Training of attention functions in children with attention deficit hyperactivity disorder

Pharmacological treatment of children with ADHD has been shown to be successful; however, medication may not normalize attention functions. The present study was based on a neuropsychological model of attention and assessed the effect of an attention training program on attentional functioning of children with ADHD. Thirty-two children with ADHD and 16 healthy children participated in the study. Children with ADHD were randomly assigned to one of the two conditions, i.e., an attention training program which trained aspects of vigilance, selective attention and divided attention, or a visual perception training which trained perceptual skills, such as perception of figure and ground, form constancy and position in space. The training programs were applied in individual sessions, twice a week, for a period of four consecutive weeks. Healthy children did not receive any training. Alertness, vigilance, selective attention, divided attention, and flexibility were examined prior to and following the interventions. Children with ADHD were assessed and trained while on ADHD medications. Data analysis revealed that the attention training used in the present study led to significant improvements of various aspects of attention, including vigilance, divided attention, and flexibility, while the visual perception training had no specific effects. The findings indicate that attention training programs have the potential to facilitate attentional functioning in children with ADHD treated with ADHD drugs.     

Asymmetry of basal ganglia in children with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatry disorder with several key symptoms, such as inattentiveness, impulsivity and hyperactivity. Neuropsychiatry studies have implicated the frontostriatal circuit in the pathological physiology of the disorder. Using magnetic resonance imaging (MRI), we examined the basal ganglia in 13 ADHD patients and eight unaffected comparison children. The volume of caudate, putamen and globus pallidus was measured. In the ADHD patients, we detected an increased left > right asymmetry of the basal ganglia. This reversal of asymmetry in the globus pallidus and caudate nucleus were statistically significant. These finding provide further evidence of morphological brain abnormalities in ADHD.     

Evaluation of oxidative stress status in children with pervasive developmental disorder and attention deficit hyperactivity disorder using urinary-specific biomarkers

Pervasive developmental disorder (PDD) and attention deficit hyperactivity disorder (ADHD) are likely to be associated with increased oxidative stress, particularly that of lipid peroxidation. We evaluated the oxidative stress status of pediatric PDD and ADHD patients using their urine samples. Urinary acrolein-lysine levels in 11 PDD and 10 ADHD children (205 ± 97 and 234 ± 75 nmol/mg Cr, respectively) appeared higher than those of the control subjects (155 ± 59 nmol/mg Cr). Measurement of urinary specific biomarkers is comfortable, non-invasive, and easy to perform in children. Our findings might provide a scientific guide for use in further clinical and biochemical studies of these disorders.     

Characteristics of attention in children with attention deficit hyperactivity disorder (an analytical review)

The information concerning specific features of different attention components (alertness, sustention and selectivity) in children with attention deficit hyperactivity disorder (ADHD) is analyzed and systematized. According to the data reviewed, behavioral and attention problems described as ADHD are not homogeneous. Literature analysis of attention characteristics in children with ADHD shows that different components can be disrupted if ADHD is diagnosed as inattentive or combined subtype, but the main deficit in this case is that of selective voluntary attention. In case of hyperactivity/impulsivity subtype of ADHD, attention is impaired mainly in its brain activation components.     

Borderline typical symptoms in adult patients with attention deficit/hyperactivity disorder

Adult attention deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD) share several clinical features, e.g. emotional lability and impulsivity. This study aimed to delineate differences and similarities between ADHD and BPD with respect to borderline typical symptomatology and gender specifics. Borderline symptomatology was assessed in 60 adult patients with ADHD with the borderline symptom list (BSL) and compared to both 60 gender- and age-matched BPD patients and control subjects. The BSL is a standardized instrument including 95 items on 7 subscales (self-perception, affect regulation, self-destruction, dysphoria, loneliness, intrusions and hostility). Adult ADHD patients showed significantly higher BSL total scores and all of the seven subscales compared to healthy controls (p < 0.001) but lower scores than BPD patients (p < 0.001). With respect to the seven subscales, the largest differences between ADHD and BPD patients were found with respect to self-destruction (d = 1.12) and affect dysregulation (d = 0.90), whereas the smallest difference was found with respect to loneliness (d = 0.36). In females, the BSL subscales "loneliness" and "hostility" did not differentiate between BPD and ADHD. Borderline typical symptoms are common in adult patients with ADHD but seem to be less pronounced than in patients with BPD. Females with ADHD and BPD share more clinical features than males. However, symptoms of self-destruction and affect dysregulation appear to be more severe in BPD patients.     

Prepotent response inhibition and reaction times in children with attention deficit/hyperactivity disorder from a Caribbean community

Impairment in inhibitory control has been postulated as an underlying hallmark of attention deficit/hyperactivity disorder (ADHD), which can be utilized as a quantitative trait for genetic studies. Here, we evaluate whether inhibitory control, measured by simple automatized prepotent response (PR) inhibition variables, is a robust discriminant function for the diagnosis of ADHD in children and can be used as an endophenotype for future genetic studies. One hundred fifty-two school children (30.9% female, 67.8% with ADHD) were recruited. The ADHD checklist was used as the screening tool, whilst the DSM-IV Mini International Neuropsychiatry Interview, neurologic interview and neurologic examination, and the WISC III FSIQ test were administered as the gold standard procedure to assert ADHD diagnosis. A Go/No-Go task using a naturalistic and automatized visual signal was administered. A linear multifactor model (MANOVA) was fitted to compare groups including ADHD status, age, and gender as multiple independent factors. Linear discriminant analysis and the receiver operating characteristic curve were used to assess the predictive performance of PR inhibition variables for ADHD diagnosis. We found that four variables of prepotent response reaction time- and prepotent response inhibition established statistically significant differences between children with and without ADHD. Furthermore, these variables generated a strong discriminant function with a total classification capability of 73, 84% specificity, 68% sensitivity, and 90% positive predictive value for ADHD diagnosis, which support reaction times as a candidate endophenotype that could potentially be used in future ADHD genetic research.     

DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder

Doublecortin and calmodulin like kinase 1 (DCLK1) is implicated in synaptic plasticity and neurodevelopment. Genetic variants in DCLK1 are associated with cognitive traits, specifically verbal memory and general cognition. We investigated the role of DCLK1 variants in three psychiatric disorders that have neuro-cognitive dysfunctions: schizophrenia (SCZ), bipolar affective disorder (BP) and attention deficit/hyperactivity disorder (ADHD). We mined six genome wide association studies (GWASs) that were available publically or through collaboration; three for BP, two for SCZ and one for ADHD. We also genotyped the DCLK1 region in additional samples of cases with SCZ, BP or ADHD and controls that had not been whole-genome typed. In total, 9895 subjects were analysed, including 5308 normal controls and 4,587 patients (1,125 with SCZ, 2,496 with BP and 966 with ADHD). Several DCLK1 variants were associated with disease phenotypes in the different samples. The main effect was observed for rs7989807 in intron 3, which was strongly associated with SCZ alone and even more so when cases with SCZ and ADHD were combined (P-value = 4 × 10(-5) and 4 × 10(-6), respectively). Associations were also observed with additional markers in intron 3 (combination of SCZ, ADHD and BP), intron 19 (SCZ+BP) and the 3'UTR (SCZ+BP). Our results suggest that genetic variants in DCLK1 are associated with SCZ and, to a lesser extent, with ADHD and BP. Interestingly the association is strongest when SCZ and ADHD are considered together, suggesting common genetic susceptibility. Given that DCLK1 variants were previously found to be associated with cognitive traits, these results are consistent with the role of DCLK1 in neurodevelopment and synaptic plasticity.     

Animal models of attention deficit/hyperactivity disorder (ADHD): a critical review

Attention deficit/hyperactivity disorder (ADHD) involves clinically heterogeneous problems including attention deficits, behavioural hyperactivity and impulsivity. Several animal models of ADHD have been proposed, ranging from models with neurotoxic lesions to genetically manipulated animals. An ADHD model is supposed to show phenomenological similarities with the disorder, i.e. it should mimic the three core symptoms (face validity). A model should also conform to an established or hypothesized pathophysiological basis of the disorder (construct validity). Finally, an animal model should be able to predict previously unknown aspects of the neurobiology of ADHD or to provide potential new treatments (predictive validity). The currently proposed models are heterogeneous with regard to their pathophysiological alterations and their ability to mimic behavioural symptoms and to predict response to medication. This might reflect the heterogeneous nature of ADHD. Since the knowledge about the biology of ADHD from human studies is limited, one cannot at present decide which model best represents ADHD or certain ADHD subtypes. Animal models with good face and predictive validity may be useful for investigations of the underlying biological substrates of ADHD. At present, the models in use should be described as animal models of ADHD-like symptoms rather than models of ADHD.     

Height, weight, IGF-I, IGFBP-3 and thyroid functions in prepubertal children with attention deficit hyperactivity disorder: effect of methylphenidate treatment

OBJECTIVE: To investigate if there are any disease-related or methylphenidate-induced aberrations in growth parameters, growth hormone insulin-like growth factor (IGF)-I, IGFBP-3 axis and the thyroid function tests in children with attention deficit hyperactivity disorder (ADHD). METHODS: Newly diagnosed and untreated prepubertal children with ADHD were longitudinally followed before and approximately every 4 months after methylphenidate treatment for up to 16 months. Height SDS, weight SDS, BMI SDS, serum GH, IGF-I, IGFBP-3, T4, free T4, T3, and TSH were measured at each visit. RESULTS: All of the examined parameters were within normal limits for age before treatment. Methylphenidate treatment did not significantly affect SDS of height, weight, BMI, IGF-I and IGFBP-3 in the long run. Serum T4 and free T4 levels showed modest reductions within normal limits in a time-dependent manner. CONCLUSIONS: Prepubertal children with ADHD had normal height, weight, BMI, serum IGF-I and IGFBP-3 and thyroid functions. Methylphenidate treatment had no sustained effects on growth parameters, IGF-I and IGFBP-3 during the follow-up period of this study. However, it caused a mild decrease in total and free T4 which may warrant further monitoring.     

Cognitive effects of polyunsaturated fatty acids in children with attention deficit hyperactivity disorder symptoms: a randomised controlled trial

This study investigated effects of PUFA and micronutrient supplementation on cognition in children with ADHD symptoms. In a randomised controlled trial, 7-12-year-old children with symptoms 2 S.D. on Conners' ADHD Index were given PUFA, PUFA+multivitamins/minerals (MVM), or placebo for 15 weeks, and then all children were given PUFA+MVM for an additional 15 weeks. After 15 weeks there were improvements in a test of the ability to switch and control attention (Creature Counting) in the PUFA groups compared to placebo (N=129, p=0.002). This improvement was also observed in the placebo group after taking PUFA from weeks 16 to 30 (N=104). There were no significant improvements in other cognitive measures, or with additional micronutrient supplementation. However, improvements in cognitive performance mediated previous parent-reported improvements in inattention, hyperactivity and impulsivity [N. Sinn, J. Bryan, Effect of supplementation with polyunsaturated fatty acids and micronutrients on ADHD-related problems with attention and behaviour, J. Dev. Behav. Pediatr. 28 (2) (2007) 82-91], suggestive of a common neurological mechanism for these symptoms.     

Anxiety and methylphenidate in attention deficit hyperactivity disorder: a double-blind placebo-drug trial

To examine the relationship between attention and anxiety and the response to methylphenidate in children with attention deficit hyperactivity disorder (ADHD), a total of 57 boys, between the ages of 7-12?years, were assessed for their attention and level of anxiety. Methylphenidate was administered for a week in a randomized double-blind drug/placebo-drug cross-over design. The levels of anxiety were evenly distributed between the inattentive and hyperactive/impulsive types. Anxiety was significantly correlated with the attention as reported by both teachers and parents. The response to methylphenidate was inversely correlated with the reported anxiety level only in boys with the hyperactive/impulsive and combined types. The higher the level of anxiety, the lower level of response to methylphenidate was observed. In the assessment and treatment of children with ADHD, the level of anxiety should be evaluated and taken into account while planning and monitoring treatment regiment.     

Effect of polyphenolic extract, Pycnogenol, on the level of 8-oxoguanine in children suffering from attention deficit/hyperactivity disorder

The purpose of this randomized, double-blind and placebo controlled study was to test the effect of polyphenolic extract of pine bark Pycnogenol^® (Pyc) on the level of oxidized purines represented by 8-oxo-7,8-dihydroguanine (8-oxoG) and on the total antioxidant status (TAS) in children with attention deficit/hyperactivity disorder (ADHD).

We have found significantly increased damage to DNA in ADHD children when compared to controls. 8-oxoG was significantly lower after 1 month of Pyc administration in comparison to the beginning state and to placebo group. TAS in ADHD children was lower in comparison to controls. After Pyc administration, TAS was elevated but statistically significant increase was recorded after 1 month of termination of Pyc application. Improvement of DNA damage and TAS after Pyc administration is associated with the improvement of attention in ADHD children.

In conclusion, Pycnogenol^® administration reduces oxidative damage to DNA, normalizes TAS and improves attention of ADHD children. Explanation of mutual relation between oxidative damage to DNA, TAS and symptoms of ADHD and mechanism of Pyc's action needs further investigations.     

Fatty acid correlates of temperament in adolescent boys with attention deficit hyperactivity disorder

Atypical fatty acid metabolism has been reported in attention deficit hyperactivity disorder (ADHD), however, its relationship with temperament in this population is unclear. The current study investigated the association between blood levels of fatty acids implicated in brain structure and function (omega-3, omega-6, omega-9) and personality traits of stability (neuroticism, conscientiousness and agreeableness) and plasticity (extraversion and openness). Twenty right-handed adolescent boys with ADHD completed a self-report NEO-FFI personality questionnaire, and had fatty acid content assessed from red blood using gas chromatography. Pearson's correlations showed no significant associations between omega-3 levels and personality. After correction for multiple comparisons, Adrenic Acid (C22:4n6) was inversely associated with stability. Oleic acid (C18:1n9) was positively associated with plasticity. Results are in line with a role of fatty acids in brain function. They suggest that those fatty acids that are involved in myelination (Adrenic, Oleic) have the strongest associations with temperament in adolescents with ADHD.     

Effects of shift work on attention deficit,hyperactivity, and impulsivity,and their relationship with chronotype

There is growing evidence that shift-work schedules cause severe disturbances to circadian rhythms and the sleep–wakefulness cycle, and that these changes in turn lead to cognitive and behavioral problems. The objective of this study is to explore the relationships between biological rhythm differences (chronotype) and impulsive behaviors and attention-deficit hyperactivity symptoms in shift workers. Seventy-nine nurses working in the daytime and 127 nurses working on night shifts were evaluated with the Barratt Impulsiveness Scale, Adult Attention Deficit Hyperactivity Disorder Self-Report Scale (ASRS), and Morningness–Eveningness questionnaire for identifying circadian preference. It was found that shift workers had more attention deficit (p < .05) and impulsivity (p < .01) when compared with daytime workers. Morning-type workers reported lower hyperactivity and ASRS total scores than evening- and intermediate-type workers. The mean impulsivity score of evening-type workers was higher than both the other groups (p < .05). It has been shown that attention deficit, hyperactivity, and impulsivity levels that appear as a result of working shifts might change in accordance with the individual’s chronotype. It might, therefore, be desirable to evaluate an individual’s chronotype to establish suitability for working shifts.     

Exploratory analysis of diffusion tensor imaging in children with attention deficit hyperactivity disorder: evidence of abnormal white matter structure

Abnormalities in the white matter microstructure of the attentional system have been implicated in the aetiology of attention deficit hyperactivity disorder (ADHD). Diffusion tensor imaging (DTI) is a promising magnetic resonance imaging (MRI) technology that has increasingly been used in studies of white matter microstructure in the brain. The main objective of this work was to perform an exploratory analysis of white matter tracts in a sample of children with ADHD versus typically developing children (TDC). For this purpose, 13 drug-naive children with ADHD of both genders underwent MRI using DTI acquisition methodology and tract-based spatial statistics. The results were compared to those of a sample of 14 age- and gender-matched TDC. Lower fractional anisotropy was observed in the splenium of the corpus callosum, right superior longitudinal fasciculus, bilateral retrolenticular part of the internal capsule, bilateral inferior fronto-occipital fasciculus, left external capsule and posterior thalamic radiation (including right optic radiation). We conclude that white matter tracts in attentional and motor control systems exhibited signs of abnormal microstructure in this sample of drug-naive children with ADHD.     

Understanding deficient emotional self-regulation in adults with attention deficit hyperactivity disorder: a controlled study

While symptoms of deficient emotional self-regulation (DESR) such as low frustration tolerance, temper outbursts, emotional impulsivity, and mood lability are commonly associated with attention deficit hyperactivity disorder (ADHD), little is known about their nature. The main aim of this post hoc study was to examine the correlates of DESR in a large sample of adults with and without ADHD. Subjects were 206 adults with ADHD and 123 adults without ADHD from a family study of ADHD. Emotional impulsivity was operationalized using items from the Barkley Current Behavior Scale. Subjects were comprehensively assessed for psychiatric comorbidity using structured diagnostic interview methodology. We used the Quality of Life, Enjoyment, and Satisfaction Questionnaire-Short Form (QLES-Q-SF) and Social Adjustment Scale-Self-report (SAS-SR) to assess quality of life and psychosocial functioning. DESR was more common among ADHD compared with non-ADHD adults, and 55 % of adults with ADHD reported extreme DESR of greater severity than 95 % of control subjects. The association of ADHD and DESR was not entirely accounted for by either current or lifetime comorbid disorders. DESR was also associated with significant functional impairment as evaluated by the QLES-Q-SF and SAS-SR, and with reduced marital status, as well as higher risk for traffic accidents and arrests. DESR adversely impacts quality of life in adults with ADHD. More work is needed to further evaluate DESR in clinical and investigational studies of subjects with ADHD.     

Cortisol responses in children and adults with attention deficit hyperactivity disorder (ADHD): a possible marker of inhibition deficits

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous disease whose neurobiological background is not completely understood. It has been proposed that deficits of the inhibitory function with an underactive behavioral inhibition system (BIS) may be in the core of ADHD. In this regard, this review summarizes all studies that examine the involvement of cortisol in ADHD. Differences in cortisol responses from different ADHD subtypes, hyperactive/impulsive, inattentive, and combined, are analyzed. In addition, we examine the role of comorbidities as confounding factors in the study of cortisol in ADHD, including comorbid disruptive behavioral disorder (DBD), as well as anxiety and depressive disorders. Because ADHD is a neurodevelopmental condition and approximately half of the children enter adulthood with the disorder, we review cortisol studies in adults and children separately. Two diverse patterns of cortisol have been reported both in children and adults with ADHD. Blunted cortisol responses to stress are associated with comorbid DBD, whereas high cortisol responses are associated to comorbid anxiety disorders. Nevertheless, the inhibitory deficits in ADHD do not appear to be related directly to cortisol deficits in either children or adults. This review increases our understanding of the heterogeneity of ADHD and could help in determining new strategies for the treatment of these patients. Future studies including gender and a more systematic methodology to study the cortisol response are needed.     

Attention deficit and hyperactivity in social anxiety disorder: relationship with trauma history and impulsivity

The aim of this study is to investigate the rate of childhood traumatic experiences and assess the relationship between childhood trauma and impulsivity in the presence of attention deficit–hyperactivity disorder (ADHD) in patients with social anxiety disorder (SAD). A total of 123 patients with a primary diagnosis of SAD were enrolled. All patients were assessed by using the clinical version of Structured Clinical Interview for DSM-IV (SCID-I/CV) and Schedule for Affective Disorders and Schizophrenia for School Age Children—Present and Lifetime version (K-SADS-PL), ADHD module. A clinical and sociodemographic data form and rating scales were filled out. We found higher rates of emotional traumatic experiences and impulsivity along with more severe symptoms of depression, anxiety and social anxiety in the group of SAD patients with childhood ADHD than in SAD patients without ADHD in childhood. The presence of ADHD is associated with higher severity in several domains in patients with SAD. Patients with SAD should be assessed carefully whether they have ADHD, especially when their SAD symptoms are severe, when they have a history of traumatic experiences or problems with impulse control.