Elephants in pyjamas: testing the weak central coherence account of autism spectrum disorders using a syntactic disambiguation task

According to the weak central coherence (CC) account individuals with autism spectrum disorders (ASD) exhibit enhanced local processing and weak part-whole integration. CC was investigated in the verbal domain. Adolescents, recruited using a 2 (ASD status) by 2 (language impairment status) design, completed an aural forced choice comprehension task involving syntactically ambiguous sentences. Half the picture targets depicted the least plausible interpretation, resulting in longer RTs across groups. These were assumed to reflect local processing. There was no ASD by plausibility interaction and consequently little evidence for weak CC in the verbal domain when conceptualised as enhanced local processing. Furthermore, there was little evidence that the processing of syntactically ambiguous sentences differed as a function of ASD or language-impairment status.

The binocular coordination of eye movements during reading in children and adults

Recent evidence indicates that each eye does not always fixate the same letter during reading and there has been some suggestion that processing difficulty may influence binocular coordination. We recorded binocular eye movements from children and adults reading sentences containing a word frequency manipulation. We found disparities of significant magnitude between the two eyes for all participants, with greater disparity magnitudes in children than adults. All participants made fewer crossed than uncrossed fixations. However, children made a higher proportion of crossed fixations than adults. We found no influence of word frequency on children’s fixations and on binocular coordination in adults.

Molecular targets of cannabidiol in neurological disorders

Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD’s beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular phar- macology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD’s relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeu- tics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent with modulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug’s action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excluding unlikely and implausible targets, the remaining molecular targets of CBD with plausible evidence for involvement in therapeutic effects in neurological disorders (e.g., voltage-dependent anion channel 1, G protein-coupled receptor 55, CaV3.x, etc.) are associated with either the regulation of, or responses to changes in, intracellular calcium levels. While no causal proof yet exists for CBD’s effects at these targets, they represent the most probable for such investigations and should be prioritized in further studies of CBD’s therapeutic mechanism of action.

Mental health, coping and family-functioning in parents of young people with obsessive-compulsive disorder and with anxiety disorders

Objective. To compare mental health, coping and family-functioning in parents of young people with obsessive-compulsive disorder (OCD), anxiety disorders, and no known mental health problems. Method. Parents of young people with OCD (N=28), other anxiety disorders (N=28), and no known mental health problems (N=62) completed the Brief Symptom Inventory (Derogatis, 1993), the Coping Responses Inventory (Moos, 1990), and the McMaster family assessment device (Epstein, Baldwin, & Bishop, 1983). Results. Parents of children with OCD and anxiety disorders had poorer mental health and used more avoidant coping than parents of non-clinical children. There were no group differences in family-functioning. Conclusion. The similarities across the parents of clinically referred children suggest that there is a case for encouraging active parental involvement in the treatment of OCD in young people.

Multi-sensory treatment for children with developmental motor speech disorders

What this paper adds? What is already known on the subject? Multi-sensory treatment approaches have been shown to impact outcome measures positively, such as accuracy of speech movement patterns and speech intelligibility in adults with motor speech disorders, as well as in children with apraxia of speech, autism and cerebral palsy. However, there has been no empirical study using multi-sensory treatment for children with speech sound disorders (SSDs) who demonstrate motor control issues in the jaw and orofacial structures (e.g. jaw sliding, jaw over extension, inadequate lip rounding/retraction and decreased integration of speech movements). What this paper adds? Findings from this study indicate that, for speech production disorders where both the planning and production of spatiotemporal parameters of movement sequences for speech are disrupted, multi-sensory treatment programmes that integrate auditory, visual and tactile–kinesthetic information improve auditory and visual accuracy of speech production. The training (practised in treatment) and test words (not practised in treatment) both demonstrated positive change in most participants, indicating generalization of target features to untrained words. It is inferred that treatment that focuses on integrating multi-sensory information and normalizing parameters of speech movements is an effective method for treating children with SSDs who demonstrate speech motor control issues.

The relationship between challenging parenting behaviour and childhood anxiety disorders

Background: This research investigates the relationship between challenging parenting behaviour and childhood anxiety disorders proposed by Bögels and Phares (2008). Challenging parenting behaviour involves the playful encouragement of children to go beyond their own limits, and may decrease children’s risk for anxiety (Bögels & Phares, 2008). Method: Parents (n = 164 mothers, 144 fathers) of 164 children aged between 3.4 and 4.8 years participated in the current study. A multi-method, multi-informant assessment of anxiety was used, incorporating data from diagnostic interviews as well as questionnaire measures. Parents completed self-report measures of their parenting behaviour (n = 147 mothers, 138 fathers) and anxiety (n = 154 mothers, 143 fathers). Mothers reported on their child’s anxiety via questionnaire as well as diagnostic interview (n = 156 and 164 respectively). Of these children, 74 met criteria for an anxiety disorder and 90 did not. Results: Fathers engaged in challenging parenting behaviour more often than mothers. Both mothers’ and fathers’ challenging parenting behaviour was associated with lower report of child anxiety symptoms. However, only mothers’ challenging parenting behaviour was found to predict child clinical anxiety diagnosis. Limitations: Shared method variance from mothers confined the interpretation of these results. Moreover, due to study design, it is not possible to delineate cause and effect. Conclusions: The finding with respect to maternal challenging parenting behaviour was not anticipated, prompting replication of these results. Future research should investigate the role of challenging parenting behaviour by both caregivers as this may have implications for parenting interventions for anxious children.

Genome-wide association study of response to cognitive behavioural therapy in children with anxiety disorders

Background Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent. Aims To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980). Method Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up. Results No variants passed a genome-wide significance threshold (P = 5×10−8) in either analysis. Four variants met criteria for suggestive significance (P<5×10−6) in association with response post-treatment, and three variants in the 6-month follow-up analysis. Conclusions This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.

A genome-wide test of the differential susceptibility hypothesis reveals a genetic predictor of differential response to psychological treatments for child anxiety disorders

Background: The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candidate genes. In this study we extended the differential susceptibility hypothesis from a candidate gene to a genome-wide approach to test whether a polygenic score of environmental sensitivity predicted response to Cognitive Behavioural Therapy (CBT) in children with anxiety disorders. Methods: We identified variants associated with environmental sensitivity using a novel method in which within-pair variability in emotional problems in 1026 monozygotic (MZ) twin pairs was examined as a function of the pairs’ genotype. We created a polygenic score of environmental sensitivity based on the whole-genome findings and tested the score as a moderator of parenting on emotional problems in 1,406 children and response to individual, group and brief parent-led CBT in 973 children with anxiety disorders. Results: The polygenic score significantly moderated the effects of parenting on emotional problems and the effects of treatment. Individuals with a high score responded significantly better to individual CBT than group CBT or brief parent-led CBT (remission rates: 70.9%, 55.5% and 41.6% respectively). Conclusions: Pending successful replication, our results should be considered exploratory. Nevertheless, if replicated, they suggest that individuals with the greatest environmental sensitivity may be more likely to develop emotional problems in adverse environments, but also benefit more from the most intensive types of treatment.

Does modulation of the endocannabinoid system have potential therapeutic utility in cerebellar ataxia?

Cerebellar ataxias represent a spectrum of disorders which are, however, linked by common symptoms of motor incoordination and are typically associated with deficient in Purkinje cell firing activity and, often, degeneration. Cerebellar ataxias currently lack a curative agent. The endocannabinoid (eCB) system includes eCB compounds and their associated metabolic enzymes, together with cannabinoid receptors, predominantly the cannabinoid CB1 receptor (CB1R) in the cerebellum; activation of this system in the cerebellar cortex is associated with deficits in motor coordination characteristic of ataxia, effects which can be prevented by CB1R antagonists. Of further interest are various findings that CB1R deficits may also induce a progressive ataxic phenotype. Together these studies suggest that motor coordination is reliant on maintaining the correct balance in eCB system signalling. Recent work also demonstrates deficient cannabinoid signalling in the mouse ‘ducky2J’ model of ataxia. In light of these points, the potential mechanisms whereby cannabinoids may modulate the eCB system to ameliorate dysfunction associated with cerebellar ataxias are considered.

Corticomuscular coherence modulation with the pattern of finger force coordination

We assess the corticomuscular coherence (CMC) of the contralateral primary motor cortex and the hand muscles during a finger force-tracking task and explore whether the pattern of finger coordination has an impact on the CMC level. Six healthy subjects (three men and three women) were recruited to conduct the force-tracking tasks comprising two finger patterns, i.e., natural combination of index and middle fingers and unnatural combination of index and middle fingers (i.e., simultaneously producing equal force strength in index and middle finger). During the conducting of the tasks with right index and middle finger, MEG and sEMG signals were recorded from left primary motor cortex (M1) and right flexor digitorum superficialis (FDS), respectively; the contralateral CMC was calculated to assess the neuromuscular interaction. Finger force-tracking tasks of Common-IM only induce beta-band CMC, whereas Uncommon-IM tasks produce CMC in both beta and low-gamma band. Compared to the force-tracking tasks of Common-IM, the Uncommon-IM task is associated with the most intensive contralateral CMC. Our study demonstrated that the pattern of finger coordination had significant impact on the CMC between the contralateral M1 and hand muscles, and more corticomuscular interaction was necessary for unnaturally coordinated finger activities to regulate the fixed neural drive of hand muscles.

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.

Coordination, inclusiveness and wage inequality between median and bottom income workers

What explains cross-national variation in wage inequality? Research in comparative political economy stresses the importance of the welfare state and wage coordination in reducing not only disposable income inequality but also gross earnings inequality. However, the cross-national variation in gross earnings inequality between median and low income workers is at odds with this conventional wisdom: the German coordinated market economy is now more unequal in this type of inequality than the UK, a liberal market economy. To solve this puzzle, I argue that non-inclusive coordination benefits median but not bottom income workers and is as a result associated with higher – rather than lower - wage inequality. I find support for this argument using a large N quantitative analysis of wage inequality in a panel of Western European countries. Results are robust to the inclusion of numerous controls, country fixed effects, and also hold with a sample of OECD countries. Taken together these findings force us to reconsider the relationship between coordination and wage inequality at the bottom of the income distribution.