Response disinhibition may be explained as an extinction deficit in an animal model of attention-deficit/hyperactivity disorder (ADHD)

Attention-deficit/hyperactivity disorder (ADHD) is a disorder affecting between 2 and 12% of grade-school children disturbing social, academic, and occupational functioning. Problems related to social adjustment and functioning and/or psychiatric problems will exist in 50-70% of adolescents and young adults diagnosed with ADHD as children. It has been suggested that altered reinforcement and extinction processes may cause the symptoms of ADHD. The present study investigated extinction processes in spontaneously hypertensive rats (SHR), possibly the best-validated animal model of ADHD. Extinction was tested after either a variable interval (VI) or a fixed interval (FI) schedule of reinforcement with and without the presence of a conditioned reinforcer (light in the water cubicle). The results indicate a slower extinction process in the SHR compared to the normal controls, especially during the initial transition from scheduled reinforcement to extinction. Also, more responses were retained in the SHR during the later part of extinction. The extinction deficit in the SHR may be linked to reinforcer unpredictability and the presence of conditioned reinforcers, and may explain response disinhibition seen in children with ADHD.     

Attention-deficit/hyperactivity disorder (ADHD) and adaptation night as determinants of sleep patterns in children

Sleep problems are a prominent feature in children with attention-deficit/hyperactivity disorder (ADHD) but their relationships to sleep structure are not consistent across studies. We aimed at further examining the sleep architecture in children with ADHD, while considering the role of the first-night effect (FNE) as a possible confounder. Twenty unmedicated children with ADHD combined type (8?C15?years old; mean 11.24, SD 2.31) and 19 healthy controls, matched for age and gender, underwent polysomnography during an adaptation and a consecutive second night. ADHD and controls displayed a typical FNE without group differences. Independently of testing night, children with ADHD spent more time in sleep and had shortened rapid eye movement (REM) sleep latency and a greater amount of REM sleep relative to controls. However, the increased REM sleep amount in ADHD children was more expressed in the second night when it was also significantly related to scores of inattention and hyperactivity. Our results (1) document similar sleep adaptation processes in children with ADHD and typically developing children, (2) reveal that REM sleep changes in association with ADHD-specific psychopathology may characterize sleep in ADHD children, which is evident only when the FNE is accounted for, (3) indicate that ADHD psychopathology and adaptation night may exert opposite effects on REM sleep in children. These results may prompt the awareness of clinicians about the importance of actual sleep alterations and their precise evaluation in children with ADHD, which could significantly contribute to better diagnostic, treatment and early prevention strategies.     

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in adult psychiatry. A 20-year register study

Abstract

Nylander L, Holmqvist M, Gustafson L, Gillberg C. Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in adult psychiatry. A 20-year register study. Nord J Psychiatry 2012;Early Online:1–7 Objective: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are increasingly recognized in adults. This study aimed to assess trends in diagnostic practice, diagnostic delay and comorbidity regarding ADHD and ASD in adult psychiatric patients. Methods: Individuals with diagnosed ADHD or ASD were identified in an adult psychiatry register comprising 56,462 patients. Results: ADHD was diagnosed in up to 2.7% and ASD in 1.3% of the patients. Most cases were diagnosed within 2 years of first contact with adult psychiatry, but some patients were treated for 10 years or more before being diagnosed with ADHD or ASD. Seventy per cent of ADHD and 56% of ASD patients were treated as outpatients only. Other psychiatric diagnoses were registered in about 60%. Affective disorders were common in patients with ADHD. Psychoses and intellectual disability were more common in ASD patients. Psychoactive substance use-related disorders were considerably more common in those with ADHD. Concomitant ADHD and ASD were seldom diagnosed in this clinical material. Conclusion: ADHD and ASD were probably much underdiagnosed in the studied group of psychiatric patients. Other psychiatric diagnoses were common, but not ADHD with concomitant ASD.     

Attention-deficit/hyperactivity disorder (ADHD) association with the DAT1 core promoter -67 T allele

Association between attention deficit hyperactivity disorder (ADHD) and the 10-repeat allele of a polymorphism (a 40 bp variable number of tandem repeats) in the dopamine transporter gene (DAT1) has been reported by several groups. In this study, we examined whether either allele of the DAT1 core promoter -67 functional polymorphism is associated with ADHD in a case/control study. The allele and genotype frequencies of the polymorphism were studied in 110 patients and 120 controls, which were matched on the basis of sex, age and ethnicity. The genotype frequencies in the patients group were as follows: AA 19.2%; AT 65.2%; TT 15.4% vs. the genotype frequencies in the control group: AA 47.5%; AT 43.3%; TT 9.2% [chi2=20.73, df=2, P相似文献   

Attention-deficit/hyperactivity disorder (ADHD) and driving risk: A review of the literature and a methodological critique

This article examines the literature on attention-deficit/ hyperactivity disorder (ADHD) and unintentional driving injury. This literature has emerged over the last decade as part of the burgeoning epidemic of road traffic death and injury, which is the number-one cause of death among young adults in North America. The available literature on observational outcome studies and experimental pharmacologic interventions is critically reviewed. A meta-analysis of behavioral outcomes and a review of effect size of pharmacologic studies are presented. Current data support the utility of stimulant medication in improving driving performance in younger ADHD drivers. A conceptual model of risk factors in young ADHD drivers is offered. The current state of screening instruments for identifying high-risk subjects within this clinical group is summarized along with a final section on emerging trends and future prospects for intervention.     

Slower extinction of responses maintained by intra-cranial self-stimulation (ICSS) in an animal model of attention-deficit/hyperactivity disorder (ADHD)

Children with attention-deficit/hyperactivity disorder (ADHD) show performance deficits and excessive motor activity during extinction and in situations where no reinforcer can be identified, suggesting an extinction deficit in ADHD possibly linked to dopamine dysfunction. The present study examined extinction of responding previously maintained by intra-cranial self-stimulation (ICSS) in spontaneously hypertensive rats (SHR), an animal model of ADHD using three different extinction procedures. Delivery of electrical pulses were terminated altogether or presented independently of responding using two different current intensities. The results showed that more responses were retained in the SHR, especially during the initial transition from ICSS-maintained responding to response-independent delivery of electrical pulses with current reduced relative to that given during reinforcement. Slower extinction of previously reinforced behavior is suggested as an alternative explanation for the frequently observed increased behavioral output that has previously been interpreted as "disinhibition" of behavior in ADHD.     

Dissecting the attention deficit hyperactivity disorder (ADHD) phenotype: sustained attention, response variability and spatial attentional asymmetries in relation to dopamine transporter (DAT1) genotype

ADHD is a childhood-onset behavioural disorder with a heterogeneous profile of neuropsychological impairment. Neuropsychological heterogeneity may, in part, reflect underlying genetic differences. Here we examined sustained attention, response variability and spatial attentional asymmetries in a sample of children and adolescents with ADHD (n=22) in relation to dopamine transporter genotype (DAT1) and also controls (n=20). Participants performed the sustained attention to response task (SART) (testing sustained attention and response variability) and the greyscales task (a perceptual measure of attentional bias). The latter has previously been shown to yield a robust leftward attentional asymmetry in healthy subjects. The 10-repeat allele of the DAT1 gene has been associated with ADHD in a number of studies and appears to have biological significance. The ADHD group was sub-divided into those individuals with two copies of the "high-risk" 10-repeat allele (high-risk DAT1) versus those with one or no copies of this allele (low-risk DAT1). The high-risk DAT1 ADHD group displayed greater response variability on the SART than either the low-risk DAT1 group or healthy controls, whereas the latter two groups did not differ. Further, the high-risk DAT1 group showed an attenuated spatial asymmetry, relative to the low-risk DAT1 ADHD group, who showed the typical leftward attentional asymmetry. Our results suggest that the 10-repeat DAT1 allele may mediate neuropsychological impairment in ADHD. The application of molecular genetics may help to define neuropsychological impaired subgroups of ADHD.     

Physiological and psychological stress responses in adults with attention-deficit/hyperactivity disorder (ADHD)

According to self-report and unsystematic observational data adult patients with attention-deficit/hyperactivity disorder suffer from increased vulnerability to daily life stressors. The present study examined psychological and physiological stress responses in adult ADHD subjects in comparison to healthy controls under laboratory conditions. Thirty-six subjects (18 patients with DSM-IV ADHD diagnosis, 18 sex- and age-matched healthy controls) underwent the Trier Social Stress Test (TSST; Kirschbaum, C., Pirke, K.-M., Hellhammer, D.H., 1993. The “Trier Social Stress Test”—a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28, 76–81), a standardized psychosocial stress protocol which contains a stress anticipation phase and a stress phase with a free speech assignment and subsequent performance of a mental arithmetic. Physiological stress measures were salivary cortisol as an indicator of the HPA axis, heart rate (HR), and time- and frequency-domain heart rate variability (HRV) parameters. Subjective stress experience was measured via self-report repeatedly throughout the experimental session. In line with previous theoretical and empirical work in the field of childhood ADHD, it was hypothesized that the ADHD and control group would exhibit comparable baseline levels in all dependent variables. For ADHD subjects, we expected attenuated responses of the physiological parameters during anticipation and presence of the standardized stressor, but elevated subjective stress ratings. Hypotheses were confirmed for the baseline condition. Consistent with our assumptions in regard to the psychological stress response, the ADHD group experienced significantly greater subjective stress. The results for the physiological variables were mixed.

While ADHD subjects revealed an attenuated HR during the stress phase, no significant group differences were found for the other parameters, although a trend was observed for both the low frequency/high frequency (LF/HF) ratio of the HRV power spectral analysis and salivary cortisol (the latter possibly indicating generally lower cortisol levels in ADHD subjects). In summary, the present findings are the first to demonstrate a significant alteration of a specific physiological stress measure (HR) and, more clearly, of psychological aspects of the stress response in adults suffering from ADHD. In regard to the physiological stress response, it is recommended that future studies employ larger sample sizes and a more comprehensive range of physiological stress parameters. Additionally, the issue of transferability of laboratory results to real life stressors needs to be addressed.     

Age-dependent and -independent changes in attention-deficit/hyperactivity disorder (ADHD) during spatial working memory performance

Objectives: Attention-deficit/hyperactivity disorder (ADHD) has been associated with spatial working memory as well as frontostriatal core deficits. However, it is still unclear how the link between these frontostriatal deficits and working memory function in ADHD differs in children and adults. This study examined spatial working memory in adults and children with ADHD, focussing on identifying regions demonstrating age-invariant or age-dependent abnormalities. Methods: We used functional magnetic resonance imaging to examine a group of 26 children and 35 adults to study load manipulated spatial working memory in patients and controls. Results: In comparison to healthy controls, patients demonstrated reduced positive parietal and frontostriatal load effects, i.e., less increase in brain activity from low to high load, despite similar task performance. In addition, younger patients showed negative load effects, i.e., a decrease in brain activity from low to high load, in medial prefrontal regions. Load effect differences between ADHD and controls that differed between age groups were found predominantly in prefrontal regions. Age-invariant load effect differences occurred predominantly in frontostriatal regions. Conclusions: The age-dependent deviations support the role of prefrontal maturation and compensation in ADHD, while the age-invariant alterations observed in frontostriatal regions provide further evidence that these regions reflect a core pathophysiology in ADHD.     

No association between catechol-O-methyltransferase (COMT) genotype and attention deficit hyperactivity disorder (ADHD) in Japanese children

Objective: This study ascertained the association between attention deficit/hyperactivity disorder (ADHD) in Japanese children and a polymorphism of catechol-O-methyltransferase (COMT), a dopamine-control gene. The secondary aim of the study was the evaluation of a putative association between methylphenidate (MPH) effect/adverse effects and the COMT genotype. Methods: To ascertain the distribution of the Val158Met variant of COMT, 50 children meeting ADHD inclusion criteria were compared with 32 healthy children. Clinical improvement and the occurrence of adverse effects were measured before and 3 months after MPH administration in children with ADHD, and analyzed for genotype association. Wechsler Intelligence Scale for Children-Third Edition (WISC-III), age, MPH dose were included as co-variables. Results: The occurrence of the COMT Val/Val genotype was significantly higher in children with ADHD (χ²(1) = 7.13, p < 0.01). However, there was no significant difference in the Val/Val genotype according to disorder, and WISC and ADHD rating scale scores, after correcting for the interaction between disorder and COMT genotype. Furthermore, no significant difference in MPH effect/adverse effects was observed in association with the COMT genotype in the ADHD group. Conclusions: These results showed a lack of association between the COMT Val/Val genotype and ADHD in Japan.     

Hyperactivity in boys with attention-deficit/hyperactivity disorder (ADHD): The role of executive and non-executive functions

Motor activity of boys (age 8–12 years) with (n = 19) and without (n = 18) ADHD was objectively measured with actigraphy across experimental conditions that varied with regard to demands on executive functions. Activity exhibited during two n-back (1-back, 2-back) working memory tasks was compared to activity during a choice-reaction time (CRT) task that placed relatively fewer demands on executive processes and during a simple reaction time (SRT) task that required mostly automatic processing with minimal executive demands. Results indicated that children in the ADHD group exhibited greater activity compared to children in the non-ADHD group. Further, both groups exhibited the greatest activity during conditions with high working memory demands, followed by the reaction time and control task conditions, respectively. The findings indicate that large-magnitude increases in motor activity are predominantly associated with increased demands on working memory, though demands on non-executive processes are sufficient to elicit small to moderate increases in motor activity as well.     

Linking state regulation,brain laterality,and self-reported attention-deficit/hyperactivity disorder (ADHD) symptoms in adults

Introduction: Many clinical studies have shown that performance of subjects with attention-deficit/hyperactivity disorder (ADHD) is impaired when stimuli are presented at a slow rate compared to a medium or fast rate. According to the cognitive–energetic model, this finding may reflect difficulty in allocating sufficient effort to regulate the motor activation state. Other studies have shown that the left hemisphere is relatively responsible for keeping humans motivated, allocating sufficient effort to complete their tasks. This leads to a prediction that poor effort allocation might be associated with an affected left-hemisphere functioning in ADHD. So far, this prediction has not been directly tested, which is the aim of the present study. Method: Seventy-seven adults with various scores on the Conners’ Adult ADHD Rating Scale performed a lateralized lexical decision task in three conditions with stimuli presented in a fast, a medium, and a slow rate. The left-hemisphere functioning was measured in terms of visual field advantage (better performance for the right than for the left visual field). Results: All subjects showed an increased right visual field advantage for word processing in the slow presentation rate of stimuli compared to the fast and the medium rate. Higher ADHD scores were related to a reduced right visual field advantage in the slow rate only. Conclusions: The present findings suggest that ADHD symptomatology is associated with less involvement of the left hemisphere when extra effort allocation is needed to optimize the low motor activation state.     

Driving-related risks and impact of methylphenidate treatment on driving in adults with attention-deficit/hyperactivity disorder (ADHD)

Summary. This study assesses driving behaviour and history of driving outcomes through a semi-structured interview in 27 clinically referred German adults with ADHD and 27 age-, gender- and education-matched non-ADHD controls. In nineteen of the ADHD-subjects a test battery of driving-related cognitive measures was performed (ART 2020) and re-assessed after at least six weeks of treatment with methylphenidate (n = 9) or after a six-week medication free period (n = 10). ADHD-subjects drove significantly more kilometres per year, were more often registered by traffic authorities and fined more frequently, were involved in more accidents and described their driving style as more insecure and hectic than controls. A high-risk driving group was delineated with 3–6 accidents per ADHD-subject. All results were controlled for intercorrelations with driving experience. Methylphenidate treatment resulted in improved information processing, e.g., better visu-motor coordination under high-stress conditions, improved visual orientation and sustained visual attention compared to baseline and our untreated control group. Correspondence: Esther Sobanski, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, J 5, 68159 Mannheim, Germany     

Temperament,executive function,and attention-deficit/hyperactivity disorder (ADHD) in adolescents: The mediating role of effortful control

Introduction: Temperament dimensions may be related to executive functions (EF) and may be involved in the expression and maintenance of symptoms of attention-deficit/hyperactivity disorder (ADHD). The current study aimed to assess whether effortful control (EC) mediates the relationship between EF and inattentive symptoms, and whether surgency (S) and negative affectivity (NA) mediate the relationships between EF and hyperactive–impulsive ADHD symptoms in adolescents.

Method: Working individually, participants aged between 12 and 16 years (N = 118; 75 with ADHD) performed tests of cognitive EF (working memory, planning, flexibility, and inhibition), and parents and teachers completed a multi-informant assessment focusing on measures of ADHD symptoms and temperament dimensions (EC, S, and NA).

Results: There were significant differences between ADHD and control participants in EF and temperament dimensions. ADHD participants had lower scores than controls in working memory, planning, and inhibition EF; they also had lower scores in EC and higher scores in S and NA. Structural equation modeling indicated differential associations between EC, S, and NA temperament dimensions, and working memory, planning and inhibition EF, and ADHD symptoms. Mediation analysis suggested that EF exerted indirect effects on the inattentive and hyperactive–impulsive symptoms, via EC; higher EF abilities were related to higher levels of EC, which in turn were related to lower scores of inattentive and hyperactive–impulsive ADHD symptoms. S and NA did not mediate relations among EF and hyperactive–impulsive symptoms.

Conclusion: The findings expand on those of previous studies of the complex relationship between temperament dimensions and EF and confirm the differential association between impairments in some EF, low EC, and the expression of inattentive and hyperactive–impulsive symptoms in adolescents, which may account for the ADHD–control group differences.     

Validation of DSM-5 age-of-onset criterion of attention deficit/hyperactivity disorder (ADHD) in adults: Comparison of life quality,functional impairment,and family function

The newly published Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) elevates the threshold of the ADHD age-of-onset criterion from 7 to 12 years. This study evaluated the quality of life and functional impairment of adults with ADHD who had symptoms onset by or after 7 years and examined the mediation effect of family function and anxiety/depression symptoms between ADHD diagnosis and quality of life and functional impairment. We assessed 189 adults with ADHD and 153 non-ADHD controls by psychiatric interview and self-administered reports on the Adult ADHD Quality of Life Scale, Weiss Functional Impairment Rating Scale, Family APGAR, and Adult Self Report Inventory-4. The ADHD group was divided into early-onset ADHD (onset <7 years, n = 147) and late-onset ADHD (onset between 7 and 12 years, n = 42). The mediation analysis was conducted to verify the mediating factors from ADHD to functional impairment and quality of life. The late-onset ADHD had more severe functional impairment at work and poorer family support than early-onset ADHD while they had comparable impairment at other domains. Less perceived family support and current anxiety/depressive symptoms partially mediated the link between ADHD diagnosis and quality of life/functional impairment both in early- and late-onset ADHD. Our data support decreased quality of life and increased functional impairment in adult ADHD, regardless of age of onset, and these adverse outcomes may be mediated by family support and anxiety/depression at adulthood. Our findings also imply that the new DSM-5 ADHD criteria do not over-include individuals without impairment.