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.     

Hair trace element concentrations in autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD)

BackgroundThe existing data demonstrate that alteration of trace element and mineral status in children with neurodevelopmental disorders including ASD and ADHD. However, comparative analysis of the specific patterns of trace element and mineral metabolism in children with ASD and ADHD was not performed. Therefore, the primary objective of the present study was to assess hair trace element and mineral levels in boys with ADHD, ASD, as well as ADHD with ASD.MethodsBoys with ADHD (n = 52), ASD (n = 53), both ADHD and ASD (n = 52), as well as neurotypical controls (n = 52) were examined. Hair analysis was performed using inductively-coupled plasma mass-spectrometry.ResultsThe obtained data demonstrate that hair Co, Mg, Mn, and V levels were significantly reduced in children with ADHD and ASD, and especially in boys with ADHD + ASD. Hair Zn was found to be reduced by 20% (p = 0.009) only in children with ADHD + ASD as compared to healthy controls. Factor analysis demonstrated that ASD was associated with significant alteration of hair Co, Fe, Mg, Mn, and V levels, whereas impaired hair Mg, Mn, and Zn content was also significantly associated with ADHD. In regression models hair Zn and Mg were negatively associated with severity of neurodevelopmental disorders. The revealed similarity of trace element and mineral disturbances in ASD and ADHD may be indicative of certain similar pathogenetic features.ConclusionThe obtained data support the hypothesis that trace elements and minerals, namely Mg, Mn, and Zn, may play a significant role in development of both ADHD and ASD. Improvement of Mg, Mn, and Zn status in children with ASD and ADHD may be considered as a nutritional strategy for improvement of neurodevelopmental disturbances, although clinical trials and experimental studies are highly required to support this hypothesis.     

Comorbidity and continuity of attention deficit hyperactivity disorder (ADHD) from childhood to adolescence in Turkey

The aim of this study was to examine clinical outcomes, psychiatric comorbidity and neuropsychological characteristics in Turkish adolescents with an attention deficit hyperactivity disorder (ADHD) diagnosis in childhood. A total of 45 children with ADHD diagnosis and 28 children with a psychiatric diagnosis other than ADHD in a 1-year cohort of 7–10-year-olds were reevaluated 6 years later using Schedule for Affective Disorders and Schizophrenia for School-Age Children Present and Lifetime version and Wechsler Intelligence Scale for Children-Revised and Stroop Test TBAG version. This study shows that the clinical outcomes and the comorbidity patterns for ADHD from childhood to adolescence in Turkey are similar to reported rates in the Western countries. In the ADHD group, 75.6 % still has impairing ADHD symptoms and 46.6 % has comorbid psychiatric disorders. The main difference is anxiety disorders being the most common comorbid disorders (37.8 %) in Turkish ADHD youth. These findings stress the high comorbidity associated with ADHD and support the importance of assessment and treatment for ADHD and comorbidities during adolescence.     

A psychophysiological marker of attention deficit/hyperactivity disorder (ADHD)--defining the EEG consistency index

This study continues our research to further validate the idea that ADHD (Attention Deficit/Hyperactivity Disorder) interferes with transition from one task to another and this interference can be quantified by a Consistency Index (CI) derived from a specific mathematical representation of EEG data. We reanalyze 32 previously reported data sets present new data for 35 boys and girls, ages 7-12, ADHD or control. Each data set contains EEG, recorded and digitized while participants perform consecutive 10-min tasks: video, reading, and math. For boys, the CI in ADHD was four times lower than in controls, p < .005, for girls this difference was two times, p < .05. ADHD/control classification based on the CI coincided with the DSM-IV criteria for 88% of the boys and for 67% of the girls. Post hoc analysis indicated that the classification utility of the CI diminished with age. A CI below 40% could be a discriminating, reliable, and reproducible marker of ADHD in young boys.     

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.     

Detection of malingered attention deficit hyperactivity disorder

The aim of the present study was to determine whether malingering of adult attention deficit hyperactivity disorder (ADHD) can be detected using a self-report rating scale. A sample of 78 university students was allocated to three different conditions. The conditions were (a) a control group, (b) a na?ve simulation group and (c) a coached simulation group. Furthermore, 12 adult students with a diagnosed ADHD participated in the present study. Participants were administered the Brown Attention Deficit Disorder Scale for Adults. While the control group and the patient group were asked to complete the scale with accuracy, the simulation groups were requested to feign an ADHD. Statistical analysis revealed that both simulation groups were able to successfully feign an ADHD. The results indicate that self-report rating measures are not sensitive enough to allow the detection of feigned ADHD.     

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.     

Adult attention deficit hyperactivity disorder: translating research into practice

Attention deficit hyperactivity disorder (ADHD) in adults is a prevalent, yet under-appreciated, under-researched and poorly understood condition. Given this, it is imperative that information and awareness regarding this condition are made more widespread, both amongst the general public and amongst healthcare professionals. Further, given our poor understanding of the aetiology of the condition, meaningful translational research that migrates into and better informs clinical practice must be a priority. In this brief review we highlight areas regarding the clinical diagnosis and management of ADHD in adults (guidelines, rating scales, pharmacotherapy, psychotherapy) as well as areas of promising translational research (genetics, neuroimaging, sleep and circadian rhythms, animal models of ADHD). We address some of the challenges presented for both clinicians and healthcare providers and research scientists working to improve the lives of those adults with ADHD.     

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.     

Role of neurotrophic factors in attention deficit hyperactivity disorder

Neurotrophins (NTs), a family of proteins including nerve growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin-3, and neurotrophin-4, are essential for neural growth, survival, and differentiation, and are therefore crucial for brain development. Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by problems of inattention and/or hyperactivity-impulsivity. ADHD is one of the most common childhood onset psychiatric disorders. Studies have suggested that both genetic and environmental factors influence the development of the disorder, although the precise causes of ADHD have not yet been identified. In this review, we assess the role of NTs in the pathophysiology of ADHD. Preclinical evidence indicates that BDNF knockout mice are hyperactive, and an ADHD rodent model exhibited decreased cerebral BDNF levels. Several lines of evidence from clinical studies, including blood level and genetic studies, have suggested that NTs are involved in the pathogenesis of ADHD and in the mechanism of biological treatments for ADHD. Future directions for research are proposed, such as using blood NTs as ADHD biomarkers, optimizing NT genetic studies in ADHD, considering NTs as a link between ADHD and other comorbid mental disorders, and investigating methods for optimally modulating NT signaling to discover novel therapeutics for treating ADHD.     

注意缺陷多动障碍儿童肠道菌群特点及与行为问题的相关性研究

分析注意缺陷多动障碍（ADHD）儿童肠道菌群特点与行为问题的相关性。

选取2022年1月到2023年5月我院收治的96例ADHD患儿和健康体检的96例儿童,分别作为研究组和对照组。对所有儿童粪便样本进行宏基因组测序并分析肠道菌群特点。采用Conners儿童行为问卷－家长版（PSQ）评估两组儿童的行为。采用Pearson相关性分析肠道菌群分布与行为问题的相关性。

研究组患儿肠道菌群α−多样性低于对照组,肠杆菌属、气味杆菌属和枸橼酸杆菌属相对丰度均高于对照组,韦荣球菌属、拟杆菌属、双歧杆菌属和普氏栖粪杆菌相对丰度均低于对照组,差异均具有统计学意义（P＜0.05）。研究组患儿Conners PSQ问卷评分高于对照组（P＜0.05）。研究组患儿Conners PSQ问卷各因子评分与肠道肠杆菌属、气味杆菌属和枸橼酸杆菌属均呈正相关（P＜0.05）,与韦荣球菌属、拟杆菌属、双歧杆菌属和普氏栖粪杆菌均呈负相关（P＜0.05）。

ADHD儿童肠道菌群构成与健康儿童不同,不同肠道菌群与患儿行为问题有相关性。

     

Serum zinc,copper, zinc-to-copper ratio,and other essential elements and minerals in children with attention deficit/hyperactivity disorder (ADHD)

BackgroundEssential trace elements and minerals play a significant role in neurodevelopment. Although certain studies demonstrated impaired essential trace element and mineral status in children with ADHD, the existing data are insufficient. The objective of the present study was to assess serum trace element and mineral levels in children with ADHD.MethodsSerum trace element and mineral levels in 68 children with ADHD and 68 neurotypical controls were assessed using ICP-MS at NexION 300D (PerkinElmer Inc., USA) equipped with ESI SC-2 DX4 autosampler (Elemental Scientific Inc., USA).ResultsSerum Cr, Mg, and Zn levels in children with ADHD were 21 % (p = 0.010), 4 % (p = 0.005), and 7 % (p = 0. 001) lower as compared to the healthy controls, respectively. In turn, serum Cu/Zn values were 11 % higher than those in the control group. Age and gender had a significant impact on serum element levels in ADHD. Particularly, preschool children were characterized by significantly increased Cu (+8 %; p = 0.034), and Cu/Zn (+19 %; p < 0.001) values, whereas serum Zn (-9 %; p = 0.004) level was decreased. In primary school-aged children only 6 % (p = 0.007) lower Mg levels were observed. Both boys and girls with ADHD were characterized by 8 % (p = 0.016) lower serum Zn levels and 10 % (p = 0.049) higher Cu/Zn values when compared to neurotypical girls. Boys with ADHD also had significantly higher Cu/Zn, exceeding the respective control values by 12 % (p = 0.021), predominantly due to a 7 % (p = 0.035) decrease in serum Zn. Serum Mg levels were also found to be significantly lower than those in neurotypical children by 5 % (p = 0.007). In adjusted regression models serum Cr (β=-0.234; p = 0.009) and Cu/Zn (β = 0.245; p = 0.029) values were significantly associated with ADHD, respectively. Two-way ANOVA revealed a significant impact of ADHD on Cr, Mg, Zn, and Cu/Zn, whereas age was associated with Cu, I, Mg, Mo, and Cu/Zn, whereas gender accounted only for variability in serum Mn levels. Principal component analysis (PCA) also revealed significant contributions of Mg, Zn, and Cu/Zn values to ADHD variability.ConclusionsHypothetically, the observed decrease of essential trace elements, namely Mg and Zn, and elevation of Cu/Zn may significantly contribute to the risk of ADHD or its severity and/or comorbidity.     

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.     

Molecular genetics of attention-deficit hyperactivity disorder (ADHD): an update

Attention-deficit hyperactivity disorder (ADHD) is a heritable and behavioral condition of childhood, affecting 5-10% of school-age children worldwide. Affected patients exhibit various behavioral problems such as carelessness, restlessness, disobedience and failure to stay quiet in class. The etiology of ADHD is not known. However, family, twin and adoption studies have provided strong evidence for a genetic etiology of the disorder. A genome-wide scan has identified six chromosomal loci with LOD scores suggestive of linkage. Animal studies suggest the involvement of the brain dopamine pathway and its alteration in ADHD but there is no direct evidence to support this hypothesis. In addition, there are at least 20 candidate genes of small effect that have been studied but none of them appear to be the major gene causing ADHD. Medical intervention along with psychosocial therapy proved to be beneficial for controlling ADHD, although some undesirable side effects have been encountered during medical treatment. In the future, identification of environmental factors, study of additive gene effects and the interaction of genes and environmental factors may provide better insight into the pathophysiology of ADHD. This may lead to an effective new treatment strategy.