Acute aerobic exercise modulates cognition and cortical excitability in adults with attention-deficit hyperactivity disorder (ADHD) and healthy controls.

Evidence suggests aerobic exercise has beneficial effects on cognitive performance in adults with attention-deficit hyperactivity disorder (ADHD). The underlying mechanisms might depend on mechanisms of exercise-mediated brain physiology. The study aims to investigate the effects of acute aerobic exercise on cortical excitability and cognitive performance, and the correlation between these phenomena in adults with ADHD. Twenty-six drug-naïve ADHD adults, and twenty-six age-, and gender-matched healthy controls were assessed with respect to cortical excitability and cognitive performance before and after acute aerobic exercise (a single session for 30 min) or a control intervention. The results show significantly enhanced intracortical facilitation (ICF) and decreased short intracortical inhibition (SICI) after aerobic exercise in healthy subjects. In contrast, SICI was significantly enhanced following acute aerobic exercise in ADHD. In ADHD, furthermore inhibitory control and motor learning were significantly improved after the acute aerobic exercise intervention. Alterations of SICI induced by aerobic exercise, and inhibitory control and motor learning improvement were significantly positively correlated in the ADHD group. Aerobic exercise had partially antagonistic effects in healthy controls, and ADHD patients. Furthermore, aerobic exercise-induced cognition-enhancing effects in ADHD depend on specific alterations of brain physiology, which differ from healthy humans.

Acute aerobic exercise at different intensities modulates inhibitory control and cortical excitability in adults with attention-deficit hyperactivity disorder (ADHD).

BACKGROUND: This study aimed to investigate the effects of different aerobic exercise intensities on inhibitory control and cortical excitability in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: The study was conducted in a within-subject design. Twenty-four adults with ADHD completed a stop signal task and received cortical excitability assessment by transcranial magnetic stimulation (TMS) before and after a single session of low-, moderate-, high-intensity aerobic exercise or a control intervention. RESULTS: Acute moderate-, and high-intensity aerobic exercise improved inhibitory control in adults with ADHD. Moreover, the improving effect was similar between moderate-, and high-intensity aerobic exercise conditions. As shown by the brain physiology results, short interval intracortical inhibition was significantly increased following both, moderate- and high-intensity aerobic exercise intervention conditions. Additionally, the alteration of short interval intracortical inhibition and inhibitory control improvement were positively correlated. CONCLUSIONS: The moderate-, and high-intensity aerobic exercise-dependent alterations of cortical excitability in adults with ADHD might partially explain the inhibitory control-improving effects of aerobic exercise in this population.

Sex-differential patterns of neuropsychological functioning in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: The sex-differential prevalence of attention-deficit/hyperactivity disorder (ADHD) varies across the lifespan, but little is known about sex differences in executive functions in adults with ADHD. METHODS: We assessed 261 adults, aged 18-40 years, diagnosed with ADHD (170 males [assigned at birth], aged 25.81 ± 5.49; 91 females, aged 27.76 ± 5.42) and 308 neurotypical adults (176 males, aged 24.62 ± 5.14; 132 female, aged 25.37 ± 5.42) via psychiatric interviews to confirm ADHD and other psychiatric diagnoses. They were assessed by the Cambridge Neuropsychological Testing Automated Battery (CANTAB) on Reaction Time (arousal/processing speed), Rapid Visual Information Processing (sustained attention), Spatial Span (spatial memory), Spatial Working Memory, Intradimentional/Extradimensional Shift (set-shifting), and Stocking of Cambridge (spatial planning). The primary analyses were adjusted for age, full-scale IQ, and co-occurring psychiatric conditions. RESULTS: Adults with ADHD had various co-occurring psychiatric conditions without sex differences in ADHD-neurotypical differences. Both adult males and females with ADHD performed poorer in all CANTAB tasks than same-sex neurotypical adults. Significant sex-moderating effects were observed in neuropsychological performance, including greater ADHD-neurotypical differences in arousal for females than males and in location memory for spatial tasks in males than females. CONCLUSION: There were no sex-moderating effects in the presence of co-occurring psychiatric conditions in adult ADHD. However, there were sex-moderating effects on how ADHD related to neuropsychological functioning in adulthood. ADHD was associated with more challenges in arousal/processing speed in females and more challenges in strategy use or inhibition in spatial memory in males.

Altered White-matter Tract Property in Adults with Attention-deficit Hyperactivity Disorder.

Although altered microstructure properties of white-matter tracts have been reported in children with attention-deficit/hyperactivity disorder (ADHD), findings from relatively few adult ADHD studies are inconsistent. This study aims to examine microstructural property over the whole brain in adults with ADHD and explore structural connectivities. Sixty-four medication-naïve adults with ADHD and 81 healthy adults received diffusion spectrum imaging. Generalized fractional anisotropy (GFA), an index indicating microstructural property, was calculated stepwise among 76 white-matter tracts. With the threshold-free clustering weighted method, the segments with the largest group difference were selected, and mean GFA (mGFA) values were calculated. Adults with ADHD had increased mGFA values in the segments located in the left frontal aslant tract, the right inferior longitudinal fasciculus, and the left perpendicular fasciculus, and reduced mGFA values in the segments located in the right superior longitudinal fasciculus (SLF) I, the left SLF II, the right frontostriatal tracts from dorsolateral prefrontal cortex and the ventrolateral prefrontal cortex, the right medial lemniscus, the right inferior thalamic radiation to the auditory cortex, and the callosal fibers. Additionally, the mGFA value of the right SLF I segment was associated with hyperactivity-impulsivity symptoms. Our findings suggest that white-matter tracts with altered microstructure properties are located within the attention networks, fronto-striato-thalamocortical regions, and those associated with attention and visual perception in adults with ADHD.

Psychiatric comorbid patterns in adults with attention-deficit hyperactivity disorder: Treatment effect and subtypes.

Psychiatric comorbidities are common in individuals with attention-deficit/hyperactivity disorder (ADHD). In this study, we sought to evaluate the effects of medication and childhood ADHD subtypes on psychiatric comorbidities among adults with ADHD as compared to healthy adult controls. We assessed 121 drug-naïve adults with ADHD, 93 treated adults with ADHD, and 145 healthy controls (age 18-36 years) using semi-structured psychiatric interviews, intelligence tests, and medical records. Drug-naïve adults with ADHD had more comorbidities than treated adults with ADHD and controls. Childhood ADHD-combined subtype, relative to ADHD-inattentive subtype, was associated with higher risks of comorbidities. Current medication treatment was associate with a higher risk for anxiety disorders, and longer treatment duration was associated with lower risks of mood disorders and sleep disorders. Our results indicate that no medication treatment, short treatment duration, and childhood ADHD-combined subtype are associated with increased risks for psychiatric comorbidities among adults with ADHD.

Gender and Age Differences in Sleep Problems in Children: Person-Oriented Approach With Multigroup Analysis.

OBJECTIVE/BACKGROUND: This study aimed to identify subtypes of sleep problems in children and to examine whether these patterns differed between gender and age groups. PARTICIPANTS: There were 3,052 children (951 elementary school boys, 943 elementary school girls, 603 junior high school boys, and 555 junior high school girls) aged 7-16 years from two school-based epidemiological samples. METHODS: Sleep problems were measured by the Sleep Habit Questionnaire based on parent reports. RESULTS: Using the latent class modeling, a person-oriented approach, with a multigroup analysis, we identified four classes of sleep problems: moderate to high sleep problems (1.1%-3.1%), sleep-related breathing problems and parasomnias dominant (14.9%-21.1%), insomnias dominant and parasomnias (1.0%-3.1%), and no or low sleep problems (74.7%-81.4%), with varied prevalence rates of sleep problems across gender and age groups. CONCLUSIONS: This study identified four classes of sleep problems across gender and age groups but with different prevalence rates of sleep problems, suggesting the complex interaction of gender and age in the subtypes of sleep problems. The gender- and age-specific interventions for sleep problems are suggested. Future studies are warranted to replicate these classes and to identify associated factors with each class.

Differential brain activations in adult attention-deficit/ hyperactivity disorder subtypes: a counting Stroop functional MRI study.

Although previous functional neuroimaging studies have found abnormal brain activations in individuals with attention deficit hyperactivity disorder (ADHD), little was known about distinct brain dysfunctions across different ADHD subtypes. The objective of the present study was to investigate the abnormal brain activations associated with two ADHD subtypes, predominantly inattentive (ADHD-PI) and combined (ADHD-C) subtypes. Twenty-five adults with ADHD-PI, 25 with ADHD-C, and 30 healthy controls (HC) participated in this study. The brain function of the participants were assessed by using the counting Stroop task inside the scanner and the Conners' Continuous Performance Test (CCPT) outside the scanner. The HC group showed greater activations in the caudate nucleus and inferior frontal gyrus (IFG) than the ADHD-PI and ADHD-C groups. The ADHD-PI group showed greater activations in the superior parietal lobule (SPL) than the ADHD-C group. In all participants with ADHD, we found negative correlations of activation in the left caudate and the left IFG with the standard deviation of the reaction time of the CCPT, and negative correlations of activation in the left SPL with the reaction time changes across different inter-stimulus intervals. Our results demonstrated altered brain activity in the frontostriatal networks of adults with ADHD-PI and the fronto-striato-parietal networks of adults with ADHD-C. Abnormalities in the parietal areas may represent the main difference between the ADHD-PI and ADHD-C subtypes.

An Open-Label, Randomized Trial of Methylphenidate and Atomoxetine Treatment in Adults With ADHD.

OBJECTIVE: To directly compare the efficacy of methylphenidate and atomoxetine in improving symptoms, social functions, and quality of life among adults with ADHD. METHOD: This was an 8-to-10-week, open-label, head-to-head, randomized clinical trial with two treatment arms: immediate-release methylphenidate (IR-methylphenidate; n = 31) and atomoxetine once daily ( n = 32). The outcome measures included ADHD symptom severity, quality of life, and functional impairments. RESULTS: We found a significant reduction in overall ADHD symptoms and improvement in social functions and quality of life for both groups at Weeks 4 to 5 and Weeks 8 to 10. There was no significant difference in the slope of improvements over time except that atomoxetine was superior to IR-methylphenidate in reducing hyperactive/impulsive symptoms at Weeks 4 to 5. There was no significant group difference in the rates of adverse effects. CONCLUSION: Both IR-methylphenidate and atomoxetine are well tolerated and efficacious in ethnic Chinese adults with ADHD.

Atomoxetine could improve intra-individual variability in drug-naïve adults with attention-deficit/hyperactivity disorder comparably with methylphenidate: A head-to-head randomized clinical trial.

OBJECTIVE: Intra-individual variability in reaction time (IIV-RT) is common in individuals with attention-deficit/hyperactivity disorder (ADHD). It can be improved by stimulants. However, the effects of atomoxetine on IIV-RT are inconclusive. We aimed to investigate the effects of atomoxetine on IIV-RT, and directly compared its efficacy with methylphenidate in adults with ADHD. METHODS: An 8-10 week, open-label, head-to-head, randomized clinical trial was conducted in 52 drug-naïve adults with ADHD, who were randomly assigned to two treatment groups: immediate-release methylphenidate (n=26) thrice daily (10-20 mg per dose) and atomoxetine once daily (n=26) (0.5-1.2 mg/kg/day). IIV-RT, derived from the Conners' continuous performance test (CCPT), was represented by the Gaussian (reaction time standard error, RTSE) and ex-Gaussian models (sigma and tau). Other neuropsychological functions, including response errors and mean of reaction time, were also measured. Participants received CCPT assessments at baseline and week 8-10 (60.4±6.3 days). RESULTS: We found comparable improvements in performances of CCPT between the immediate-release methylphenidate- and atomoxetine-treated groups. Both medications significantly improved IIV-RT in terms of reducing tau values with comparable efficacy. In addition, both medications significantly improved inhibitory control by reducing commission errors. CONCLUSION: Our results provide evidence to support that atomoxetine could improve IIV-RT and inhibitory control, of comparable efficacy with immediate-release methylphenidate, in drug-naïve adults with ADHD. Shared and unique mechanisms underpinning these medication effects on IIV-RT awaits further investigation.

Psychiatric comorbidities of adults with early- and late-onset attention-deficit/hyperactivity disorder.

OBJECTIVE: We evaluated the psychiatric comorbidities in adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder as a function of recalled symptom onset before and after the age of 7 years and whether the childhood attention-deficit/hyperactivity disorder symptoms were associated with psychiatric comorbidities. METHOD: In all, 214 adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder and 174 non-attention-deficit/hyperactivity disorder controls (aged 17-40 years) received psychiatric interviews to confirm their previous and current attention-deficit/hyperactivity disorder status and other psychiatric diagnoses. Demographics and risks of lifetime psychiatric disorders were compared among three groups: (1) attention-deficit/hyperactivity disorder, onset <7 years (early-onset); (2) attention-deficit/hyperactivity disorder, onset between 7 and 12 years (late-onset) and (3) non-attention-deficit/hyperactivity disorder controls. We also tested the effects of attention-deficit/hyperactivity disorder symptoms on the risk of later psychiatric comorbidities by Cox regression analyses. RESULTS: Regardless of the age of onset, attention-deficit/hyperactivity disorder was significantly associated with a wide range of psychiatric comorbidities. There were similar comorbid patterns between early- and late-onset attention-deficit/hyperactivity disorder. Regardless of attention-deficit/hyperactivity disorder diagnosis, increased severity of attention-deficit/hyperactivity disorder symptoms was associated with higher risks of oppositional defiant disorder, conduct disorder, dysthymia and sleep disorder but not major depression, which was associated with the attention-deficit/hyperactivity disorder diagnosis. CONCLUSION: Our findings suggest that elevating the threshold of age of onset to 12 years in Diagnostic and Statistical Manual of Mental disorders, 5th edition would not over-diagnose attention-deficit/hyperactivity disorder in the adult population. Recalled childhood attention-deficit/hyperactivity disorder symptom severity was correlated with conduct disorder, oppositional defiant disorder, dysthymia and sleep disorders.

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

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

Prediction of childhood ADHD symptoms to quality of life in young adults: adult ADHD and anxiety/depression as mediators.

Childhood attention-deficit/hyperactivity disorder (ADHD) symptoms may persist, co-occur with anxiety and depression (ANX/DEP), and influence quality of life (QoL) in later life. However, the information about whether these persistent ADHD and ANX/DEP mediate the influence of childhood ADHD on adverse QoL in adulthood is lacking. This study aimed to determine whether adult ADHD symptoms and/or ANX/DEP mediated the association between childhood ADHD and QoL. We assessed 1382 young men aged 19-30 years in Taiwan using self-administered questionnaires for retrospective recall of ADHD symptoms at ages 6-12, and assessment of current ADHD and ANX/DEP symptoms, and QoL. We conducted mediation analyses and compared the values of mediation ratio (PM) by adding mediators (adult ADHD and ANX/DEP), individually and simultaneously into a regression model with childhood ADHD as an independent variable and QoL as a dependent variable. Our results showed that both adult ADHD and ANX/DEP symptoms significantly mediated the association between childhood ADHD and QoL (PM=0.71 for ANX/DEP, PM=0.78 for adult ADHD symptoms, and PM=0.91 for both). The significance of negative correlations between childhood ADHD and four domains of adult QoL disappeared after adding these two mediators in the model. Our findings suggested that the strong relationship between childhood ADHD and adult life quality can be explained by the presence of persistent ADHD symptoms and co-occurring ANX/DEP. These two mediators are recommended to be included in the assessment and intervention for ADHD to offset the potential adverse life quality outcome in ADHD.

A head-to-head randomized clinical trial of methylphenidate and atomoxetine treatment for executive function in adults with attention-deficit hyperactivity disorder.

Results regarding the effects of methylphenidate and atomoxetine on executive functions were inconsistent and no study has directly compared the efficacy of these two medications in improving executive functions in adults with attention-deficit hyperactivity disorder (ADHD). We conducted an 8-10 wk, open-label, head-to-head, randomized clinical trial involving adults with a clinical diagnosis of ADHD confirmed by psychiatric interview. The two treatment arms were immediate-release methylphenidate (IR-methylphenidate) (n = 31) and atomoxetine once daily (n = 32). Executive functions were assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB), including spatial working memory, spatial span, intra-extra dimensional set shifts, rapid visual information processing and Stockings of Cambridge (SOC). In addition to the symptom assessments at baseline (week 0), visit 2 (week 4-5) and visit 3 (week 8­10), they received CANTAB assessments at baseline and visit 3 (60.4 ± 6.3 d). Compared to baseline, adults treated with atomoxetine showed significant improvement in spatial working memory, spatial short-term memory, sustained attention and spatial planning at visit 3; adults treated with IR-methylphenidate showed significant improvement in spatial working memory at visit 3. Comparing the magnitude of improvement in executive functions between these two medications, the effect was generally similar for the two groups, although atomoxetine might have significantly greater efficacy than IR-methylphenidate in terms of improving spatial planning (SOC). Our results provide evidence to support that both IR-methylphenidate and atomoxetine improved various executive functions in adults with ADHD with greater improvement in atomoxetine than IR-methylphenidate in spatial planning.

Psychiatric comorbidities in adolescents with attention-deficit hyperactivity disorder and their siblings.

OBJECTIVE: Despite high psychiatric comorbidities in adolescents with clinical diagnosis of attention-deficit hyperactivity disorder (ADHD), little is known about psychiatric comorbidities in their siblings. We investigated the psychiatric comorbid conditions in adolescents with ADHD, their siblings, and healthy control subjects from their school. METHOD: The sample included 136 adolescent probands with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), diagnostic criteria; 136 siblings (47 affected and 89 unaffected) and 136 age- and sex-matched healthy school control subjects. All participants and their parents received the structured psychiatric interviews for current and lifetime DSM-IV psychiatric disorders of the participants. RESULTS: The rate of ADHD (34.6%) in the siblings of probands with ADHD was about 7 times higher than in the general population. Probands with ADHD were significantly more likely than unaffected siblings (OR 6.38; 95% CI 3.43 to 11.88) and healthy school control subjects (OR 9.60; 95% CI 5.31 to 17.34) to have a DSM-IV psychiatric disorder, including oppositional defiant disorder (ODD), conduct disorder (CD), tic disorders, major depressive disorder, specific phobia (more than control subjects only), nicotine use disorder, and sleep disorders. The affected siblings were significantly more likely than healthy school control subjects to have ODD, CD, specific phobia, and to have consumed alcohol (ORs ranging from 2.30 to 20.16). CONCLUSIONS: Our findings suggest that siblings of probands with ADHD have increased risks for ADHD and that the affected siblings have more psychiatric comorbidities than healthy school control subjects. It warrants early identification of ADHD symptoms and other psychiatric comorbid conditions as well in siblings of adolescents with ADHD.