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Objective: To examine whether putatively atypical neuronal activity during internal attention in ADHD yields insights into processes underlying emotion dysregulation. Methods: We used a word processing paradigm to assess neural activations in adults with ADHD ( N = 46) compared to controls ( N = 43). We measured effects of valence, applied partial-least squares correlation analysis to assess multivariate brainbehavior relationships and ran subgroup analyses to isolate results driven by pure ADHD ( N = 18). Results: During internal attention, ADHD, compared to controls, have (1) increased activation in the right angular gyrus (rAG), which appears driven by pure, not comorbid, ADHD and (2) diminished activation in the insula and fronto-striatal circuitry. Diminished activations were driven by negatively-valenced internal attention and negatively correlated with increased affective lability within the ADHD group. Conclusion: Internal attention in ADHD is associated with increased rAG activation, possibly reflecting difficulty converging external and internal information, and diminished activation within emotion regulation circuitry.

Introduction: There has been no study in the literature evaluating serum tumor necrosis factor-like weak inducer of apoptosis (TWEAK) levels in attention-deficit/hyperactivity disorder (ADHD). Therefore, we performed the present study to specifically measure serum TWEAK levels to see whether or not its eventual alterations might have an etiopathogenetic significance in children with ADHD. Subjects and methods: A total of 49 treatment-naive children with ADHD and 39 healthy controls were included in the present study. The severities of ADHD and conduct disorder symptoms were assessed via parent- and teacher-rated questionnaires. Venous blood samples were collected, and serum TWEAK levels were measured. Results: Serum TWEAK levels of the ADHD group were significantly lower than the control group. Conclusions: This study shows that ADHD patients have decreased serum TWEAK levels, suggesting a possible involvement of TWEAK in the etiopathogenesis of ADHD.

Objective: Among screen-addicted children, there is a risk of insulin resistance (IR), obesity, hypertriglyceridemia and diabetes mellitus type 2 due to decreased physical activity and irregular eating habits. Most recently, relations of screen addiction (SA) and attention-deficit hyperactivity disorder (ADHD) with obesity have been reported. Herein, we aimed to investigate the presence of IR and dependent factors in screen-addicted children with and without obesity. Method: A total of 108 children in the age range of 11-17 years were included in the study. Cases were divided into three groups according to ADHD and SA scale scores. In these three groups, there were equal numbers of obese and non-obese patients. Homeostasis model assessment for insulin resistance (HOMA-IR) of the patients was assessed at baseline. Body fat analysis was performed with TANITA BC-420 MA body composition analyzers. All cases wore pedometers for 3 days to determine their basal metabolic rates (BMR) during active and sedentary periods. Carbohydrate, fat and calorie consumption was calculated using a professional nutrition program. Results: There were no statistically significant differences between the SA and non-SA groups on the energy consumption, BMR and fat mass and dietary contents. There was no effect of ADHD and SA on HOMA-IR values. Conclusion: We did not find any association between SA and IR. Also dependent factors were similar between groups. New studies are needed to determine how SA affects obesity., Ege University Scientific Research Projects (EGEBAP) [2013-TIP-017], This project was supported by Ege University Scientific Research Projects (EGEBAP) with grant number 2013-TIP-017.

Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with obesity, however, the potential causality between the traits remains unclear. We examined both genetic and prenatal evidence for causality using Mendelian Randomisation (MR) and polygenic risk scores (PRS). We conducted bi-directional MR on ADHD liability and six obesity-related traits using summary statistics from the largest available meta-analyses of genome-wide association studies. We also examined the shared genetic aetiology between ADHD symptoms (inattention and hyperactivity) and body mass index (BMI) by PRS association analysis using longitudinal data from Northern Finland Birth Cohort 1986 (NFBC1986, n = 2984). Lastly, we examined the impact of the prenatal environment by association analysis of maternal pre-pregnancy BMI and offspring ADHD symptoms, adjusted for PRS of both traits, in NFBC1986 dataset. Through MR analyses, we found evidence for bidirectional causality between ADHD liability and obesity-related traits. PRS association analyses showed evidence for genetic overlap between ADHD symptoms and BMI. We found no evidence for a difference between inattention and hyperactivity symptoms, suggesting that neither symptom subtype is driving the association. We found evidence for association between maternal pre-pregnancy BMI and offspring ADHD symptoms after adjusting for both BMI and ADHD PRS (association p-value = 0.027 for inattention, p = 0.008 for hyperactivity). These results are consistent with the hypothesis that the co-occurrence between ADHD and obesity has both genetic and prenatal environmental origins.

ObjectiveThis study investigated the effects of a school-based skill-training intervention in attention control and executive functions for pupils with hyperactivity-impulsivity (H-I) and cognitive control (CC) deficits. The main aim was to examine whether the intervention differently influenced H-I and CC, and whether cognitive abilities or conduct problems moderated response to the intervention.MethodElementary school pupils from 41 schools participated the study and were divided into an intervention group (n = 71) and a waitlist control group (n = 77). Intervention outcomes were assessed with an inventory assessing executive function difficulties (including H-I and CC) completed by classroom teachers.ResultsSignificant intervention effects and positive changes were detected in CC but not in H-I. Significant intervention effects were found mainly among pupils with low levels of conduct problems.ConclusionsThe results suggest that a skill-training intervention has specific positive effects on CC, but conduct problems may diminish response to intervention.

Analyses of the polygenic architecture of childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder (ADHD) in a Danish population-based case-cohort sample identify differences among ADHD subgroups with respect to common and rare variants. Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset in childhood (childhood ADHD); two-thirds of affected individuals continue to have ADHD in adulthood (persistent ADHD), and sometimes ADHD is diagnosed in adulthood (late-diagnosed ADHD). We evaluated genetic differences among childhood (n = 14,878), persistent (n = 1,473) and late-diagnosed (n = 6,961) ADHD cases alongside 38,303 controls, and rare variant differences in 7,650 ADHD cases and 8,649 controls. We identified four genome-wide significant loci for childhood ADHD and one for late-diagnosed ADHD. We found increased polygenic scores for ADHD in persistent ADHD compared with the other two groups. Childhood ADHD had higher genetic overlap with hyperactivity and autism compared with late-diagnosed ADHD and the highest burden of rare protein-truncating variants in evolutionarily constrained genes. Late-diagnosed ADHD had a larger genetic overlap with depression than childhood ADHD and no increased burden in rare protein-truncating variants. Overall, these results suggest a genetic influence on age at first ADHD diagnosis, persistence of ADHD and the different comorbidity patterns among the groups.

Objective: To evaluate the executive functions and social reciprocity of children and adolescents diagnosed with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) and compared them with healthy controls. Material and Method: Patients aged 6-17 years diagnosed with ASD (n=33) and ADHD (n=37) and healthy controls in the same age range (n=33) were included in the study. Behavioral Rating Inventory of Executive Functions (BRIEF) sub-scales and Social Responsiveness Scale (SRS) were used for evaluating executive function areas and social responsiveness. Results: Our results revealed that children and adolescents with ASD and ADHD were significantly impaired for all BRIEF sub-scales except emotional control and that the significant increase in sub-scale scores expressing deterioration continued after adjustment for SES, verbal IQ scores, and gender. ASD patients received significantly higher SRS scores compared to ADHD and control groups and ADHD patients also had significantly higher values compared to the controls. Conclusion: Further studies with parent-report scales that allow easier and faster evaluation of executive functions and social reciprocity will contribute to better understanding of the personal needs of children with neurodevelopmental disorders and the finding of new treatments.

Background: Epidemiological studies suggest a link between eczema and attention deficit hyperactivity disorder (ADHD), but underlying mechanisms have not been examined. Objective: We aim to investigate the association between eczema and subsequent ADHD symptoms in the Growing Up in Singapore Towards healthy Outcomes cohort and explore the role of pro-inflammatory cytokines and gut microbiome. Methods: The modified International Study of Asthma and Allergies in Childhood questionnaire and Computerized Diagnostic Interview Schedule for Children Version IV were administered to assess reported eczema within the first 18 months and presence of ADHD symptoms at 54 months, respectively. Skin prick testing at 18 months, cytokines in maternal blood during pregnancy and cord blood and the mediating role of the gut microbiome at 24 months were assessed. Results: After adjusting for confounders, eczema with or without a positive skin prick test was associated with doubling the risk of ADHD symptoms. No differences in maternal and cord blood cytokines were observed in children with and without eczema, or children with and without ADHD. Gut microbiome dysbiosis was observed in children with eczema and children with ADHD. Children with eczema also had lower gut bacterial Shannon diversity. However, the relationship between eczema and ADHD was not mediated by gut microbiome. Conclusion: Early life eczema diagnosis is associated with a higher risk of subsequent ADHD symptoms in children. We found no evidence for underlying inflammatory mechanism or mediation by gut microbiome dysbiosis. Further research should evaluate other mechanisms underlying the link between eczema and ADHD. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT01174875], identifier [NCT01174875]. Ministry of Health (MOH) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version This work was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore-NMRC/TCR/004-NUS/2008; NMRC/TCR/012- NUHS/2014. ET was supported by the National Medical Research Council (NMRC) Transition Award grant [MOH-TA18nov003] from NMRC, Singapore.

Contains fulltext : 287469.pdf (Publisher’s version ) (Open Access) Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental conditions, with considerable overlap in their genetic etiology. We dissected their shared and distinct genetic etiology by cross-disorder analyses of large datasets. We identified seven loci shared by the disorders and five loci differentiating them. All five differentiating loci showed opposite allelic directions in the two disorders and significant associations with other traits, including educational attainment, neuroticism and regional brain volume. Integration with brain transcriptome data enabled us to identify and prioritize several significantly associated genes. The shared genomic fraction contributing to both disorders was strongly correlated with other psychiatric phenotypes, whereas the differentiating portion was correlated most strongly with cognitive traits. Additional analyses revealed that individuals diagnosed with both ASD and ADHD were double-loaded with genetic predispositions for both disorders and showed distinctive patterns of genetic association with other traits compared with the ASD-only and ADHD-only subgroups. These results provide insights into the biological foundation of the development of one or both conditions and of the factors driving psychopathology discriminatively toward either ADHD or ASD.

Objectives Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder and Sluggish Cognitive Tempo (SCT) might be a second inattention disorder that might be even affected by different attention pathways. SCT is characterized by daydreaming, mental confusion, staring blankly and hypoactivity. In the present study, we evaluated 5 common variants (rs6265, rs3746544, rs1051312, rs133946 and rs133945) located in 3 candidate genes (BDNF, SNAP25 and SYN III) that are known to take part in synaptic plasticity and neurotransmitter transmission. Methods We tested the effects of these variants on neuropsychological findings assessed by a computer-based neuropsychological test battery in children with inattention symptoms (SCT and/or ADHD). Results BDNF (rs6265), SNAP25 (rs3746544 and rs1051312) and SYN III (rs133946 and rs133945) polymorphisms were associated with variable cognitive measures. BDNF gene (rs6265) polymorphism Met allele carriers and SNAP25 gene (rs3746544) T allele carriers had an association with the attention domain. SNAP25 gene (rs1051312) C allele carriers were only associated with reaction time scores. Cognitive flexibility, which is one of the key components of executive function evaluation and shifting attention test scores were associated with BDNF (rs6265) Met allele and SYN III (rs133946) gene G allele. SYN III (rs133945) gene C allele carriers had an association with verbal memory correct hit scores. Conclusions As a conclusion, BDNF, SNAP25 and SYN III genes were associated with specific neurocognitive outcomes in children with inattention symptoms. It is important to note that exploring genotyping effects on neurocognitive functions instead of a heterogeneous psychiatric diagnosis can improve our understanding of psychopathologies., Ege University [TTU-2018-20009], This study was supported by the Ege University Scientific Research Projects Coordinator [TTU-2018-20009].

Attention-deficit/hyperactivity disorder (ADHD) in adults is understudied, especially regarding neural mechanisms such as oscillatory control of attention sampling. We report an electroencephalography (EEG) study of such cortical mechanisms, in ADHD-diagnosed adults during administration of Test of Variables of Attention (TOVA), a gold-standard continuous performance test for ADHD that measures the ability to sustain attention and inhibit impulsivity. We recorded 53 adults (28 female, 25 male, aged 18-60), and 18 matched healthy controls, using 128-channel EEG. We analyzed sensor-space features established as neural correlates of attention: timing-sensitivity and phase-synchrony of response activations, and event-related (de)synchronization (ERS/D) of alpha and theta frequency band activity; in frontal and parietal scalp regions. TOVA test performance significantly distinguished ADHD adults from neurotypical controls, in commission errors, response time variability (RTV) and d' (response sensitivity). The ADHD group showed significantly weaker target-locked and responselocked amplitudes, that were strongly right-lateralized at the N2 wave, and weaker phase synchrony (longer reset poststimulus). They also manifested significantly less parietal prestimulus 8-Hz theta ERS, less frontal and parietal poststimulus 4-Hz theta ERS, and more frontal and parietal prestimulus alpha ERS during correct trials. These differences may reflect excessive modulation of endogenous activity by strong entrainment to stimulus (alpha), combined with deficient modulation by neural entrainment to task (theta), which in TOVA involves monitoring stimulus spatial location (not predicted occurrence onset which is regular and task-irrelevant). Building on the hypotheses of theta coding for relational structure and rhythmic attention sampling, our results suggest that ADHD adults have impaired attention sampling in relational categorization tasks.

Background Attention-deficit/hyperactivity disorder (ADHD) is associated with negative life outcomes and recent studies have linked it to increased mortality. These studies have examined nationwide registers or clinic-referred samples and mostly included participants up until the age of 30. No studies have investigated mortality associated with subthreshold levels of ADHD symptoms. Our aim was to analyze mortality in a perinatal risk cohort of 46-year-old adults with childhood ADHD (cADHD) and milder childhood attention problems (including hyperactivity and inattention; cAP) compared with a group with similar birth risks but no or low levels of childhood ADHD symptoms (Non-cAP). Causes of death obtained from a national register were examined. Methods Mortality was analyzed with Cox proportional hazard models for all-cause mortality, cause-specific mortality (natural and unnatural causes), and age-specific mortality (under and over age 30). All models were adjusted with gender. The total n in the study was 839 (cADHD n = 115; cAP n = 216; Non-cAP n = 508). Results By the age of 46, 11 (9.6%) deaths occurred in the cADHD group, 7 (3.2%) in the cAP group, and 20 (3.9%) in the Non-cAP group. The cADHD group had the highest mortality risk (adjusted hazard ratio = 2.15; 95% CI 1.02, 4.54). Mortality was not elevated in the cAP group (adjusted hazard ratio = 0.72; 95% CI .30, 1.72). Mortality in the cADHD group was mainly attributed to unnatural causes of death (adjusted hazard ratio = 2.82; 95% CI 1.12, 7.12). The mortality risk in the cADHD group was sixfold before age 30 (adjusted hazard ratio = 6.20; 95% CI 1.78, 21.57). Conclusions Childhood ADHD was associated with a twofold risk of premature death by the age of 46 in this prospective longitudinal cohort study. Our results corroborate previous findings and the morbidity of ADHD. Subthreshold levels of childhood ADHD symptoms were not linked to increased mortality. Our results suggest that mortality risk is higher in young than middle adulthood. Future studies should examine mortality associated with ADHD in different ages in adulthood to identify those in greatest risk of premature death.

This study was designed to provide more insight into the relationship between social support and externalizing behavior in forensic patients with ADHD. Because ADHD is highly associated with psychosocial impairment, we expected poor social support and attachment insecurity (i.e., preoccupied, fearful, and dismissive attachment) to be associated with higher levels of externalizing behaviors in forensic patients with ADHD. Self-reports of 32 forensic male outpatients with ADHD (M age = 35.34) were compared with self-reports of healthy (n = 32; M age = 33.84), and ‘at risk’ control males with (a history of) psychological problems (n = 30; M age = 36.47) from the general population. In addition, associations between social support, attachment and externalizing behaviors (i.e., aggression, antisociality, anger and hostility) were examined within the sample as a whole. Analyses of variance showed that forensic patients with ADHD had higher levels of externalizing behaviors and insecure attachment, and lower levels of secure attachment compared to both healthy and at risk controls. Multivariate regression analyses showed that social support was not associated with any of the externalizing behaviors, after accounting for attachment. In contrast, insecure attachment was associated with higher levels of all externalizing behaviors examined. Finally, insecure attachment best explained antisociality and hostility, suggesting that attachment is more important than other psychopathological risk factors that distinguish the different groups.

Attention deficit and hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders of childhood. It affects similar to 10% of the world's population of children, and about 30-50% of those diagnosed in childhood continue to show ADHD symptoms later, with 2-5% of adults having the condition. Current diagnosis of ADHD is based on the clinical evaluation of the patient, and on interviews performed by clinicians with parents and teachers of the children, which, together with the fact that it shares common symptoms and frequent comorbidities with other neurodevelopmental disorders, makes the accurate and timely diagnosis of the disorder a difficult task. Despite the large effort to identify reliable biomarkers that can be used in a clinical environment to support clinical diagnosis, this goal has never been achieved hitherto. In the present study, infrared spectroscopy was used together with multivariate statistical methods (hierarchical clustering and partial least-squares discriminant analysis) to develop a model based on the spectra of blood serum samples that is able to distinguish ADHD patients from healthy individuals. The developed model used an approach where the whole infrared spectrum (in the 3700-900 cm(-1) range) was taken as a holistic imprint of the biochemical blood serum environment (spectroscopic biomarker), overcoming the need for the search of any particular chemical substance associated with the disorder (molecular biomarker). The developed model is based on a sensitive and reliable technique, which is cheap and fast, thus appearing promising to use as a complementary diagnostic tool in the clinical environment. Scientific and Technological Research Council of Turkey-TUBITAK 1001 ProjectTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [116Z294]; Portuguese Science Foundation (Fundacao para a Ciencia e a Tecnologia; FCT-Lisbon) [UIDB/EQU/00102/2020, UIDP/EQU/00102/2020]; COMPETE-EU This research was funded by the Scientific and Technological Research Council of Turkey-TUBITAK 1001 Project, grant number 116Z294. R.F. thanks the Portuguese Science Foundation (Fundacao para a Ciencia e a Tecnologia; FCT-Lisbon) for financial support to the Coimbra Chemistry Centre (CQC) through the projects UIDB/EQU/00102/2020 and UIDP/EQU/00102/2020 (national funds), also funded by COMPETE-EU.

Attentional biomarkers in attention deficit hyperactivity disorder are difficult to detect using only behavioural testing. We explored whether attention measured by a low-cost EEG system might be helpful to detect a possible disorder at its earliest stages. The GokEvolution application was designed to train attention and to provide a measure to identify attentional problems in children early on. Attention changes registered with NeuroSky MindWave in combination with the CARAS-R psychological test were used to characterise the attentional profiles of 52 non-ADHD and 23 ADHD children aged 7 to 12 years old. The analyses revealed that the GokEvolution was valuable in measuring attention through its use of EEG–BCI technology. The ADHD group showed lower levels of attention and more variability in brain attentional responses when compared to the control group. The application was able to map the low attention profiles of the ADHD group when compared to the control group and could distinguish between participants who completed the task and those who did not. Therefore, this system could potentially be used in clinical settings as a screening tool for early detection of attentional traits in order to prevent their development. Ministerio de Ciencia e Innovación PID2019-110739GB-I00/ AEI/10.13039/501100011033 Ministerio de Ciencia, Innovación y Universidades PSI2015-65500-P

Background There is an ongoing debate as to whether attention-deficit hyperactivity disorder (ADHD) in highly intelligent individuals has a similar presentation as in average intelligent individuals. The aim of this study was to examine the cognitive correlates of ADHD in highly intelligent children and adolescents with ADHD. Method Two independent samples (N = 204 and N = 84) of (1) high intelligence quotient (IQ) (IQ ≥ 120) children and adolescents with ADHD were used, carefully matched on age, gender, ADHD severity, and IQ with (2) control participants with high intelligence, (3) participants with ADHD with an average intelligence (IQ 90–110), and (4) control participants with an average intelligence. These samples were selected from the Dutch node of the International Multicenter ADHD Genetics (NeuroIMAGE) and Tracking Adolescents’ Individual Lives Survey (TRAILS) cohorts, respectively, in which a large battery of cognitive tasks was administered. Linear mixed models were used to examine the main effects of ADHD and IQ and their interaction on cognitive performance. Results ADHD-control group differences were not moderated by IQ; mostly equally large ADHD-control differences in cognitive performance were found for high versus average intelligent groups. The small moderating effects found mostly indicated somewhat milder cognitive problems in highly intelligent individuals with ADHD. Overall, highly intelligent children and adolescents with ADHD performed at the level of the average intelligent control children. Conclusions Our findings indicate the cognitive profile of ADHD is similar in highly versus average intelligent individuals with ADHD, although ADHD-related cognitive deficits may be easily overlooked in the high intelligence population when compared to the typical (i.e., average intelligent) control group.

Background Attention-deficit/hyperactivity disorder (ADHD) is a psychosocially impairing and cost-intensive mental disorder, with first symptoms occurring in early childhood. It can usually be diagnosed reliably at preschool age. Early detection of children with ADHD symptoms and an early, age-appropriate treatment are needed in order to reduce symptoms, prevent secondary problems and enable a better school start. Despite existing ADHD treatment research and guideline recommendations for the treatment of ADHD in preschool children, there is still a need to optimise individualised treatment strategies in order to improve outcomes. Therefore, the ESCApreschool study (Evidence-Based, Stepped Care of ADHD in Preschool Children aged 3 years and 0 months to 6 years and 11 months of age (3;0 to 6;11 years) addresses the treatment of 3–6-year-old preschool children with elevated ADHD symptoms within a large multicentre trial. The study aims to investigate the efficacy of an individualised stepwise-intensifying treatment programme. Methods The target sample size of ESCApreschool is 200 children (boys and girls) aged 3;0 to 6;11 years with an ADHD diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) or a diagnosis of oppositional defiant disorder (ODD) plus additional substantial ADHD symptoms. The first step of the adaptive, stepped care design used in ESCApreschool consists of a telephone-assisted self-help (TASH) intervention for parents. Participants are randomised to either the TASH group or a waiting control group. The treatment in step 2 depends on the outcome of step 1: TASH responders without significant residual ADHD/ODD symptoms receive booster sessions of TASH. Partial or non-responders of step 1 are randomised again to either parent management and preschool teacher training or treatment as usual. Discussion The ESCApreschool trial aims to improve knowledge about individualised treatment strategies for preschool children with ADHD following an adaptive stepped care approach, and to provide a scientific basis for individualised medicine for preschool children with ADHD in routine clinical care. Trial registration The trial was registered at the German Clinical Trials Register (DRKS) as a Current Controlled Trial under DRKS00008971 on 1 October 2015. This manuscript is based on protocol version 3 (14 October 2016).

Known comorbidities for Attention-Deficit Hyperactivity Disorder (ADHD) include conduct problems, substance use disorder and gaming. Comorbidity with conduct problems may increase the risk for substance use disorder and gaming in individuals with ADHD. The aim of the study was to build a causal model of the relationships between ADHD and comorbid conduct problems, and alcohol, nicotine, and other substance use, and gaming habits, while accounting for age and sex. We used a state-of-the-art causal discovery algorithm to analyze a case-only sample of 362 ADHD-diagnosed individuals in the ages 12–24 years. We found that conduct problem severity mediates between ADHD severity and nicotine use, but not with more severe alcohol or substance use. More severe ADHD-inattentive symptoms lead to more severe gaming habits. Furthermore, our model suggests that ADHD severity has no influence on severity of alcohol or other drug use. Our findings suggest that ADHD severity is a risk factor for nicotine use, and that this effect is fully mediated by conduct problem severity. Finally, ADHD-inattentive severity was a risk factor for gaming, suggesting that gaming dependence has a different causal pathway than substance dependence and should be treated differently. By identifying these intervention points, our model can aid both researchers and clinicians.

Amaç: Bu çalışmanın amacı erişkin dikkat eksikliği ve hiperaktivite bozukluğu (DEHB) hastalarında nörobilişsel işlevler ile zihin okuma performansı ve dürtüsellik arasındaki ilişkiyi saptamaktır. Yöntem: Çalışmaya erişkin DEHB tanısı konulmuş olan 18-65 yaş arasında 30 hasta ile 30 sağlıklı kontrol alındı. Tüm katılımcılara DSM-IV Eksen I Bozuklukları için Yapılandırılmış Klinik Görüşme (SCID-I), Erişkin DEHB Öz Bildirim Ölçeği (EDHÖ), Barratt Dürtüsellik Ölçeği (BDÖ), Gözlerden Zihin Okuma Testi (GZOT) ve nöropsikolojik testler (Sayı Dizisi Testi, İşitsel Sessiz Üç Harf Sıralaması Testi, Rey İşitsel Sözel Öğrenme ve Bellek Testi, Görsel Kopyalama Testi, Kontrollü Kelime Çağrışım Testi ve Stroop Testi) uygulandı. Bulgular: DEHB grubunda EDHÖ ve BDÖ puan ortalamaları kontrol grubuna göre yüksek saptandı. GZOT puan ortalaması karşılaştırıldığında iki grup arasında anlamlı farklılık bulunmadı. DEHB grubunda İşitsel Sessiz Üç Harf Sıralaması Testi puanı, Stroop kelime okuma hata sayısı alt testi puanı ve kontrollü kelime çağrışım testinin perseverasyon puanı kontrol grubuna göre yüksek saptandı. Korelasyon analizinde BDÖ dikkatsel dürtüsellik alt ölçek puanı ile ileri sayı dizisi test puanı arasında; BDÖ motor dürtüsellik alt ölçek puanı ile REY 1 ve REY 5 test puanı arasında; BDÖ plansızlık alt ölçek puanı ile REY 5 test puanı arasında; BDÖ toplam puanı ile ileri sayı dizisi, REY 1, REY 5, REY1-5 ve REY 7 test puanları arasında negatif yönde anlamlı ilişki saptandı. Sonuç: Erişkin DEHB hastalarında sözel bellek işlevleri dürtüsellik ile ilişkilidir. DEHB hastalarında dürtüsellik, yürütücü işlevler ve zihin kuramı birbirinden bağımsız işlevler olabilir., Objective: The aim of this study was to determine the relationship between neurocognitive functions, reading the mind in the eyes performance and impulsivity in adult attention deficit and hyperactivity disorder (ADHD) patients. Methods: Thirty subjects who had a diagnosis of ADHD and 30 control subjects aging between 18-65 years were included into the study. Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders Axis I (SCID l), Adult ADHD Self-Report Scale (ASRS), Barratt Impulsivity Scale (BIS), Reading the Mind in the Eyes Test (RMET) and neuropsychological tests (Digit Span Test, Auditory Consonant Trigram-ACT, Rey Verbal Learning Test, Visual Reproduction Test, Controlled Oral Word Association Test-COWAT and Stroop Task) were performed to all participants. Results: ASRS and Barratt Impulsivity Scale scores were significantly higher in ADHD group than the control group. No difference was found in RMET scores between the adult ADHD and the control groups. ACT, Stroop word reading mistake subscale and COWAT perseveration scores were found to be ADHD group than the control group. Correlation analyses revealed that there was a significant and negative relationship between BIS inattention score and digit span forward test score; BIS motor impulsivity score and REY 1, REY 5 scores; BIS non-planning score and REY 5 score; BIS total score and digit span forward, REY 1, REY 5, REY 7 scores. Conclusion: Verbal memory functions are related with impulsivity in ADHD patients. Impulsivity, executive functions and theory of mind may be independent functions in patients with ADHD.

Objective: Androgen exposure is hypothesized to play a role in the development of autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and disruptive behavior disorders/DBDs (oppositional defiant disorder/ODD and conduct disorder/CD). The aim of this cross-sectional study was to investigate ASD, ADHD, and DBD (ODD and CD) traits in children and adolescents with congenital adrenal hyperplasia (CAH), a natural cause of prenatal androgen excess in females. Methods: Forty-five children and adolescents (27 girls, mean age 11.1 +/- 3; 18 boys, mean age 10.8 +/- 3.6) with CAH and their unaffected siblings (16 girls, mean age 11.4 +/- 3.9; 14 boys, mean age 12.6 +/- 4.2) were included in the study. Parents completed the Social Communication Questionnaire, to measure ASD symptoms; and the Turgay DSM-IV-Based Child and Adolescent Disruptive Behavioral Disorders Screening and Rating Scale to assess ADHD and DBD traits. Results: In this study, boys but not girls with CAH showed higher autistic traits. There was no significant difference between either girls or boys with CAH and their unaffected counterparts with respect to inattention or hyperactivity symptoms. Boys with CAH showed more ODD symptoms than the unaffected boys. There was a trend for boys to have more CD symptoms compared to unaffected boys. Conclusions: Our study does not support the hypothesis that prenatal androgen exposure is associated with ASD, ADHD or DBDs. Postnatal/circulating androgen levels, higher testosterone/cortisol ratio, lower basal cortisol or dysregulation in HPA axis might be related to higher autistic traits or increased DBDs symptoms found in boys with CAH. Further investigations with larger groups are needed to clarify these associations., Amaç: Yapılan araştırmalar sonucunda, prenatal androjen maruziyetinin otizm spektrum bozukluğu (OSB), dikkat eksikliği hiperaktivite bozukluğu (DEHB), yıkıcı davranış bozuklukları/YDB (karşıt olma karşı gelme bozukluğu/ KOKG ve davranım bozukluğu/DB) ve bunların subklinik belirtilerinin gelişmesinde rolü olduğu düşünülmektedir. Bu araştırmanın amacı kız çocuklarda prenatal dönemde aşırı androjen maruziyetine yol açan konjenital adrenal hiperplazi (KAH) tanısı almış çocuk ve ergenlerde otizm spektrum bozukluğu özellikleri, DEHB ve YDB (KOKG ve DB) belirtilerinin sıklığının araştırılmasıdır. Yöntem: KAH tanısı konmuş 45 çocuk ve ergen olgu (27 kız, ortalama yaş: 11.1±3; 18 erkek, ortalama yaş: 10.8±3.6) ve bu olguların etkilenmemiş akrabaları (16 kız, ortalama yaş: 11.4±3.9; 14 erkek, otalama yaş: 12.6±4.2) çalışmaya alınmıştır. Sosyal İletişim Ölçeği ve Turgay Yıkıcı Davranım Bozuklukları için DSM-IV’e Dayalı Tarama ve Değerlendirme Ölçeği (T-DSM-IV-S), sırasıyla otizm spektrum bozukluğu özellikleri, DEHB ve YDB (KOKG ve DB) belirtilerinin sıklığını değerlendirmek üzere ebeveynler tarafından doldurulmuştur. Bulgular: Bu araştırmanın sonucunda KAH tanısı konan erkek olgularda OSB özelliklerinin görülme sıklığının etkilenmemiş erkek akrabalarla karşılaştırıldığında artmış olduğu gösterilmiştir. KAH tanısı konan ve etkilenmemiş kız olgular arasında OSB özellikleri sıklığı açısından bir fark bulunmamıştır. KAH tanısı konmuş kız ve erkek olgularla bu olguların etkilenmemiş kız ve erkek akrabaları arasında dikkat eksikliği ve hiperaktivite belirtilerinin sıklığı açısından bir fark bulunmamıştır. KAH tanısı konan erkek olgularda KOKG belirtileri sıklığı etkilenmemiş erkek akrabalara göre artmıştır. KAH tanısı konan erkek olgularda DB belirtileri sıklığının etkilenmemiş erkek akrabalara göre artış eğilimi gösterdiği belirlenmiştir. Sonuç: Araştırmamız prenatal androjen maruziyetinin OSB, DEHB ve YDB ile ilişkili olduğu hipotezini desteklememektedir. KAH tanısı konan erkek çocuklarda artmış YDB belirtileri sıklığı postnatal androjen düzeyleri, yüksek testosterone/kortizol oranı, düşük bazal kortizol düzeyi veya hipotalomopitiüter aks disregülasyonu ile ilişkili olabilir. Daha geniş bir örneklemle yapılacak olan araştırmaların sözü geçen bağlantıları değerlendirmek üzere yararlı olacağı düşünülmektedir. (Anadolu Psikiyatri Derg 2020; 21(4):435-442)

Summary Background The use of medications to treat attention deficit hyperactivity disorder (ADHD) has increased, but the prevalence of ADHD medication use across different world regions is not known. Our objective was to determine regional and national prevalences of ADHD medication use in children and adults, with a specific focus on time trends in ADHD medication prevalence. Methods We did a retrospective, observational study using population-based databases from 13 countries and one Special Administrative Region (SAR): four in Asia and Australia, two in North America, five in northern Europe, and three in western Europe. We used a common protocol approach to define study populations and parameters similarly across countries and the SAR. Study populations consisted of all individuals aged 3 years or older between Jan 1, 2001, and Dec 31, 2015 (dependent on data availability). We estimated annual prevalence of ADHD medication use with 95% CI during the study period, by country and region and stratified by age and sex. We reported annual absolute and relative percentage changes to describe time trends. Findings 154·5 million individuals were included in the study. ADHD medication use prevalence in 2010 (in children aged 3–18 years) varied between 0·27% and 6·69% in the countries and SAR assessed (0·95% in Asia and Australia, 4·48% in North America, 1·95% in northern Europe, and 0·70% in western Europe). The prevalence of ADHD medication use among children increased over time in all countries and regions, and the absolute increase per year ranged from 0·02% to 0·26%. Among adults aged 19 years or older, the prevalence of any ADHD medication use in 2010 varied between 0·003% and 1·48% (0·05% in Asia and Australia, 1·42% in North America, 0·47% in northern Europe, and 0·03% in western Europe). The absolute increase in ADHD medication use prevalence per year ranged from 0·0006% to 0·12%. Methylphenidate was the most commonly used ADHD medication in most countries. Interpretation Using a common protocol and data from 13 countries and one SAR, these results show increases over time but large variations in ADHD medication use in multiple regions. The recommendations of evidence-based guidelines need to be followed consistently in clinical practice. Further research is warranted to describe the safety and effectiveness of ADHD medication in the short and long term, and to inform evidence-based guidelines, particularly in adults. Funding None

A large body of research demonstrated that individuals with attention deficit hyperactivity disorder (ADHD) suffer from various neuropsychological deficits. In contrast, less is known and only divergent evidence exists on perceptual functions of individuals with ADHD. This is problematic as neuropsychological and perceptual functions are closely interrelated and are often difficult to disentangle in behavioral assessments. This study presents the conduct and results of a systematic literature review on perceptual functions in children and adults with ADHD. This review considers studies using psychophysical methods (objective measurements) and self- and informant reports (subjective measurements). Results indicate that individuals with ADHD have altered perceptual functions in various domains as compared to typically developing individuals. Increased perceptual functions in individuals with ADHD were found with regard to olfactory detection thresholds, whereas reduced perceptual functions were evident for aspects of visual and speech perception. Moreover, individuals with ADHD were found to experience discomfort to sensory stimuli at a lower level than typically developing individuals. Alterations of perceptual functions in individuals with ADHD were shown to be moderated by various factors, such as pharmacological treatment, cognitive functions, and symptom severity. We conclude by giving implications for daily life functioning and clinical practice.

Modern environments are full of information, and place high demands on the attention control mechanisms that allow the selection of information from one (focused attention) or multiple (divided attention) sources, react to changes in a given situation (stimulus-driven attention), and allocate effort according to demands (task-positive and task-negative activity). We aimed to reveal how attention deficit hyperactivity disorder (ADHD) affects the brain functions associated with these attention control processes in constantly demanding tasks. Sixteen adults with ADHD and 17 controls performed adaptive visual and auditory discrimination tasks during functional magnetic resonance imaging (fMRI). Overlapping brain activity in frontoparietal saliency and default-mode networks, as well as in the somato-motor, cerebellar, and striatal areas were observed in all participants. In the ADHD participants, we observed exclusive activity enhancement in the brain areas typically considered to be primarily involved in other attention control functions: During auditory-focused attention, we observed higher activation in the sensory cortical areas of irrelevant modality and the default-mode network (DMN). DMN activity also increased during divided attention in the ADHD group, in turn decreasing during a simple button-press task. Adding irrelevant stimulation resulted in enhanced activity in the salience network. Finally, the irrelevant distractors that capture attention in a stimulus-driven manner activated dorsal attention networks and the cerebellum. Our findings suggest that attention control deficits involve the activation of irrelevant sensory modality, problems in regulating the level of attention on demand, and may encumber top-down processing in cases of irrelevant information. (C) 2018 Elsevier B.V. All rights reserved.

Neuropsychological research on adults with ADHD showed deficits in various aspects of attention. However, the majority of studies failed to explore the change of performance over time, so-called time-on-task effects. As a consequence, little is known about sustained attention performance of adults with ADHD. The aim of the present study was therefore to test the hypothesis of sustained attention deficits of adults with ADHD. Twenty-nine adults with ADHD and 30 healthy individuals were assessed on four 20-min tests of sustained attention, measuring alertness, selective attention, divided attention and flexibility. The deterioration of performance over time (time-on-task effects) was compared between patients with ADHD and healthy individuals to conclude on sustained attention performance. Compared to healthy individuals, patients with ADHD showed significant deficits of medium size in selective attention and divided attention. Furthermore, medium sustained attention deficits was observed in measures of alertness, selective attention and divided attention. This study supports the notion of sustained attention deficits of adults with ADHD.

RATIONALE: The dopaminergic system has been implicated in visuospatial attention and inhibition, but the exact role has yet to be elucidated. Scarce literature suggests that attenuation of dopaminergic neurotransmission negatively affects attentional focusing and inhibition. To the best of our knowledge, this is the first study that evaluated the effect of dopaminergic antagonism on stopping performance. METHODS: Dopaminergic neurotransmission was attenuated in 28 healthy male participants by using 2 mg haloperidol. A repeated-measures placebo-controlled crossover design was implemented, and performance indices of attention and inhibition were assessed in the visual spatial cueing task (VSC) and stop signal task (SST). Additionally, the effect of haloperidol on motoric parameters was assessed. It was expected that haloperidol as contrasted to placebo would result in a reduction of the "validity effect," the benefit of valid cueing as opposed to invalid cueing of a target in terms of reaction time. Furthermore, an increase in stop signal reaction time (SSRT) in the SST was expected. RESULTS AND CONCLUSION: Results partially confirmed the hypothesis. Haloperidol negatively affected inhibitory motor control in the SST as indexed by SSRT, but there were no indications that haloperidol affected bias or disengagement in the VSC task as indicated by a lack of an effect on RTs. Pertaining to secondary parameters, motor activity increased significantly under haloperidol. Haloperidol negatively affected reaction time variability and errors in both tasks, as well as omissions in the SST, indicating a decreased sustained attention, an increase in premature responses, and an increase in lapses of attention, respectively.

OBJECTIVE: Current data about Attention Deficit Hyperactivity Deficiency (ADHD) guideline use in the Netherlands are absent. This study analysed ADHD guideline use among different healthcare workers, and the use of key elements from these guidelines to diagnose ADHD.METHOD: A survey assessing ADHD guideline use was distributed throughout the Netherlands to various health care professionals. Only professionals involved during the diagnostic process were included.RESULTS: Response rate among GPs was low (111/1450), but high among other health care professionals (251/287). A total of 362 surveys were analysed, 186 responders (51%) were involved during the diagnostic process. Overall guideline use was 64.5%; the national multidisciplinary guideline or a guideline made by a professional's own institution were most used. Psychiatrists, psychologists and paediatricians reported compliance with key elements of the guidelines such as gathering information from a third party (> 90%) and carrying out a developmental history (> 88%). Use of a standardized interview (CONCLUSION: Despite low general use of guidelines, psychiatrists, psychologists and paediatricians use similar key elements of ADHD guidelines. This study provides opportunities to improve care through increasing familiarity with ADHD guidelines and the use of standardized interviews.

OBJECTIVES: In this study, we examined the consequences of ignoring violations of assumptions underlying the use of sum scores in assessing attention problems (AP) and if psychometrically more refined models improve predictions of relevant outcomes in adulthood.METHODS: Tracking Adolescents' Individual Lives data were used. AP symptom properties were examined using the AP scale of the Child Behavior Checklist at age 11. Consequences of model violations were evaluated in relation to psychopathology, educational attainment, financial status, and ability to form relationships in adulthood.RESULTS: Results showed that symptoms differed with respect to information and difficulty. Moreover, evidence of multidimensionality was found, with two groups of items measuring sluggish cognitive tempo and attention deficit hyperactivity disorder symptoms. Item response theory analyses indicated that a bifactor model fitted these data better than other competing models. In terms of accuracy of predicting functional outcomes, sum scores were robust against violations of assumptions in some situations. Nevertheless, AP scores derived from the bifactor model showed some superiority over sum scores.CONCLUSION: These findings show that more accurate predictions of later-life difficulties can be made if one uses a more suitable psychometric model to assess AP severity in children. This has important implications for research and clinical practice.

Aim Attention Deficit Hyperactivity Disorder (ADHD) is a lifespan disorder associated with considerable economic cost. While the economic burden of ADHD has been widely estimated, there is considerable variation in reported costs between studies, which typically focus on health outcomes only, lack adequate control and fail to correct for the influence of genetic and shared environmental factors. The aim of this study is to overcome these limitations to reach a fuller understanding of the economic burden of ADHD. Method Using the Danish National Registers 5269 adults with a diagnosis of ADHD in adulthood who had not received a diagnosis in childhood were identified. Excluding cases with missing data, comorbid diagnoses, and cases without a same sex sibling free of any diagnosed psychiatric diagnoses, a final cohort was formed consisting of 460 sibling dyads. Using a cross-sectional method focusing on the year 2010, cost differences between each adult with ADHD and their sibling were calculated from data retrieved from health, education, crime, employment and social care registers. Results Adults with ADHD had considerably lower disposable income and paid less tax than their siblings. They also received more state benefits, had higher costs for health, social care, and crime than their siblings. The total average costs difference for the year 2010 was 20,134 euros more than their sibling for each adult with ADHD. Conclusion ADHD is associated with considerable costs which are borne by both the individual and the state and underlines the need to consider the wider economic impact of ADHD beyond income and healthcare utilisation costs.

Gabriele Masi,1 Pamela Fantozzi,1 Arianna Villafranca,1 Annalisa Tacchi,1 Federica Ricci,1 Laura Ruglioni,1 Emanuela Inguaggiato,1 Chiara Pfanner,1 Samuele Cortese2 1IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Calambrone, Pisa, Italy; 2Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK Purpose: Methylphenidate (MPH), the first-line medication in children with attention-deficit/hyperactivity disorder (ADHD), is associated with increased risk of sleep disorders. Melatonin has both hypnotic and chronobiotic properties that influence circadian rhythm sleep disorders. This study explores the effectiveness of melatonin in children with ADHD who developed sleep problems after starting MPH. Patients and methods: This study, based on a clinical database, included 74 children (69 males, mean age 11.6±2.2 years) naturalistically treated with MPH (mean dosage 33.5±13.5 mg/d). The severity of sleep disorder (sleep onset delay) was recorded at baseline and after a follow-up of at least 4 weeks using a seven-point Likert scale according to the Clinical Global Impression Severity score. Effectiveness of melatonin on sleep (mean dosage 1.85±0.84 mg/d) after 4 weeks was assessed using a seven-point Likert scale according to the Clinical Global Impression Improvement (CGI-I) score, and patients who scored 1 (very much improved) or 2 (much improved) were considered responders. Results: Clinical severity of sleep disorders was 3.41±0.70 at the baseline and 2.13±1.05 after the follow-up (P

AmaçDikkat Eksikliği Hiperaktivite Bozukluğu‟nda (DEHB) önemli fonksiyonel kayıplaraneden olan öfke, irritabilite ve engellenme toleranssızlığı gibi duygu düzenleme güçlükleri(DDG) görülebilir. Bu araştırmada DEHB tanılı çocuk ve ergenler ile sağlıklı kontrolgrubunu duygu düzenleme özellikleri bakımından karşılaştırmak, duygu düzenleme güçlüğüile ilişkili olabilecek faktörleri incelemek amaçlanmıştır.Gereç ve YöntemAraştırma Namık Kemal Üniversitesi Tıp Fakültesi, Çocuk ve ErgenPsikiyatri polikliniğinde DSM-V tanı kriterlerine göre DEHB tanısı konulan 6-18 yaşaralığında 72 çocuk-ergen ve 30 sağlıklı kontrol ile yürütülmüştür. Okul Çağı Çocukları içinDuygulanım Bozuklukları ve Şizofreni Görüşme Çizelgesi – Şimdi ve Yaşam Boyu Şekli(ÇDŞG – ŞY) yarı yapılandırılmış görüşme formu kullanılarak komorbiditeler belirlenmiştir.Çocukluk Çağı Davranış Değerlendirme Ölçeği (ÇDDÖ) ile duygu düzenleme güçlüğü(DDG=dikkat+anksiyete/depresyon+agresyon alt ölçekleri) puanı elde edilmiştir.BulgularDEHB grubunda DDG puanı 1--89.45±19.33 iken, sağlıklı kontrol grubundaDDG puanı 164.13±9.94 olarak bulunmuştur. İki grup arasında DDG puanları bakımındananlamlı fark saptanmıştır (p˂0.001**). DEHB grubu klinik özellikler bakımındandeğerlendirildiğinde eş psikiyatrik bozuklukların DDG ile ilişkili olmadığı, DEHB bileşikgörünüm özelliklerinin ise DDG için önemli yordayıcı olduğu sonucu elde edilmiştir(p=0.011*).SonuçBu araştırmanın sonuçları DEHB tanılı bireylerde DDG‟nün sağlıklı kontrollere göreanlamlı düzeyde fazla olduğu ve DEHB bileşik görünümün DDG için yordayıcı olduğusonucunu ortaya koymuştur. DEHB‟ye eşlik eden duygu düzenleme güçlüğü, kişide dahafazla işlevsellik kaybına yol açtığı ve bozukluğun yetişkin yaşta devamı ileilişkilendirildiğinden, DEHB tanı ve tedavi sürecinde ayrıca ele alınması gereken önemliklinik özelliklerdendir., AimEmotion regulation difficulties(ERD) such as anger, irritability and frustration intolerance leading to severefunctional losses may be observed in attention deficit-hyperactivity disorder(ADHD). The purpose of this study was to compare children and adults diagnosedwith ADHD and a healthy control group in terms of emotion regulationcharacteristics and to examine factors potentially associated with ERD.MethodThe study was performed with 72children/adults aged 6-18 diagnosed with ADHD based on DSM-V diagnosticcriteria at the XXXXXX Child and Adolescent Psychiatry Polyclinic, Turkey, and30 healthy controls. The Schedule for Affective Disorders and Schizophrenia forSchool-Age Children – Present and Lifetime Version (K-SADS-PL), asemi-structured interview form, was used to determine comorbidities. ERD scores(ERD=attention+anxiety/depression+aggression subscales) were determined usingthe Childhood Behavior Checklist (CBCL).ResultsMean ERD scores were 189.45±19.33in the ADHD group and 164.13±9.94 in the healthy control group. A significantdifference was determined in ERD scores between the two groups (p˂0.001**).When the ADHD group was evaluated in terms of clinical characteristics,comorbid psychiatric disorders were not associated with ERD, but combined typeADHD characteristics emerged as significant predictors for ERD (r=0.43,r2=0.18, p=0.001**).ConclusionThe results of this research revealedsignificantly greater ERD in individuals diagnosed with ADHD compared tohealthy controls, and that combined type ADHD is a predictor for ERD. Since ERDaccompanying ADHD lead to greater function loss in the individual and areassociated with persistence of the disorder in adulthood, these are importantclinical characteristics also requiring evaluation during the diagnosis andtreatment of ADHD.

Aims Several studies indicate the similarity between the symptoms of fetal alcohol syndrome and attention-deficit hyperactivity disorder (ADHD). This study hypothesized that prenatal exposure to ethanol (EtOH) can be used as an animal model of ADHD in Wistar rats. Methods At the first stage of the study, alcohol was delivered to the pregnant dams (237-252 g) by intra-gastric route throughout Gestation Days 8-20 at a dose of 6 g/kg/day. Untreated control group with isocaloric sucrose intubation was also included. Of the 16 male pups (174-180 g), 8 were in the fetal alcohol effects (FAE) group and 8 were in the untreated control group. Subjects went through behavior shaping, discrimination learning and reversal learning. Number of sessions to learn the tasks, response frequency to inhibitory (S-) and excitatory (S+) stimulus features, response latency and inter-response time (IRT) were measured. Results Significant differences were obtained on only the reversal task. Rats with FAE needed greater number of sessions to learn the reversal task, and they had a higher frequency of incorrect responses in specifically the latter part of the sessions. Conclusion Our results suggest that reversal learning of FAE rats exhibits deficit in the inhibition of pre-learned responses. Responses behaviorally mimicked attention deficit and impulsivity symptoms of human ADHD. However, the experimental design of the study was not conducive to hyperactivity. Accordingly, rats with FEA can be an alternative to other models since it is not, for example, based on a symptom that is atypical (such as hypertension) to ADHD. Short summary Significant difference was obtained in a reversal task between male rats prenatally exposed to ethanol and matched controls. The greater number of sessions for learning and higher frequency of incorrect responses behaviorally mimicked symptoms of ADHD, suggesting that rats with fetal ethanol effects can serve as a useful animal model.

Introduction: Inattention is one of the core symptoms of Attention Deficit Hyperactivity Disorder (ADHD). Most of patients with ADHD show motor impairment, consisting in the persistence of neurological soft signs (NSS). Our aim was to evaluate attentional and motor functioning in an ADHD sample and healthy children (HC) and possible link between attentional dysfunction and motor impairment in ADHD.Method: Twenty-seven drug-naive patients with ADHD and 23 HC were tested with a test battery, measuring different aspects of attention. Motor evaluation has provided three primary variables: overflow movements (OM), dysrhythmia and total speed of timed activities.Results: Compared to HC, patients were impaired in a considerable number of attentional processes and showed a greater number of NSS. Significant correlations between disturbances of attention and motor abnormalities were observed in ADHD group.Conclusion: Our findings suggest that attentional processes could be involved in the pathophysiology of the NSS and add scientific evidence to the predictive value of NSS as indicators of the severity of functional impairment in ADHD. Given the marked improvement or complete resolution of NSS following treatment with methylphenidate, we suggest that evaluation of NSS is useful to monitor the effectiveness of pharmacological treatment with MPH in ADHD.

This study aimed to evaluate the baseline sleep habits of children with ADHD and the effects of treatment with methylphenidate (MPH) and atomoxetine (ATX) on sleep parameters. Treatment naive children with clinically normal intelligence diagnosed with ADHD were enrolled in the study. Children were treated naturalistically with MPH and ATX. Treatments were started at 0.5 mg/ kg/ day and titrated weekly to a maximum of 1.2 mg/ kg/ day. The daily equivalent dose was calculated according to clinician toolkits of Utah Academy of Child and Adolescent Psychiatry. DSM-IV Based Screening and Assessment Scale for Disruptive Behavior Disorders- Parent form (DBSASDBD) and Clinical Global Impression Scale were used to assess ADHD symptoms and Children's Sleep Habits Questionnaire (CSHQ)- Short Form was used to assess the sleep habits and problems before and after the treatment. Both MPH and ATX reduced symptom severity of ADHD in all domains and also reduced total CSHQ scores with similar effect sizes. (0.7 for MPH vs. 0.8 for ATX). The rate of clinically significant sleep problems at baseline was 93.5 %. At the end-point, 83.9 % of the sample still displayed clinically significant sleep problems while none of the children were judged to have moderate-severe sleep problems. Our results suggest that both ATX and MPH may selectively improve different sleep domains in children with ADHD. Studies using standardized dosing schemes for longer durations and evaluating sleep with objective measurements may clarify the differential effects of treatments on sleep among children with ADHD. WOS:000573651300010 2-s2.0-85083851580 PubMed: 32361211

The aim of the present study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), which allows a depletion of noradrenergic terminals in a dose-dependent manner, on attention in rats as measured using the five-choice serial-reaction time task (5CSRTT). In addition, we investigated whether the effects of DSP4 treatment can be reversed by atomoxetine. Atomoxetine is a selective noradrenaline reuptake inhibitor and has been shown to be effective in the treatment of attention deficit hyperactivity disorder. Wistar rats were trained in the 5CSRTT and treated with one of the three doses of DSP4 (10, 20 or 50 mg/kg) or saline. Following DSP4 treatment, rats were injected with three doses of atomoxetine (0.1, 0.5 or 1 mg/kg) or saline and tested in the 5CSRTT. The treatment with DSP4 caused a reduction in activity and a decline of performance in parameters related to attention in the 5CSRTT. Whether or not these impairments are due to attention deficits or changes in explorative behaviour and activity remains to be investigated. The treatment with atomoxetine had no beneficial effect on the rats' performance regardless of the DSP4 treatment. The present findings support the role of noradrenaline in modulating attentional processes and call for future studies regarding the effects of atomoxetine on attention in rats.

This article presents a review of the studies that have analysed the motor skills of ADHD children without medication and the influence of medication on their motor skills. The following two questions guided the study: What is the evidence of impairment of motor skills and aspects of motor control among children with ADHD aged between 6 and 16 years? What are the effects of ADHD medication on motor skills and motor control? The following keywords were introduced in the main databases: attention disorder and/or ADHD, motor skills and/or handwriting, children, medication. Of the 45 articles retrieved, 30 described motor skills of children with ADHD and 15 articles analysed the influence of ADHD medication on motor skills and motor control. More than half of the children with ADHD have difficulties with gross and fine motor skills. The children with ADHD inattentive subtype seem to present more impairment of fine motor skills, slow reaction time, and online motor control during complex tasks. The proportion of children with ADHD who improved their motor skills to the normal range by using medication varied from 28% to 67% between studies. The children who still show motor deficit while on medication might meet the diagnostic criteria of developmental coordination disorder (DCD). It is important to assess motor skills among children with ADHD because of the risk of reduced participation in activities of daily living that require motor coordination and attention.

This article presents a review of the studies that have analysed the motor skills of ADHD children without medication and the influence of medication on their motor skills. The following two questions guided the study: What is the evidence of impairment of motor skills and aspects of motor control among children with ADHD aged between 6 and 16 years? What are the effects of ADHD medication on motor skills and motor control? The following keywords were introduced in the main databases: attention disorder and/or ADHD, motor skills and/or handwriting, children, medication. Of the 45 articles retrieved, 30 described motor skills of children with ADHD and 15 articles analysed the influence of ADHD medication on motor skills and motor control. More than half of the children with ADHD have difficulties with gross and fine motor skills. The children with ADHD inattentive subtype seem to present more impairment of fine motor skills, slow reaction time, and online motor control during complex tasks. The proportion of children with ADHD who improved their motor skills to the normal range by using medication varied from 28% to 67% between studies. The children who still show motor deficit while on medication might meet the diagnostic criteria of developmental coordination disorder (DCD). It is important to assess motor skills among children with ADHD because of the risk of reduced participation in activities of daily living that require motor coordination and attention.

Exposure to lead even at low levels correlates with attention-deficit/hyperactivity disorder (ADHD). However, lead-contaminated environments are often contaminated with other heavy metals that could exacerbate lead-induced ADHD. We conducted this study to evaluate the relationship between multiple heavy metals and child behaviors, and the involvement of S100 calcium-binding protein beta (S100 beta) expression in child ADHD in Guiyu, an internationally-known e-waste contaminated recycling town. Two hundred and forty kindergarten children, 3- to 7-years of age, who lived in Guiyu, were recruited for this study. Child behavioral assessment was derived from parent and teacher ratings. Serum S100 beta was assayed by an enzyme-linked immunosorbent assay (ELISA). Lead (Pb), cadmium (Cd) and manganese (Mn) levels in whole blood were measured using graphite furnace atomic absorption spectrometry (GFAAS). The prevalence of children with ADHD symptoms in Guiyu was 18.6%, with the percentage of children suspected to have behavior problems being 46.2% or 46.5%, based on the Rutter parents' or teachers' scale scores, respectively. Child blood levels of Pb, Cd, and Mn correlated with certain behavioral abnormalities, such as conduct problems and antisocial behavior. Serum S100 beta levels were associated with heavy metal levels in blood, and certain behavioral abnormalities. These findings suggest that exposure to various environmental heavy metals in Guiyu might result in child behavior disorders. Results also indicate that S100 beta may provide information for laboratory evaluation of neurotoxicity. (C) 2014 Elsevier Inc. All rights reserved.

This study investigated the stability and state-related characteristics of electroencephalographic (EEG) deviances in attention-deficit/hyperactivity disorder (ADHD). Three minutes resting EEG with eyes closed and eyes open were compared between 21 children with ADHD and 29 typically developing children. Across resting conditions, children with ADHD exhibited divergent topographic distribution for theta, alpha and beta power compared to typically developing children. In addition, less alpha and theta suppression to eye opening was found in children with ADHD, but only in those without comorbid ODD/CD. Findings of the present study refer to a consistent divergence in topographic distribution in ADHD across resting state conditions, yet demonstrate that state-related factors and comorbidity may also contribute to resting EEG deviances in ADHD. The state-related findings are in accord with several theoretical accounts emphasizing the role of contextual and state factors defining deficits in ADHD.

OBJECTIVE: In adulthood, depressive mood is often comorbid with ADHD, but its role in ADHD-inattentiveness and especially relations with mind wandering remains to be elucidated. This study investigated the effects of laboratory-induced dysphoric mood on task-unrelated mind wandering and its consequences on cognitive task performance in college students with high (n = 46) or low (n = 44) ADHD-Inattention symptomatology and Hyperactivity/Impulsivity symptoms in the normal range.METHODS: These non-clinical high/low ADHD-Inattention symptom groups underwent negative or positive mood induction after which mind wandering frequency was measured in a sustained attention (SART), and a reading task. Effects of ruminative response style and working memory capacity on mind wandering frequency were also investigated.RESULTS: Significantly higher frequencies of self -reported mind wandering in daily life, in the SART and reading task were reported in the ADHD-Inattention symptom group, with detrimental effects on text comprehension in the reading task. Induced dysphoric mood did specifically enhance the frequency of mind wandering in the ADHD-Inattention symptom group only during the SART, and was related to their higher self-reported intrusive ruminative response styles. Working memory capacity did not differ between high/low attention groups and did not influence any of the reported effects.CONCLUSIONS: These combined results suggest that in a non-clinical sample with high ADHD-inattention symptoms, dysphoric mood and a ruminative response style seem to be more important determinants of dysfunctional mind wandering than a failure in working memory capacity/executive control, and perhaps need other ways of remediation, like cognitive behavioral therapy or mindfulness training.

Contains fulltext : 169834.pdf (Publisher’s version ) (Open Access) Contains fulltext : 169834pos.pdf (Author’s version postprint ) (Open Access) BACKGROUND: Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis. METHODS: In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0.0156. FINDINGS: Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0.15), amygdala (d=-0.19), caudate (d=-0.11), hippocampus (d=-0.11), putamen (d=-0.14), and intracranial volume (d=-0.10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0.95) and thalamus (p=0.39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (21 years): in the accumbens (Cohen's d=-0.19 vs -0.10), amygdala (d=-0.18 vs -0.14), caudate (d=-0.13 vs -0.07), hippocampus (d=-0.12 vs -0.06), putamen (d=-0.18 vs -0.08), and intracranial volume (d=-0.14 vs 0.01). There was no difference between children and adults for the pallidum (p=0.79) or thalamus (p=0.89). Case-control differences in adults were non-significant (all p>0.03). Psychostimulant medication use (all p>0.15) or symptom scores (all p>0.02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0.5). INTERPRETATION: With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. FUNDING: National Institutes of Health. 10 p.

Background Methylphenidate (MPH), the first choice medication for attention-deficit hyperactivity disorder (ADHD), is associated with serious adverse effects like arrhythmia. Evidence on the association of ADHD with immune and oxidant-antioxidant imbalances offers potential for antioxidant and/or immunomodulatory nutritional supplements as ADHD therapy. One small randomised trial in ADHD suggests, despite various limitations, therapeutic benefit from Pycnogenol®, a herbal, polyphenol-rich extract. Methods This phase III trial is a 10-week, randomised, double-blind, placebo and active treatment controlled multicentre trial with three parallel treatment arms to compare the effect of Pycnogenol® to MPH and placebo on the behaviour of 144 paediatric ADHD and attention-deficit disorder (ADD) patients. Evaluations of behaviour (measured by the ADHD-Rating Scale (primary endpoint) and the Social-emotional Questionnaire (SEQ)), immunity (plasma cytokine and antibody levels, white blood cell counts and faecal microbial composition), oxidative stress (erythrocyte glutathione, plasma lipid-soluble vitamins and malondialdehyde and urinary 8-OHdG levels, as well as antioxidant enzyme activity and gene expression), serum zinc and neuropeptide Y level, urinary catecholamines and physical complaints (Physical Complaints Questionnaire) will be performed in week 10 and compared to baseline. Acceptability evaluations will be based on adherence, dropouts and reports of adverse events. Dietary habits will be taken into account. Discussion This trial takes into account comorbid behavioural and physical symptoms, as well as a broad range of innovative immune and oxidative biomarkers, expected to provide fundamental knowledge on ADHD aetiology and therapy. Research on microbiota in ADHD is novel. Moreover, the active control arm is rather unseen in research on nutritional supplements, but of great importance, as patients and parents are often concerned with the side effects of MPH. Trial registration Clinicaltrials.gov number: NCT02700685. Registered on 18 January 2016. EudraCT 2016-000215-32. Registered on 4 October 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1879-6) contains supplementary material, which is available to authorized users.

Contains fulltext : 181902.pdf (Publisher’s version ) (Open Access) Nutrition plays an important role in neurodevelopment. This insight has led to increasing research into the efficacy of nutrition-related interventions for treating neurodevelopmental disorders. This review discusses an elimination diet as a treatment for attention deficit hyperactivity disorder and autism spectrum disorder, with a focus on the efficacy of the food additives exclusion diet, gluten-free/casein-free diet and oligoantigenic diet. Furthermore, we discuss the potential mechanisms of elimination diets' effects in these neurodevelopmental disorders. The main candidate mechanism is the microbiome-gut-brain axis possibly involving complex interactions between multiple systems, including the metabolic, immune, endocrine, and neural system. We conclude with practical implications and future directions into the investigation of an elimination diet's efficacy in the treatment of attention deficit hyperactivity disorder and autism spectrum disorder.

Contains fulltext : 169889.pdf (Publisher’s version ) (Open Access) Attention Deficit Hyperactivity Disorder (ADHD) is characterized by poor cognitive control/attention and hypofunctioning of the dorsal anterior cingulate cortex (dACC). In the current study, we investigated for the first time whether real-time fMRI neurofeedback (rt-fMRI) training targeted at increasing activation levels within dACC in adults with ADHD leads to a reduction of clinical symptoms and improved cognitive functioning. An exploratory randomized controlled treatment study with blinding of the participants was conducted. Participants with ADHD (n = 7 in the neurofeedback group, and n = 6 in the control group) attended four weekly MRI training sessions (60-min training time/session), during which they performed a mental calculation task at varying levels of difficulty, in order to learn how to up-regulate dACC activation. Only neurofeedback participants received continuous feedback information on actual brain activation levels within dACC. Before and after the training, ADHD symptoms and relevant cognitive functioning was assessed. Results showed that both groups achieved a significant increase in dACC activation levels over sessions. While there was no significant difference between the neurofeedback and control group in clinical outcome, neurofeedback participants showed stronger improvement on cognitive functioning. The current study demonstrates the general feasibility of the suggested rt-fMRI neurofeedback training approach as a potential novel treatment option for ADHD patients. Due to the study's small sample size, potential clinical benefits need to be further investigated in future studies. TRIAL REGISTRATION: ISRCTN12390961.

AimsTo determine comorbidity patterns in treatment-seeking substance use disorder (SUD) patients with and without adult attention deficit hyperactivity disorder (ADHD), with an emphasis on subgroups defined by ADHD subtype, taking into account differences related to gender and primary substance of abuse.DesignData were obtained from the cross-sectional International ADHD in Substance use disorder Prevalence (IASP) study.SettingForty-seven centres of SUD treatment in 10 countries.ParticipantsA total of 1205 treatment-seeking SUD patients.MeasurementsStructured diagnostic assessments were used for all disorders: presence of ADHD was assessed with the Conners' Adult ADHD Diagnostic Interview for DSM-IV (CAADID), the presence of antisocial personality disorder (ASPD), major depression (MD) and (hypo)manic episode (HME) was assessed with the Mini International Neuropsychiatric Interview-Plus (MINI Plus), and the presence of borderline personality disorder (BPD) was assessed with the Structured Clinical Interview for DSM-IV Axis II (SCID II).FindingsThe prevalence of DSM-IV adult ADHD in this SUD sample was 13.9%. ASPD [odds ratio (OR)=2.8, 95% confidence interval (CI)=1.8-4.2], BPD (OR=7.0, 95% CI=3.1-15.6 for alcohol; OR=3.4, 95% CI=1.8-6.4 for drugs), MD in patients with alcohol as primary substance of abuse (OR=4.1, 95% CI=2.1-7.8) and HME (OR=4.3, 95% CI=2.1-8.7) were all more prevalent in ADHD(+) compared with ADHD(-) patients (PConclusionsTreatment-seeking substance use disorder patients with attention deficit hyperactivity disorder are at a very high risk for additional externalizing disorders.

BackgroundThe results of twin and sibling studies suggest that executive functioning is a prime candidate endophenotype in attention deficit hyperactivity disorder (ADHD). However, studies have not assessed the co-segregation of executive function (EF) deficits from parents to offspring directly, and it is unclear whether executive functioning is an ADHD endophenotype in adolescents, given the substantial changes in prefrontal lobe functioning, EF and ADHD symptoms during adolescence.MethodWe recruited 259 ADHD and 98 control families with an offspring average age of 17.3 years. All participants were assessed for ADHD and EF [inhibition, verbal (VWM) and visuospatial working memory (VsWM)]. Data were analysed using generalized estimating equations (GEEs).ResultsParental ADHD was associated with offspring ADHD and parental EF was associated with offspring EF but there were no cross-associations (parental ADHD was not associated with offspring EF or vice versa). Similar results were found when siblings were compared. EF deficits were only found in affected adolescents and not in their unaffected siblings or (un)affected parents.ConclusionsThe core EFs proposed to be aetiologically related to ADHD, that is working memory and inhibition, seem to be aetiologically independent of ADHD in adolescence. EF deficits documented in childhood in unaffected siblings were no longer present in adolescence, suggesting that children ‘grow out’ of early EF deficits. This is the first study to document ADHD and EF in a large family sample with adolescent offspring. The results suggest that, after childhood, the majority of influences on ADHD are independent from those on EF. This has potential implications for current aetiological models of causality in ADHD.