Cross-national differences in questionnaires do not necessarily reflect comparable differences in disorder prevalence.

PURPOSE: To examine whether the widely used Strengths and Difficulties Questionnaire (SDQ) can validly be used to compare the prevalence of child mental health problems cross nationally. METHODS: We used data on 29,225 5- to 16-year olds in eight population-based studies from seven countries: Bangladesh, Brazil, Britain, India, Norway, Russia and Yemen. Parents completed the SDQ in all eight studies, teachers in seven studies and youth in five studies. We used these SDQ data to calculate three different sorts of "caseness indicators" based on (1) SDQ symptoms, (2) SDQ symptoms plus impact and (3) an overall respondent judgement of 'definite' or 'severe' difficulties. Respondents also completed structured diagnostic interviews including extensive open-ended questions (the Development and Well-Being Assessment, DAWBA). Diagnostic ratings were all carried out or supervised by the DAWBA's creator, working in conjunction with experienced local professionals. RESULTS: As judged by the DAWBA, the prevalence of any mental disorder ranged from 2.2% in India to 17.1% in Russia. The nine SDQ caseness indicators (three indicators times three informants) explained 8-56% of the cross-national variation in disorder prevalence. This was insufficient to make meaningful prevalence estimates since populations with a similar measured prevalence of disorder on the DAWBA showed large variations across the various SDQ caseness indicators. CONCLUSIONS: The relationship between SDQ caseness indicators and disorder rates varies substantially between populations: cross-national differences in SDQ indicators do not necessarily reflect comparable differences in disorder rates. More generally, considerable caution is required when interpreting cross-cultural comparisons of mental health, particularly when these rely on brief questionnaires

Atypical audiovisual speech integration in infants at risk for autism

The language difficulties often seen in individuals with autism might stem from an inability to integrate audiovisual information, a skill important for language development. We investigated whether 9-month-old siblings of older children with autism, who are at an increased risk of developing autism, are able to integrate audiovisual speech cues. We used an eye-tracker to record where infants looked when shown a screen displaying two faces of the same model, where one face is articulating/ba/and the other/ga/, with one face congruent with the syllable sound being presented simultaneously, the other face incongruent. This method was successful in showing that infants at low risk can integrate audiovisual speech: they looked for the same amount of time at the mouths in both the fusible visual/ga/− audio/ba/and the congruent visual/ba/− audio/ba/displays, indicating that the auditory and visual streams fuse into a McGurk-type of syllabic percept in the incongruent condition. It also showed that low-risk infants could perceive a mismatch between auditory and visual cues: they looked longer at the mouth in the mismatched, non-fusible visual/ba/− audio/ga/display compared with the congruent visual/ga/− audio/ga/display, demonstrating that they perceive an uncommon, and therefore interesting, speech-like percept when looking at the incongruent mouth (repeated ANOVA: displays x fusion/mismatch conditions interaction: F(1,16) = 17.153, p = 0.001). The looking behaviour of high-risk infants did not differ according to the type of display, suggesting difficulties in matching auditory and visual information (repeated ANOVA, displays x conditions interaction: F(1,25) = 0.09, p = 0.767), in contrast to low-risk infants (repeated ANOVA: displays x conditions x low/high-risk groups interaction: F(1,41) = 4.466, p = 0.041). In some cases this reduced ability might lead to the poor communication skills characteristic of autism

Enhanced visual search in infancy predicts emerging autism symptoms

In addition to core symptoms, i.e., social interaction and communication difficulties and restricted and repetitive behaviours, autism is also characterized by aspects of superior perception [1]. One well-replicated finding is that of superior performance in visual search tasks, in which participants have to indicate the presence of an odd-one-out element amongst a number of foils [2,3,4,5]. Whether these aspects of superior perception contribute to the emergence of core autism symptoms remains debated [6,4]. Perceptual and social interaction skills could reflect co-expressed but biologically independent pathologies, as suggested by a “fractionable” phenotype model of autism [7]. A developmental test of this hypothesis is now made possible by longitudinal cohorts of infants at high risk, such as of younger siblings of children with ASD. Around 20% of younger siblings are diagnosed with autism themselves [8], and up to another 30% manifest elevated levels of autism symptoms [9]. We used eye-tracking to measure spontaneous orienting to letter targets (O, S, V and +) presented amongst distractors (the letter X, Figure 1). At 9 and 15 months, emerging autism symptoms were assessed using the Autism Observation Scale for Infants (AOSI; 10) and at 2 years of age using the Autism Diagnostic Observation Schedule (ADOS; 11). Enhanced visual search performance at 9-month predicted a higher level of autism symptoms at 15 months and at 2 years. Infant perceptual atypicalities are thus intrinsically linked to the emerging autism phenotype

The ethics of ‘Trials within Cohorts’ (TwiCs): 2nd international symposium - London, UK. 7-8 November 2016

On 7-8 th November 2016, 60 people with an interest in the ‘ Trials within Cohorts ’ (TwiCs) approach for randomised controlled trial design met in London. The purpose of this 2 nd TwiCs international symposium was to share perspectives and experiences on ethical aspects of the TwiCs design, discuss how TwiCs relate to the current ethical frame- work, provide a forum in which to discuss and debate ethical issues and identify future directions for conceptual and empirical research. The symposium was supported by the Wellcome Trust and the NIHR CLAHRC Yorkshire and Humber and organised by members of the TwiCs network led by Clare Relton and attended by people from the UK, the Netherlands, Norway, Canada and USA. The two-day sympo- sium enabled an international group to meet and share experiences of the TwiCs design (also known as the ‘ cohort multiple RCT design ’ ), and to discuss plans for future research. Over the two days, invited plenary talks were interspersed by discussions, posters and mini pre- sentations from bioethicists, triallists and health research regulators. Key findings of the symposium were: (1) It is possible to make a compelling case to ethics committees that TwiCs designs are ap- propriate and ethical; (2) The importance of wider considerations around the ethics of inefficient trial designs; and (3) some questions about the ethical requirements for content and timing of informed consent for a study using the TwiCs design need to be decided on a case-by-case basis

Sex- and sub region-dependent modulation of arcuate kisspeptin neurones by vasopressin and vasoactive intestinal peptide.

A population of kisspeptin neurones located in the hypothalamic arcuate nucleus (ARN) very likely represent the gonadotrophin-releasing hormone pulse generator responsible for driving pulsatile luteinising hormone secretion in mammals. As such, it has become important to understand the neural inputs that modulate the activity of ARN kisspeptin (ARNKISS ) neurones. Using a transgenic GCaMP6 mouse model allowing the intracellular calcium levels ([Ca2+ ]i ) of individual ARNKISS neurones to be assessed simultaneously, we examined whether the circadian neuropeptides vasoactive intestinal peptide (VIP) and arginine vasopressin (AVP) modulated the activity of ARNKISS neurones directly. To validate this methodology, we initially evaluated the effects of neurokinin B (NKB) on [Ca2+ ]i in kisspeptin neurones residing within the rostral, middle and caudal ARN subregions of adult male and female mice. All experiments were undertaken in the presence of tetrodotoxin and ionotropic amino acid antagonists. NKB was found to evoke an abrupt increase in [Ca2+ ]i in 95%-100% of kisspeptin neurones throughout the ARN of both sexes. By contrast, both VIP and AVP were found to primarily activate kisspeptin neurones located in the caudal ARN of female mice. Although 58% and 59% of caudal ARN kisspeptin neurones responded to AVP and VIP, respectively, in female mice, only 0%-8% of kisspeptin neurones located in other ARN subregions responded in females and 0%-12% of cells in any subregion in males (P < 0.05). These observations demonstrate unexpected sex differences and marked heterogeneity in functional neuropeptide receptor expression amongst ARNKISS neurones organised on a rostro-caudal basis. The functional significance of this unexpected influence of VIP and AVP on ARNKISS neurones remains to be established.This work was supported by University of Otago Health Science Division Masters Scholarship (DS) and the New Zealand Health Research Council. DS designed and performed the calcium imaging studies. GK performed the immunohistochemistry studies. WH provided essential reagents. RP designed the research and analysed data, AH designed the research, analysed data and co‐wrote the manuscript alongside the other authors