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

Autism spectrum disorder, essential fatty acids and infant feeding

 Dr Brown’s research identified the importance of breastfeeding duration and essential fatty acids in children. Her research found that children who were breastfed for a longer duration in infancy were significantly less likely to have a diagnosis of autism or show signs of a fatty acid deficiency.

Transcranial magnetic stimulation in autism spectrum disorder: challenges, promise, and roadmap for future research

Autism Spectrum Disorder (ASD) is a behaviorally defined complex neurodevelopmental syndrome characterized by impairments in social communication, by the presence of restricted and repetitive behaviors, interests and activities, and by abnormalities in sensory reactivity. Transcranial magnetic stimulation (TMS) is a promising, emerging tool for the study and potential treatment of ASD. Recent studies suggest that TMS measures provide rapid and noninvasive pathophysiological ASD biomarkers. Furthermore, repetitive TMS (rTMS) may represent a novel treatment strategy for reducing some of the core and associated ASD symptoms. However, the available literature on the TMS use in ASD is preliminary, composed of studies with methodological limitations. Thus, off-label clinical rTMS use for therapeutic interventions in ASD without an investigational device exemption and outside of an IRB approved research trial is premature pending further, adequately powered and controlled trials. Leaders in this field have gathered annually for a two-day conference (prior to the 2014 and 2015 International Meeting for Autism Research, IMFAR) to share recent progress, promote collaboration across laboratories, and establish consensus on protocols. Here we review the literature in the use of TMS in ASD in the context of the unique challenges required for the study and exploration of treatment strategies in this population. We also suggest future directions for this field of investigations. While its true potential in ASD has yet to be delineated, TMS represents an innovative research tool and a novel, possibly transformative approach to the treatment of neurodevelopmental disorders. Autism Res 2015. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Atypical neural activity in males but not females with autism spectrum disorder

The medial prefrontal cortex (mPFC) and the right temporo-parietal junction (rTPj) are highly involved in social understanding, a core area of impairment in autism spectrum disorder (ASD). We used fMRI to investigate sex differences in the neural correlates of social understanding in 27 high-functioning adults with ASD and 23 matched controls. There were no differences in neural activity in the mPFC or rTPj between groups during social processing. Whole brain analysis revealed decreased activity in the posterior superior temporal sulcus in males with ASD compared to control males while processing social information. This pattern was not observed in the female sub-sample. The current study indicates that sex mediates the neurobiology of ASD, particularly with respect to processing social information.

Evaluating discussion board engagement in the MoodSwings online self-help program for bipolar disorder: protocol for an observational prospective cohort study

BACKGROUND: Online, self-guided programs exist for a wide range of mental health conditions, including bipolar disorder, and discussion boards are often part of these interventions. The impact engagement with these discussion boards has on the psychosocial well-being of users is largely unknown. More specifically we need to clarify the influence of the type and level of engagement on outcomes. The primary aim of this exploratory study is to determine if there is a relationship between different types (active, passive or none) and levels (high, mid and low) of discussion board engagement and improvement in outcome measures from baseline to follow up, with a focus on self-reported social support, stigma, quality of life and levels of depression and mania. The secondary aim of this study is to identify any differences in demographic variables among discussion users.

METHODS/DESIGN: The present study is a sub-study of the MoodSwings 2.0 3-arm randomised controlled trial (discussion board only (arm 1), discussion board plus psychoeducation (arm 2), discussion board, psychoeducation plus cognitive behavioural therapy-based tools (arm 3)). Discussion engagement will be measured via online participant activity monitoring. Assessments include online self-report as well as blinded phone interviews at baseline, 3, 6, 9 and 12 months follow up.

DISCUSSION: The results of this study will help to inform future programs about whether or not discussion boards are a beneficial inclusion in online self-help interventions. It will also help to determine if motivating users to actively engage in online discussion is necessary, and if so, what level of engagement is optimal to produce the most benefit. Future programs may benefit through being able to identify those most likely to poorly engage, based on demographic variables, so motivational strategies can be targeted accordingly.

Altered expression of two zinc transporters, SLC30A5 and SLC30A6, underlies a mammary gland disorder of reduced zinc secretion into milk

Two cases of zinc deficiency in breastfed neonates were investigated where zinc levels in the mothers' milk were reduced by more than 75 % compared to normal. The objective of this study was to find the molecular basis of the maternal zinc deficiency condition. Significant reductions in mRNA expression and protein levels of the zinc transporters SLC30A5 and SLC30A6 were found in maternal tissue, suggesting a causal link to the zinc-deficient milk. Novel splice variants of the SLC30A6 transcript were detected. No modifications were found in coding regions, or in transcription binding sites of promoter regions or in 5' and 3' untranslated regions of both transporters in lymphoblasts and fibroblasts isolated from both mothers. Altered DNA methylation in SLC30A5 at two CpG sites was detected and may account for the reduced levels of SLC30A5 mRNA and protein in lymphoblasts. Reduced SLC30A6 mRNA and protein levels in lymphoblasts may be secondary to reduced SLC30A5 expression, as they function as a heterodimer in zinc transport. In conclusion, two cases of zinc deficiency are linked to low levels of the SLC30A5 and SLC30A6 zinc transporters. These two zinc transporters have not been previously associated with zinc deficiency in milk.

Exploring behavioral sleep problems in children with ADHD and comorbid Autism Spectrum Disorder

OBJECTIVE: This study (a) compared behavioral sleep problems in children with comorbid ADHD and autism spectrum disorder (ASD) with those with ADHD and (b) examined child/family factors associated with sleep problems. METHOD: Cross-sectional study comparison of 392 children with a confirmed ADHD diagnosis (ADHD+ASD, n=93, ADHD, n=299) recruited from 21 peadiatric practises in Victoria, Australia. Data were collected from parents. Key measures included the Child Sleep Habits Questionnaire (CSHQ). RESULTS: Children with ADHD + ASD experienced similar levels and types of behavioral sleep problems compared with those with ADHD. In both groups, the presence of co-occurring internalizing and externalizing comorbidities was associated with sleep problems. Sleep problems were also associated with parent age in the ADHD + ASD group and poorer parent mental health in the ADHD group. CONCLUSION: Findings suggest comorbid ASD is not associated with increased behavioral sleep problems in children with ADHD and that co-occurring internalizing and externalizing comorbidities may flag children in these groups with sleep problems.