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1.  The prevalence and effects of Adult Attention-Deficit/hyperactivity Disorder (ADHD) on the performance of workers: Results from the WHO World Mental Health Survey Initiative 
To estimate the prevalence and workplace consequences of adult attention-deficit/hyperactivity disorder (ADHD).
Ann ADHD screen was administered to 18–44 year-old respondents in ten national surveys in the WHO World Mental Health (WMH) Survey Initiative (n = 7075 in paid or self employment; response rate 45.9–87.7% across countries). Blinded clinical reappraisal interviews were administered in the US to calibrate the screen. Days out of role were measured in the WHO Disability Assessment Schedule (WHO-DAS). Questions were also asked about ADHD treatment.
An average of 3.5% of workers in the ten countries was estimated to meet DSM-IV criteria for adult ADHD (inter-quartile range: 1.3–4.9%). ADHD was more common among males than females and less common among professionals than other workers. ADHD was associated with a statistically significant 22.1 annual days of excess lost role performance compared to otherwise similar respondents without ADHD. No difference in the magnitude of this effect was found by occupation, education, age, gender, or partner status. This effect was most pronounced in Colombia, Italy, Lebanon, and the US. Although only a small minority of workers with ADHD ever received treatment for this condition, higher proportions were treated for comorbid mental-substance disorders.
ADHD is a relatively common condition among working people in the countries studied and is associated with high work impairment in these countries. This impairment, in conjunction with the low treatment rate and the availability of cost-effective therapies, suggests that ADHD would be a good candidate for targeted workplace screening and treatment programs.
Main messages
A high proportion of childhood ADHD persists into adulthood.
An average of 3.5% of workers in nationally representative surveys carried out in 10 countries met criteria for current DSM-IV adult ADHD.
Workers with ADHD have an average 8.4 excess sickness absence days per year and even higher annualized average excess numbers of workdays associated with reduced work quantity (21.7 days) and quality (13.6 days).
Only a small majority of these workers are treated for ADHD despite evidence that such treatment can be quite effective in improving functioning.
Policy implications
ADHD is a good candidate for targeted workplace screening and treatment programs.
Evaluation is needed to determine the extent to which best-practices outreach and treatment interventions would result in improvements in work performance that have a positive return-on-investment from the employer perspective.
PMCID: PMC2665789  PMID: 18505771
ADHD; Work loss; Functioning
2.  Childhood and persistent ADHD symptoms associated with educational failure and long-term occupational disability in adult ADHD 
Few studies have examined the impact of childhood attention deficit hyperactivity disorder (ADHD) symptoms on adult ADHD functional outcomes. To address this issue dimensionally, ADHD symptoms in childhood and adulthood and their relation to educational deficits and work disability are studied in a clinical sample of adult patients with previously untreated ADHD. About 250 adults diagnosed systematically with ADHD according to DSM-IV were prospectively recruited. Primary outcomes were high school dropout and being out of the work last year. Childhood ADHD symptoms, sex differences, comorbidities of other mental disorders, and adult ADHD symptoms were examined by historical data, clinician interviews, and questionnaires. High levels of ADHD symptom severity in childhood were related to dropping out of high school [odds ratio (OR) = 3.0], as were higher numbers of hyperactive–impulsive symptoms in childhood. Significantly, more women than men were long-term work disabled (OR = 2.0). After adjusting for age and gender, persisting high levels of ADHD inattention symptoms in adulthood (OR = 2.5), number of comorbid disorders, and particularly anxiety disorders were significantly related to long-term work disability. Childhood hyperactive–impulsive symptoms and overall severity of childhood ADHD symptoms were associated with high school dropout rates; however, persisting ADHD inattention symptoms and comorbid mental disorders in adulthood were more correlated to occupational impairment. These findings underline proposals for studies on early recognition and interventions for ADHD and psychiatric comorbidity. They further suggest that inattentive symptoms be a focus of adult ADHD treatment and that workplace interventions be considered to prevent long-term work disability.
PMCID: PMC4033786  PMID: 24497125
Attention deficit; Adult ADHD; School dropout; Comorbidity; Occupational disability
3.  Does Executive Functioning (EF) Predict Depression in Clinic-Referred Adults?: EF Tests vs. Rating Scales 
Journal of affective disorders  2012;145(2):270-275.
Deficits in executive functioning (EF) are implicated in neurobiological and cognitive-processing theories of depression. EF deficits are also associated with Attention-deficit/hyperactivity disorder (ADHD) in adults, who are also at increased risk for depressive disorders. Given debate about the ecological validity of laboratory measures of EF, we investigated the relationship between depression diagnoses and symptoms and EF as measured by both rating scales and tests in a sample of adults referred for evaluation of adult ADHD.
Data from two groups of adults recruited from an ADHD specialty clinic were analyzed together: Adults diagnosed with ADHD (N=146) and a clinical control group of adults referred for adult ADHD assessment but not diagnosed with the disorder ADHD (N=97). EF was assessed using a rating scale of EF deficits in daily life and a battery of tests tapping various EF constructs. Depression was assessed using current and lifetime SCID diagnoses (major depression, dysthymia) and self-report symptom ratings.
EF as assessed via rating scale predicted depression across measures even when controlling for current anxiety and impairment. Self-Management to Time and Self-Organization and Problem-Solving showed the most robust relationships. EF tests were weakly and inconsistently related to depression measures.
Prospective studies are needed to rigorously evaluate EF problems as true risk factors for depressive onset.
EF problems in everyday life were important predictors of depression. Researchers and clinicians should consistently assess for the ADHD-depression comorbidity. Clinicians should consider incorporating strategies to address EF deficits when treating people with depression.
PMCID: PMC3519951  PMID: 22858220
executive functioning; depressive disorders; attention-deficit/hyperactivity disorder; ADHD; neuropsychological tests; rating scales
4.  Attentional Control and Subjective Executive Function in Treatment-Naive Adults with Attention Deficit Hyperactivity Disorder 
PLoS ONE  2014;9(12):e115227.
We investigated performance-derived measures of executive control, and their relationship with self- and informant reported executive functions in everyday life, in treatment-naive adults with newly diagnosed Attention Deficit Hyperactivity Disorder (ADHD; n = 36) and in healthy controls (n = 35). Sustained attentional control and response inhibition were examined with the Test of Variables of Attention (T.O.V.A.). Delayed responses, increased reaction time variability, and higher omission error rate to Go signals in ADHD patients relative to controls indicated fluctuating levels of attention in the patients. Furthermore, an increment in NoGo commission errors when Go stimuli increased relative to NoGo stimuli suggests reduced inhibition of task-irrelevant stimuli in conditions demanding frequent responding. The ADHD group reported significantly more cognitive and behavioral executive problems than the control group on the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). There were overall not strong associations between task performance and ratings of everyday executive function. However, for the ADHD group, T.O.V.A. omission errors predicted self-reported difficulties on the Organization of Materials scale, and commission errors predicted informant reported difficulties on the same scale. Although ADHD patients endorsed more symptoms of depression and anxiety on the Achenbach System of Empirically Based Assessment (ASEBA) than controls, ASEBA scores were not significantly associated with T.O.V.A. performance scores. Altogether, the results indicate multifaceted alteration of attentional control in adult ADHD, and accompanying subjective difficulties with several aspects of executive function in everyday living. The relationships between the two sets of data were modest, indicating that the measures represent non-redundant features of adult ADHD.
PMCID: PMC4278892  PMID: 25545156
5.  Preparatory neural networks are impaired in adults with attention-deficit/hyperactivity disorder during the antisaccade task☆ 
NeuroImage : Clinical  2012;2:63-78.
Adults with attention-deficit/hyperactivity disorder (ADHD) often display executive function impairments, particularly in inhibitory control. The antisaccade task, which measures inhibitory control, requires one to suppress an automatic prosaccade toward a salient visual stimulus and voluntarily make an antisaccade in the opposite direction. ADHD patients not only have longer saccadic reaction times, but also make more direction errors (i.e., a prosaccade was executed toward the stimulus) during antisaccade trials. These deficits may stem from pathology in several brain areas that are important for executive control. Using functional MRI with a rapid event-related design, adults with combined subtype of ADHD (coexistence of attention and hyperactivity problems), who abstained from taking stimulant medication 20 h prior to experiment onset, and age-match controls performed pro- and antisaccade trials that were interleaved with pro- and anti-catch trials (i.e., instruction was presented but no target appeared, requiring no response). This method allowed us to examine brain activation patterns when participants either prepared (during instruction) or executed (after target appearance) correct pro or antisaccades. Behaviorally, ADHD adults displayed several antisaccade deficits, including longer and more variable reaction times and more direction errors, but saccade metrics (i.e., duration, velocity, and amplitude) were normal. When preparing to execute an antisaccade, ADHD adults showed less activation in frontal, supplementary, and parietal eye fields, compared to controls. However, activation in these areas was normal in the ADHD group during the execution of a correct antisaccade. Interestingly, unlike controls, adults with ADHD produced greater activation than controls in dorsolateral prefrontal cortex during antisaccade execution, perhaps as part of compensatory mechanisms to optimize antisaccade production. Overall, these data suggest that the saccade deficits observed in adults with ADHD do not result from an inability to execute a correct antisaccade but rather the failure to properly prepare (i.e., form the appropriate task set) for the antisaccade trial. The data support the view that the executive impairments, including inhibitory control, in ADHD adults are related to poor response preparation.
► The neural correlates of inhibitory control in adults with ADHD were examined. ► We used an interleaved pro and antisaccade task simultaneously with functional MRI. ► This enabled the dissociation of automatic versus voluntary control. ► Patients had less activity in fronto-parietal areas during antisaccade preparation. ► Overall, antisaccade deficits in ADHD adults likely arise from poor preparation.
PMCID: PMC3777763  PMID: 24179760
ADHD; Saccade; fMRI; Preparation; Inhibition
6.  The Adult ADHD Self-Report Scale (ASRS): utility in college students with attention-deficit/hyperactivity disorder 
PeerJ  2014;2:e324.
Background. The number of students with Attention Deficit/Hyperactivity Disorder (ADHD) enrolled in colleges and universities has increased markedly over the past few decades, giving rise to questions about how best to document symptoms and impairment in the post-secondary setting. The aim of the present study was to investigate the utility and psychometric properties of a widely-used rating scale for adults with ADHD, the Adult ADHD Self-Report Scale (ASRS-V1.1), in a sample of post-secondary students with ADHD.
Methods. A total of 135 college students (mean age = 24, 42% males) with ADHD were recruited from Student Disability Services in post-secondary institutions. We compared informant responses on the ASRS administered via different modalities. First, students’ self-report was ascertained using the ASRS Screener administered via telephone interview, in which they were asked to provide real-life examples of behavior for each of the six items. Next, students self-reported symptoms on the 18-item paper version of the ASRS Symptom Checklist administered about 1–2 weeks later, and a collateral report using an online version of the 18-item ASRS Symptom Checklist. Students also completed self-report measures of everyday cognitive failure (CFQ) and executive functioning (BDEFS).
Results. Results revealed moderate to good congruency between the 18-item ASRS-Self and ASRS-Collateral reports (correlation = .47), and between student self-report on the 6-item telephone-based and paper versions of the ASRS, with the paper version administered two weeks later (correlation = .66). The full ASRS self-report was related to impairment, such as in executive functioning (correlation = .63) and everyday cognitive failure (correlation = .74). Executive functioning was the only significant predictor of ASRS total scores.
Discussion. Current findings suggest that the ASRS provides an easy-to-use, reliable, and cost-effective approach for gathering information about current symptoms of ADHD in college and university students. Collateral reports were moderately related to self-reports, although we note the difficulty in obtaining informant reports for this population. Use of a telephone interview to elicit behavioral descriptions for each item may be useful in future research that is required to specifically test the utility of the ASRS in, for example, documenting and confirming current reports of impairment due to ADHD symptoms and its positive and negative predictive power for diagnosis.
PMCID: PMC3970798  PMID: 24711973
ASRS; ADHD; Validation; College students
7.  When Diagnosing ADHD in Young Adults Emphasize Informant Reports, DSM Items, and Impairment 
This study examined several questions about the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in young adults using data from a childhood-diagnosed sample of 200 individuals with ADHD (age M = 20.20 years) and 121 demographically similar non-ADHD controls (total N = 321).
We examined the use of self-versus informant ratings of current and childhood functioning and evaluated the diagnostic utility of adult-specific items versus items from the Diagnostic and Statistical Manuel of Mental Disorders (DSM).
Results indicated that although a majority of young adults with a childhood diagnosis of ADHD continued to experience elevated ADHD symptoms (75%) and clinically significant impairment (60%), only 9.6%–19.7% of the childhood ADHD group continued to meet DSM–IV–TR (DSM, 4th ed., text rev.) criteria for ADHD in young adulthood. Parent report was more diagnostically sensitive than self-report. Young adults with ADHD tended to underreport current symptoms, while young adults without ADHD tended to overreport symptoms. There was no significant incremental benefit beyond parent report alone to combining self-report with parent report. Non-DSM-based, adult-specific symptoms of ADHD were significantly correlated with functional impairment and endorsed at slightly higher rates than the DSM-IV-TR symptoms. However, DSM-IV-TR items tended to be more predictive of diagnostic group membership than the non-DSM adult-specific items due to elevated control group item endorsement.
Implications for the assessment and treatment of ADHD in young adults are discussed (i.e., collecting informant reports, lowering the diagnostic threshold, emphasizing impairment, and cautiously interpreting retrospective reports).
PMCID: PMC3919146  PMID: 22774792
adult ADHD; diagnosis; assessment
8.  The Impact of Depressive Symptoms in Adults with ADHD Symptoms on Family Function and ADHD Symptoms of Their Children 
Psychiatry Investigation  2014;11(2):124-130.
People with attention-deficit/hyperactivity disorder (ADHD) exhibit considerable impairment in social, academic, or occupational functioning. The present study aimed to examine the patterns of associations between ADHD symptoms, depression, and family functioning.
The sample consisted of 1,022 adults randomly selected from a district in Seoul, South Korea. Several self-assessment scales were utilized to rate ADHD symptoms (both past and current), current symptoms of depression, and level of family functioning. ADHD symptoms in the children of these participants were also assessed. Pearson's correlation and multiple linear regression analyses were performed; structural equation modeling (SEM) was conducted to determine the best fitting model.
Adult ADHD symptoms were positively associated with depressive symptoms. Depressive symptoms, in turn, mediated the relationship between adult ADHD symptoms and cohesion among family members. In addition, depressive symptoms mediated the relationship between adult ADHD symptoms and their children's ADHD symptoms.
The relationship between adult ADHD symptoms and family dysfunction may be influenced by depressive symptoms. When treating ADHD in adults, clinicians should pay attention to the presence or absence of depression.
PMCID: PMC4023085  PMID: 24843366
Attention-deficit/hyperactivity disorder; Depression; Adult; Family; Structural equation modeling
9.  Clinical and Functional Outcome of Childhood ADHD 33 Years Later 
Archives of general psychiatry  2012;69(12):1295-1303.
Prospective studies of childhood attention deficit/hyperactivity disorder (ADHD) have not extended beyond early adulthood.
To test whether children diagnosed with ADHD at mean age 8 (probands) have worse educational, occupational, economic, social, marital outcomes; higher rates of ongoing ADHD, antisocial personality disorder (ASPD), substance disorders (SD); adult onset psychiatric disorders, psychiatric hospitalizations and incarcerations, than non-ADHD comparisons, at mean age 41. To test for: positive associations between probands’ ongoing ADHD and ASPD, and SD’s; and for worse social and occupational functioning in probands without ongoing psychiatric disorders, than comparisons.
Prospective, 33 year follow-up study, with blind clinical assessments.
Research clinic.
135 Caucasian males with ADHD in childhood, free of conduct disorder, and 136 male comparisons without childhood ADHD (65% and 76% of original cohort, respectively).
Main Outcome Measures
Occupational, economic, and educational attainment; marital history; occupational and social functioning; ongoing and lifetime psychiatric disorders; psychiatric hospitalizations, and incarcerations.
Probands had significantly worse educational, occupational, economic, social outcomes, and more divorces than comparisons; higher rates of ongoing ADHD (22% vs 5%, p<.001), ASPD (16% vs 0%, p<.001)and SD (14% vs 5%, p<.01), but not more mood or anxiety disorders (p’s=.36 and .33). Ongoing ADHD was weakly related to ongoing SD (phi=.19, p=.04), and ASPD+SD (phi=.20, p=.04). Lifetime, probands had significantly more ASPD and SD’s, but not mood or anxiety disorders, and more psychiatric hospitalizations and incarcerations than comparisons. Relative to comparisons, psychiatric disorders with onsets at age 21 or beyond were not significantly elevated in probands. Probands without ongoing psychiatric disorders had worse social, but not occupational, functioning.
The multiple disadvantages predicted by childhood ADHD well into adulthood began in adolescence, without increased onsets of new disorders after age 20. Findings highlight the importance of extended monitoring and treatment of children with ADHD.
PMCID: PMC3597443  PMID: 23070149
10.  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.
PMCID: PMC4009378  PMID: 23413201
Attention deficit hyperactivity disorder; Emotion; Comorbidity; Adult
11.  Attention Deficit Hyperactivity Disorder (ADHD) among longer-term prison inmates is a prevalent, persistent and disabling disorder 
BMC Psychiatry  2010;10:112.
ADHD is a common and disabling disorder, with an increased risk for coexisting disorders, substance abuse and delinquency. In the present study, we aimed at exploring ADHD and criminality. We estimated the prevalence of ADHD among longer-term prison inmates, described symptoms and cognitive functioning, and compared findings with ADHD among psychiatric outpatients and healthy controls.
At Norrtälje Prison, we approached 315 male inmates for screening of childhood ADHD by the Wender Utah Rating Scale (WURS-25) and for present ADHD by the Adult ADHD Self-Report Screener (ASRS-Screener). The response rate was 62%. Further, we assessed 34 inmates for ADHD and coexisting disorders. Finally, we compared findings with 20 adult males with ADHD, assessed at a psychiatric outpatient clinic and 18 healthy controls.
The estimated prevalence of adult ADHD among longer-term inmates was 40%. Only 2 out of 30 prison inmates confirmed with ADHD had received a diagnosis of ADHD during childhood, despite most needed health services and educational support. All subjects reported lifetime substance use disorder (SUD) where amphetamine was the most common drug. Mood and anxiety disorders were present among half of subjects; autism spectrum disorder (ASD) among one fourth and psychopathy among one tenth. Personality disorders were common; almost all inmates presented conduct disorder (CD) before antisocial personality disorder (APD). Prison inmates reported more ADHD symptoms during both childhood and adulthood, compared with ADHD psychiatric outpatients. Further, analysis of executive functions after controlling for IQ showed both ADHD groups performed poorer than controls on working memory tests. Besides, on a continuous performance test, the ADHD prison group displayed poorer results compared with both other groups.
This study suggested ADHD to be present among 40% of adult male longer-term prison inmates. Further, ADHD and coexisting disorders, such as SUD, ASD, personality disorders, mood- and anxiety disorders, severely affected prison inmates with ADHD. Besides, inmates showed poorer executive functions also when controlling for estimated IQ compared with ADHD among psychiatric outpatients and controls. Our findings imply the need for considering these severities when designing treatment programmes for prison inmates with ADHD.
PMCID: PMC3016316  PMID: 21176203
12.  Prospective Follow-up of Girls with Attention-deficit/Hyperactivity Disorder into Early Adulthood: Continuing Impairment Includes Elevated Risk for Suicide Attempts and Self-Injury 
To perform a 10-year prospective follow-up of a childhood-ascertained (6–12 years), ethnically and socioeconomically diverse sample of girls with attention-deficit/hyperactivity disorder (ADHD) (N = 140: Combined type [ADHD-C} n = 93; Inattentive Type [ADHD-I] n = 47) plus a matched comparison group (N = 88). Girls were recruited from schools, mental health centers, pediatricians, and via advertisements; extensive evaluations confirmed ADHD vs. comparison status.
Ten-year outcomes (age range 17–24 years; retention rate = 95%) included symptoms (ADHD, externalizing, internalizing), substance use, eating pathology, self-perceptions, functional impairment (global, academic, service utilization), self-harm (suicide attempts, self-injury), and driving behavior.
Participants with childhood-diagnosed ADHD continued to display higher rates of ADHD and comorbid symptoms, showed more serious impairment (both global and specific), and had higher rates of suicide attempts and self-injury than the comparison sample, with effect sizes from medium to very large; yet the groups did not differ significantly in terms of eating pathology, substance use, or driving behavior. ADHD-C and ADHD-I types rarely differed significantly, except for suicide attempts and self-injury, which were highly concentrated in ADHD-C. Domains of externalizing behavior, global impairment, and service utilization, and self-harm (suicide attempts and self-injury) survived stringent control of crucial childhood covariates (age, demographics, comorbidities, IQ).
Girls with childhood ADHD maintain marked impairment by early adulthood, spreading from symptoms to risk for serious self-harm. In future research we address the viability of different diagnostic conceptions of adult ADHD and their linkages with core life impairments.
PMCID: PMC3543865  PMID: 22889337
attention-deficit/hyperactivity disorder (ADHD); females; longitudinal; comorbidity; impairment; suicide; self-injury
13.  Attention deficit/hyperactivity disorders with co-existing substance use disorder is characterized by early antisocial behaviour and poor cognitive skills 
BMC Psychiatry  2013;13:336.
Attention Deficit/Hyperactivity Disorder (ADHD) is associated with an increased risk of co-existing substance abuse. The Swedish legislation on compulsory healthcare can be applied to persons with severe substance abuse who can be treated involuntarily during a period of six months. This context enables a reliable clinical assessment of ADHD in individuals with severe substance use disorder (SUD).
In the context of compulsory care for individuals with severe SUD, male patients were assessed for ADHD, co-morbid psychiatric symptoms, psychosocial background, treatment history, and cognition. The data from the ADHD/SUD group (n = 60) was compared with data from (1) a group of individuals with severe substance abuse without known ADHD (SUD group, n = 120), as well as (2) a group with ADHD from an outpatient psychiatric clinic (ADHD/Psych group, n = 107).
Compared to the general SUD group in compulsory care, the ADHD/SUD group had already been significantly more often in compulsory care during childhood or adolescence, as well as imprisoned more often as adults. The most common preferred abused substance in the ADHD/SUD group was stimulant drugs, while alcohol and benzodiazepine abuse was more usual in the general SUD group. Compared to the ADHD/Psych group, the ADHD/SUD group reported more ADHD symptoms during childhood and performed poorer on all tests of general intellectual ability and executive functions.
The clinical characteristics of the ADHD/SUD group differed from those of both the SUD group and the ADHD/Psych group in several respects, indicating that ADHD in combination with SUD is a particularly disabling condition. The combination of severe substance abuse, poor general cognitive ability, severe psychosocial problems, including indications of antisocial behaviour, and other co-existing psychiatric conditions should be considered in treatment planning for adults with ADHD and SUD.
PMCID: PMC3878757  PMID: 24330331
ADHD; SUD; Co-morbidity; Compulsory care; Adults; Cognition
14.  Executive Cognitive Dysfunction and ADHD in Cocaine Dependence: Searching for a Common Cognitive Endophenotype for Addictive Disorders 
Background: Cocaine-dependent individuals (CDI) present executive cognitive function (ECF) deficits, but the impact of psychiatric comorbidities such as Attention-Deficit Hyperactivity Disorder (ADHD) on neuropsychological functioning is still poorly understood. The aim of this study was to investigate if CDI with ADHD (CDI + ADHD) would have a distinct pattern of executive functioning when compared with CDI without ADHD (CDI).
Methods: We evaluated 101 adults, including 69 cocaine-dependent subjects (divided in CDI and CDI + ADHD) and 32 controls. ECF domains were assessed with Digits Forward (DF), Digits Backward (DB), Stroop Color Word Test (SCWT), the Wisconsin Card Sorting Test (WCST), and the Frontal Assessment Battery (FAB). DSM-IV criteria for ADHD were used for diagnosis and previous ADHD symptoms (in the childhood) were retrospectively assessed by the Wender-Utah Rating Scale (WURS).
Results: There were no significant differences between CDI + ADHD, CDI, and controls in estimated intellectual quotient (IQ), socioeconomic background, education (in years), and pre-morbid IQ (p > 0.05). SCWT and WCST scores did not differ across groups (p > 0.05). Nevertheless, CDI and CDI + ADHD performed more poorly than controls in total score of the FAB (p < 0.05). Also, CDI + ADHD did worse than CDI on DF (F = 4.756, p = 0.011), DB (F = 8.037, p = 0.001), Conceptualization/FAB (F = 4.635, p = 0.012), and Mental flexibility/FAB (F = 3.678, p = 0.029). We did not find correlations between cocaine-use variables and neuropsychological functioning, but previous ADHD symptoms assessed by WURS were negatively associated with DF (p = 0.016) and with the total score of the FAB (p = 0.017).
Conclusion: CDI + ADHD presented more pronounced executive alterations than CDI and CDI exhibited poorer cognitive functioning than controls. Pre-existing ADHD symptoms may have a significant negative impact on executive dysfunction in CDI. It remains to be investigated by future studies if symptoms such as impulsivity or a pre-existing ECF dysfunction could represent underlying cognitive endophenotypes that would substantially increase the risk for acquiring addictive disorders.
PMCID: PMC3801150  PMID: 24155725
executive dysfunction; ADHD; cocaine; addiction; impulsivity; prefrontal cortex
15.  Motor regulation problems and pain in adults diagnosed with ADHD 
Most children who are diagnosed with attention deficit-hyperactivity disorder (ADHD) have moderate-to-severe motor problems using the Motor Function Neurological Assessment battery (MFNU). The MFNU focuses on specific muscle adjustment problems associated with ADHD, especially motor inhibition problems and high muscle tone. Here we investigated whether adults with ADHD/hyperkinetic disorder (HKD) have similar motor problems. In our clinical experience, adults with ADHD often complain about back, shoulder, hip, and leg pain. We also investigate reported pain in adults with ADHD.
Twenty-five adult outpatients diagnosed with ADHD/HKD who were responders to methylphenidate (MPH) were compared to 23 non-ADHD controls on 16 MFNU subtests and using a ‘total score’ (‘TS’) parameter. The MFNU test leader was blinded to group identity. The two groups were also compared using the Pain Drawing and Numerical Pain Rating Scale.
The adult ADHD group had significantly (p < .001) more motor problems (higher TS) than controls. On the muscle regulation subtests, 36–96% of the ADHD group showed ‘moderate’ to ‘severe’ problems compared to 13–52% of the control group, and 80% of the ADHD group reported widespread pain. Highly significant differences were found between the ADHD and control groups for the variables ‘pain level’ (p < .001) and ‘pain location’ (p < .001). Significant correlations were found between TS and ‘pain location’ and between TS and ‘pain level’.
These findings suggest that similar to children with ADHD, adults diagnosed with ADHD also have motor inhibition problems and heightened muscle tone. The presence of significantly higher pain levels and more widespread pain in the ADHD group compared to non-ADHD controls might indicate that pain is a long-term secondary effect of heightened muscle tone and restricted movement that can be demonstrated in children and adults by the MFNU battery.
PMCID: PMC3652792  PMID: 23642255
ADHD; Motor problems; MFNU; Muscular regulation; Tonus; Inhibition; Pain; Adult
16.  Atomoxetine Improved Attention in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder and Dyslexia in a 16 Week, Acute, Randomized, Double-Blind Trial 
The purpose of this study was to evaluate atomoxetine treatment effects in attention-deficit/hyperactivity disorder (ADHD-only), attention-deficit/hyperactivity disorder with comorbid dyslexia (ADHD+D), or dyslexia only on ADHD core symptoms and on sluggish cognitive tempo (SCT), working memory, life performance, and self-concept.
Children and adolescents (10–16 years of age) with ADHD+D (n=124), dyslexia-only (n=58), or ADHD-only (n=27) received atomoxetine (1.0–1.4 mg/kg/day) or placebo (ADHD-only subjects received atomoxetine) in a 16 week, acute, randomized, double-blind trial with a 16 week, open-label extension phase (atomoxetine treatment only). Changes from baseline were assessed to weeks 16 and 32 in ADHD Rating Scale-IV-Parent-Version:Investigator-Administered and Scored (ADHDRS-IV-Parent:Inv); ADHD Rating Scale-IV-Teacher-Version (ADHDRS-IV-Teacher-Version); Life Participation Scale—Child- or Parent-Rated Version (LPS); Kiddie-Sluggish Cognitive Tempo (K-SCT) Interview; Multidimensional Self Concept Scale (MSCS); and Working Memory Test Battery for Children (WMTB-C).
At week 16, atomoxetine treatment resulted in significant (p<0.05) improvement from baseline in subjects with ADHD+D versus placebo on ADHDRS-IV-Parent:Inv Total (primary outcome) and subscales, ADHDRS-IV-Teacher-Version Inattentive subscale, K-SCT Interview Parent and Teacher subscales, and WMTB-C Central Executive component scores; in subjects with Dyslexia-only, atomoxetine versus placebo significantly improved K-SCT Youth subscale scores from baseline. At Week 32, atomoxetine-treated ADHD+D subjects significantly improved from baseline on all measures except MSCS Family subscale and WMTB-C Central Executive and Visuo-spatial Sketchpad component scores. The atomoxetine-treated dyslexia-only subjects significantly improved from baseline to week 32 on ADHDRS-IV-Parent:Inv Inattentive subscale, K-SCT Parent and Teacher subscales, and WMTB-C Phonological Loop and Central Executive component scores. The atomoxetine-treated ADHD-only subjects significantly improved from baseline to Week 32 on ADHDRS-Parent:Inv Total and subscales, ADHDRS-IV-Teacher-Version Hyperactive/Impulsive subscale, LPS Self-Control and Total, all K-SCT subscales, and MSCS Academic and Competence subscale scores.
Atomoxetine treatment improved ADHD symptoms in subjects with ADHD+D and ADHD-only, but not in subjects with dyslexia-only without ADHD. This is the first study to report significant effects of any medication on SCT.
Clinical Trials Registration
This study was registered at:, NCT00607919.
PMCID: PMC3842866  PMID: 24206099
17.  Atomoxetine for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children with ADHD and dyslexia 
The objective of this study was to assess the effects of atomoxetine on treating attention-deficit/hyperactivity disorder (ADHD), on reading performance, and on neurocognitive function in youth with ADHD and dyslexia (ADHD+D).
Patients with ADHD (n = 20) or ADHD+D (n = 36), aged 10-16 years, received open-label atomoxetine for 16 weeks. Data from the ADHD Rating Scale-IV (ADHDRS-IV), Kaufman Test of Educational Achievement (K-TEA), Working Memory Test Battery for Children (WMTB-C), and Life Participation Scale for ADHD-Child Version (LPS-C) were assessed.
Atomoxetine demonstrated significant improvement for both groups on the ADHDRS-IV, LPS-C, and K-TEA reading comprehension standard and composite scores. K-TEA spelling subtest improvement was significant for the ADHD group, whereas the ADHD+D group showed significant reading decoding improvements. Substantial K-TEA reading and spelling subtest age equivalence gains (in months) were achieved for both groups. The WMTB-C central executive score change was significantly greater for the ADHD group. Conversely, the ADHD+D group showed significant phonological loop score enhancement by visit over the ADHD group. Atomoxetine was well tolerated, and commonly reported adverse events were similar to those previously reported.
Atomoxetine reduced ADHD symptoms and improved reading scores in both groups. Conversely, different patterns and magnitude of improvement in working memory component scores existed between ADHD and ADHD+D patients. Though limited by small sample size, group differences in relation to the comparable changes in improvement in ADHD symptoms could suggest that brain systems related to the therapeutic benefit of atomoxetine in reducing ADHD symptoms may be different in individuals with ADHD+D and ADHD without dyslexia.
Trial Registration
Clinical Trial Registry: NCT00191048
PMCID: PMC2805604  PMID: 20003507
18.  Treatment Outcomes with Lisdexamfetamine Dimesylate in Children Who Have Attention-Deficit/Hyperactivity Disorder with Emotional Control Impairments 
The purpose of this study was to assess lisdexamfetamine dimesylate (LDX) treatment effects based on baseline emotional control dysfunction in children with attention-deficit/hyperactivity disorder (ADHD) categorized with or without impairments of executive function (EF) emotional control.
Post-hoc analyses of a 7 week, open-label LDX study in children with ADHD (American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision [DSM-IV-TR] defined) and impairments in EF control of emotional response. At baseline, participants were dichotomized by Behavior Rating Inventory of EF (BRIEF) emotional control domain T-scores of ≥65 (with impairment) or <65 (without impairment). ADHD Rating Scale-IV (ADHD-RS-IV), BRIEF Global Executive Composite and emotional control domain, Expression and Emotion Scale for Children (EESC) scores, Pearson correlations for BRIEF versus ADHD-RS-IV and EESC, and Clinical Global Impressions scores were assessed at baseline and end of study (week 7)/early termination (EOS/ET) by baseline category of BRIEF emotional control impairment. Safety assessments included treatment-emergent adverse events (TEAEs).
At baseline and EOS/ET, respectively, 53.0% and 20.7% met criteria for emotional control impairment. Participants with and without emotional control impairments had similar ADHD-RS-IV change scores. Mean (SD) change from baseline for those with and without emotional control impairments were −20.8 (12.89) and −14.6 (11.25) for BRIEF global scores and −16.0 (13.19) and −5.0 (9.48) for BRIEF emotional control domain scores. Participants with emotional control impairments had greater mean EESC total score changes. BRIEF emotional control domain and all ADHD-RS-IV scores indicated moderate correlations between change scores (all p<0.0001). Overall, 84.9% of participants had TEAEs (mostly mild-to-moderate in severity); 3.8% discontinued because of TEAEs.
The proportion of children with behavioral impairments in EF control of emotional response decreased during LDX treatment. ADHD symptoms improved in both groups. The moderate correlations between EF behaviors and ADHD symptoms suggest there may be utility in evaluating behavioral domains beyond core ADHD symptoms.
PMCID: PMC3749705  PMID: 23952185
19.  A Population-Based Study of Attention Deficit/Hyperactivity Disorder Symptoms and Associated Impairment in Middle-Aged Adults 
PLoS ONE  2012;7(2):e31500.
Attention deficit/hyperactivity disorder (ADHD) is the most prevalent childhood psychiatric condition. It frequently persists into adulthood and can have serious health and other adverse consequences. The majority of previous adult ADHD studies have focused on young adults so that relatively little is known about ADHD symptoms and their effects in mid and late life. In addition, effects of subclinical levels of attention deficit and hyperactivity have not been studied in detail. In this study we investigated ADHD symptoms and related impairment in a large population-based sample of middle-aged Australian adults (n = 2091; 47% male). Applying the WHO adult ADHD Self Report Screener (ASRS) we observed that 6.2% of participants had scores that were previously associated with ADHD diagnosis. No significant gender difference in the distribution of ASRS scores was observed. Multiple regression analyses indicated strong positive correlations between symptoms of ADHD and depression/anxiety and significant negative associations (p<0.01) with employment, financial stress, relationship quality, health and well-being measures in this age group. Importantly, associations were highly significant even when few ADHD symptoms were reported. Compared to the hyperactivity component, the inattention trait was particularly strongly associated and remained significant after controlling for depression/anxiety symptoms. Our study confirms previous findings and significantly adds to existing literature especially for an age-group that has not been well-studied. Our results suggest that ADHD symptoms continue to be associated with ill-health and functional impairment in mid-life and are, therefore, likely to be a major, previously unrecognized source of late-life morbidity with associated social and economic costs. Thus, there is a compelling need for better understanding and development of age-appropriate approaches to the diagnosis and treatment of ADHD in mid- to late-life.
PMCID: PMC3275565  PMID: 22347487
20.  ADHD in girls and boys – gender differences in co-existing symptoms and executive function measures 
BMC Psychiatry  2013;13:298.
ADHD is diagnosed and treated more often in males than in females. Research on gender differences suggests that girls may be consistently underidentified and underdiagnosed because of differences in the expression of the disorder among boys and girls. One aim of the present study was to assess in a clinical sample of medication naïve boys and girls with ADHD, whether there were significant gender x diagnosis interactions in co-existing symptom severity and executive function (EF) impairment. The second aim was to delineate specific symptom ratings and measures of EF that were most important in distinguishing ADHD from healthy controls (HC) of the same gender.
Thirty-seven females with ADHD, 43 males with ADHD, 18 HC females and 32 HC males between 8 and 17 years were included. Co-existing symptoms were assessed with self-report scales and parent ratings. EF was assessed with parent ratings of executive skills in everyday situations (BRIEF), and neuropsychological tests. The three measurement domains (co-existing symptoms, BRIEF, neuropsychological EF tests) were investigated using analysis of variance (ANOVA) and random forest classification.
ANOVAs revealed only one significant diagnosis x gender interaction, with higher rates of self-reported anxiety symptoms in females with ADHD. Random forest classification indicated that co-existing symptom ratings was substantially better in distinguishing subjects with ADHD from HC in females (93% accuracy) than in males (86% accuracy). The most important distinguishing variable was self-reported anxiety in females, and parent ratings of rule breaking in males. Parent ratings of EF skills were better in distinguishing subjects with ADHD from HC in males (96% accuracy) than in females (92% accuracy). Neuropsychological EF tests had only a modest ability to categorize subjects as ADHD or HC in males (73% accuracy) and females (79% accuracy).
Our findings emphasize the combination of self-report and parent rating scales for the identification of different comorbid symptom expression in boys and girls already diagnosed with ADHD. Self-report scales may increase awareness of internalizing problems particularly salient in females with ADHD.
PMCID: PMC3827008  PMID: 24206839
ADHD; Gender; Comorbidity; Executive functions; BRIEF
21.  Obesity in Men With Childhood ADHD: A 33-Year Controlled, Prospective, Follow-up Study 
Pediatrics  2013;131(6):e1731-e1738.
To compare BMI and obesity rates in fully grown men with and without childhood attention-deficit/hyperactivity disorder (ADHD). We predicted higher BMI and obesity rates in: (1) men with, versus men without, childhood ADHD; (2) men with persistent, versus men with remitted, ADHD; and (3) men with persistent or remitted ADHD versus those without childhood ADHD.
Men with childhood ADHD were from a cohort of 207 white boys (referred at a mean age of 8.3 years), interviewed blindly at mean ages 18 (FU18), 25 (FU25), and 41 years (FU41). At FU18, 178 boys without ADHD were recruited. At FU41, 111 men with childhood ADHD and 111 men without childhood ADHD self-reported their weight and height.
Men with childhood ADHD had significantly higher BMI (30.1 ± 6.3 vs 27.6 ± 3.9; P = .001) and obesity rates (41.4% vs 21.6%; P = .001) than men without childhood ADHD. Group differences remained significant after adjustment for socioeconomic status and lifetime mental disorders. Men with persistent (n = 24) and remitted (n = 87) ADHD did not differ significantly in BMI or obesity rates. Even after adjustment, men with remitted (but not persistent) ADHD had significantly higher BMI (B: 2.86 [95% CI: 1.22 to 4.50]) and obesity rates (odds ratio: 2.99 [95% CI: 1.55 to 5.77]) than those without childhood ADHD.
Children with ADHD are at increased risk of obesity as adults. Findings of elevated BMI and obesity rates in men with remitted ADHD require replication.
PMCID: PMC4074659  PMID: 23690516
ADHD; adults; BMI; longitudinal follow-up; obesity; weight
22.  Self-Reported quality of life in adults with attention-deficit/hyperactivity disorder and executive function impairment treated with lisdexamfetamine dimesylate: a randomized, double-blind, multicenter, placebo-controlled, parallel-group study 
BMC Psychiatry  2013;13:253.
This study examined the effects of lisdexamfetamine dimesylate (LDX) on quality of life (QOL) in adults with attention-deficit/hyperactivity disorder (ADHD) and clinically significant executive function deficits (EFD).
This report highlights QOL findings from a 10-week randomized placebo-controlled trial of LDX (30–70 mg/d) in adults (18–55 years) with ADHD and EFD (Behavior Rating Inventory of EF-Adult, Global Executive Composite [BRIEF-A GEC] ≥65). The primary efficacy measure was the self-reported BRIEF-A; a key secondary measure was self-reported QOL on the Adult ADHD Impact Module (AIM-A). The clinician-completed ADHD Rating Scale version IV (ADHD-RS-IV) with adult prompts and Clinical Global Impressions-Severity (CGI-S) were also employed. The Adult ADHD QoL (AAQoL) was added while the study was in progress. A post hoc analysis examined the subgroup having evaluable results from both AIM-A and AAQoL.
Of 161 randomized (placebo, 81; LDX, 80), 159 were included in the safety population. LDX improved AIM-A multi-item domain scores versus placebo; LS mean difference for Performance and Daily Functioning was 21.6 (ES, 0.93, P<.0001); Impact of Symptoms: Daily Interference was 14.9 (ES, 0.62, P<.0001); Impact of Symptoms: Bother/Concern was 13.5 (ES, 0.57, P=.0003); Relationships/Communication was 7.8 (ES, 0.31, P=.0302); Living With ADHD was 9.1 (ES, 0.79, P<.0001); and General Well-Being was 10.8 (ES, 0.70, P<.0001). AAQoL LS mean difference for total score was 21.0; for subscale: Life Productivity was 21.0; Psychological Health was 12.1; Life Outlook was 12.5; and Relationships was 7.3. In a post hoc analysis of participants with both AIM-A and AAQoL scores, AIM-A multi-item subgroup analysis scores numerically improved with LDX, with smaller difference for Impact of Symptoms: Daily Interference. The safety profile of LDX was consistent with amphetamine use in previous studies.
Overall, adults with ADHD/EFD exhibited self-reported improvement on QOL, using the AIM-A and AAQoL scales in line with medium/large ES; these improvements were paralleled by improvements in EF and ADHD symptoms. The safety profile of LDX was similar to previous studies.
Trial registration, NCT01101022
PMCID: PMC3854089  PMID: 24106804
Lisdexamfetamine dimesylate; LDX; ADHD; Quality of life; Executive function
23.  How Representative are Participants in a Clinical Trial for ADHD? Comparison With Adults From a Large Observational Study 
The Journal of clinical psychiatry  2010;71(12):1612-1616.
Clinical trials have demonstrated that pharmacotherapies can safely treat ADHD in adulthood. Eligibility criteria in these trials may significantly limit their external validity by excluding a significant portion of adults with ADHD in the general population. In particular, exclusion criteria may frequently exclude individuals with comorbid mental health conditions, which are common in the adult ADHD population.
The authors addressed the representativeness of clinical trials by comparing 146 adult Clinical Trial participants with DSM-IV ADHD, and a Community Sample comprised of 124 adults with DSM-IV ADHD and 123 non-ADHD controls. Subjects were compared on socioeconomic status, Hollingshead Occupational code, cognitive measures, lifetime psychopathology and global assessment of function (GAF) ratings.
Adults with ADHD in the Community Sample had higher rates of lifetime psychiatric comorbidity, lower GAF, and lower occupational codes than those in the Clinical Trial. The clinical trial eligibility criteria would have excluded 61% of Community Sample ADHD adults. This excluded portion of the Community sample had higher rates of lifetime psychiatric comorbidity and lower GAF than clinical trial participants.
Adults with ADHD participating in the Clinical Trial had less evidence of functional impairment and endorsed less psychiatric comorbidity than the majority of Community Sample subjects with ADHD. This suggests that findings from clinical trials may have limited external validity for adults with ADHD in the general population, particularly for those adults with ADHD with the greatest burden of comorbid psychopathology.
PMCID: PMC3737773  PMID: 20816030
24.  The Structure and Diagnosis of Adult ADHD: An Analysis of Expanded Symptom Criteria from the Adult ADHD Clinical Diagnostic Scale (ACDS) 
Archives of general psychiatry  2010;67(11):1168-1178.
Controversy exists about the appropriate criteria for a diagnosis of adult attention-deficit/hyperactivity disorder (ADHD)
To examine the structure and symptoms most predictive of DSM-IV adult ADHD.
Data come from clinical interviews in enriched sub-samples of the National Comorbidity Survey Replication (NCS-R) (n = 131) and a survey of a large managed healthcare plan (n = 214). The clinician-administered Adult ADHD Clinical Diagnostic Scale (ACDS) was used to assess childhood ADHD and expanded symptoms of current adult ADHD. Analyses examined stability of symptoms from childhood to adulthood, the structure of adult ADHD, and the adult symptoms most predictive of current clinical diagnoses.
The ACDS was administered telephonically by clinical research interviewers with extensive experience in diagnosis and treatment of adult ADHD.
An enriched sample of community respondents
DSM-IV/ACDS diagnoses of adult ADHD
Almost half (45.7%) of respondents who had childhood ADHD continued to meet full DSM-IV criteria for current adult ADHD, with 94.9% of these cases having current attention-deficit disorder and 34.6% current hyperactivity disorder. Adult persistence was much greater for inattention than hyperactivity-impulsivity. Additional respondents met full criteria for current adult ADHD despite not having met full childhood criteria. A three-factor structure of adult symptoms included executive functioning, inattention-hyperactivity, and impulsivity. Stepwise logistic regression found executive functioning problems to be the most consistent and discriminating predictors of adult DSM-IV/ACDS ADHD.
These findings document the greater persistence of inattentive than hyperactive/impulsive childhood symptoms of ADHD in adulthood, but also show that inattention in not specific to ADHD, as it is strongly associated with other adult mental disorders. Executive functioning problems, in comparison, are more specific and consistently important predictors of DSM-IV adult ADHD despite not being in DSM-IV, suggesting that the number of executive functioning symptoms should be increased in DSM-V/ICD-11.
PMCID: PMC3131739  PMID: 21041618
25.  Pediatric bipolar spectrum disorder and ADHD: comparison and comorbidity in the LAMS clinical sample 
Bipolar disorders  2011;13(5-6):509-521.
To compare attention-deficit hyperactivity disorder (ADHD), bipolar spectrum disorders (BPSD), and comorbidity in the Longitudinal Assessment of Manic Symptoms (LAMS) study.
Children ages 6–12 were recruited at first visit to clinics associated with four universities. A BPSD diagnosis required that the patient exhibit episodes. Four hypotheses were tested: (i) children with BPSD + ADHD would have younger age of mood symptom onset than those with BPSD but no ADHD; (ii) children with BPSD + ADHD would have more severe ADHD and BPSD symptoms than those with only one disorder; (iii) global functioning would be more impaired in children with ADHD + BPSD than children with either diagnosis alone; and (iv) the ADHD + BPSD group would have more additional diagnoses.
Of 707 children, 538 had ADHD, 162 had BPSD, 117 had both ADHD and BPSD, and 124 had neither. Comorbidity (16.5%) was slightly less than expected by chance (17.5%). Age of mood symptom onset was not different between the BPSD + ADHD group and the BPSD-alone group. Symptom severity increased and global functioning decreased with comorbidity. Comorbidity with other disorders was highest for the ADHD + BPSD group, but higher for the ADHD-alone than the BPSD-alone group. Children with BPSD were four times as likely to be hospitalized (22%) as children with ADHD alone.
The high rate of BPSD in ADHD reported by some authors may be better explained as a high rate of both disorders in child outpatient settings rather than ADHD being a risk factor for BPSD. Co-occurrence of the two disorders is associated with poorer global functioning, greater symptom severity, and more additional comorbidity than for either single disorder.
PMCID: PMC3201827  PMID: 22017220
ADHD; bipolar; comorbidity; impairment; severity

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