Lowered social motivation is associated with adolescent attention deficit hyperactivity disorder and social anxiety symptoms.

BACKGROUND: Difficulties in social skills are highly prevalent in children and adolescents with attention deficit hyperactivity disorder (ADHD), however, the reasons for these social difficulties are poorly understood. This study aimed to understand social motivation in children (aged 5-8) and adolescents (aged 13-17) with and without ADHD, and the relationship between social anxiety and social motivation in youth with ADHD. METHOD: 204 parents of children and adolescents with and without ADHD completed online questionnaires on social motivation, social anxiety, and ADHD symptoms. RESULTS: Adolescents with ADHD had significantly lower social motivation than typically developing adolescents, and children with ADHD. Higher social anxiety significantly predicted lowered social motivation in participants with ADHD. CONCLUSIONS: These findings indicate a unique pattern of social motivation in ADHD, specifically a reduction during adolescence, reflecting social intervention inefficacy. Additionally, these findings establish a link between social motivation and social anxiety, suggesting that they may act as barriers to social intervention.

Social difficulties in adolescent attention deficit hyperactivity disorder: Social motivation, social anxiety and symptom severity as contributing factors.

BACKGROUND: Many interventions have been developed to address the social difficulties commonly experienced by adolescents with attention-deficit/hyperactivity disorder (ADHD), yet they are largely ineffective. OBJECTIVE: This study examined social impairment among adolescents with and without ADHD, determining whether gender, social anxiety, age, and ADHD symptom type (inattention and hyperactivity/impulsivity) and severity are associated with social impairment. METHOD: Parents and primary caregivers of adolescents (aged 13-17) with (n = 76) and without ADHD (n = 36) completed the Strengths and Weaknesses of ADHD and Normal Behavior, Social Responsiveness Scale 2nd Edition, and Spence Children's Anxiety Scale. RESULTS: Adolescents with ADHD scored significantly higher than TD adolescents across social impairment domains. ADHD symptoms were associated with severity of impairment in all domains excluding Social Motivation. Hyperactivity/impulsivity and social anxiety predicted social impairment, whereas gender did not. CONCLUSION: Adolescents with ADHD are more likely to experience social impairment than TD adolescents, and interventions targeting symptom reduction and social anxiety may improve these social impairments.

Impairments in Emotion Recognition and Positive Emotion Regulation Predict Social Difficulties in Adolescent With ADHD.

BACKGROUND: Emotional dysregulation, poor emotion recognition and impaired response inhibition have been highlighted as potential contributors to social difficulties in adolescents with attention-deficit/hyperactivity disorder (ADHD). It is currently unknown how these areas of impairment relate to one another; therefore, this study aims to identify the areas of emotion regulation which are associated with social difficulties in adolescents with ADHD, and determine whether emotion regulation mediates the relationship between deficits in response inhibition and emotion recognition, and social functioning, in this cohort. METHODS: Thirty Australian adolescents (Male = 21) with ADHD completed measures of response inhibition, emotion recognition, and emotion regulation. RESULTS: Positive emotion regulation was significantly associated with social difficulties. Although emotion recognition significantly predicted social difficulties, there was no relationship between emotion recognition and emotion regulation in this sample, ruling out emotion regulation as a mediator of emotion recognition and social difficulties. Whilst response inhibition was significantly correlated with positive emotion regulation, positive emotion regulation did not mediate the relationship between response inhibition and social difficulties. CONCLUSIONS: Difficulties recognising and regulating emotions appear to independently contribute to social difficulties in adolescents with ADHD. Interventions to increase emotional understanding and developing strategies to down-regulate positive emotions may be beneficial.

Concept: A randomised multicentre trial of first line chemotherapy comparing three weekly cabazitaxel versus weekly paclitaxel in HER2 negative metastatic breast cancer.

BACKGROUND: Paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer (MBC) patients. However, with response rates of 21.5-53.7% and significant risk of peripheral neuropathy, there is need for better chemotherapy. PATIENTS AND METHODS: This open-label phase II/III trial randomised HER2-negative MBC patients 1:1 to either 6 cycles of three-weekly cabazitaxel (25 mg/m2), or, weekly paclitaxel (80 mg/m2) over 18 weeks. The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), time to response (TTR), overall survival (OS), safety and tolerability and quality of life (QoL). RESULTS: 158 patients were recruited. Comparing cabazitaxel to paclitaxel, median PFS was 6.7 vs 5.8 months (HR 0.87; 80%CI 0.70-1.08, P = 0.4). There was no difference in median OS (20.6 vs 18.2 months, HR 1.00; 95%CI 0.69-1.45, P = 0.99), ORR (41.8% vs 36.7%) or TTR (HR 1.09; 95%CI 0.68-1.75, P = 0.7). Grade ≥3 adverse events occurred in 41.8% on cabazitaxel and 46.8% on paclitaxel; the most common being neutropenia (16.5%) and febrile neutropenia (12.7%) cabazitaxel and neutropenia (8.9%) and lung infection (7.6%) paclitaxel. Peripheral neuropathy of any grade occurred in 54.5% paclitaxel vs 16.5% cabazitaxel. Mean EQ-5D-5L single index utility score (+0.05; 95%CI 0.004-0.09, P = 0.03) and visual analogue scale score (+7.7; 95%CI 3.1-12.3, P = 0.001) were higher in cabazitaxel vs paclitaxel. CONCLUSIONS: Three-weekly cabazitaxel in HER2-negative MBC does not significantly improve PFS compared to weekly paclitaxel, although it has a lower risk of peripheral neuropathy with better patient reported QoL outcomes. It is well tolerated and requires fewer hospital visits.

Training inhibitory control in adolescents with elevated attention deficit hyperactivity disorder traits: a randomised controlled trial of the Alfi Virtual Reality programme.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is characterised by significant deficits in attention and inhibition. These deficits are associated with negative sequelae that emerge in childhood and often continue throughout adolescence. Despite these difficulties adolescents with ADHD often demonstrate poor treatment compliance with traditional interventions (eg, psychostimulant medication). Virtual reality (VR) presents an innovative means of delivering engaging cognitive interventions for adolescents with ADHD and offers the potential to improve compliance with such interventions. The current parallel, randomised controlled trial aims to evaluate the effects of a VR intervention (Alfi) designed to improve inhibition in adolescents with ADHD. METHODS AND ANALYSIS: A sample of 100 adolescents (aged 13-17) with elevated ADHD symptoms will be recruited from secondary schools and ADHD organisations located in the state of Victoria, Australia. Participants will be randomly assigned to either an 8-week VR intervention or a usual care control. The VR intervention involves the completion of 14 sessions, each 20 min in duration. Participants will complete computerised assessments of inhibition and risk-taking preintervention and immediately postintervention. Parents/guardians will complete online questionnaires about their child's ADHD symptoms and social functioning at each of these timepoints. The primary outcome is change in inhibition performance in adolescents who received the intervention from preintervention to postintervention compared with adolescents in the control condition. Secondary outcomes include change in risk-taking, ADHD symptoms and social functioning in adolescents who received the intervention from preintervention to postintervention compared with adolescents in the control condition. If the intervention is shown to be effective, it may offer a supplementary approach to traditional interventions for adolescents with ADHD experiencing inhibitory control difficulties. ETHICS AND DISSEMINATION: This trial has ethics approval from the Monash University Human Research Ethics Committee (HREC) (21530) and the Victorian Department of Education and Training HREC (2020_004271). Results will be disseminated through peer-reviewed journals, conference proceedings and community activities. Individual summaries of the results will be provided to participants on request. TRIAL REGISTRATION NUMBER: ACTRN12620000647932.

Digital cognitive training in children with attention-deficit/hyperactivity disorder: a study protocol of a randomised controlled trial.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders and is a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with daily functioning. Children with ADHD are developmentally vulnerable, with the disorder linked to emotional regulation difficulties, behavioural disturbances, as well as academic challenges. Emerging evidence suggests that children with ADHD may benefit from cognitive training interventions, including those focused on attention. This study aims to assess the immediate and long-term efficacy of an attention training intervention in children with ADHD. METHODS AND ANALYSIS: This study is a preregistered, parallel, double blind, randomised controlled trial. Participants will comprise 104 children with a diagnosis of ADHD aged 5-8 years 11 months. Participants will be randomly allocated to either an adaptive, digital game-based (1) attention training programme (intervention) or (2) a numeracy programme (control). Both programmes will be delivered on a touchscreen tablet, and children will complete five 20 min sessions per week for a 5-week period at home (25 sessions in total). Assessments of the primary outcome (ie, attention and inhibitory control) and secondary outcomes (ie, selective attention, interference control, sustained attention, inhibition, behavioural attention, impairment in everyday functioning, working memory and executive functioning) will occur at preintervention, immediately postintervention and at 3-month follow-up. Multivariate linear regression will be employed to examine primary and secondary outcomes. The data analyst will be blinded to group membership. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Monash University HREC (20495). Results will be disseminated through peer-reviewed journals, conference presentations, media outlets, the internet and various community/stakeholder activities. TRIAL REGISTRATION NUMBER: ACTRN12620000964910, UTN U1111-1250-2620.

Impact of the COVID-19 Lockdown in Malaysia: An Examination of the Psychological Well-Being of Parent-Child Dyads and Child Behavior in Families With Children on the Autism Spectrum.

Background: The COVID-19 pandemic lockdowns have adversely impacted children on the autism spectrum and their families, especially in Malaysia where this population is often marginalized. The current quantitative research aimed to investigate the impact of the Malaysian COVID-19 lockdown on the behavior and psychological distress of children formally diagnosed with an autism spectrum condition (ASC) as well as the psychological distress and well-being of their parents, in comparison with a typically developing (TD) control group. Methods: The children's ages ranged between 5 and 17 years. The sample included 72 ASC parent-child dyads and 62 TD parent-child dyads. The primary caregiver completed an online survey including the following: demographic and diagnostic information; ASC symptoms; children's inattention, hyperactivity/impulsivity, perceived stress, depression, and anxiety; parents' perceived stress, depression, anxiety, and well-being based on their experience pre- and mid-lockdown (March 18th to June 9th 2020) in Malaysia. Results: Among the ASC group, no significant pre- and mid-lockdown change was found in ASC symptoms (p > 0.05). There were no significant gender differences (boys/girls) in all the child scales. The 2 [diagnosis (ASC, TD)] × 2 [lockdown (pre-lockdown, mid-lockdown)] mixed-model ANOVAs revealed main effects of lockdown on children's attention, hyperactivity/impulsivity, anxiety, and parents' perceived stress, depression, and psychological well-being (p < 0.005). There was a main effect of diagnosis in all child and parent variables, except parents' perceived stress (p >0.005). However, there was no significant interaction effect between diagnosis and lockdown (p >0.005). All child behavior (inattention and hyperactivity/impulsivity) and child psychological distress (anxiety, depression, and perceived stress) were significantly correlated in both the ASC and TD groups (p < 0.005). On the other hand, only some of the parent variables were significantly correlated with child variables (p < 0.0045) in the ASC group while none of the parent variables were significantly correlated with the child variables (p > 0.005) in the TD group. Conclusion: The results provide preliminary evidence indicating negative effects of the Malaysian lockdown on both children on the autism spectrum and TD children, as well as their parents. These quantitative results will be triangulated with the qualitative interview data to provide a holistic understanding of the impact of the pandemic, informing translational policy and practice recommendations.

Gamified Attention Training in the Primary School Classroom: A Cluster-Randomized Controlled Trial.

Objective: This randomized controlled trial evaluated the efficacy of attention training delivered in class on cognitive attention processes, inattention, hyperactivity, working memory, and numeracy in primary school children. Method: Eight classes (n = 98 children; 5-9 years) were cluster randomized to gamified attention training, a placebo program, or a no-contact control condition. Assessments were conducted at baseline, immediately after the 5-week intervention (posttraining), and 6 months later (follow-up). Results: Posttraining, attention training was associated with reduced inattention and hyperactivity within the classroom compared with controls, and reduced hyperactivity at home compared with the no-contact control. At follow-up, reduced hyperactivity within the classroom compared with the no-contact control persisted. No effects of training on cognitive attention processes, working memory, and numeracy were observed posttraining. Conclusion: Classroom-based attention training has select benefits in reducing inattention and hyperactivity, but may not promote gains in cognitive or academic skills in primary school children.

Training attention in children with acquired brain injury: a study protocol of a randomised controlled trial of the TALI attention training programme.

INTRODUCTION: Childhood inattention has been linked with poor academic outcomes, and increased lifetime social, occupational and psychiatric morbidity. Children with an acquired brain injury (ABI) are particularly susceptible to attention deficits and may benefit from interventions aimed at enhancing attention. The primary objective of this study is to evaluate the short-term efficacy of the TALI Train programme, compared with a placebo, on the outcome of attention in children with ABI. METHODS AND ANALYSIS: The study is a parallel, double-blind, randomised controlled trial. Participants will consist of 80 children with a diagnosis of ABI aged 4-9 years 11 months. Participants will be randomly allocated to either (1) TALI Train (intervention group), an adaptive game-based attention training programme, or (2) a non-adaptive placebo programme (control group). Both programmes are delivered on a touchscreen tablet, and children complete five 20 min sessions per week for a 5-week period at home. Assessment of selective, sustained and executive attention (primary outcomes), and behavioural attention, working memory, social skills and mathematics ability (secondary outcomes) will occur at baseline, post-training, and at 3-month and 6-month follow-up to assess immediate and long-term efficacy of TALI Train compared with placebo. Assessments will be completed at the Royal Children's Hospital in Melbourne, Australia. All assessments and analyses will be undertaken by researchers blinded to group membership. Latent growth curve modelling will be employed to examine primary and secondary outcomes. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Royal Children's Hospital Human Research Ethics Committee (HREC) (38132) and the Monash University HREC (17446). Results will be disseminated through peer-reviewed journals, conference presentations, media outlets, the internet and various community/stakeholder activities. TRIAL REGISTRATION NUMBER: ACTRN12619000511134.

Impact of Attention Training on Academic Achievement, Executive Functioning, and Behavior: A Randomized Controlled Trial.

Children with intellectual and developmental disabilities (IDD) experience significant difficulties in attention, learning, executive functions, and behavioral regulation. Emerging evidence suggests that computerized cognitive training may remediate these impairments. In a double blind controlled trial, 76 children with IDD (4-11 years) were randomized to either an attention training (n = 38) or control program (n = 38). Both programs were completed at home over a 5-week period. Outcome measures assessed literacy, numeracy, executive functioning, and behavioral/emotional problems, and were conducted at baseline, post-training, and 3-month follow-up. No training effects were observed at post-training; however, children in the training group showed greater improvements in numeracy skills at the 3-month follow-up. These results suggest that attention training may be beneficial for children with IDD; however, the modest nature of the intervention effects indicate that caution should be taken when interpreting clinical significance.

Visual attention and academic performance in children with developmental disabilities and behavioural attention deficits.

Despite well-documented attention deficits in children with intellectual and developmental disabilities (IDD), distinctions across types of attention problems and their association with academic attainment has not been fully explored. This study examines visual attention capacities and inattentive/hyperactive behaviours in 77 children aged 4 to 11 years with IDD and elevated behavioural attention difficulties. Children with autism spectrum disorder (ASD; n = 23), Down syndrome (DS; n = 22), and non-specific intellectual disability (NSID; n = 32) completed computerized visual search and vigilance paradigms. In addition, parents and teachers completed rating scales of inattention and hyperactivity. Concurrent associations between attention abilities and early literacy and numeracy skills were also examined. Children completed measures of receptive vocabulary, phonological abilities and cardinality skills. As expected, the results indicated that all groups had relatively comparable levels of inattentive/hyperactive behaviours as rated by parents and teachers. However, the extent of visual attention deficits varied as a result of group; namely children with DS had poorer visual search and vigilance abilities than children with ASD and NSID. Further, significant associations between visual attention difficulties and poorer literacy and numeracy skills were observed, regardless of group. Collectively the findings demonstrate that in children with IDD who present with homogenous behavioural attention difficulties, at the cognitive level, subtle profiles of attentional problems can be delineated.

Computerised attention training for children with intellectual and developmental disabilities: a randomised controlled trial.

BACKGROUND: Children with intellectual and developmental disabilities (IDD) experience heightened attention difficulties which have been linked to poorer cognitive, academic and social outcomes. Although, increasing research has focused on the potential of computerised cognitive training in reducing attention problems, limited studies have assessed whether this intervention could be utilised for those with IDD. This study aimed to assess the efficacy of a computerised attention training programme in children with IDD. METHODS: In a double-blind randomised controlled trial, children (n = 76; IQ < 75) aged 4-11 years were assigned to an adaptive attention training condition or a nonadaptive control condition. Both conditions were completed at home over a 5-week period and consisted of 25 sessions, each of 20-min duration. Outcome measures (baseline, posttraining and 3-month follow-up) assessed core attention skills (selective attention, sustained attention and attentional control) and inattentive/hyperactive behaviour. RESULTS: Children in the attention training condition showed greater improvement in selective attention performance compared to children in the control condition (SMD = 0.24, 95% CI 0.02, 0.45). These improvements were maintained 3 months after training had ceased (SMD = 0.26, 95% CI 0.04, 0.48). The attention training programme was not effective in promoting improvements in sustained attention, attentional control or inattentive/hyperactive behaviours. CONCLUSIONS: The findings suggest that attention training may enhance some aspects of attention (selective attention) in children with IDD, but the small to medium effect sizes indicate that further refinement of the training programme is needed to promote larger, more global improvements.

Violations of Personal Space in Young People with Autism Spectrum Disorders and Williams Syndrome: Insights from the Social Responsiveness Scale.

Interpersonal distance regulation is crucial for successful social interactions. We investigated personal space awareness in Williams syndrome (WS) and autism spectrum disorder (ASD) compared to typical development. Parents reported that individuals with WS and ASD were significantly more likely than those developing typically to invade the personal space of others. WS individuals were reported to have the least awareness of the personal space boundaries of others. Despite the suggested opposing social profiles of WS and ASD, some similarities are present in the ability, or indeed inability, to regulate interpersonal distance during social interactions. Findings are discussed in relation to implications of atypical amygdala function, inhibitory control and anxiety on real-world behaviour for such socially vulnerable groups.

The interplay between anxiety and social functioning in Williams syndrome.

The developmental disorder Williams syndrome (WS) has been associated with an atypical social profile of hyper-sociability and heightened social sensitivity across the developmental spectrum. In addition, previous research suggests that both children and adults with WS have a predisposition towards anxiety. The current research aimed to explore the profiles of social behaviour and anxiety across a broad age range of individuals with the disorder (n = 59, ages 6-36 years). We used insights from parental reports on two frequently used measures, the Spence Children's Anxiety Scale (SCAS-P) and the Social Responsiveness Scale (SRS). Severity of anxiety was correlated with a greater degree of social dysfunction as measured by the SRS in this group. We split the group according to high or low anxiety as measured by the SCAS-P and explored the profile of social skills for the two groups. Individuals high and low in anxiety differed in their social abilities. The results emphasise the need to address anxiety issues in this disorder and to consider how components of anxiety might relate to other features of the disorder.

Gait profiles as indicators of domain-specific impairments in executive control across neurodevelopmental disorders.

In neurodevelopmental disorders, unique profiles of executive control and attention appear to co-occur with poor motor coordination. However, less is known about how syndrome-specific cognitive profiles interact with motor control and impact behavioural outcomes in neurodevelopmental disorders such as Williams syndrome (WS) and Down syndrome (DS). Here we aimed to examine the extent to which specific components of executive function interact with gait control when performing cognitive dual-tasks (verbal fluency, digit span) in WS and DS. Spatiotemporal gait characteristics and intra-individual variability of gait were assessed in individuals with WS who were matched on spatial ability to individuals with DS, and chronologically age (CA) matched controls. During the concurrent verbal fluency task, the WS group had greater dual-task costs on spatiotemporal gait parameters and variability than CA controls. Conversely, individuals with DS had selective gait interference during the concurrent digit span task when compared to CA controls, but only under increased demands on cognitive control where there was greater variability in step timing in DS. The interrelationships between cognitive-motor interference and behavioural measures of executive functioning appeared to differentiate between WS and DS, and emphasise the importance of task modality in unpacking the executive control profile in these neurodevelopmental disorders. These findings support the notion that associated cerebellar-cortico abnormalities may produce quite distinct profiles of executive control across cognitive and motor domains that impact on behavioural outcomes in neurodevelopmental disorders.

Linking social behaviour and anxiety to attention to emotional faces in Williams syndrome.

The neurodevelopmental disorder Williams syndrome (WS) has been associated with a social phenotype of hypersociability, non-social anxiety and an unusual attraction to faces. The current study uses eye tracking to explore attention allocation to emotionally expressive faces. Eye gaze and behavioural measures of anxiety and social reciprocity were investigated in adolescents and adults with WS when compared to typically developing individuals of comparable verbal mental age (VMA) and chronological age (CA). Results showed significant associations between high levels of behavioural anxiety and attention allocation away from the eye regions of threatening facial expressions in WS. The results challenge early claims of a unique attraction to the eyes in WS and suggest that individual differences in anxiety may mediate the allocation of attention to faces in WS.

Electrostatic interactions play an essential role in the binding of oleic acid with α-lactalbumin in the HAMLET-like complex: a study using charge-specific chemical modifications.

Human α-lactalbumin made lethal to tumor cells (HAMLET) and its analogs are partially unfolded protein-oleic acid (OA) complexes that exhibit selective tumoricidal activity normally absent in the native protein itself. To understand the nature of the interaction between protein and OA moieties, charge-specific chemical modifications of lysine side chains involving citraconylation, acetylation, and guanidination were employed and the biophysical and biological properties were probed. Upon converting the original positively-charged lysine residues to negatively-charged citraconyl or neutral acetyl groups, the binding of OA to protein was eliminated, as were any cytotoxic activities towards osteosarcoma cells. Retention of the positive charges by converting lysine residues to homoarginine groups (guanidination); however, yielded unchanged binding of OA to protein and identical tumoricidal activity to that displayed by the wild-type α-lactalbumin-oleic acid complex. With the addition of OA, the wild-type and guanidinated α-lactalbumin proteins underwent substantial conformational changes, such as partial unfolding, loss of tertiary structure, but retention of secondary structure. In contrast, no significant conformational changes were observed in the citraconylated and acetylated α-lactalbumins, most likely because of the absence of OA binding. These results suggest that electrostatic interactions between the positively-charged basic groups on α-lactalbumin and the negatively-charged carboxylate groups on OA molecules play an essential role in the binding of OA to α-lactalbumin and that these interactions appear to be as important as hydrophobic interactions.