Cortisol Response to Stress in Adults with Attention Deficit Hyperactivity Disorder

Background:

Differences in the cortisol response have been reported between children exhibiting the inattentive and hyperactive/impulsive subtypes of attention deficit hyperactivity disorder. However, there is no such information about adults. The aim of the present study was to determine the possible differences between the combined and inattentive subtypes in the cortisol response to stress.

Methods:

Ninety-six adults with attention deficit hyperactivity disorder, 38 inattentive and 58 combined, without any medical or psychiatric comorbidities and 25 healthy controls were included. The Trier Social Stress Test was used to assess physiological stress responses. Clinical data and subjective stress levels, including the Perceived Stress Scale, were also recorded.

Results:

No significant differences in the cortisol response to the Trier Social Stress Test were found between patients and controls. However, albeit there were no basal differences, lower cortisol levels at 15 (P=.015), 30 (P=.015), and 45 minutes (P=.045) were observed in the combined compared with the inattentive subtype after the stress induction; these differences disappeared 60 minutes after the stress. In contrast, the subjective stress responses showed significant differences between attention deficit hyperactivity disorder patients and controls (P<.001), but no differences were seen between attention deficit hyperactivity disorder subtypes. In turn, subjective stress measures, such as the Perceived Stress Scale, positively correlated with the whole cortisol stress response (P<.027).

Conclusions:

Both the combined and inattentive attention deficit hyperactivity disorder adults exhibited a normal cortisol response to stress when challenged. Nevertheless, the inattentive patients displayed a higher level of cortisol after stress compared with the combined patients. Despite the differences in the cortisol response, adults with attention deficit hyperactivity disorder reported high levels of subjective stress in their every-day life.     

Substance Use in Undergraduate Students With Histories of Attention-Deficit/Hyperactivity Disorder (ADHD): The Role of Impulsivity

Background: Emerging adulthood (18–25 years old) is regarded as a time of identity exploration that includes a peak in risky behaviors, such as substance use and misuse. Attention-deficit/hyperactivity disorder (ADHD) is also associated with greater levels of risky behaviors, including substance use and misuse; however, there is a lack of research on substance use by emerging adults with ADHD, in particular the potential mechanisms that may facilitate this risk. Objectives: The present study builds on the existing research regarding the association between ADHD and substance use by examining roles of multiple facets of impulsivity in facilitating this association during emerging adulthood. Methods: In a sample of 197 undergraduate students (24 students with an ADHD diagnostic history), we assessed for components of impulsivity (e.g., urgency, sensation-seeking) and rates of alcohol abuse, tobacco use, cannabis use, illicit drug use, and stimulant medication misuse within the past year. Results: Findings indicate that facets of impulsivity, as a whole, explained the association between an ADHD diagnostic history and both illicit drug use and alcohol abuse such that students with ADHD histories tended to report higher levels of impulsivity, which increased risk of alcohol abuse and illicit drug use. Higher levels of specific facets of impulsivity, particularly negative urgency, also facilitated associations between having ADHD and engaging in most forms of substance use tested herein. Conclusions/Importance: Specific facets of impulsivity appear to be important mediators of the association between ADHD and substance use, and should be considered as potential targets of substance use interventions for this population.     

DAT1 and COMT Effects on Delay Discounting and Trait Impulsivity in Male Adolescents with Attention Deficit/Hyperactivity Disorder and Healthy Controls

Choice impulsivity has been linked to dopamine function and is consistently observed in attention deficit/hyperactivity disorder (ADHD) as a preference for smaller-immediate over larger-delayed rewards using choice-delay paradigms. More sophisticated delay discounting paradigms have yielded inconsistent results. Context and sample characteristics may have contributed to these variations. In this study we examine the effect of type (real vs hypothetical) and magnitude of reward as well as of variation in dopamine genes on choice impulsivity. We selected 36 male adolescents with ADHD-combined subtype (ADHD-CT) and 32 controls (mean age=15.42, SD=2.05) to form four roughly equally sized subgroups on the basis of DAT1_10/6 haplotype dosage (2 copies and <2 copies). Participants, who were also genotyped for the COMT_val158met and DRD4_48bp−VNTR polymorphisms, performed a hypothetical and a real-time discounting task and provided self-ratings of trait impulsivity. The ADHD-CT group discounted rewards more steeply than controls only in the hypothetical task, with delay, but not reward magnitude, influencing choices. They also rated themselves as more impulsive compared with controls. DAT1_10/6 dosage and the COMT_Val158Met genotype predicted trait impulsivity and discounting rates in the hypothetical task, but not in the real-time task. Our results directly link variation in genes putatively influencing dopamine signaling in the prefrontal cortex (COMT_Val158Met) and the striatum (DAT1_10/6) with discounting rates in a hypothetical task (but not a real-time task) and self-ratings of trait impulsivity in ADHD-CT and healthy controls. The lack of magnitude effects in the hypothetical task suggests that discounting in this task may be influenced by different processes in ADHD-CT than in healthy controls.     

注意力缺陷多动障碍的药物治疗研究进展

目的介绍近年来治疗注意力缺陷多动障碍的药物研究进展。方法综述常用的注意力缺陷多动障碍的治疗药物及其临床应用。结果与结论注意力缺陷多动障碍的治疗药物各有优缺点,中西药物合理配合使用,能使患者获得更为高效、安全的治疗效果。     

A Simple Behavioral Paradigm to Measure Impulsive Behavior in an Animal Model of Attention Deficit Hyperactivity Disorder (ADHD) of the Spontaneously Hypertensive Rats

Impulsiveness is an important component of many psychiatric disorders including Attention-deficit/hyperactivity disorder (ADHD). Although the neurobiological basis of ADHD is unresolved, behavioral tests in animal models have become indispensable tools for improving our understanding of this disorder. In the punishment/extinction paradigm, impulsivity is shown by subjects that persevere with responding despite punishment or unrewarded responses. Exploiting this principle, we developed a new behavioral test that would evaluate impulsivity in the most validated animal model of ADHD of the Spontaneously Hypertensive rat (SHR) as compared with the normotensive “control” strain, the Wistar Kyoto rat (WKY). In this paradigm we call the Electro-Foot Shock aversive water Drinking test (EFSDT), water-deprived rats should pass over an electrified quadrant of the EFSDT apparatus to drink water. We reasoned that impulsive animals show increased frequency to drink water even with the presentation of an aversive consequence (electro-shock). Through this assay, we showed that the SHR was more impulsive than the WKY as it demonstrated more “drinking attempts” and drinking frequency. Methylphenidate, the most widely used ADHD medication, significantly reduced drinking frequency of both SHR and WKY in the EFSDT. Thus, the present assay may be considered as another behavioral tool to measure impulsivity in animal disease models, especially in the context of ADHD.     

Symptom Dimensions of Attention Deficit Hyperactivity Disorder and Nicotine Withdrawal Symptoms

Research suggests that Attention Deficit Hyperactivity Disorder (ADHD) and nicotine withdrawal symptoms are related; however, it is unknown how this relationship extends across ADHD symptom gradations, differs between inattention and hyperactivity-impulsivity symptom types, and generalizes to a national sample. This study examined cross-sectional associations between childhood ADHD symptom indexes (total, inattention, and hyperactivity-impulsivity) and lifetime DSM-IV nicotine withdrawal symptoms. Results showed that each ADHD symptom index associated with almost every withdrawal symptom (Ps < .01). After controlling for hyperactivity-impulsivity and inattention symptom overlap, inattention (but not hyperactivity-impulsivity) retained incremental associations with most withdrawal symptoms. These findings are relevant for understanding mechanisms of ADHD and smoking comorbidity.     

Attention-Deficit/Hyperactivity Disorder and Attention Networks

Research attempting to elucidate the neuropathophysiology of attention-deficit/hyperactivity disorder (ADHD) has not only shed light on the disorder itself, it has simultaneously provided new insights into the mechanisms of normal cognition and attention. This review will highlight and integrate this bidirectional flow of information. Following a brief overview of ADHD clinical phenomenology, ADHD studies will be placed into a wider historical perspective by providing illustrative examples of how major models of attention have influenced the development of neurocircuitry models of ADHD. The review will then identify major components of neural systems potentially relevant to ADHD, including attention networks, reward/feedback-based processing systems, as well as a ‘default mode'' resting state network. Further, it will suggest ways in which these systems may interact and be influenced by neuromodulatory factors. Recent ADHD imaging data will be selectively provided to both illustrate the field''s current level of knowledge and to show how such data can inform our understanding of normal brain functions. The review will conclude by suggesting possible avenues for future research.     

可乐定治疗共患注意缺陷多动障碍的抽动障碍患儿的临床疗效

目的:探讨可乐定治疗共患注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)的抽动障碍(tic disorder,TD)患儿的临床疗效。方法:对符合美国精神障碍诊断与统计手册第4版(DSM-IV)中TD和ADHD标准的儿童予系统的可乐定治疗,逐渐调整至目标剂量,并维持治疗12周。以耶鲁综合抽动严重程度量表(YGTSS)评定抽动症状;根据家长填写的ADHD评定量表(ADHD-RS-IV)评定注意缺陷多动症状;并观察药物不良反应。结果:本研究完成系统可乐定滴定并维持治疗12周的共患ADHD的TD患儿40例,男36例,女4例;年龄6.50～14.50(9.84±2.90)岁。完成剂量滴定患儿的目标剂量5μg/(kg.d),最大剂量不超过0.2 mg/d。治疗后抽动总分(9.78±7.76)分,运动抽动分(7.52±4.85)分,发声抽动分(2.26±3.27)分,功能受损程度评分(8.50±5.70)分;治疗前抽动总分(21.34±8.66)分,运动抽动分(15.41±4.68)分,发声抽动分(5.93±7.10)分,功能受损程度评分(21.16±11.76)分。治疗后运动抽动及发声抽动的数量、频度、强度和复杂性均较治疗前显著减少(P<0.05)。治疗后ADHD总分(12.63±9.07)分,注意缺陷评分(7.43±4.74)分,多动-冲动评分3.0分;治疗前ADHD总分(31.05±8.51)分,注意缺陷评分(17.55±3.08)分,多动-冲动评分13.0分。治疗后家长ADHD症状评定量表总分及分量表分较治疗前均显著下降(P<0.05)。结论:可乐定治疗共患ADHD的TD患儿的运动抽动、发声抽动、注意力缺陷、多动-冲动均有明显疗效,能改善患儿生活质量。     

A Comparison of Methamphetamine-Dependent Inpatients With and Without Childhood Attention Deficit Hyperactivity Disorder Symptomatology

Abstract

Methamphetamine-dependent inpatients (N = 51) were screened for childhood attention deficit hyperactivity disorder (ADHD) using the Wender Utah Rating Scale upon admission to 30-day inpatient treatment. Baseline assessments included neuropsychological tests of executive function, memory, information processing, verbal fluency, attention, motor skills, and the Brief Symptom Inventory (BSI), a measure of psychiatric symptomatology. The thirty-six participants (70.6%) screening positive for ADHD reported significantly more frequent methamphetamine use prior to baseline. Baseline cognitive functioning was similar between groups, but the presumptive ADHD participants exhibited significantly worse psychiatric symptomatology. At three-week follow-up, 41 participants (80.4%) repeated the neuropsychological battery and BSI. All 10 non-completers screened positive for ADHD. The entire sample improved with abstinence in most neuropsychological domains except memory. The presumptive ADHD group failed to improve on tests of attention. All participants demonstrated significant reductions in psychiatric symptoms with abstinence. Methamphetamine-dependent individuals with ADHD symptoms are common and pose a significant treatment challenge.     

The Effects of Drugs used for the Treatment of Attention Deficit Hyperactivity Disorder (ADHD) on Pregnancy Outcome and Breast-feeding: A Critical Review

Attention deficit/hyperactivity disorder (ADHD) is a neurobehavioral condition found in 5-10% of school-age children and in 2-5% of adults. Stimulants affecting the dopaminergic, noradrenergic and/or serotonergic systems are commonly used for treatment in children and adults, including women of childbearing age. The data on the effects of stimulants (methylphenidate and amphetamines) in pregnancy are generally reassuring, but methylphenidate might slightly increase the rate of cardiac malformations and of spontaneous abortions, while amphetamines might slightly increase the risk for premature birth, low birth weight and other pregnancy complications. Bupropion, a dopamine and norepinephrine reuptake inhibitor, when used as an antidepressant, appears to be safe in pregnancy. The data on the use of atomoxetine, guanfacine and clonidine in pregnancy are scarce. Importantly, there are practically no data on the long-term neurodevelopmental effects of most of these drugs. The published data on the development of children born to methamphetamine-abusing women may be misleading since these women generally use other drugs, including alcohol, and the home environment where the child is raised may not be optimal. The treating physician should judge the need for treatment during pregnancy in relation to the severity of the clinical symptoms. If needed, methylphenidate is preferred over amphetamines because breast feeding is possible. If one uses non-stimulant medications, bupropion seems to be the preferred drug.     

盐酸哌甲酯控释片治疗注意缺陷多动障碍不同临床亚型患儿疗效的对比研究

目的 比较盐酸哌甲酯控释片(专注达)治疗注意缺陷多动障碍(ADHD)的不同临床亚型儿童的疗效.方法 采用自身前后对照试验设计.按照ADHD的DSM-Ⅳ诊断标准,分别收集注意缺陷为主型(IT)患儿、冲动为主型(HT)患儿以及混合型(CT)患儿各20例,分成三组,分别接受治疗各7天,并于治疗期末评定主要疗效评定指标:家长评定的Conners量表、教师评定的Conners量表.次要疗效指标:儿童行为量表.结果 疗效:哌甲酯控释片治疗7天后,不同临床亚型患儿的主要疗效评定指标和次要疗效指标均出现明显改善,其中注意缺陷为主型(IT)患儿在学习问题、不注意-被动以及注意力的改善程度等方面明显优于其他两组儿童(P＜0.05);冲动-多动为主型(HT)患儿在品行问题、心身障碍、冲动-多动以及多动指数的改善明显优于其他两组儿童(P＜0.05),同时对于CBCL中的交往不良、多动、攻击性和违纪的改善也明显优于其他两组儿童(P＜0.05);混合型主要在多动指数和焦虑方面呈现较大改善.结论 盐酸哌甲酯控释片对于不同亚型的注意力缺陷多动障碍儿童的疗效存在差异.     

托莫西汀与哌甲酯治疗注意缺陷多动障碍患儿的疗效和安全性比较

目的:比较托莫西汀与哌甲酯治疗注意缺陷多动障碍患儿的疗效和安全性。方法:选择我院收治的注意缺陷多动障碍患儿共52例,随机分为托莫西汀组与哌甲酯组各26例,治疗结束后观察两组患儿的治疗有效率、ADHDRS-IV-Parent:Inv评分以及CPRS-R:S评分。结果:托莫西汀组与哌甲酯组的治疗有效率相近。治疗后托莫西汀组与哌甲酯组的ADHDRS-IV-Parent:Inv各项评分均明显下降,与治疗前比较差异均有统计学意义(P<0.05)。治疗后托莫西汀组与哌甲酯组CPRS-R:S评分的分数均明显下降,与治疗前比较差异均有统计学意义(P<0.05)。托莫西汀组的多动分变化值大于哌甲酯组,差异有统计学意义(P<0.05),两组患儿在治疗过程中均未发现严重的药物不良反应。结论:托莫西汀的疗效与哌甲酯相近,都具有良好的安全性,值得临床推广。     

The Association Between Attention Deficit Hyperactivity Disorder and Nicotine Use Among Adolescents and Young Adults

Previous research indicates that youths with attention deficit hyperactivity disorder (ADHD) are more susceptible to nicotine use compared to those without ADHD, and one explanation for this association is the self-medication theory. The present study examines nicotine use in a prospective sample derived from a community sampling procedure rather than a clinical setting. Nicotine use was measured through young adulthood (mean ages: 18, 20, and 22), and three groups were compared based on childhood status: ADHD only, ADHD externalizers, and control groups. Results indicated that at all three data points, individuals with childhood ADHD plus an externalizing disorder reported higher nicotine use on all variables compared to the ADHD group absent of an externalizing disorder and the comparison group of non-ADHD youths. The group differences were significant even after controlling for possible confounding variables (age, gender, and current treatment with psychostimulant medication). Study results are discussed in light of the self-medication hypothesis and of the importance of including nicotine prevention programs for adolescents and young adults with ADHD and externalizing problems.     

盐酸哌甲酯控释片治疗儿童注意缺陷多动障碍的心血管安全性

目的：探讨盐酸哌甲酯控释片治疗儿童注意缺陷多动障碍（ADHD）对心血管系统的影响。方法：回顾性分析98例ADHD患儿的临床资料。所有患儿均服用盐酸哌甲酯控释片治疗,初始剂量为18 mg/d,2周后如临床症状缓解不理想调整至36 mg/d。经过SNAP-Ⅳ量表评估有效,家长能够坚持治疗,服药满3个月为1个观察周期。观察治疗前后患儿心血管系统安全性指标的变化。结果：与治疗前比较,患儿治疗后心率加快（P<0.05）,收缩压、舒张压无明显变化（P>0.05）;心率变异性和心力减速力降低（P<0.05）,但均处于正常范围。不同用药剂量人群的总体不良反应发生率及心血管指标差异无统计学意义（P>0.05）。结论：盐酸哌甲酯控释片治疗儿童ADHD对心血管系统的影响较小,但长期用药的影响还有待进一步研究证实。     

Effect of Atomoxetine on the Cognitive Functions in Treatment of Attention Deficit Hyperactivity Disorder in Children with Congenital Hypothyroidism: A Pilot Study

Background:

With early initiation of thyroxine supplementation, children with congenital hypothyroidism (CH) retain some subtle deficits, such as attention and inhibitory control problems. This study assessed the effects of atomoxetine on cognitive functions in treatment of attention deficit hyperactivity disorder (ADHD) symptoms in children with CH.

Methods:

In a 6-month, open-labeled pilot study, 12 children were recruited and received atomoxetine. The measures of efficacy were scores on the Swanson, Nolan and Pelham Teacher and Parent Rating Scale, version IV (SNAP-IV) and Clinical Global Impression-Severity scale (CGI-S). The cognitive functions were evaluated with the Wechsler Intelligence Scale for Chinese Children, Digit Span, Wisconsin Card Sorting Test, and Stroop test.

Results:

A statistically significant difference was found between the mean CGI-S and SNAP-IV scores before and after treatment (p < 0.01). All the indicators of cognitive functions at the endpoint were improved compared with those at baseline. No serious adverse events were reported.

Conclusion:

Atomoxetine appears to be useful in improving ADHD symptoms, as well as cognitive functions, in children with CH. Larger, randomized, double-blinded, clinical trials are required to replicate these results.     

Current Investigational Drugs for the Treatment of Attention-Deficit/Hyperactivity Disorder

Introduction: Symptoms of attention-deficit/hyperactivity disorder (ADHD) were first described more than 100 years ago. It is a common neurobehavioral disorder that begins in childhood and often persists into adulthood. Treatment for ADHD has been available since Bradley first prescribed amphetamines for hyperkinetic boys more than 70 years ago. Although multiple effective medications for the treatment of ADHD are on the market, all have limitations. Stimulants are controlled substances and may not be effective or tolerable for all patients. The non-stimulants are not as effective as stimulants and have their own side effect profiles.

Areas Covered: In this review, the limitations of currently available medications including methylphenidates, amphetamines, atomoxetine, extended-release guanfacine and extended-release clonidine are considered and drugs in development for the treatment of ADHD are examined. Although the main focus is on phase I and II trials, drugs which may soon be marketed are also discussed.

Expert opinion: Multiple drugs are currently in development, with several targeting novel receptors originally identified using animal models. Since ADHD appears to be complex disorder associated with multiple genes, these models have often not predicted effectiveness in humans. Until there is a better understanding of the genetics of ADHD, drug development will remain challenging.     

An Open-Label Pilot Study of Methylphenidate in the Treatment of Cocaine Dependent Patients with Adult Attention Deficit/ Hyperactivity Disorder

Abstract

A multi-site, open-label study of methylphenidate for treating patients with comorbid diagnoses of attention deficit/hyperactivity disorder and cocaine dependence was performed. Forty-one participants, who met DSM-IV criteria for adult attention deficit/hyperactivity disorder and cocaine dependence, were enrolled into this ten week outpatient study. The targeted total daily dose of methylphenidate was 60 mg (20 mg TID). Participants received individual substance abuse therapy throughout the trial. Safety measures included adverse events, vital signs, and electrocardiograms. Methylphenidate's efficacy was assessed by both objective and subjective measures. Seventy percent of the participants completed final study measures. Safety measures indicated that methylphenidate was well tolerated by the participants. Subjective efficacy measures suggested that participants evidenced improvement in both cocaine dependence and adult attention deficit/hyperactivity disorder symptoms. Quantitative benzoylecgonine indicated that only those participants categorized as being compliant showed improvement. A double-blind, placebo-controlled study of methylphenidate for this population may be warranted.     

小儿黄龙颗粒对注意缺陷多动障碍亚型的疗效分析

目的:探讨小儿黄龙颗粒对注意缺陷多动障碍(ADHD)不同亚型的治疗效果。方法:回顾性分析2018年12月至2020年10月江西省儿童医院诊治的90例注意缺陷多动障碍患儿临床资料,根据注意缺陷多动障碍亚型不同进行分类,将注意力障碍为主型的患儿纳入A组(n=30)、将多动/冲动型患儿纳入B组(n=30)、将混合型患儿纳入C组(n=30)。比较三组治疗前、治疗8周后症状(采用SNAP-Ⅳ评定量表)、临床疗效[采用Conners简明症状问卷(ASQ)]及中医证候主症积分。结果:治疗后,三组SNAP-Ⅳ症状评分、ASQ评分均较治疗前降低,差异有统计学意义(P<0.05);三组神思涣散、多动不宁、性急易怒、多言多语评分均较治疗前降低,差异有统计学意义(P<0.05)。结论:小儿黄龙颗粒对各分型ADHD患儿均有一定疗效,可显著改善患儿临床症状,降低中医证候主症积分。