Maternal choline supplementation lessens the behavioral dysfunction produced by developmental manganese exposure in a rodent model of ADHD.

Studies in children have reported associations between elevated manganese (Mn) exposure and ADHD-related symptoms of inattention, impulsivity/hyperactivity, and psychomotor impairment. Maternal choline supplementation (MCS) during pregnancy/lactation may hold promise as a protective strategy because it has been shown to lessen cognitive dysfunction caused by numerous early insults. Our objectives were to determine whether (1) developmental Mn exposure alters behavioral reactivity/emotion regulation, in addition to impairing learning, attention, impulse control, and sensorimotor function, and (2) MCS protects against these Mn-induced impairments. Pregnant Long-Evans rats were given standard diet, or a diet supplemented with additional choline throughout gestation and lactation (GD 3 - PND 21). Male offspring were exposed orally to 0 or 50 mg Mn/kg/day over PND 1-21. In adulthood, animals were tested in a series of learning, attention, impulse control, and sensorimotor tasks. Mn exposure caused lasting dysfunction in attention, reactivity to errors and reward omission, learning, and sensorimotor function, recapitulating the constellation of symptoms seen in ADHD children. MCS lessened Mn-induced attentional dysfunction and partially normalized reactivity to committing an error or not receiving an expected reward but provided no protection against Mn-induced learning or sensorimotor dysfunction. In the absence of Mn exposure, MCS produces lasting offspring benefits in learning, attention, and reactivity to errors. To conclude, developmental Mn exposure produces a constellation of deficits consistent with ADHD symptomology, and MCS offered some protection against the adverse Mn effects, adding to the evidence that maternal choline supplementation is neuroprotective for offspring and improves offspring cognitive functioning.

Is prevention of ADHD and comorbid conditions in adolescents possible?

OBJECTIVES: To examine how the concept of prevention is applicable to adolescent ADHD, which preventive interventions may be feasible, and which methods can be used to evaluate effectiveness. METHOD: Following a literature search for prevention clinical trials relevant to adolescent ADHD, selected studies are critically reviewed to identify suitable targets and promising interventions. RESULTS: There is some evidence from controlled studies that interventions delivered to prepubertal children at high risk for ADHD or diagnosed with ADHD may decrease the incidence or persistence of ADHD in adolescence. Uncontrolled follow-up of clinical samples and population studies suggest that treatment of adolescents with ADHD can decrease the risk for several negative functional outcomes in youth. A controlled trial found a specific cognitive training intervention to decrease risky driving. CONCLUSIONS: Prevention of ADHD and associated negative outcomes is possible and of high clinical relevance. Assessing prevention effects is methodologically challenging, but feasible.

The protective effect of thymoquinone or/and thymol against monosodium glutamate-induced attention-deficit/hyperactivity disorder (ADHD)-like behavior in rats: Modulation of Nrf2/HO-1, TLR4/NF-κB/NLRP3/caspase-1 and Wnt/ß-Catenin signaling pathways in rat model.

Both thymoquinone (TQ) and thymol (T) have been proved to possess a positive impact on human health. In this research, we aimed to investigate the effect of these compounds separately and together on the Attention-deficit/hyperactivity disorder (ADHD)-like behavior induced by monosodium glutamate (MSG) in rats. Forty male, Spargue Dawley rat pups (postnatal day 21), were randomly allocated into five groups: Normal saline (NS), MSG, MSG+TQ, MSG+T, and MSG+TQ+T. MSG (0.4 mg/kg/day), TQ (10 mg/kg/day) and T (30 mg/kg/day) were orally administered for 8 weeks. The behavioral tests proved that rats treated with TQ and/or T showed improved locomotor, attention and cognitive functions compared to the MSG group with more pronounced effect displayed with their combination. All treated groups showed improvement in MSG-induced aberrations in brain levels of GSH, IL-1ß, TNF-α, GFAP, glutamate, calcium, dopamine, norepinephrine, Wnt3a, ß-Catenin and BDNF. TQ and/or T treatment also enhanced the mRNA expression of Nrf2, HO-1 and Bcl2 while reducing the protein expression of TLR4, NFκB, NLRP3, caspase 1, Bax, AIF and GSK3ß as compared to the MSG group. However, the combined therapy showed more significant effects in all measured parameters. All of these findings were further confirmed by the histopathological examinations. Current results concluded that the combined therapy of TQ and T had higher protective effects than their individual supplementations against MSG-induced ADHD-like behavior in rats.

Adherence to Mediterranean diet and attention-deficit/hyperactivity disorder in children: A case control study.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders. The Mediterranean diet as a plant-based diet has a beneficial effect on mental health. The present study was designed to investigate the association between adherence to Mediterranean diet and odds of ADHD in Iranian children. METHODS: This age and gender matched case-control study was conducted on 360 children 7-13 years old in Yazd, Iran. Children were categorized into new diagnosed case (n = 120) and control groups (n = 240). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSMIV-TR) was used to diagnose ADHD. A validated food frequency questionnaire was used to measure food intake. The association of adherence to the Mediterranean with the odds ratio of ADHD examined by logistic regression. RESULTS: After adjusting for potential confounders including energy intake, parents' educational level, economic status, family history ADHD and physical activity, the children in the highest tertile of adherence to Mediterranean diet had a lower odd of ADHD (odds ratio [OR]: 0.49; 95% Confidence Interval [CI]: 0.27-0.89) compared to the children in the lowest. In addition, an association was observed between increasing trend adherence to Mediterranean diet and decrease odds of ADHD after full adjustments (P for trend <0.001). CONCLUSION: We found that higher adherence to Mediterranean diet containing vegetables, legumes, fruits and nuts, grains, and fish could decrease the odds of ADHD in primary school children. Further studies are suggested to approve our vision.

How the placenta-brain lipid axis impacts the nutritional origin of child neurodevelopmental disorders: Focus on attention deficit hyperactivity disorder and autism spectrum disorder.

Dietary fish is a rich source of omega-3 (n-3) fatty acids, and as such, is believed to have played an important role in the evolution of the human brain and its advanced cognitive function. The long chain polyunsaturated fatty acids, particularly the n-3 docosahexanoic acid (DHA), are critical for proper neurological development and function. Both low plasma DHA and obesity in pregnancy are associated with neurodevelopmental disorders such as attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in childhood, and n-3 supplementation has been shown to improve symptoms, as reviewed herein. The mechanisms underlying the connection between maternal obesity, n-3 fatty acid levels and offspring's neurological outcomes are poorly understood, but we review the evidence for a mediating role of the placenta in this relationship. Despite promising data that n-3 fatty acid supplementation mitigates the effect of maternal obesity on placental lipid metabolism, few clinical trials or animal studies have considered the neurological outcomes of offspring of mothers with obesity supplemented with n-3 FA in pregnancy.

Breastmilk Feeding during the First 4 to 6 Months of Age and Childhood Disease Burden until 10 Years of Age.

BACKGROUND: Breastfeeding is recommended due to its beneficial effects on human health. However, the effect of breastfeeding on health differs, resulting in various childhood diseases. OBJECTIVE: Our purpose was to investigate the association between breastfeeding at least in the first 4 months and the subsequent development of 15 certainly defined childhood diseases until 10 years of age, the all-cause hospitalization rate and growth at 6-7 years of age. METHODS: Participants included propensity-score matched 188,052 children born between January 2008 and December 2009, who were followed up till 10 years of age. Data were taken from the National Investigation of birth Cohort in Korea study 2008 database. Risk ratios were obtained using a modified Poisson regression and weighted risk differences using binomial regression. RESULTS: Compared to formula feeding, breastfeeding was associated with decreased risks of febrile convulsion, attention deficit hyperactivity disorder and autism spectrum disorder, pneumonia, acute bronchiolitis, hypertrophic pyloric stenosis, asthma, all-cause hospitalization, overweight/obesity and short stature. Exclusive breastfeeding at 4 to 6 months of age had similar results to exclusive breastfeeding over 6 months of age. CONCLUSIONS: Breastfeeding in early infancy reduces the risk for various childhood diseases, all-cause hospitalization rate, obesity, and short stature during childhood.

Maternal exposure to pesticides during pregnancy and risk for attention-deficit/hyperactivity disorder in offspring: A protocol for systematic review and meta-analysis.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is the most common psychiatric disorder in childhood. Studies explored the association of maternal exposure to pesticides during pregnancy with a risk of offspring developing ADHD, but have reported inconclusive results. Here, we will perform a systematic review and meta-analysis of observational studies to assess a possible association between them. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. PubMed, Embase, Web of Science, the Cochrane Library, and the PsycINFO will be searched from inception to May 2021. Observational studies investigating the association of maternal exposure to pesticides during pregnancy with a risk of offspring developing ADHD will be considered. The Newcastle-Ottawa Scales or the scale of the Agency for Healthcare Research and Quality will be used to assess the methodological quality of the included studies according to their study design. A fixed or random-effect model will be used to synthesize data depend on the heterogeneity test. STATA version 12.0 will be used to conduct the meta-analysis. RESULTS: This study will provide a high-quality evaluation of association between maternal exposure to pesticides during pregnancy and risk for ADHD in offspring. CONCLUSION: This study will present evidence on whether maternal exposure to pesticides during pregnancy is a risk factor for ADHD in offspring.

Longer-Term Outcomes of the Incredible Years Parenting Intervention.

Conduct problems can develop into behavior disorders and put children at risk for other mental health problems. Parenting interventions have been shown to successfully reduce conduct problems and are often expected to prevent the development of broader mental health problems. Few studies have evaluated the longer-term and broader effects of these interventions. To what extent are parenting intervention effects sustained in the years after the intervention? And do effects pertain to conduct problems specifically, or do they also affect broader aspects of children's mental health? We used a randomized controlled trial to assess the longer-term (2.5 years) effects of the Incredible Years parenting intervention on children's conduct problems in an indicated prevention setting (N = 387; 79% retention rate). Using a multi-method (survey and computerized tasks) and multi-informant (parents, teachers, and children) approach, we tested whether initial effects on conduct problems were sustained, and whether Incredible Years had broader effects on children's peer problems, emotional problems, attention-deficit/hyperactivity disorder (ADHD) symptoms, attention and inhibition deficits, and service use. Incredible Years, relative to control (no intervention), led to sustained reductions in parent-reported conduct problems (Cohen's d = 0.31), but not teacher- and child-reported conduct problems. There were no broader benefits: Incredible Years did not reduce children's peer problems, emotional problems, ADHD-symptoms, attention and inhibition deficits, or their service use. Improvements in parents' perceptions of child conduct problems sustained until 2.5 years later. Our findings do not show benefits of Incredible Years as a preventive intervention for children's broader mental health.

Risk and Protective Factors in Autism Spectrum Disorders: A Case Control Study in the Lebanese Population.

Autism spectrum disorders (ASD) are among the most common childhood neurodevelopmental disorders. Identification of risk and protective factors are necessary to improve the guidance of prevention and intervention strategies. Our study aims to determine the potential risk and protective factors in ASD in the Lebanese population. Our case-control study included 100 ASD patients and 100 healthy matched controls recruited from all the Lebanese districts. The data collected from the questionnaires was analyzed using SPSS 23.0. Independent Student T-test and Chi-Square test were carried out for the bivariate analysis of the data. In addition, the variables revealing a p-value < 0.05 were used for the multivariate logistic regression analysis. Multivitamins intake, especially omega 3 and vitamin B (Odds Ratio (OR) = 0.257; 95% Confidence Interval (CI) [0.115-0.579]), rich cereal diet (OR = 0.212; 95% CI [0.089-0.510]), and supplementation in iron during pregnancy (OR = 0.229; 95% CI [0.083-0.627]) were identified as protective factors against ASD. On the other hand, stress during pregnancy (OR = 6.339; 95% CI [2.845-14.125]), the presence of ASD patients in the family (OR = 7.878; 95% CI [1.877-33.065]) and the presence of attention deficit hyperactivity disorder (ADHD) patients in the family (OR = 6.981; 95% CI [1.362-35.789]) were associated with ASD. This study shed light on risk and protective factors associated with ASD in the Lebanese population. Further rigorous research, taking into consideration these factors, is needed to assist in early detection, prevention and subsequent intervention targeting ASD and its associated comorbidities, given that our study is not experimental and does not prove causality.

The Importance of Marine Omega-3s for Brain Development and the Prevention and Treatment of Behavior, Mood, and Other Brain Disorders.

Most of the global population is deficient in long-chain marine omega-3s. In particular, docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for brain and eye development. Additionally, DHA plays a significant role in mental health throughout early childhood and even into adulthood. In the brain, DHA is important for cellular membrane fluidity, function and neurotransmitter release. Evidence indicates that a low intake of marine omega-3s increases the risk for numerous mental health issues, including Attention Deficit Hyperactivity Disorder (ADHD), autism, bipolar disorder, depression and suicidal ideation. Studies giving supplemental marine omega-3s have shown promise for improving numerous mental health conditions. This paper will review the evidence surrounding marine omega-3s and mental health conditions.

Empirically derived dietary patterns and food groups intake in relation with Attention Deficit/Hyperactivity Disorder (ADHD): A systematic review and meta-analysis.

BACKGROUND AND AIMS: Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent chronic psychiatric condition in children world wide. This study was aimed to provide an overview of food groups and dietary patterns in ADHD children as a systematic review. METHODS: The relation between dietary patterns and this disorder was also investigated through meta-analysis. Databases including Google Scholar, SCOPUS, ISI Web of science, and PubMed were searched up to June 2017. Studies on posteriori derived dietary patterns and food intakes of ADHD children were included. The achieved Relative Risks (RR) and Odds Ratio (OR) were pooled together for ADHD to compare the most and the least adherence to major dietary patterns. The heterogeneity was assessed by Cochran's Q test and I-squared methods. RESULTS: This systematic review consisted of 6 dietary patterns and 6 foods or macronutrients studies. In this regard, 6 dietary patterns studies (n: 8816) were included in the meta-analysis. The pooled analysis established that "healthy" dietary pattern significantly decreased the risk of ADHD (OR: 0·63; 95% CI: 0·41, 0·96), whereas "Western" (OR: 1.92; 95% CI: 1.13, 3.26; p:0.016) and "junk food" (OR: 1.51; 95% CI: 1.06, 2.16; p: 0.024) dietary patterns increased it. CONCLUSIONS: "Healthy" dietary pattern highly loaded with vegetables, fruits, legumes, and fish has decreased the odds of ADHD up to 37%. In addition, adherence to "junk food" pattern containing sweetened beverages and desserts as well as "Western" dietary pattern including red meat, refined grains, processed meats, and hydrogenated fat increased it.

[The prevention of externalizing disturbances]. / Prävention externaler Störungen ­ zum Stand der Forschung.

The prevention of externalizing disturbances Abstract. Objectives: Externalizing disturbances (attention deficit-hyperactivity disorders, oppositional defiant disorders, conduct disorders) in children and adolescents have a high prevalence, are stable over time, and precipitate a high individual and economic burden. Method: This review article presents the state of research based on selected current meta-analyzes and systematic reviews. Additionally, evidenced-based German-language prevention programs are discussed. Results: As in treatment, a multimodal approach to prevention is recommended which aims at reducing externalizing symptoms in specific settings. Interventions that focus on the specific environment in the family and the (pre-)school are preferable. Child-focused interventions are especially important in the context of peer-related problematic behavior because parent-based or teacher-based interventions may be less able to affect peer interactions. Conclusions: Comprehensive parent-based and (pre-)school-based preventive interventions of externalizing disturbances should be implemented. These should also include child-based approaches and additional parent-based group interventions. The effects of these interventions should be tested in large-scale studies.

Association Between Greenness Surrounding Schools and Kindergartens and Attention-Deficit/Hyperactivity Disorder in Children in China.

Importance: Few studies have investigated the association between greenness and childhood attention-deficit/hyperactivity disorder (ADHD). Objective: To evaluate the association between greenness surrounding schools or kindergartens and symptoms of ADHD in children. Design, Setting, and Participants: This population-based cross-sectional study was performed between April 2012 and January 2013 in 7 cities in northeastern China. This analysis included 59 754 children (aged 2-17 years) from 94 schools and kindergartens, who had resided in the study area for 2 years or longer. Data were analyzed from April 15, 2019, to October 10, 2019. Exposures: Greenness surrounding each child's school or kindergarten was estimated using 2 satellite image-derived vegetation indexes: the normalized difference vegetation index and the soil-adjusted vegetation index. Main Outcomes and Measures: Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) scales were used to measure ADHD symptoms (9 inattention symptoms and 9 hyperactivity-impulsivity symptoms). Parents or guardians rated the frequency of each of 18 ADHD symptoms during the preceding 6 months. Children with 6 or more symptoms of either inattention or hyperactivity-impulsivity were defined as having ADHD symptoms. Generalized linear mixed models were applied to estimate the association between greenness and ADHD symptoms. Results: The mean (SD) age of the 59 754 study participants was 10.3 (3.6) years, and 29 494 (49.4%) were girls. A total of 2566 participants (4.3%) had ADHD symptoms. Greenness levels differed substantially across schools and kindergartens. The normalized difference vegetation index within 500 m of a school or kindergarten ranged from -0.09 to 0.77. Greater greenness levels were associated with lower odds of ADHD symptoms. In covariate-adjusted models, a 0.1-unit increase in normalized difference vegetation index or soil-adjusted vegetation index within 500 m of a school or kindergarten was significantly associated with lower odds of ADHD symptoms (odds ratios, 0.87 [95% CI, 0.83-0.91] and 0.80 [95% CI, 0.74-0.86], respectively; P < .001 for both). The associations were robust in a series of sensitivity analyses. Conclusions and Relevance: These findings suggest that there may be a beneficial association between school-based greenness and ADHD symptoms in Chinese children. Future longitudinal and mechanistic studies are needed to confirm the findings of this cross-sectional analysis and further explore potential mechanisms of this association.

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.

Exposure to antibiotics in the first 24 months of life and neurocognitive outcomes at 11 years of age.

RATIONALE: Antibiotics are commonly prescribed for infants. In addition to increasing concern about antibiotic resistance, there is a concern about the potential negative impact of antibiotics on the gut microbiota and health and development outcomes. OBJECTIVE: The aim of this study was to investigate the association between early life antibiotic exposure and later neurocognitive outcomes. METHODS: Participants were infants born to mothers enrolled in the probiotics study. The initial study was designed to evaluate the effect of two different probiotics on allergy outcomes in childhood. Antibiotic exposure was based on parent report and categorised according to the following timing of the first exposure: 0-6 months, 6-12 months, 12-24 months or not at all. At 11 years of age, children's neurocognitive outcomes were assessed using psychologist-administered, parent-report and self-report measures. The relationship between the timing of antibiotic exposure and neurocognitive outcomes was examined using regression models. RESULTS: Of the 474 participants initially enrolled, 342 (72%) children had a neurocognitive assessment at 11 years of age. After adjustment for mode of delivery, probiotic treatment group assignment, income and breastfeeding, children who had received antibiotics in the first 6 months of life had significantly lower overall cognitive and verbal comprehension abilities, increased risk of problems with metacognition, executive function, impulsivity, hyperactivity, attention-deficit hyperactivity disorder, anxiety and emotional problems. CONCLUSIONS: These results provide further evidence that early exposure to antibiotics may be associated with detrimental neurodevelopmental outcomes.

An Analysis of Response Shifts in Teacher Reports Associated with the Use of a Universal School-Based Intervention to Reduce Externalising Behaviour.

School-based psychosocial interventions are a widely used approach to prevent or reduce externalising behaviour. However, evaluating the effects of such interventions is complicated by the fact that the interventions may not only change the target behaviour, but also the way that informants report on that behaviour. For example, teachers may become more aware of bullying behaviour after delivering lessons on the topic, resulting in increased teacher reports of the behaviour. In this study, we used multi-group confirmatory factor analysis to evaluate whether teachers exposed to the Promoting Alternative Thinking Strategies (PATHS) intervention changed the way they reported on child externalising behaviour. Using data from the z-proso study (802 participants; 51% male; 69 teachers), teacher reports of aggressive behaviour, attention deficit hyperactivity disorder and non-aggressive conduct disorder symptoms were compared pre- and post- intervention and across the intervention and control conditions. There was no evidence that teacher reporting was affected by exposure to the intervention. This helps bolster the interpretation of intervention effects as reflecting changes in child behaviour, rather than in the manner of informant reporting.

Improving neurodevelopmental outcomes in children with congenital heart disease: protocol for a randomised controlled trial of working memory training.

INTRODUCTION: Executive function (EF) impairments are among the most prevalent neurodevelopmental morbidities in youth with congenital heart disease (CHD). To date, no studies have investigated the efficacy of cognitive interventions to improve EF outcomes in children with CHD. METHODS AND ANALYSIS: This is a single-centre, single-blinded, two-arm randomised controlled trial to test the efficacy of Cogmed Working Memory Training (Cogmed) versus standard of care in children with CHD after open-heart surgery in infancy. Participants will consist of 100 children with CHD aged 7-12 years who underwent open-heart surgery before the age of 12 months. Participants are randomly allocated to either an intervention group including training on the home-based Cogmed intervention for a duration of approximately 5 weeks or a control group who receive the standard of care. We will evaluate the efficacy of Cogmed at post-treatment and 3 months after completion of the intervention. Baseline, post-treatment and 3-month follow-up assessments will include specific measures of EF, cognitive and social functioning, and attention deficit hyperactivity disorder (ADHD) symptoms. The primary outcome of this study is the change in standardised mean score on the List Sorting Working Memory test from the National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function. Secondary outcomes include measures of social skills, inhibitory control, cognitive flexibility and behavioural EF as well as ADHD symptoms as measured by the Behavior Rating Inventory of Executive Function, Second Edition, and the Conners Third Edition. The efficacy of the intervention will be evaluated by comparing within-subject differences (baseline to post-treatment, baseline to 3-month follow-up) between the two groups using an intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has received Institutional Review Board (IRB) approval from Boston's Children's Hospital IRB (P00022440) and the Human Protection Agency from the US Department of Defense. TRIAL REGISTRATION NUMBER: NCT03023644; Pre-results.

Neurosteroid replacement therapy using the allopregnanolone-analogue ganaxolone following preterm birth in male guinea pigs.

BACKGROUND: Children born preterm, especially boys, are at increased risk of developing attention deficit hyperactivity disorder (ADHD) and learning difficulties. We propose that neurosteroid-replacement therapy with ganaxolone (GNX) following preterm birth may mitigate preterm-associated neurodevelopmental impairment. METHODS: Time-mated sows were delivered preterm (d62) or at term (d69). Male preterm pups were randomized to ganaxolone (Prem-GNX; 2.5 mg/kg subcutaneously twice daily until term equivalence), or preterm control (Prem-CON). Surviving male juvenile pups underwent behavioural testing at d25-corrected postnatal age (CPNA). Brain tissue was collected at CPNA28 and mature myelinating oligodendrocytes of the hippocampus and subcortical white matter were quantified by immunostaining of myelin basic protein (MBP). RESULTS: Ganaxolone treatment returned the hyperactive behavioural phenotype of preterm-born juvenile males to a term-born phenotype. Deficits in MBP immunostaining of the preterm hippocampus and subcortical white matter were also ameliorated in animals receiving ganaxolone. However, during the treatment period weight gain was poor, and pups were sedated, ultimately increasing the neonatal mortality rate. CONCLUSION: Ganaxolone improved neurobehavioural outcomes in males suggesting that neonatal treatment may be an option for reducing preterm-associated neurodevelopmental impairment. However, dosing studies are required to reduce the burden of unwanted side effects.

Effect of probiotic supplementation on cognitive function in children and adolescents: a systematic review of randomised trials.

Available reviews have shown potential effects of probiotics on neurobehavioral outcomes through 'gut-brain axis' mechanism in adults. However, reviews on cognitive function in children and adolescents are lacking. Therefore, we conducted a systematic review of randomised controlled trials (RCTs) of the effect of probiotic supplementation on cognitive function in children and adolescents. A search of four databases (Cochrane Central Register of Controlled Trials, PsycARTICLES, Scopus, PubMed) was conducted to identify RCTs published from January 1990 to December 2018. Seven studies met the inclusion criteria and their cognitive outcomes were analysed. Only one study found a positive result with Lactobacillus rhamnosus GG (LGG) 1×1010 cfu supplementation with outcomes on attention deficit hyperactivity disorder (ADHD) or Asperger syndrome (AS) manifestations as diagnosed using the International Classification of Diseases-10 criteria. The supplementations were administered to Finnish mothers for 4 weeks before delivery and continuously given for 6 months after delivery if they breastfed, or to the children. ADHD or AS was diagnosed at the age of 13 years in 17.1% children in the placebo and none in the probiotic group (P=0.008). This study found significant differences in species composition and number of cells belonging to the genus Bifidobacterium between healthy children and children who later developed ADHD or AS at different time points. Six remaining studies with varying strains, durations of intervention, start-time of administration, and outcomes demonstrated no difference in cognition after probiotic supplementation. Metagenomic analyses on gut microbiota composition were not performed in any of these studies. In conclusion, the favourable effect of probiotic supplementation on cognitive function in children and adolescents was observed in one study with LGG supplementation by a risk reduction of developing ADHD or AS (i.e. autism). More long-term and follow-up trials using probiotics identifying the effect on cognition are warranted before routine use.

[Attention deficit hyperactivity disorder beyond adolescence. Time to think different?] / Trastorno por déficit de atención e hiperactividad más allá de la adolescencia ¿Tiempo de pensar diferente?

ADHD is a neurodevelopmental disorder characterized by a pattern of severe inattention-disorganization and/or hyperactivity-impulsivity beyond what is expected for individuals with a comparable development level. These behaviors impair daily life activities of patients in more than one environment and impact their performance and abilities compared with their peers. Extensive reviews have been published about the psychiatric comorbidities associated with ADHD but little attention has been given to the overall impact of ADHD on health. This study reviews some of the most common problems in medical care associated with ADHD like smoking, substance use, accident risk, sleep disorders, obesity, hypertension, diabetes, and early mortality. Today, a close follow-up of patient with ADHD is necessary not only from the psychiatric perspective but also in regard to general medicine issues to prevent the impact on health of those medical co-morbidities. Such conditions can end in severe chronic diseases with consequences and high cost for the individuals, the families and the society far beyond the academic and emotional impact frequently described as associated to ADHD. This condition has serious repercussions on health which need a medical multidisciplinary approach.