Effects of stochastic vestibular stimulation on cognitive performance in children with ADHD.

Previous work has shown that exposure to auditory white noise (WN) can improve cognitive performance in children with ADHD, but it is unknown whether this improvement generalizes to other sensory modalities. To address this knowledge gap, we tested the effect of Stochastic Vestibular Stimulation (SVS) on cognitive performance and reaction time (RT) variability in two groups: children with ADHD and typically developing children (TDC). Children with ADHD (N=42) and TDC (N=28) performed three cognitive tasks (Spanboard, Word Recall and N-back tasks) at two different occasions, with and without exposure to SVS, in a double blinded design. The results showed no main effects of SVS on neither performance nor RT variability for children in any of the groups, and no interactions between SVS and group. Based on these results we conclude that, using our stimulation protocol, the positive effects of WN exposure on cognition in children with ADHD do not generalize to Stochastic Vestibular Stimulation.

The ability to maintain rhythm is predictive of ADHD diagnosis and profile.

Attention deficit hyperactivity disorder (ADHD) is the most prevalent neuropsychiatric disorder in the world. Currently, the diagnosis is based mainly on interviews, resulting in uncertainties in the clinical assessment. While some neuropsychological tests are used, their specificity and selectivity are low, and more reliable biomarkers are desirable. Previous research indicates that ADHD is associated with morphological changes in the cerebellum, which is essential for motor ability and timing. Here, we compared 29 children diagnosed with ADHD to 96 age-matched controls on prism adaptation, eyeblink conditioning, and timed motor performance in a finger tapping task. Prism adaptation and timing precision in the finger tapping task, but not performance on eyeblink conditioning, differed between the ADHD and control groups, as well as between children with and without Deficits in Attention, Motor control, and Perception (DAMP) - a more severe form of ADHD. The results suggest finger tapping can be used as a cheap, objective, and unbiased biomarker to complement current diagnostic procedures.

Healthcare utilization and psychiatric morbidity in violent offenders: findings from a prospective cohort study.

PURPOSE: Although persistent offenders with histories of imprisonment and violence have disproportionate high rates of psychiatric disorders, little is known of their psychiatric healthcare utilization (HCU) and HCU-associated factors. This study aimed to explore psychiatric HCU, psychiatric morbidity, and psychotropic prescription drugs in violent offenders with a history of incarceration. METHODS: Male offenders aged 18-25 (n = 266) imprisoned for violent and/or physical sexual offenses were clinically assessed in 2010-2012 and prospectively followed in Swedish national registries through 2017. Register-based information regarding HCU, psychiatric morbidity, and psychotropic drugs was tracked and compared with a general population group (n = 10,000) and across offending trajectory groups. Baseline risk factors were used to explain prospective psychiatric HCU in violent offenders. RESULTS: Violent offenders used less general healthcare and psychiatric outpatient care, but more psychiatric inpatient care and were more often given psychiatric diagnoses and psychotropic drugs than the general population. Participants previously assigned to persisting offending trajectory groups had higher rates of psychiatric HCU than those assigned to a desisting trajectory. In multivariable regression models, psychiatric HCU was associated with anxiety disorders, prior psychiatric contact, placement in a foster home, psychopathic traits, low intellectual functioning, and persistent offending. CONCLUSIONS: Violent offenders are burdened by extensive and serious psychiatric morbidity and typically interact with psychiatric healthcare as inpatients rather than outpatients. Knowledge about their backgrounds, criminal behaviors, and psychiatric statuses can aid the planning of psychiatric services for this troublesome group.

Bumetanide for autism: Open-label trial in six children.

AIM: Bumetanide, a diuretic agent, that reduces intracellular chloride-thereby reinforcing GABAergic inhibition-has been reported to improve core symptoms of autism in children. Given the positive results reported from French trials of bumetanide in children with autism, we decided to evaluate its effects in a small-scale pilot study, in advance of a larger randomised controlled study (RCT). METHODS: This was an open-label three-month trial of bumetanide on six children (five boys), aged 3-14 years with autism. Ratings according to the Parental Satisfaction Survey (PASS) were used after four and twelve weeks to assess symptom change. Blood electrolyte status was monitored. RESULTS: Improvement in the PASS domain "Communicative and cognitive abilities" was marked or very marked in four children, and two had some improvements. Few negative side effects were reported. CONCLUSION: Our small cohort responded well to bumetanide, particularly with regard to "Communicative and cognitive abilities". Taken with the evidence from larger-scale RCTs, we suggest that bumetanide should be considered for inclusion in ethically approved treatment/management trials for children with autism, subject to rigorous follow-up in large-scale RCTs.

Improvement of Autism Symptoms After Comprehensive Intensive Early Interventions in Community Settings.

BACKGROUND: Preschool children with autism in southern Sweden participated in a comprehensive Naturalistic Developmental Behavioral Intervention (NDBI) program. AIMS: To evaluate the ongoing NDBI program by comparing the pre- and postintervention outcomes in terms of improved autism symptom severity. METHOD: The improvement of Autism Diagnostic Observation Schedule (ADOS-R) test results between baseline and evaluation among children participating in the NDBI program (n = 67) was compared with the results among children receiving community treatment as usual (n = 27) using analysis of covariance. RESULTS: The study showed that children in the NDBI group improved their ADOS-R total scores between baseline and evaluation (-0.8 scores per year; 95% CI [-1.2, -0.4]), whereas no improvement was detected in the comparison group (+0.1 scores per year; 95% CI [-0.7, +0.9]). The change in the NDBI group versus the change in the comparison group was statistically significant after adjusting for possible confounders as well. Children in the NDBI group also significantly improved their ADOS severity scores, but the scores were not significantly different from those of the comparison group. CONCLUSIONS: The results from the current naturalistic study must be interpreted cautiously, but they do support earlier studies reporting on improvement of autism symptoms after early intensive interventions. Results from observational studies are difficult to interpret, but it is nevertheless of uttermost importance to evaluate costly autism intervention programs. The results do indicate that children with autism benefit from participating in early comprehensive intensive programs.

Incremental clinical utility of continuous performance tests in childhood ADHD - an evidence-based assessment approach.

Despite extensive research on attention deficit hyperactivity disorder (ADHD), there are still uncertainties regarding the clinical utility of different ADHD assessment methods. This study aimed to examine the incremental clinical utility of Conners' continuous performance test (CPT) II and QbTest in diagnostic assessments and treatment monitoring of attention deficit hyperactivity disorder (ADHD). Retrospective data from child and adolescent psychiatric records of two populations were studied. The diagnostic clinical utility of Conners' CPT II and QbTest was analysed using receiver operator characteristics (ROC) and post-test probability in 80 children with and 38 without ADHD. Dose titrations of central stimulants in 56 children with ADHD were evaluated using QbTest and the Swanson, Nolan, Pelham, version IV (SNAP-IV) scale. Conners' CPT II, but not QbTest, had incremental clinical utility in diagnostic assessment of children with ADHD when teacher and parent ratings were inconclusive. QbTest proved useful in titration of central stimulant treatment when parent ratings were inconclusive. Continuous performance tests were found to be clinically useful when rating scales were inconclusive.

Cotinine Validation of Self-Reported Smoking During Pregnancy in the Swedish Medical Birth Register.

INTRODUCTION: Self-reported data on smoking during pregnancy from the Medical Birth Register of Sweden (MBR) are widely used. However, underreporting of such behavior may occur, leading to biases. It is of importance to validate the smoking data in the MBR. The main objective was to investigate the agreement between self-reported smoking data from the MBR and cotinine levels in maternal serum among women from the general population in the region of Skåne, Sweden. We also estimated the transfer of cotinine from mother to fetus. METHODS: From a cohort used previously to investigate the relationship between intrauterine environmental exposures and offspring neuropsychiatric outcomes, there were 204 control children retrieved from the MBR with data on maternal smoking in early pregnancy registered. Data on maternal and umbilical cord cotinine at delivery were available for these children from a regional biobank. RESULTS: There was a high agreement between cotinine levels and MBR smoking data (κ = 0.82) and a high correlation between cotinine levels in maternal and umbilical cord serum (r s = 0.90, P < .001). Of the self-reported nonsmokers, 95% (95% confidence interval: 89% to 97%) were classified as nonsmokers after cotinine measurements. CONCLUSION: In these data, we found that the agreement between mothers' self-reported smoking habits during pregnancy and their levels of serum cotinine was high, as was the transfer of cotinine from mother to fetus. This indicates that birth register data on pregnancy smoking in Sweden could be considered a valid measure.

Manganese and selenium concentrations in umbilical cord serum and attention deficit hyperactivity disorder in childhood.

Existing evidence on the effects of manganese and selenium during fetal life on neurodevelopmental disorders is inadequate. This study aims to investigate the hypothesized relationship between fetal exposure to manganese and selenium and attention deficit hyperactivity disorder (ADHD) diagnosis in childhood. Children born between 1978 and 2000 with ADHD (n=166) were identified at the Department of Child and Adolescent Psychiatry in Malmö, Sweden. Controls from the same region (n=166) were selected from the Medical Birth Register and were matched for year of birth and maternal country of birth. Manganese and selenium were measured in umbilical cord serum. The median cord serum concentrations of manganese were 4.3µg/L in the cases and 4.1µg/L in the controls. The corresponding concentrations of selenium were 47 and 48µg/L. When the exposures were analyzed as continuous variables no associations between cord manganese or selenium concentration and ADHD were observed. However, children with selenium concentrations above the 90th percentile had 2.5 times higher odds (95% confidence interval 1.3-5.1) of having ADHD compared to those with concentrations between the 10th and 90th percentiles. There was no significant interaction between manganese and selenium exposure (p=0.08). This study showed no association between manganese concentrations in umbilical cord serum and ADHD. The association between ADHD diagnoses in children with relatively high cord selenium was unexpected and should be interpreted with caution.

The LEADING Guideline: Reporting Standards for Expert Panel, Best-Estimate Diagnosis, and Longitudinal Expert All Data (LEAD) Studies.

Accurate assessments of symptoms and diagnoses are essential for health research and clinical practice but face many challenges. The absence of a single error-free measure is currently addressed by assessment methods involving experts reviewing several sources of information to achieve a more accurate or best-estimate assessment. Three bodies of work spanning medicine, psychiatry, and psychology propose similar assessment methods: The Expert Panel, the Best-Estimate Diagnosis, and the Longitudinal Expert All Data (LEAD). However, the quality of such best-estimate assessments is typically very difficult to evaluate due to poor reporting of the assessment methods and when it is reported, the reporting quality varies substantially. Here we tackle this gap by developing reporting guidelines for such studies, using a four-stage approach: 1) drafting reporting standards accompanied by rationales and empirical evidence, which were further developed with a patient organization for depression, 2) incorporating expert feedback through a two-round Delphi procedure, 3) refining the guideline based on an expert consensus meeting, and 4) testing the guideline by i) having two researchers test it and ii) using it to examine the extent previously published articles report the standards. The last step also demonstrates the need for the guideline: 18 to 58% (Mean = 33%) of the standards were not reported across fifteen randomly selected studies. The LEADING guideline comprises 20 reporting standards related to four groups: The Longitudinal design; the Appropriate data; the Evaluation - experts, materials, and procedures; and the Validity group. We hope that the LEADING guideline will be useful in assisting researchers in planning, reporting, and evaluating research aiming to achieve best-estimate assessments.

Eating problems and overlap with ADHD and autism spectrum disorders in a nationwide twin study of 9- and 12-year-old children.

AIM. To establish the prevalence of restrictive eating problems, the overlap and association with attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorders (ASD) and to estimate the heritability of eating problems in a general population sample of twins aged 9 and 12. METHODS. Parents of all Swedish 9- and 12-year-old twin pairs born between 1993 and 1998 (n = 12,366) were interviewed regarding symptoms of ADHD, ASD, and eating problems (EAT-P). Intraclass correlations and structural equation modelling were used for evaluating the influence of genetic and environmental factors. Cross-twin, cross-trait correlations were used to indicate a possible overlap between conditions. RESULTS. The prevalence of eating problems was 0.6% in the study population and was significantly higher in children with ADHD and/or ASD. Among children with eating problems, 40% were screened positive for ADHD and/or ASD. Social interaction problems were strongly associated with EAT-P in girls, and impulsivity and activity problems with EAT-P in boys. The cross-twin, cross-trait correlations suggested low correlations between EAT-P and ADHD or EAT-P and ASD. Genetic effects accounted for 44% of the variation in liability for eating problems. CONCLUSIONS. In the group with eating problems, there was a clear overrepresentation of individuals with ADHD and/or ASD symptoms.

Offending Trajectories in Violent Offenders: Criminal History and Early Life Risk Factors.

The understanding of offending, and thus its possible prevention, is expanded through longitudinal studies on criminal trajectories depicting early life risk factors. This longitudinal study aimed to explore criminal trajectories, criminal histories, and early life risk factors in a cohort of violent offenders. A Swedish nationally representative cohort of male violent offenders (n = 266), clinically assessed while imprisoned aged 18 to 25, was followed through national registers from age 15 to 25-34. Substantial differences in criminal histories between violent offenders and a matched comparison group (n = 10,000) were demonstrated. Five trajectory groups were identified: four persisting and one desisting. Although differences were observed between persisting trajectory groups, a higher prevalence of early life risk factors was generally displayed compared to the desisting, especially in conduct problems and experiences of out-of-home placements. Neurocognitive ability and prevalence of ADHD and autism were similar across trajectories. Severe early life risks highlight the population's need for early interventions.

A longitudinal investigation of parental ratings and performance metrics for executive functioning and symptom severity in clinically referred youth with ADHD.

There remains a knowledge gap concerning the persistence of attention deficit hyperactivity disorder (ADHD) over the longer term. The current study aimed to investigate the change in parent-rated, and performance-based metrics of executive functioning (EF) and the relationship between these EF metrics and ADHD symptoms in individuals with ADHD from childhood/adolescence to young adulthood. This was done by examining possible improvements in parent-rated EF and performance-based measures of inattention and inhibition over a three-year interval and their relationship to ADHD outcomes in 137 clinically referred youth with ADHD (mean age = 12.4 years, SD = 3.1). Participants' parents completed the Behavior Rating Inventory of Executive Function (BRIEF) and the Swanson-Nolan-Pelham Scale at baseline and follow-up. Participants completed the Conners' Continuous Performance Test, Version II (CPT II) at baseline and follow-up. Statistical analyses were performed with Linear Mixed Models. The sex- and age-standardized measures Commission and Hit reaction time (RT) subscales of the CPT II and parent-rated metacognitive, and behavior regulation composites of the BRIEF were largely stable between measuring points. CPT Omissions, Hit RT standard error (reaction time variability), and parent-rated ADHD symptom scores improved slightly. BRIEF composites and reaction time variability were related to ADHD symptoms using longitudinal data. Overall, behavioral aspects of EF, as observed by parents in the home context, appear to play a significant role in the trajectory of childhood ADHD.

Neurocognitive and cerebellar function in ADHD, autism and spinocerebellar ataxia.

The cerebellum plays a major role in balance, motor control and sensorimotor integration, but also in cognition, language, and emotional regulation. Several neuropsychiatric disorders such as attention deficit-hyperactivity disorder (ADHD), autism spectrum disorder (ASD), as well as neurological diseases such as spinocerebellar ataxia type 3 (SCA3) are associated with differences in cerebellar function. Morphological abnormalities in different cerebellar subregions produce distinct behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. The specific contribution of the cerebellum to typical development may therefore involve the optimization of the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains. Here, we review cerebellar structural and functional differences between healthy and patients with ADHD, ASD, and SCA3, and explore how disruption of cerebellar networks affects the neurocognitive functions in these conditions. We discuss how cerebellar computations contribute to performance on cognitive and motor tasks and how cerebellar signals are interfaced with signals from other brain regions during normal and dysfunctional behavior. We conclude that the cerebellum plays a role in many cognitive functions. Still, more clinical studies with the support of neuroimaging are needed to clarify the cerebellum's role in normal and dysfunctional behavior and cognitive functioning.

Exposure to local, source-specific ambient air pollution during pregnancy and autism in children: a cohort study from southern Sweden.

Evidence of air pollution exposure, namely, ambient particulate matter (PM), during pregnancy and an increased risk of autism in children is growing; however, the unique PM sources that contribute to this association are currently unknown. The aim of the present study was to investigate local, source-specific ambient PM exposure during pregnancy and its associations with childhood autism, specifically, and autism spectrum disorders (ASD) as a group. A cohort of 40,245 singleton births from 2000 to 2009 in Scania, Sweden, was combined with data on locally emitted PM with an aerodynamic diameter < 2.5 µm (PM2.5). A flat, two-dimensional dispersion model was used to assess local PM2.5 concentrations (all-source PM2.5, small-scale residential heating- mainly wood burning, tailpipe exhaust, and vehicle wear-and-tear) at the mother's residential address during pregnancy. Associations were analyzed using binary logistic regression. Exposure to local PM2.5 during pregnancy from each of the investigated sources was associated with childhood autism in the fully adjusted models. For ASD, similar, but less pronounced, associations were found. The results add to existing evidence that exposure to air pollution during pregnancy may be associated with an increased risk of childhood autism. Further, these findings suggest that locally produced emissions from both residential wood burning and road traffic-related sources (tailpipe exhaust and vehicle wear-and-tear) contribute to this association.

The Three-year Outcome of Emotional Symptoms in Clinically Referred Youth with ADHD and their Relationship to Neuropsychological Functions.

Background: Further knowledge is needed regarding long-term outcome of emotional symptoms, and the interplay between these symptoms and neuropsychological functioning in youth with attention deficit hyperactivity disorder (ADHD). Objective: We aimed to explore the effect of performance-based neurocognitive functions and parent-rated behavioral executive functioning (EF) on self-rated and parent-rated internalizing symptoms longitudinally in clinically referred youth with ADHD (n = 137; mean age = 12.4 years). We also aimed to examine the change in self-rated emotional symptoms in the ADHD group and a Control group (n = 59; mean age = 11.9 years). Method: At baseline, and three years later, parents completed rating scales of their child's ADHD symptoms (Swanson Nolan Pelham Scale, Version IV - SNAP-IV), emotional symptoms (Five To Fifteen Questionnaire, Strengths, and Difficulties Questionnaire), and EF (Behavior Rating Inventory of Executive Function). At the same time, the child completed self-report measures of Anxiety, Depression, and Anger Inventories (the Beck Youth Inventories) and neurocognitive measures (Conner's Continuous Performance Test, Version II (CPT-II), Working Memory and Processing Speed composites (Wechsler Intelligence Scales). Statistical analyses were linear and logistic mixed models. Results: Using longitudinal data, parent- and self-ratings of emotional symptoms were associated with parent-ratings of EF behavior in youth with ADHD. Plan/organizing deficits were associated with Anxiety and Anger over and above other metacognitive subscales, while Emotional Control was related to Anger over and above other behavior regulation subscales. In the ADHD group, Anger symptoms improved across measuring points. When controlling for age, Anxiety, and Depression symptoms were largely stable in both groups, however at higher levels in the ADHD group. The differences in anxiety and depression symptoms across groups decreased over time. Conclusions: The current study emphasizes the importance of identification, monitoring, and treatment of emotional symptoms, and behavioral aspects of EF in youth with ADHD.

The Winding Road to Equal Care: Attitudes and Experiences of Prescribing ADHD Medication among Pediatric Psychiatrists: A Qualitative Study.

Evidence is lacking on how to understand the reasons for variations, both in prevalence of ADHD and ADHD medication prescribing patterns in children and adolescents, within Region Skåne. These variations are not in line with current national clinical guidelines and seem to have increased over time. This qualitative interview study illuminates pediatric psychiatrists' attitudes toward ADHD and their experiences of prescribing ADHD medication. Eleven pediatric psychiatrists described the complex interplay of variables that they experienced while assessing a child, which had influence on their decision to prescribe medication. Being part of a local unit's culture influenced how ADHD medications were prescribed. They wished that the assessment of the child's symptoms was consistent with guidelines in every unit but noted that such alignment was not implemented. They pointed out that an ADHD diagnosis is dependent on the surrounding's motivation and capacity to adapt to the present state of the child. The participants described how they balanced clinical guidelines with demands from the family, as well as from society at large. Their personal attitudes and clinical experiences towards diagnosing and prescribing medications to children with ADHD influenced their decisions. The study adds information about how attitudes may lead to variation in diagnostics and therapy.

Perinatal, maternal, and fetal characteristics of children diagnosed with attention-deficit-hyperactivity disorder: results from a population-based study utilizing the Swedish Medical Birth Register.

AIM: The aim of this study was to evaluate the impact of pre- and perinatal factors on the risk of developing attention-deficit-hyperactivity disorder (ADHD). METHOD: We investigated the medical history of 237 children (206 male; 31 female) from Malmö, Sweden born between 1986 and 1996 and in whom a diagnosis of ADHD (Diagnostic and Statistical Manual of Mental Disorders-IIIR or IV) was subsequently made at the Department of Child and Adolescent Psychiatry, Lund University, and a reference group of 31,775 typically developing children from Malmö using data from the Swedish Medical Birth Register. RESULTS: The results of multiple logistic regression analysis revealed that ADHD was significantly associated with a young maternal age (odds ratio [OR] for 5 y increase 0.87; 95% confidence interval [CI] 0.76-0.99), maternal smoking (OR 1.35; 95% CI 1.14-1.60), maternal birthplace in Sweden (OR 2.04; 95% CI 1.45-2.94), and preterm birth <32 weeks (OR 3.05; 95% CI 1.39-6.71), and a male predominance (OR 6.38; 95% CI 4.37-9.32). Apgar scores at 5 minutes below 7 were significantly associated with ADHD in the univariable analysis (OR 2.60; 95% CI 1.15-5.90). The population-attributable fraction of ADHD caused by the perinatal factors studied was estimated to be 2.8%. INTERPRETATION: The results indicate that the studied factors constitute weak risk factors for developing ADHD.

A longitudinal investigation of cognitive functioning and its relationship to symptom severity and academic functioning in treatment seeking youth with AHDH.

BACKGROUND: Children with ADHD tend to present with poorer cognitive functioning leaving them more vulnerable to a range of negative outcomes. To date, only a handful of longitudinal studies have examined the stability of Wechsler composite scores in children and adolescents with ADHD, and none of them used a more recent version of the Wechsler Intelligence Scales for Children (WISC), than the WISC-III. OBJECTIVE: The present study investigates the cognitive stability and its longitudinal relationship with the severity of the child's ADHD symptoms and school grades. METHOD: Cognitive functioning was measured with the fourth editions of the WISC-IV or the Wechsler Adult Intelligence Scales (WAIS-IV) at baseline and at a 3-4-year follow-up in children with ADHD (n = 125, mean age = 11.40 years, SD = 3.27) and a Control group of schoolchildren (n = 59, mean age = 11.97 years, SD = 2.15). The stability of cognitive functioning and the relationship between cognitive functioning, ADHD and grades were evaluated using linear mixed models and logistic regression. RESULTS: Standardized composite scores of Full scale IQ, Verbal Comprehension, and Processing Speed declined between baseline and follow-up in the ADHD group. ADHD symptom scores were associated with Working Memory scores. Together, the severity of concurrent ADHD symptoms and lower scores for verbal comprehension at baseline and follow-up were associated with an increased risk of not achieving grades at follow-up in youth with ADHD. CONCLUSIONS: Youth with ADHD often present with cognitive impairments, not improved over time. Together these increase the risk of poorer academic outcomes. Concurrent evaluation of symptom severity and cognitive functions can add potentially useful information in terms of treatment planning, and school supports to prevent school failure.

The relationship between intelligence and global adaptive functioning in young people with or without neurodevelopmental disorders.

Previous studies have shown an association between IQ and adaptive global functioning, i.e. how well a person is functioning in different domains of life. However, it is unclear to what extent such an association applies in children with neurodevelopmental disorders (NDDs). The study group consisted of 550 population-screened children assessed with the K-SADS, WISC-IV, and the C-GAS. Approximately half of the sample had been diagnosed with one or several NDDs (ADHD, autism, language disorder and tic disorder). A factorial ANOVA with IQ level and the presence of NDD was conducted, with C-GAS score as the dependent variable. Results revealed a significant interaction effect between IQ-group and NDD-status. In the non-NDD group (49% girls), higher IQ scores were clearly linked with better global adaptive functioning. Among children with NDDs (35% girls), however, higher IQ scores were not clearly associated with better functioning. Thus, the association between IQ and adaptive functioning were found to differ depending on the presence of NDD. These results have implications for the interpretation of IQ test results in neurodevelopmental assessments and point towards the importance of providing support based on an assessment of needs and functioning rather than scores from IQ tests.