Reduced motor imagery efficiency is associated with online control difficulties in children with probable developmental coordination disorder

Recent evidence indicates that the ability to correct reaching movements in response to unexpected target changes (i.e., online control) is reduced in children with developmental coordination disorder (DCD). Recent computational modeling of human reaching suggests that these inefficiencies may result from difficulties generating and/or monitoring internal representations of movement. This study was the first to test this putative relationship empirically. We did so by investigating the degree to which the capacity to correct reaching mid-flight could be predicted by motor imagery (MI) proficiency in a sample of children with probable DCD (pDCD). Thirty-four children aged 8 to 12 years (17 children with pDCD and 17 age-matched controls) completed the hand rotation task, a well-validated measure of MI, and a double-step reaching task (DSRT), a protocol commonly adopted to infer one's capacity for correcting reaching online. As per previous research, children with pDCD demonstrated inefficiencies in their ability to generate internal action representations and correct their reaching online, demonstrated by inefficient hand rotation performance and slower correction to the reach trajectory following unexpected target perturbation during the DSRT compared to age-matched controls. Critically, hierarchical moderating regression demonstrated that even after general reaching ability was controlled for, MI efficiency was a significant predictor of reaching correction efficiency, a relationship that was constant across groups. Ours is the first study to provide direct pilot evidence in support of the view that a decreased capacity for online control of reaching typical of DCD may be associated with inefficiencies generating and/or using internal representations of action.

Serotonin 1a receptor and associated G-protein activation in schizophrenia and bipolar disorder

Abnormalities in the serotonergic signalling system, including the serotonin 1a receptor, have been implicated in the pathogenesis of schizophrenia and bipolar 1 disorder. However, there is no consensus on whether the density of the serotonin 1a receptor and/or the activity of the G-proteins linking the receptor to the intracellular cascade are altered in these disease states. To address these issues, tissue obtained postmortem from four cortical regions was used to measure [3H] 8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) binding and 8-OH-DPAT-stimulated guanosine 5′-[γ-thio]triphosphate (GTPγS) binding to determine if either parameter is altered in schizophrenia or bipolar I disorder. There was an effect of diagnosis on the level of [3H] 8-OH-DPAT binding that may indicate a global change in the density of serotonin 1a receptors, although this effect did not reach significance in any individual brain region. The activation of serotonin 1a receptors did not differ significantly with diagnoses. However, in the outer cortical layers, there appeared to be a dissociation between the number of receptors available and the extent of ligand-induced GTPγS binding, suggesting considerable receptor reserve. In addition, comparing gender independent of diagnoses, a decrease in the levels of serotonin 1a receptors was observed in the cortex of female subjects. These data indicates that there may be subtle changes in serotonin 1a receptors across the cortex in schizophrenia or bipolar I disorder and suggests a gender discordance in receptor levels.

N-Ethylmaleimide sensitive factor in the cortex of subjects with schizophrenia and bipolar I disorder

N-Ethylmaleimide sensitive factor (NSF) is a presynaptic protein that has been suggested to be differentially expressed in the cortex of schizophrenic subjects through both high-throughput proteomic and genomic screening studies. Thus, to expand upon these studies we measured NSF using Western blotting in four regions of the cortex (BA9, 10, 40 and 46), in a cohort comprising 20 schizophrenic subjects, 8 bipolar I disorder subjects, and 20 control subjects. There was no significant difference in NSF levels between diagnostic cohorts in any of the four cortical regions. These findings highlight the importance of validating findings from high-throughput screening studies and do not support changes in cortical NSF as being of significance in schizophrenia or bipolar 1 disorder.

Regionally specific changes in levels of cortical S100β in bipolar 1 disorder but not schizophrenia

Objective: To determine if levels of the glial-derived proteins S100β and glial acidic fibrillary protein (GFAP) and the pro- and antiapoptotic proteins p53 and Bcl-2 were altered in the cortex of subjects with schizophrenia or bipolar 1 disorder.
Method: Levels of S100β, GFAP, p53 and Bcl-2 were measured in cortex (Brodmann's Areas (BAs) 9, 10, 46 and 40) of control subjects and subjects with schizophrenia, bipolar 1 disorder and in the cortex of rats treated with haloperidol or lithium using protein-specific antibodies and western blot analysis.
Results: Levels of S100β were decreased in BA 9 and increased in BA 40 from subjects with bipolar 1 disorder. Levels of this protein were not altered in other CNS regions, in schizophrenia or in the cortex of rats treated with haloperidol or lithium. No changes in levels of the other three proteins were detected across diagnoses.
Conclusions: Regionally selective changes in cortical S100β may be associated with the pathology of bipolar 1 disorder and may reflect derangements in neuronal death or survival

Virtual worlds for people with autism spectrum disorder: a case study in Second Life

PURPOSE: The purpose of this study is to explore the use of virtual worlds by people with autism spectrum disorder (ASD), with a particular focus on the virtual world Second Life™. METHOD: Case study methodology was selected to explore the experiences of Wolf, a participant with ASD, in Second Life. Wolf participated in three in-depth interviews. The interviews were analyzed using a content analysis to identify themes and sub-themes. RESULTS: Analysis identified four main themes: social factors and communication, empowerment, virtual world versus physical world, and social cues and body language. CONCLUSION: Anecdotally Wolf's experiences suggest that people with ASD enjoy using a virtual world and may feel more comfortable communicating in the virtual world context than the physical world. Virtual worlds offer a venue for people with ASD to be a part of a virtual society, lowers communication barriers experienced in the physical world, and gives the participant a unique opportunity to create and maintain friendships. Virtual worlds offer an arena for people with ASD to meet their peers on equal terms, not being dependent on social cues, which in the physical world can be a barrier for communication for this group. Further research in this area is required. Implications for Rehabiliation People with autism spectrum disorder enjoy using a virtual world and may feel more comfortable communicating in the virtual world context than the physical world. Virtual worlds offer a venue for people with autism spectrum disorder to be a part of a virtual society. Virtual worlds offer an arena for people with autism spectrum disorder to meet their peers on equal terms, not being dependent on social cues, which in the physical world can be a barrier for this group.

Diet and bipolar disorder: a review of its relationship and potential therapeutic mechanisms of action

OBJECTIVES: It is well accepted that diet quality has an important role in the prevention and treatment of several physical diseases. However, its influence on mental health has received far less attention, although there is increasing evidence to support a relationship with depression. In this narrative review, investigations into the relationship between diet and bipolar disorder are examined and the potential implications in the management and treatment of bipolar disorder are reviewed. METHODS: The authors provide a narrative review of the relevant information. RESULTS: Research is limited, although there are preliminary findings to suggest a relationship between diet and bipolar disorder. Findings from cross-sectional research suggest that people with bipolar disorder consume an unhealthier dietary pattern. This has significant treatment implications as bipolar disorder has a high comorbidity with several physical diseases. In addition, diet also influences several biological processes that are dysregulated in bipolar disorder, namely monoaminergic activity, immune/inflammatory processes, oxidative stress, mitochondrial activity, and neuroprogression. CONCLUSIONS: The role of diet in bipolar disorder requires further attention in research as it presents as a factor that may contribute to the worsening course of this condition and may potentially enhance current treatment outcomes.

Reduced mu suppression and altered motor resonance in euthymic bipolar disorder: evidence for a dysfunctional mirror system?

Social cognitive difficulties are common in the acute phase of bipolar disorder and, to a lesser extent, during the euthymic stage, and imaging studies of social cognition in euthymic bipolar disorder have implicated mirror system brain regions. This study aimed to use a novel multimodal approach (i.e., including both transcranial magnetic stimulation (TMS) and electroencephalogram (EEG)) to investigate mirror systems in bipolar disorder. Fifteen individuals with euthymic bipolar disorder and 16 healthy controls participated in this study. Single-pulse TMS was applied to the optimal site in the primary motor cortex (M1), which stimulates the muscle of interest during the observation of hand movements (goal-directed or interacting) designed to elicit mirror system activity. Single EEG electrodes (C3, CZ, C4) recorded mu rhythm modulation concurrently. Results revealed that the patient group showed significantly less mu suppression compared to healthy controls. Surprisingly, motor resonance was not significantly different overall between groups; however, bipolar disorder participants showed a pattern of reduced reactivity on some conditions. Although preliminary, this study indicates a potential mirror system deficit in euthymic bipolar disorder, which may contribute to the pathophysiology of the disorder.

N-Acetyl Cysteine (NAC) in the treatment of obsessive-compulsive disorder: a 16-week, double-blind, randomised, placebo-controlled study

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling mental illness for which pharmacological and psychosocial interventions are all too often inadequate. Recent preclinical and clinical studies have implicated dysfunction of glutamatergic neurotransmission in the pathophysiology of OCD. The amino acid-based nutraceutical N-acetyl cysteine (NAC) is a safe and readily available agent that has been found to modify the synaptic release of glutamate in subcortical brain regions via modulation of the cysteine-glutamate antiporter. OBJECTIVE: The aim of this study was to assess the efficacy and safety of NAC in treating OCD. METHODS: A 16-week, double-blind, placebo-controlled, randomised trial using 3 g/day of NAC (1.5 g twice daily) in 44 participants (aged 18-70 years) with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)-diagnosed OCD, during 2013-2015. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (YBOCS), conducted every 4 weeks. RESULTS: Analysis of the full sample (intention-to-treat) with repeated measures mixed linear modelling revealed a nonsignificant time × treatment interaction for the YBOCS scale total score (p = 0.39). A per-protocol analysis removing protocol violators also failed to show a significant time × treatment interaction for YBOCS total score (p = 0.15). However, a significant time × treatment interaction was observed for the YBOCS 'Compulsions' subscale in favour of NAC (p = 0.013), with a significant reduction observed at week 12 (dissipating at week 16). At 16 weeks, only four (20 %) participants were considered 'responders' (YBOCS ≥35 % reduction at endpoint) versus four (27 %) in the placebo group. The NAC was well-tolerated, aside from more cases of heartburn occurring compared with placebo (p = 0.045). CONCLUSION: Further research involving NAC for OCD may require larger samples to detect moderate or small effect sizes, involve dosage or formulation differences, use in concert with exposure therapy, or an additional post-study observational period to mitigate study withdrawal. TRIAL REGISTRATION: ACTRN12613000310763.

The relationship between problem gambling and attention deficit hyperactivity disorder

Recent studies indicate that treatment-seeking problem gamblers display elevated rates of ADHD and that adolescents who screen positive for ADHD are more likely to engage in gambling, develop gambling problems, and experience a greater severity in gambling problems. This study aimed to (a) compare the prevalence of ADHD in treatment-seeking problem gamblers to the general population; (b) investigate the relationships between ADHD and problem gambling severity, cluster B personality disorders, motor impulsivity, alcohol use, substance use, gender, and age; and (c) investigate the degree to which these factors moderate the relationship between ADHD and problem gambling severity. Participants included 214 adults (154 males, 58 females, 2 unspecified) who sought treatment for their gambling problems at a specialist gambling agency in Melbourne, Australia. Almost one-quarter (24.9 %) of treatment-seeking problem gamblers screened positively for ADHD, which was significantly higher than the 14 % prevalence in a community sample. ADHD was significantly positively correlated with problem gambling severity, motor impulsivity, and cluster B personality disorders, but was not associated with alcohol and substance use, gender or age. None of the factors significantly moderated the relationship between ADHD and problem gambling severity. These findings suggest that a considerable proportion of treatment-seeking problem gamblers report ADHD and that their clinical profile is complicated by the presence of high impulsivity and cluster B personality disorders. They highlight the need for specialist gambling agencies to develop screening, assessment, and management protocols for co-occurring ADHD to enhance the effectiveness of treatment.

An investigation of the potential association between mercury and Autism Spectrum Disorder: an interdisciplinary approach

 Dr Shandley took a novel approach to investigate the mercury-autism hypothesis. Her studies unearthed conflicting results. Contrary to previous biological studies, autistic children did not demonstrate a pattern of mercury toxicity. However, in a world first study, Dr Shandley found that the rate of autism among children with a family history of mercury sensitivity was 6-7 times higher than the general population.

Future directions for pharmacotherapies for treatment-resistant bipolar disorder

Current pharmacological treatments for bipolar disorder (BD) are limited and efficacy has historically been discovered through serendipity. There is now scope for new drug development, focused on the underlying biology of BD that is not targeted by current therapies. The need for novel treatments is urgent when considering treatment resistant BD, where current therapies have failed. While established drugs targeting the monoamine systems continue to be worthwhile, new biological targets including inflammatory and oxidative an nitrosative pathways, apoptotic and neurotrophic pathways, mitochondrial pathways, the N-methyl-Daspartate (NMDA)-receptor complex, the purinergic system, neuropeptide system, cholinergic system and melatonin pathways are all being identified as potential anchors for the discovery of new agents. Many agents are experimental and efficacy data is limited, however further investigation may provide a new line for drug discovery, previously stalled by lack of corporate interest.

Autism spectrum disorder symptoms in children with ADHD: a community-based study

This study examined the prevalence of autism spectrum disorder (ASD) symptoms in a community-based sample of children with attention-deficit/hyperactivity disorder (ADHD) and non-ADHD controls. We also examined the relationship between ASD symptoms and ADHD subtype, ADHD symptom severity and child gender. Participants were 6-10-year-old children (164 ADHD; 198 non-ADHD control) attending 43 schools in Melbourne, Australia, who were participating in the Children's Attention Project. ADHD was assessed in two stages using the parent and teacher Conners' 3 ADHD index and the Diagnostic Interview Schedule for Children IV (DISC-IV). ASD symptoms were identified using the Social Communication Questionnaire (SCQ). Unadjusted and adjusted linear and logistic regression examined continuous and categorical outcomes, respectively. Children with ADHD had more ASD symptoms than non-ADHD controls (adjusted mean difference=4.0, 95% confidence interval (CI) 2.8; 5.3, p<0.001, effect size=0.7). Boys with ADHD had greater ASD symptom severity than girls with ADHD (adjusted mean difference=2.9, 95% CI 0.8; 5.2, p=0.01, effect size=0.4). Greater ADHD symptom severity was associated with greater ASD symptom severity (regression co-efficient=1.6, 95% CI 1.2; 2.0, p<0.001). No differences were observed by ADHD subtype. Greater hyperactive/impulsive symptoms were associated with greater ASD symptoms (regression coefficient=1.0; 95% CI 0.0; 2.0, p=0.04) however, this finding attenuated in adjusted analyses (p=0.45). ASD symptoms are common in children with ADHD. It is important for clinicians to assess for ASD symptoms to ensure appropriate intervention.

Mechanisms of anxiety related attentional biases in children with Autism Spectrum Disorder

Children with autism spectrum disorder (ASD) have high levels of anxiety. It is unclear whether they exhibit threat-related attentional biases commensurate with anxiety disorders as manifest in non-ASD populations, such as facilitated attention toward, and difficulties disengaging engaging from, threatening stimuli. Ninety children, 45 cognitively able with ASD and 45 age, perceptual-IQ, and gender matched typically developing children, aged 7–12 years, were administered a visual dot probe task using threatening facial pictures. Parent-reported anxiety symptoms were also collected. Children with ASD showed similarly high levels of anxiety compared with normative data from an anxiety disordered sample. Children with ASD had higher levels of parent-reported anxiety but did not show differences in disengaging from, or facilitated attention toward, threatening facial stimuli compared with typically developing children. In contrast to previously published studies of anxious children, in this study there were no differences in attentional biases in children with ASD meeting clinical cutoff for anxiety and those who did not. There were no correlations between attentional biases and anxiety symptoms and no gender differences. These findings indicate the cognitive mechanisms underlying anxiety in cognitively able children with ASD could differ from those commonly found in anxious children which may have implications for both understanding the aetiology of anxiety in ASD and for anxiety interventions