Diagnosing and treating attention-deficit/hyperactivity disorder in adults

Adult attention deficit/hyperactivity disorder (ADHD) is a valid and impairing psychiatric disorder. In this article, we review the diagnosis of ADHD in adults, focusing on symptom presentation differences between pediatric and adult ADHD as well as the importance of assessing functional impairments. Differentiating ADHD from other clinical disorders is often the most difficult part of making an ADHD diagnosis in adults. Psychiatric comorbidities are also described and discussed as potential impact factors upon not only diagnosing ADHD but also treatment of adult ADHD. Especially in those adults with psychiatric comorbidities, treatments need to be multimodal and include both pharmacotherapy and psychosocial interventions.     

Circadian pattern of motor activity in adults with attention-deficit/hyperactivity disorder

This study aims to describe the 24-hour activity rhythm in adults with attention-deficit/hyperactivity disorder (ADHD). A total of 18 ADHD patients and 37 healthy controls (HCs) wore an actigraph for 7 days. ADHD patients showed higher motor activity than HCs at 4:00, 6:00, 15:00 and 16:00 hour. Within the theoretical framework of the two-process model of sleep regulation, the observed data may be explained by lower homeostatic sleep pressure in ADHD. This could lead to an increase in motor activity in the second half of the night, when sleep need decreases more rapidly, and in the first half of the afternoon, when patients do not experience the typical post-lunch dip.     

Emotional symptoms and their contribution to functional impairment in adults with attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a severe neurodevelopmental disorder beginning in childhood and consisting of the core symptoms of inattention, hyperactivity, and impulsivity. The disorder is often accompanied by functional impairment in daily life. Research showed that severe impairment cannot be fully explained by the core symptoms of ADHD. Accordingly, emotional symptoms in ADHD and their influence on functional impairment have increasingly become the focus of research in recent years. The aim of the current study was to investigate the relationship between ADHD core symptoms, emotional symptoms, and functional impairment. We assumed that emotional symptoms might form part of adult ADHD and that the connection between ADHD core symptoms and functional impairment may be partly mediated by emotional symptoms. Data of 176 participants from an ADHD Special Consultations Unit were included. Of these participants, 146 were diagnosed with ADHD, while 30 received no such diagnosis. We developed a structural equation model which included core symptoms, emotional symptoms, and four domains of daily impairment (family life, social life, work, and organization). As predicted, results indicate that emotional symptoms are directly linked to adult ADHD and bear a strong negative influence on different domains of daily life. The results of different analyses showed a mediation of the relationship between ADHD core symptoms and impairment through emotional symptoms: While the connection between inattention and work and organization was partly mediated, the connections between impulsivity and family life and between inattention and social life were shown to be fully mediated through emotional symptoms.     

Developmental comorbidity in attention-deficit/hyperactivity disorder

With the present review, we intend to highlight the importance of considering the age- and development-dependent occurrence of comorbidity in ADHD and to outline distinct trajectories of symptom progression with possible impact on course and outcome of ADHD. The review will focus on introducing the concepts of "developmental epidemiology" and "developmental comorbidity". Psychiatric and non-psychiatric age-dependent comorbidity can be seen in the majority of children, adolescents and adults with ADHD, resulting in a severe impairment of everyday life with considerable functional and psychosocial problems. Concerning the temporal order of occurrence, psychiatric conditions may be present before the appearance of first definite ADHD symptoms ("pre-comorbidity", such as temperament factors, sleep disturbance, autism spectrum disorders and atopic eczema). They may coincide with the time when ADHD symptoms reach a clinically significant level ("simultaneous comorbidity": enuresis, encopresis, developmental dyslexia). The majority of comorbidity, however, appears after the onset of ADHD in the course of disease ("post-comorbidity": tic disorder, depression and suicidality, anxiety disorders, obsessive compulsive disorder, bipolar disorder, conduct and substance use disorders, obesity and personality disorders). The aetio-pathophysiology of ADHD and its comorbid disorders and also the nature of comorbidity itself being highly heterogeneous, we additionally discuss possible models of comorbidity. In the future, longitudinal data on distinct patterns of symptom and comorbidity progression would help to refine disease classification systems, strengthen the power of future genetic studies and finally allow for more specific treatment strategies.     

Emotional dysregulation in children with attention-deficit/hyperactivity disorder

Emotional dysregulation is increasingly recognized as a core feature of attention-deficit/hyperactivity disorder (ADHD). The purpose of the present systematic literature review was to identify published data related to the neuropsychology of emotional dysregulation in children with ADHD. The literature obtained is discussed in the contexts of deficits in emotional control, impairments in executive function, the emotional components of comorbidities, neurophysiological and autonomic correlates of emotional dysregulation, and the significance of multiple neuropsychological pathways of ADHD on emotional dysregulation. These various lines of evidence are used to create a patient-oriented conceptual model framework of the pathway from stimulus to inappropriate internalized (sadness, moodiness) or externalized (anger, aggressiveness) emotional responses. The article concludes by calling for continued research into the development of reliable and universally accepted measures of emotional dysregulation in order to provide children affected with ADHD, and their caregivers, some explanation for their emotional lability and, ultimately, to be used as tools to evaluate potential treatments.     

Intolerance of uncertainty in children with attention-deficit/hyperactivity disorder

Intolerance of uncertainty (IU) has often been studied in the context of internalizing disorders, but no studies to our knowledge have explored the relation between IU and externalizing disorders. Given the proposed link between IU and emotion regulation, the current study sought to examine levels of IU in an externalizing clinical population with known emotion regulation difficulties—attention-deficit/hyperactivity disorder (ADHD). IU levels in this population were compared to a clinical population known to experience elevated levels of IU. Participants in present study were ninety-three children (36 anxiety disorder, 28 ADHD, 29 unaffected children) ages 7–13, who completed the Intolerance of Uncertainty Scale—Short Version (IUS). Responses on the IUS were converted to total IU, prospective IU, and inhibitory IU. A linear mixed model analysis of covariance was conducted while controlling for age, sex, and ADHD medications. A significant interaction was observed between diagnostic status and IU scale. Planned contrasts indicated that children with anxiety disorders and ADHD reported significantly higher levels of IU relative to unaffected children, and children with ADHD reported comparable levels of inhibitory IU relative to children with anxiety disorders. The current results contribute to a growing literature on the link between IU and psychopathology. IU appears to be a transdiagnostic construct present among children with internalizing and externalizing disorders, and may be broadly associated with emotion regulation deficits rather than specific disorder symptoms.     

Verbal fluency in adults diagnosed with attention-deficit hyperactivity disorder (ADHD) in childhood

It has been increasingly believed that attention-deficit hyperactivity disorder (ADHD) is a disorder with lifelong course associated with cognitive difficulties including among others, language production, verbal learning, and verbal fluency. However, research is limited to children and adolescents, and very few researchers have examined the impact of ADHD in adulthood on the cognitive domain. The aim of the present study is to examine the performance of adults, diagnosed with ADHD in childhood, on semantic and phonemic verbal fluency tasks. It is hypothesized that adults with ADHD will perform worse on both tasks than matched controls. Sixty university students (30 diagnosed with ADHD in childhood and 30 matched controls) of mean age 20.5 participated in the study. They all completed two verbal fluency tasks. The ADHD group had statistically significant lower scores than the non-ADHD group on the phonemic, but not the semantic task. The study provides some evidence that ADHD in childhood has a negative impact on adults’ phonemic verbal fluency. This finding could be probably explained by the fact that phonemic fluency is considered more cognitively demanding and impacting more on the frontal lobe functions, known to be impaired in ADHD, than semantic fluency.     

Differential brain development with low and high IQ in attention-deficit/hyperactivity disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) and intelligence (IQ) are both heritable phenotypes. Overlapping genetic effects have been suggested to influence both, with neuroimaging work suggesting similar overlap in terms of morphometric properties of the brain. Together, this evidence suggests that the brain changes characteristic of ADHD may vary as a function of IQ. This study investigated this hypothesis in a sample of 108 children with ADHD and 106 typically developing controls, who participated in a cross-sectional anatomical MRI study. A subgroup of 64 children also participated in a diffusion tensor imaging scan. Brain volumes, local cortical thickness and average cerebral white matter microstructure were analyzed in relation to diagnostic group and IQ. Dimensional analyses investigated possible group differences in the relationship between anatomical measures and IQ. Second, the groups were split into above and below median IQ subgroups to investigate possible differences in the trajectories of cortical development. Dimensionally, cerebral gray matter volume and cerebral white matter microstructure were positively associated with IQ for controls, but not for ADHD. In the analyses of the below and above median IQ subgroups, we found no differences from controls in cerebral gray matter volume in ADHD with below-median IQ, but a delay of cortical development in a number of regions, including prefrontal areas. Conversely, in ADHD with above-median IQ, there were significant reductions from controls in cerebral gray matter volume, but no local differences in the trajectories of cortical development.In conclusion, the basic relationship between IQ and neuroanatomy appears to be altered in ADHD. Our results suggest that there may be multiple brain phenotypes associated with ADHD, where ADHD combined with above median IQ is characterized by small, more global reductions in brain volume that are stable over development, whereas ADHD with below median IQ is associated more with a delay of cortical development.     

Separate and overlapping relationships of inattention and hyperactivity/impulsivity in children and adolescents with attention-deficit/hyperactivity disorder

There is debate regarding the dimensional versus categorical nature of attention-deficit/hyperactivity disorder (ADHD). This study utilized confirmatory factor analysis to examine this issue. ADHD symptoms rated on interviews and rating scales from a large sample of individuals (ages 3–17, 74 % male, 75 % Caucasian) with ADHD were examined (n = 242). Four potential factor structures were tested to replicate prior findings in a sample with a wide age range and included only participants who met DSM-IV-TR diagnostic criteria for ADHD. Correlations with executive function measures were performed to further assess the separability and validity of the derived factors. The data support a bifactor model with a general ADHD factor and two specific factors, inattention and hyperactivity/impulsivity. Importantly, the individual factors were also differentially correlated with executive functioning measures. This study adds to a growing literature suggesting both a general component to ADHD, as well as dimensional traits of inattention and hyperactivity/impulsivity, associated with distinct executive functioning profiles. The presence of a general underlying factor contraindicates separating the inattentive and combined subtypes of ADHD into distinct disorders.     

Omega-3 fatty acid status in attention-deficit/hyperactivity disorder

Lower levels of long-chain polyunsaturated fatty acids, particularly omega-3 fatty acids, in blood have repeatedly been associated with a variety of behavioral disorders including attention-deficit/hyperactivity disorder (ADHD). The exact nature of this relationship is not yet clear. We have studied children with ADHD who exhibited skin and thirst symptoms classically associated with essential fatty acid (EFA) deficiency, altered plasma and red blood cell fatty acid profiles, and dietary intake patterns that do not differ significantly from controls. This led us to focus on a potential metabolic insufficiency as the cause for the altered fatty acid phenotype. Here we review previous work and present new data expanding our observations into the young adult population. The frequency of thirst and skin symptoms was greater in newly diagnosed individuals with ADHD (n = 35) versus control individuals without behavioral problems (n = 112) drawn from the Purdue student population. A follow up case-control study with participants willing to provide a blood sample, a urine sample, a questionnaire about their general health, and dietary intake records was conducted with balancing based on gender, age, body mass index, smoking and ethnicity. A number of biochemical measures were analyzed including status markers for several nutrients and antioxidants, markers of oxidative stress, inflammation markers, and fatty acid profiles in the blood. The proportion of omega-3 fatty acids was found to be significantly lower in plasma phospholipids and erythrocytes in the ADHD group versus controls whereas saturated fatty acid proportions were higher. Intake of saturated fat was 30% higher in the ADHD group, but intake of all other nutrients was not different. Surprisingly, no evidence of elevated oxidative stress was found based on analysis of blood and urine samples. Indeed, serum ferritin, magnesium, and ascorbate concentrations were higher in the ADHD group, but iron, zinc, and vitamin B6 were not different. Our brief survey of biochemical and nutritional parameters did not give us any insight into the etiology of lower omega-3 fatty acids, but considering the consistency of the observation in multiple ADHD populations continued research in this field is encouraged.     

Prevalence of sexual dysfunctions and other sexual disorders in adults with attention-deficit/hyperactivity disorder compared to the general population

Attention-deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention and/or hyperactivity and impulsivity that lead to dysfunctioning in daily life. One of the affected areas of life that has so far not been studied in ADHD is sexual functioning. The goal of this study was to assess prevalence of sexual dysfunctions and other sexual disorders among adults with ADHD. A total of n = 136 adult patients treated in a Dutch outpatient ADHD clinic filled out two questionnaires to screen for sexual dysfunctions and other sexual disorders. We compared the prevalence of sexual dysfunctions and other sexual disorders in our ADHD patient population to results from two large surveys among the general Dutch population. We found that 39% of the male and 43% of the female ADHD patients had symptoms of a sexual dysfunction, and 17% of the male and 5% of the female ADHD patients had symptoms of any other sexual disorder. Only one male patient had received a diagnosis of a sexual disorder at this clinic prior to study participation. In conclusion, sexual dysfunctions and other sexual disorders are highly prevalent in adults with ADHD. Screening for sexual disorders should be therefore standard procedure during diagnostic assessment.     

Emotion recognition in children and adolescents with attention-deficit/hyperactivity disorder (ADHD)

Children with attention-deficit/hyperactivity disorder (ADHD) are impaired in social adaptation and display deficits in social competence. Deficient emotion recognition has been discussed to underlie these social problems. However, comorbid conduct problems have not been considered in the majority of studies conducted so far, and the influence of medication on emotion recognition has rarely been studied. Here, emotion recognition performance was assessed in children with ADHD without medication compared with children with ADHD under stimulant medication and a matched control group. In order to rule out confounding by externalizing symptoms, children with comorbid conduct problems were excluded. Video clips with neutral faces developing a basic emotion (happiness, sadness, disgust, fear and anger) were presented in order to assess emotion recognition. Results indicated between-group differences neither concerning the number of correctly identified emotions nor concerning reaction times and their standard deviations. Thus, we suggest that ADHD per se is not associated with deficits in emotion recognition.     

miRNA profiling in the hippocampus of attention-deficit/hyperactivity disorder rats

Attention-deficit/hyperactivity disorder (ADHD) is characterized by attention deficit, hyperactivity, impulsivity, and learning and memory impairment. Although the pathogenesis of learning and memory impairment is still unknown, some studies have suggested an association with hippocampus dysfunction. We aimed to explore the role of miRNAs in the learning and memory impairments observed in ADHD. Differentially expressed hippocampal micro-ribonucleic acids (miRNAs) in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) were detected on an Illumina HiSeq. 2000 genome analyzer. A total of 25 differentially expressed miRNAs (fold-change ≥ 2 and P-value < 0.05) were identified. The target genes of these differentially expressed miRNAs were predicted using online tools (TargetScan and miRDB). Gene ontology and pathway analysis of the predicted target genes were carried out to assess their putative biological functions. Meanwhile, quantitative real-time PCR was used to validate the HiSeq results, revealing that three miRNAs (miR-1-b, miR-741-3p, and miR-206-3p) were upregulated and four (miR-182, miR-471-5p, miR-183-5p, and miR-211-5p) were downregulated in the SHR group compared with the WKY group. In addition, we confirmed that Dyrk1a is regulated by miR-211-5p. These results help us understand the contribution of miRNAs in the hippocampus to ADHD and provide new insights into the pathogenesis of this condition.     

A genomewide scan for loci involved in attention-deficit/hyperactivity disorder

Attention deficit/hyperactivity disorder (ADHD) is a common heritable disorder with a childhood onset. Molecular genetic studies of ADHD have previously focused on examining the roles of specific candidate genes, primarily those involved in dopaminergic pathways. We have performed the first systematic genomewide linkage scan for loci influencing ADHD in 126 affected sib pairs, using a approximately 10-cM grid of microsatellite markers. Allele-sharing linkage methods enabled us to exclude any loci with a lambda(s) of > or =3 from 96% of the genome and those with a lambda(s) of > or =2.5 from 91%, indicating that there is unlikely to be a major gene involved in ADHD susceptibility in our sample. Under a strict diagnostic scheme we could exclude all screened regions of the X chromosome for a locus-specific lambda(s) of >/=2 in brother-brother pairs, demonstrating that the excess of affected males with ADHD is probably not attributable to a major X-linked effect. Qualitative trait maximum LOD score analyses pointed to a number of chromosomal sites that may contain genetic risk factors of moderate effect. None exceeded genomewide significance thresholds, but LOD scores were >1.5 for regions on 5p12, 10q26, 12q23, and 16p13. Quantitative-trait analysis of ADHD symptom counts implicated a region on 12p13 (maximum LOD 2.6) that also yielded a LOD >1 when qualitative methods were used. A survey of regions containing 36 genes that have been proposed as candidates for ADHD indicated that 29 of these genes, including DRD4 and DAT1, could be excluded for a lambda(s) of 2. Only three of the candidates-DRD5, 5HTT, and CALCYON-coincided with sites of positive linkage identified by our screen. Two of the regions highlighted in the present study, 2q24 and 16p13, coincided with the top linkage peaks reported by a recent genome-scan study of autistic sib pairs.     

The potential role of fatty acids in attention-deficit/hyperactivity disorder

As currently defined, attention-deficit/hyperactivity disorder (ADHD) encompasses a broad constellation of behavioural and learning problems and its definition and diagnosis remain controversial. The aetiology of ADHD is acknowledged to be both complex and multifactorial. The proposal considered here is that at least some features of ADHD may reflect an underlying abnormality of fatty acid metabolism. Clinical and biochemical evidence is discussed which suggests that a functional deficiency of certain long-chain polyunsaturated fatty acids could contribute to many of the features associated with this condition. The implications in terms of fatty acid treatment proposals are also discussed; such a form of treatment is relatively safe compared to existing pharmacological interventions, although further studies are still needed in order to evaluate its potential efficacy in the management of ADHD symptoms.     

Gender differences in self- and investigator-rated psychopathology in adult attention-deficit/hyperactivity disorder

Despite the growing interest in the diagnosis of ADHD in adults, most of the knowledge in ADHD still relies on research with children and adolescents. Gender differences in adult ADHD patients were neglected for a long time and only few studies have focused this topic. The goal of this study was to investigate differences in ADHD psychopathology in male and female adults. We examined gender differences in ADHD core and associated symptoms and in personality traits in adults with ADHD. In order to discriminate between general and ADHD-specific gender differences, we compared data of adult ADHD patients with two control groups (patients with substance abuse and healthy controls). Regarding differences in ADHD core symptoms-attention problems, hyperactivity, and impulsivity-between male and female subjects, we found inconsistent results depending on the applied diagnostic instruments. Using standardized self-report, there were no gender differences regarding attention problems and hyperactivity but regarding impulsivity. Results of a semi-standardized interview (WRAADDS) according to the Utah criteria of adult ADHD showed no gender differences regarding impulsivity and hyperactivity but regarding attention problems. Moreover, differences were found between female and male healthy controls in the domains "over reactivity" and "hot temper" but not in the group of ADHD patients. Thus, it seems that gender differences in normal population were leveled by the disorder. Concerning general personality traits, some differences between male and female ADHD patients were also present in healthy controls, suggesting no ADHD-specific effect of gender. In conclusion, male and female ADHD patients seem to be more similar than different regarding ADHD-related psychopathology and general personality traits.     

Neurofeedback treatment for attention-deficit/hyperactivity disorder in children: a comparison with methylphenidate

Clinical trials have suggested that neurofeedback may be efficient in treating attention-deficit/hyperactivity disorder (ADHD). We compared the effects of a 3-month electroencephalographic feedback program providing reinforcement contingent on the production of cortical sensorimotor rhythm (12–15 Hz) and beta1 activity (15–18 Hz) with stimulant medication. Participants were N = 34 children aged 8–12 years, 22 of which were assigned to the neurofeedback group and 12 to the methylphenidate group according to their parents' preference. Both neurofeedback and methylphenidate were associated with improvements on all subscales of the Test of Variables of Attention, and on the speed and accuracy measures of the d2 Attention Endurance Test. Furthermore, behaviors related to the disorder were rated as significantly reduced in both groups by both teachers and parents on the IOWA-Conners Behavior Rating Scale. These findings suggest that neurofeedback was efficient in improving some of the behavioral concomitants of ADHD in children whose parents favored a nonpharmacological treatment.