Online motor control in children with developmental coordination disorder: chronometric analysis of double-step reaching performance

Background
Although there are a number of plausible accounts to explain movement clumsiness in children [or developmental coordination disorder (DCD)], the cause(s) of the disorder remain(s) an issue of debate. One aspect of motor control that is particularly important to the fluid expression of skill is rapid online control (ROC). Data on DCD have been conflicting. While some recent work using double-step reaching suggests no difficulty in online control, others suggest deficits (e.g. based on sequential pointing). To help resolve this debate, we suggest two things: use of recent neuro-computational models as a framework for investigating motor control in DCD, and more rigorous investigation of double-step reaching. Our working assumption here is that ROC is only viable through the seamless integration of predictive (or forward) models of movement and feedback-based mechanisms.

Aim
The aim of this chronometric study was to explore ROC in children with DCD using a double-step reaching paradigm. We predicted slower online adjustments in DCD based on the argument that these children manifest a core difficulty in predictive control.

Methods
Participants were a group of 17 children with DCD and 27 typically developing children aged between 7 and 12 years. Visual targets were presented on a 17-inch LCD touch screen, inclined to an angle of 15° from horizontal. The children were instructed to press each target as it appeared as quickly and accurately as possible. For 80% of the trials, the central target location remained unchanged for the duration of the movement (non-jump trials), while for the remaining 20% of trials, the target jumped at movement onset to one of the two peripheral locations (jump trials). Reaction time (RT), movement time (MT) and reaching errors were recorded.

Results
For both groups, RT did not vary according to trial condition, while children with DCD were slower to initiate movement. Further, the MT of children with DCD was prolonged to a far greater extent on jump trials relative to controls, with a large effect size. As well, children with DCD committed significantly more errors, notably a reduced ability to inhibit central responses on jump trials.

Conclusion
Our findings help reconcile some disparate findings in the literature using similar tasks. The pattern of performance in children with DCD suggests impairment in the ability to make rapid online adjustments that are based on a predictive (or internal) model of the action. These results pave the way for future kinematic investigation.

Study protocol for a randomised controlled trial of internet-based cognitive-behavioural therapy for obsessive-compulsive disorder.

Obsessive-Compulsive Disorder (OCD) is a common chronic psychiatric disorder that constitutes a leading cause of disability. Although Cognitive-Behaviour Therapy (CBT) has been shown to be an effective treatment for OCD, this specialised treatment is unavailable to many due to access issues and the social stigma associated with seeing a mental health specialist. Internet-based psychological treatments have shown to provide effective, accessible and affordable treatment for a range of anxiety disorders, and two Randomised Controlled Trials (RCTs) have demonstrated the efficacy and acceptability of internet-based CBT (iCBT) for OCD, as compared to waitlist or supportive therapy. Although these initial findings are promising, they do not isolate the specific effect of iCBT. This paper details the study protocol for the first randomised control trial evaluating the efficacy of therapist-assisted iCBT for OCD, as compared to a matched control intervention; internet-based therapist-assisted progressive relaxation training (iPRT). It will aim to examine whether therapist-assisted iCBT is an acceptable and efficacious treatment, and to examine how effectiveness is influenced by patient characteristics.

Coupling online control and inhibitory systems in children with developmental coordination disorder: goal-directed reaching

For children with Developmental Coordination Disorder (DCD), the real-time coupling between frontal executive function and online motor control has not been explored despite reported deficits in each domain. The aim of the present study was to investigate how children with DCD enlist online control under task constraints that compel the need for inhibitory control. A total of 129 school children were sampled from mainstream primary schools. Forty-two children who met research criteria for DCD were compared with 87 typically developing controls on a modified double-jump reaching task. Children within each skill group were divided into three age bands: younger (6-7 years), mid-aged (8-9), and older (10-12). Online control was compared between groups as a function of trial type (non-jump, jump, anti-jump). Overall, results showed that while movement times were similar between skill groups under simple task constraints (non-jump), on perturbation (or jump) trials the DCD group were significantly slower than controls and corrected trajectories later. Critically, the DCD group was further disadvantaged by anti-jump trials where inhibitory control was required; however, this effect reduced with age. While coupling online control and executive systems is not well developed in younger and mid-aged children, there is evidence of age-appropriate coupling in older children. Longitudinal data are needed to clarify this intriguing finding. The theoretical and applied implications of these results are discussed.

Influence of birth cohort on age of onset cluster analysis in bipolar I disorder

Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.

Lithium blocks 45Ca2+ uptake into platelets in bipolar affective disorder and controls.

The basal uptake of radiolabelled 45Ca2+ into platelets and the effect of 1 mM lithium on uptake was measured in manic (n = 13) and depressed (n = 15) patients with bipolar disorder and in controls (n = 13). Lithium was significantly associated with inhibition of uptake of 45Ca2+ into platelets in all three groups. There were no significant intergroup differences in either basal levels of calcium uptake or the effects of lithium on calcium uptake (analysis of variance).

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-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.

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.

Leptin in bipolar disorder: a systematic review and meta-analysis

BACKGROUND: Bipolar disorder (BD) is a psychiatric disorder associated with increased rates of obesity and inflammation. Leptin is an adipokine that is mainly produced by the white adipose tissue in response to insulin. It stimulates the immune system, increasing the production of pro-inflammatory cytokines. There is currently uncertainty regarding possible alterations in peripheral leptin levels across the mood states in BD. METHODS: This study comprises a between-group meta-analysis comparing serum and plasma leptin levels in people with BD in mania, depression or euthymia and healthy controls. We conducted a systematic search for all possibly eligible-English and non-English peer-reviewed articles. We calculated the effect size (ES) utilizing Hedges' adjusted g using random effects. RESULTS: Eleven studies were included in the meta-analyses, providing data on 1118 participants. Serum and plasma leptin levels were not altered in subjects with BD when compared to healthy controls in mania (g=-0.99, 95% CI -2.43 to 0.43, P=0.171), in depression (g=0.17, 95% CI -0.45 to 0.79, P=0.584), or in euthymia (g=0.03, 95% CI -0.39 to 0.46, P=0.882). However, we did observe a stronger association between leptin levels and both age and BMI in patients with BD in euthymia compared to healthy controls, such that the greater the age of the individuals, the greater the difference in leptin levels between BD and controls; and the higher the BMI, the greater the difference in leptin levels between BD and controls. CONCLUSIONS: Our meta-analysis provides evidence that leptin levels are not altered in BD across the mood spectrum compared to healthy controls. The disproportionate increase of leptin levels with increase in BMI in BD speaks in favour of a potential inflammatory role of white adipose tissue in BD and a disproportionate increase of leptin levels with increase in age.

Effect of strontium addition on ferroelectric phase transition of PZT thin films prepared by chemical route

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of a nanostructured dendrimer-naloxonazine complex on endogenous opioid peptides mu(1) receptor-mediated post-ictal antinociception

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of unsaturated fatty acids on myocardial performance, metabolism and morphology

Diets rich in saturated fatty acids are one of the most important causes of atherosclerosis in men, and have been replaced with diets rich in unsaturated fatty acids (UFA) for the prevention of this disorder. However, the effect of UFA on myocardial performance, metabolism and morphology has not been completely characterized. The objective of the present investigation was to evaluate the effects of a UFA-rich diet on cardiac muscle function, oxidative stress, and morphology. Sixty-day-old male Wistar rats were fed a control (N = 8) or a UFA-rich diet (N = 8) for 60 days. Myocardial performance was studied in isolated papillary muscle by isometric and isotonic contractions under basal conditions after calcium chloride (5.2 mM) and ss-adrenergic stimulation with 1.0 mu M isoproterenol. Fragments of the left ventricle free wall were used to study oxidative stress and were analyzed by light microscopy, and the myocardial ultrastructure was examined in left ventricle papillary muscle. After 60 days the UFA-rich diet did not change myocardial function. However, it caused high lipid hydroperoxide (176 +/- 5 vs 158 +/- 5, P < 0.0005) and low catalase (7 +/- 1 vs 9 +/- 1, P < 0.005) and superoxide-dismutase (18 +/- 2 vs 27 +/- 5, P < 0.005) levels, and discrete morphological changes in UFA-rich diet hearts such as lipid deposits and mitochondrial membrane alterations compared to control rats. These data show that a UFA-rich diet caused myocardial oxidative stress and mild structural alterations, but did not change mechanical function.

Obsessive-compulsive disorder and personality disorder - Evidence from the British National Survey of Psychiatric Morbidity 2000

Background Previous studies indicate that most individuals with obsessive-compulsive disorder (OCD) have comorbid personality disorders (PDs), particularly from the anxious cluster. However, the nature and strength of this association remains unclear, as the majority of previous studies have relied heavily on clinical populations. We analysed the prevalence of screen positive personality disorder in a representative sample of adults with OCD living in private households in the UK. Methods A secondary analysis of data from the 2000 British National Survey of Psychiatric Morbidity. The prevalence of PD, as determined by the SCID-II questionnaire, was compared in participants with OCD, with other neuroses and non-neurotic controls. Within the OCD group we also analysed possible differences relating to sex and subtypes of the disorder. Results the prevalence of any screen positive PD in the OCD group (N = 108) was 74%, significantly greater than in both control groups. The most common screen positive categories were paranoid, obsessive-compulsive, avoidant, schizoid and schizotypal. Compared to participants with other neuroses, OCD cases were more likely to screen positively for paranoid, avoidant, schizotypal, dependent and narcissistic PDs. Men with OCD were more likely to screen positively for PDs in general, cluster A PDs, antisocial, obsessive-compulsive and narcissistic categories. The presence of comorbid neuroses in people with OCD had no significant effect on the prevalence of PD. Conclusions Personality pathology is highly prevalent among people with OCD who are living in the community and should be routinely assessed, as it may affect help-seeking behaviour and response to treatment.

Effect of Citrus aurantium l. essential oil on muscle regeneration in mdx mice

Duchenne muscular dystrophy (DMD) is a severe X-linked recessive disorder characterized by the progressive loss of muscular strength. Mdx mutant mice show a marked deficiency in dystrophin, which was related to muscle membrane stability. The aim of this study was to verify the possible protective anti-inflammatory effect of citrus oil on mdx muscle fibers. Thus, adult male and female mdx mice (014/06-CEEA) were divided into control and citrus-treated. After 60 days of treatment, one ml of blood was collected for creatine kinase (CK) test. Diaphragm, sternomastoideus, anterior tibial and gastrocnemius muscles were removed and processed according to histological routine methods. The observed alterations indicate a direct effect of citrus. Recent studies have improved the diagnosis of muscular diseases but with no definitions of efficient treatments. Intervention with several therapies is important to many patients presenting muscular dystrophy, which enables them to live longer and be more active, while there is no development of gene therapies.