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ImportanceThe 16p11.2 BP4-BP5 duplication is the copy number variant most frequently associated with autism spectrum disorder (ASD), schizophrenia, and comorbidities such as decreased body mass index (BMI).ObjectivesTo characterize the effects of the 16p11.2 duplication on cognitive, behavioral, medical, and anthropometric traits and to understand the specificity of these effects by systematically comparing results in duplication carriers and reciprocal deletion carriers, who are also at risk for ASD.Design, setting, and participantsThis international cohort study of 1006 study participants compared 270 duplication carriers with their 102 intrafamilial control individuals, 390 reciprocal deletion carriers, and 244 deletion controls from European and North American cohorts. Data were collected from August 1, 2010, to May 31, 2015 and analyzed from January 1 to August 14, 2015. Linear mixed models were used to estimate the effect of the duplication and deletion on clinical traits by comparison with noncarrier relatives.Main outcomes and measuresFindings on the Full-Scale IQ (FSIQ), Nonverbal IQ, and Verbal IQ; the presence of ASD or other DSM-IV diagnoses; BMI; head circumference; and medical data.ResultsAmong the 1006 study participants, the duplication was associated with a mean FSIQ score that was lower by 26.3 points between proband carriers and noncarrier relatives and a lower mean FSIQ score (16.2-11.4 points) in nonproband carriers. The mean overall effect of the deletion was similar (-22.1 points; P 100) compared with the deletion group (P

BACKGROUND: The recurrent ~600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders. OBJECTIVE: To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion. METHODS: We collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls. RESULTS: When compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations. CONCLUSIONS: The 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.

Background: The few studies that have evaluated syntax in autism spectrum disorder (ASD) have yielded conflicting findings: some suggest that once matched on mental age, ASD and typically developing controls do not differ for grammar, while others report that morphosyntactic deficits are independent of cognitive skills in ASD. There is a need for a better understanding of syntax in ASD and its relation to, or dissociation from, nonverbal abilities. Aims: Syntax in ASD was assessed by evaluating subject and object relative clause comprehension in adolescents and adults diagnosed with ASD with a performance IQ within the normal range, and with or without a history of language delay. Methods & Procedures: Twenty-eight participants with ASD (mean age 21.8) and 28 age-matched controls (mean age 22.07) were required to point to a character designated by relative clauses that varied in syntactic complexity. Outcomes & Results: Scores indicate that participants with ASD regardless of the language development history perform significantly worse than age-matched controls with object relative clauses. In addition, participants with ASD with a history of language delay (diagnosed with high-functioning autism in the DSM-IV-TR) perform worse on subject relatives than ASD participants without language delay (diagnosed with Asperger syndrome in the DSM-IV-TR), suggesting that these two groups do not have equivalent linguistic abilities. Performance IQ has a positive impact on the success of the task for the population with ASD. Conclusions & Implications: This study reveals subtle grammatical difficulties remaining in adult individuals with ASD within normal IQ range as compared with age-matched peers. Even in the absence of a history of language delay in childhood, the results suggest that a slight deficit may nevertheless be present and go undetected by standardized language assessments. Both groups with and without language delay have a similar global performance on relative clause comprehension; however, the study also indicates that the participants with reported language delay show more difficulty with subject relatives than the participants without language delay, suggesting the presence of differences in linguistic abilities between these subgroups of ASD.

Facial expression processing and the attribution of facial emotions to a context were investigated in adults with Down syndrome (DS) in two experiments. Their performances were compared with those of a child control group matched for receptive vocabulary. The ability to process faces without emotional content was controlled for, and no differences appeared between the two groups. Specific impairments were found in the DS group according to the task modalities and the type of facial emotional expressions. In the emotion matching condition, the DS adults showed overall difficulties whereas in the identification and recognition conditions they were particularly impaired when processing the neutral expression. In the emotion attribution task, they exhibited difficulties with the sad expression only and the analysis of their error pattern revealed that they rarely selected this expression throughout the task. The sad emotion was the only one that showed a significant relationship with the facial expression processing tasks. (Contains 5 tables and 4 figures.)

Face processing and facial expression recognition was investigated in 17 adults with Down syndrome, and results were compared with those of a child control group matched for receptive vocabulary. On the tasks involving faces without emotional content, the adults with Down syndrome performed significantly worse than did the controls. However, their performance was good on the tests with complete faces. On the facial expression tasks, participants with Down syndrome exhibited particular difficulties with the neutral and surprised expressions. Analysis of their error pattern suggest they had a tendency to judge faces more positively than did the controls. Finally, there were significant relationships among emotional processing, receptive vocabulary, and inhibition measures; nonverbal reasoning ability was not related to any of the tasks.

The circumstances under which empathy is altered in ASD remain unclear, as previous studies did not systematically find differences in brain activation between ASD and controls in empathy-eliciting paradigms, and did not always monitor whether differences were primarily due to ASD "per se", or to conditions overlapping with ASD, such as alexithymia and anxiety. Here, we collected fMRI data from 47 participants (22 ASD) viewing pictures depicting hands and feet of unknown others in painful, disgusting, or neutral situations. We computed brain activity for painful and disgusting stimuli (vs. neutral) in whole brain and in regions of interest among the brain areas typically activated during the perception of nociceptive stimuli. Group differences in brain activation disappeared when either alexithymia or anxiety – both elevated in the ASD group – were controlled for. Regression analyses indicated that the influence of symptoms was mainly shared between autistic symptomatology, alexithymia and anxiety or driven by unique contributions from alexithymia or anxiety. Our results suggest that affective empathy may be affected in ASD, but that this association is complex. The respective contribution of alexithymia and anxiety to decreased affective empathy of people with ASD may be due to the association of those psychiatric conditions with reduced motor resonance/Theory of Mind. [ABSTRACT FROM AUTHOR]

Atypical patterns of face-scanning in individuals with autism spectrum disorder (ASD) may contribute to difficulties in social interactions, but there is little agreement regarding what exactly characterizes face-viewing in ASD. In addition, little research has examined how face-viewing is modulated by the emotional expression of the stimuli, in individuals with or without ASD. We used eye-tracking to explore viewing patterns during perception of dynamic emotional facial expressions in relatively large groups of individuals with ( n = 57) and without ASD ( n = 58) and examined diagnostic- and age-related effects, after subgrouping children and adolescents (≤18 years), on the one hand, and adults (>18 years), on the other. Results showed that children/adolescents with ASD fixated the mouth of happy and angry faces less than their typically developing (TD) peers, and conversely looked more to the eyes of happy faces. Moreover, while all groups fixated the mouth in happy faces more than in other expressions, children/adolescents with ASD did relatively less so. Correlation analysis showed a similar lack of relative orientation towards the mouth of smiling faces in TD children/adolescents with high autistic traits, as measured by the Autism-Spectrum Quotient (AQ). Among adults, participants with ASD only attended less to the eyes for neutral faces. Our study shows that the emotional content of a face influences gaze behaviour, and that this effect is not fully developed in children/adolescents with ASD. Interestingly, this lack of differentiation observed in the younger ASD group was also seen in younger TD individuals with higher AQ scores. Autism Res 2017, 10: 901-910. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Clinical observations have shown that GABA-acting benzodiazepines exert paradoxical excitatory effects in autism, suggesting elevated intracellular chloride (Cl–)i and excitatory action of GABA. In a previous double-blind randomized study, we have shown that the diuretic NKCC1 chloride importer antagonist bumetanide, that decreases (Cl–)i and reinforces GABAergic inhibition, reduces the severity of autism symptoms. Here, we report results from an open-label trial pilot study in which we used functional magnetic resonance imaging and neuropsychological testing to determine the effects of 10 months bumetanide treatment in adolescents and young adults with autism. We show that bumetanide treatment improves emotion recognition and enhances the activation of brain regions involved in social and emotional perception during the perception of emotional faces. The improvement of emotion processing by bumetanide reinforces the usefulness of bumetanide as a promising treatment to improve social interactions in autism. [ABSTRACT FROM PUBLISHER]

Individuals with Autism Spectrum Disorder (ASD) seem to have difficulties looking others in the eyes, but the substrate for this behavior is not well understood. The subcortical pathway, which consists of superior colliculus, pulvinar nucleus of the thalamus, and amygdala, enables rapid and automatic face processing. A specific component of this pathway – i.e., the amygdala – has been shown to be abnormally activated in paradigms where individuals had to specifically attend to the eye-region; however, a direct examination of the effect of manipulating the gaze to the eye-regions on all the components of the subcortical system altogether has never been performed. The subcortical system is particularly important as it shapes the functional specialization of the face-processing cortex during development. Using functional MRI, we investigated the effect of constraining gaze in the eye-region during dynamic emotional face perception in groups of participants with ASD and typical controls. We computed differences in activation in the subcortical face processing system (superior colliculus, pulvinar nucleus of the thalamus and amygdala) for the same stimuli seen freely or with the gaze constrained in the eye-region. Our results show that when constrained to look in the eyes, individuals with ASD show abnormally high activation in the subcortical system, which may be at the basis of their eye avoidance in daily life.