the visual memory [spatial recognition memory (SRM), delayed matching to sample (DMS), paired associates learning (PAL)] and sustained attention (rapid visual information processing; RVP).Results: Youths with ASD performed significantly worse than TD youths on most of the tasks; the significance disappeared in the superior intelligence quotient (IQ) subgroup. The response latency on the tasks did not differ between the ASD and TD groups. Age had significant main effects on SRM, DMS, RVP and part of PAL tasks and had an interaction with diagnosis in DMS and RVP performance. There was no significant difference between autism and AS on visual tasks.Conclusions: Our findings implied that youths with ASD had a wide range of visual memory and sustained attention impairment that was moderated by age and IQ, which supports temporal and frontal lobe dysfunction in ASD. The lack of difference between autism and AS implies that visual memory and sustained attention cannot distinguish these two ASD subtypes, which supports DSM-5 ASD criteria.

Based on our previous finding of a seven-miRNA (hsa-miR-34a, miR-449a, miR-564, miR-432, miR-548d, miR-572 and miR-652) signature as a potential biomarker for schizophrenia, this study aimed to examine if hospitalization could affect expressions of these miRNAs. We compared their expression levels between acute state and partial remission state in people with schizophrenia (n=48) using quantitative PCR method. Further, to examine whether the blood and brain show similar expression patterns, the expressions of two miRNAs (hsa-miR-34a and hsa-miR-548d) were examined in the postmortem brain tissue of people with schizophrenia (n=25) and controls (n=27). The expression level of the seven miRNAs did not alter after ~2 months of hospitalization with significant improvement in clinical symptoms, suggesting the miRNAs could be traits rather than state-dependent markers. The aberrant expression seen in the blood of hsa-miR-34a and hsa-miR-548d were not present in the brain samples, but this does not discount the possibility that the peripheral miRNAs could be clinically useful biomarkers for schizophrenia. Unexpectedly, we found an age-dependent increase in hsa-miR-34a expressions in human cortical (Brodmann area 46 (BA46)) but not subcortical region (caudate putamen). The correlation between hsa-miR-34a expression level in BA46 and age was much stronger in the controls than in the cases, and the corresponding correlation in the blood was only seen in the cases. The association between the miRNA dysregulations, the disease predisposition and aging warrants further investigation. Taken together, this study provides further insight on the candidate peripheral miRNAs as stable biomarkers for the diagnostics of schizophrenia.

Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder with complex genetic underpinning in its etiology. Copy number variations (CNVs) as one of the genetic factors associated with ASD have been addressed in recent genome-wide association studies (GWAS). However, the significance of CNV has not been well investigated in non-Caucasian ASD population. To identify the pathogenic CNVs responsible for ASD in Han Chinese, we performed a segment-based GWAS of CNV in 335 ASD cases and 1093 healthy controls using Affymetrix single nucleotide polymorphism (SNP) array by focusing on case-specific CNVs. PARK2 was one of the important genes with several case-specific regions overlapped on it. The findings were validated in the initial screen sample set and replicated in another sample set by real-time quantitative PCR (qPCR). A total of six CNVs at 6q26 that spanned different exons of PARK2 were identified. The PARK2 expression level was down-regulated at exon-dependent manner in cases with either deletion or duplication. The result revealed that the gene function might be disrupted by exonic deletion and duplication. We also observed that the ASD case with exonic duplication demonstrated a more severe interference of PARK2 expression and the clinical feature than the ones with deletion at the exons 2–4 of the PARK2 gene. Our finding provides evidence to support that CNVs affecting PARK2 function might contribute to genetic etiology of a proportion of cases with ASD. The intriguing results of this work warrant further study on characterizing the functional impact of various exonic CNVs on the PARK2 gene. ClinicalTrials.gov NCT00494754