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Objectives: To test the retinal dopaminergic hypothesis, which posits deficient blue color perception in ADHD, resulting from hypofunctioning CNS and retinal dopamine, to which blue cones are exquisitely sensitive. Also, purported sex differences in red color perception were explored., Methods: 30 young adults diagnosed with ADHD and 30 healthy young adults, matched on age and gender, performed a psychophysical task to measure blue and red color saturation and contrast discrimination ability. Visual function measures, such as the Visual Activities Questionnaire (VAQ) and Farnsworth-Munsell 100 hue test (FMT), were also administered., Results: Females with ADHD were less accurate in discriminating blue and red color saturation relative to controls but did not differ in contrast sensitivity. Female control participants were better at discriminating red saturation than males, but no sex difference was present within the ADHD group., Conclusion: Poorer discrimination of red as well as blue color saturation in the female ADHD group may be partly attributable to a hypo-dopaminergic state in the retina, given that color perception (blue-yellow and red-green) is based on input from S-cones (short wavelength cone system) early in the visual pathway. The origin of female superiority in red perception may be rooted in sex-specific functional specialization in hunter-gather societies. The absence of this sexual dimorphism for red colour perception in ADHD females warrants further investigation.

Background: To investigate the impact of exogenous covert attention on chromatic (blue and red) and achromatic visual perception in adults with and without Attention Deficit Hyperactivity Disorder (ADHD). Exogenous covert attention, which is a transient, automatic, stimulus-driven form of attention, is a key mechanism for selecting relevant information in visual arrays., Methods: 30 adults diagnosed with ADHD and 30 healthy adults, matched on age and gender, performed a psychophysical task designed to measure the effects of exogenous covert attention on perceived color saturation (blue, red) and contrast sensitivity., Results: The effects of exogenous covert attention on perceived blue and red saturation levels and contrast sensitivity were similar in both groups, with no differences between males and females. Specifically, exogenous covert attention enhanced the perception of blue saturation and contrast sensitivity, but it had no effect on the perception of red saturation., Conclusion: The findings suggest that exogenous covert attention is intact in adults with ADHD and does not account for the observed impairments in the perception of chromatic (blue and red) saturation.

Background: An open-label pilot study of individualized homeopathy for attention deficit hyperactivity disorder (ADHD) was conducted to assess the potential for future studies with a focus on the feasibility of the recruitment plan and outcome measure schedules; identification of any group characteristics of participants who respond significantly to the therapy; and establishing the length of time required for an improvement in ADHD symptoms., Patients and Methods: Participants (aged 6-16) were recruited through community advertisement and outreach. Participants completed 1 screening and 9 individualized homeopathic follow-up consultations. ADHD symptoms were assessed using the Conners 3 - Parent Questionnaire administered at each consultation. The pre- and post-study difference in Conners Global Index - Parent (CGI-P) T-score was evaluated for each participant. Baseline data of those who showed a statistically significant improvement (responders) were compared to those who did not (non-responders)., Results: 35 participants were enrolled over 11 months. 80% completed all 10 consultations in a median of 12.1 months. 63% had a statistically significant improvement in the primary outcome, first occurring after a mean of 4.5 visits. Overall scores for participants completing at least 2 data points decreased from a baseline median of 85.5 to 74.0 (p < 0.001, CI 95%). There were no significant baseline differences between responders and non-responders. No serious adverse events related to the therapy were reported., Conclusion: The change in the median CGI-P T-score from baseline to the end of this open-label pilot study was statistically significant. The research methods are feasible. Future studies are warranted., Trial Registration: NCT01141634., (© 2014 S. Karger GmbH, Freiburg.)

Purpose: The purpose of this study is to examine the relationships among self-reported screening measures of attention deficit hyperactivity disorder (ADHD), other psychiatric problems, and driving-related outcomes in a provincially representative sample of adults 18 years and older living in the province of Ontario, Canada., Methods: The study examined the results of the Centre for Addictions and Mental Health (CAMH) Ontario Monitor, an ongoing repeated cross-sectional telephone survey of Ontario adults over a 2-year period. Measures included ADHD measures (Adult ADHD Self-Report Scale-V1.1 [ASRS-V1.1], previous ADHD diagnosis, ADHD medication use); psychiatric distress measures (General Health Questionnaire [GHQ12], use of pain, anxiety, and depression medication); antisocial behavior measure (The Antisocial Personality Disorder Scale from the Mini-International Neuropsychiatric Interview [APD]); substance use and abuse measures (alcohol, cannabis, and cocaine), Alcohol Use Disorders Identification Test (AUDIT), Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), driving-related outcomes (driving after drinking, driving after cannabis use, street racing, collisions in past year), and sociodemographics (gender, age, vehicle-kilometers traveled)., Results: A total of 4,014 Ontario residents were sampled, of which 3,485 reported having a valid driver's license. Overall, 3.22% screened positive for ADHD symptoms on the ASRS-V1.1 screening tool. A greater percentage of those who screened positive were younger, reported previous ADHD diagnosis and medication use, distress, antisocial behavior, anti-anxiety and antidepressant medication use, substance use, and social problems compared to those who screened negative. However, there were no statistically significant differences between those who screened positive or negative for ADHD symptoms on self-reported driving after having 2 or more drinks in the previous hour; within an hour of using cannabis, marijuana, or hash; or in a street race or collision involvement as a driver in the past year. When a sequential regression was conducted to predict self-reported collisions, younger age and higher weekly kilometers driven showed higher odds of collision involvement, and the odds ratio for cannabis use ever approached statistical significance., Discussion: This study is the first population-based study of a representative sample of adults 18 years and older living in Ontario, Canada. These results showed no relationship between the ADHD screen and collision when age, sex, and kilometers driven are controlled for. However, these analyses are based on self-report screeners and not psychiatric diagnoses and a limited sample of ADHD respondents. Thus, these results should be interpreted with caution.

Objectives: Although sleep disorders have been reported to affect more than half of adults with attention-deficit/hyperactivity disorder (ADHD), the association between sleep and ADHD is poorly understood. The aims of our study were to investigate sleep-related variables in adults with ADHD and to assess if any differences exist between ADHD of the predominantly inattentive (ADHD-I) and combined (ADHD-C) subtypes., Methods: We used the Epworth sleepiness scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and the fatigue severity scale (FSS) to collect data on daytime sleepiness, sleep quality, and fatigue in 126 subjects (45 ADHD-I and 81 ADHD-C subjects)., Results: Approximately 85% of subjects reported excessive daytime sleepiness or poor sleep quality. The most common sleep concerns were initial insomnia, interrupted sleep, and feeling too hot. When examining ADHD subtype differences, ADHD-I subtypes reported poorer sleep quality and more fatigue than ADHD-C subtypes. Partial correlation analyses revealed that interrelationships between sleep quality, daytime sleepiness, and fatigue differ between ADHD subtypes; in ADHD-I subtypes fatigue was associated with sleep quality, while in the ADHD-C subtypes fatigue was associated with both sleep quality and daytime sleepiness. There also appears to be a subtype×gender interaction that affects the perception of fatigue, as subjective fatigue was markedly higher in ADHD-I women than in ADHD-C women., Conclusion: Altogether our data indicate that the interplay of variables associated with daytime function and sleep varies between ADHD subtypes. This finding may have considerable relevance in the management and pathophysiologic understanding of ADHD, and thus lead to tailored treatments for ADHD subtypes., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

The understanding that sleep can give rise to, or exacerbate symptoms of attention-deficit/hyperactivity disorder (ADHD), and that good sleep hygiene improves attention and concentration tasks has sparked interest in the investigation of possible etiological relationships between sleep disorders and ADHD. Studies indicate that 30% of children and 60-80% of adults with ADHD have symptoms of sleep disorders such as daytime sleepiness, insomnia, delayed sleep phase syndrome, fractured sleep, restless legs syndrome, and sleep disordered breathing. The range and diversity of findings by different researchers have posed challenges in establishing whether sleep disturbances are intrinsic to ADHD or whether disturbances occur due to co-morbid sleep disorders. As a result, understanding of the nature of the relationship between sleep disturbances/disorders and ADHD remains unclear. In this review, we present a comprehensive and critical account of the research that has been carried out to investigate the association between sleep and ADHD, as well as discuss mechanisms that have been proposed to account for the elusive relationship between sleep disturbances, sleep disorders, and ADHD., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Increasing evidence suggests that symptoms of attention deficit hyperactivity disorder (ADHD) could persist into adult life in a substantial proportion of cases. The aim of the present study was to investigate the impact of (1) adverse events, (2) personality traits and (3) genetic variants chosen on the basis of previous findings and (4) their possible interactions on adult ADHD severity. One hundred and ten individuals diagnosed with adult ADHD were evaluated for occurrence of adverse events in childhood and adulthood, and personality traits by the Temperament and Character Inventory (TCI). Common polymorphisms within a set of nine important candidate genes (SLC6A3, DBH, DRD4, DRD5, HTR2A, CHRNA7, BDNF, PRKG1 and TAAR9) were genotyped for each subject. Life events, personality traits and genetic variations were analyzed in relationship to severity of current symptoms, according to the Brown Attention Deficit Disorder Scale (BADDS). Genetic variations were not significantly associated with severity of ADHD symptoms. Life stressors displayed only a minor effect as compared to personality traits. Indeed, symptoms' severity was significantly correlated with the temperamental trait of Harm avoidance and the character trait of Self directedness. The results of the present work are in line with previous evidence of a significant correlation between some personality traits and adult ADHD. However, several limitations such as the small sample size and the exclusion of patients with other severe comorbid psychiatric disorders could have influenced the significance of present findings., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Adults with ADHD smoke cigarettes at a higher rate than normal subjects. Nicotine has been shown to significantly improve clinical ADHD symptoms as measured by the Clinical Global Impression scale (CGI) as well as by measures of attention, vigour and arousal in ADHD subjects. In this study we hypothesized that the allele 113bp in D15S1360 marker at CHRNA7 and the 2 bp deletion allele at CHRFAM7A are associated with increased smoking in a sample of 90 DSM-IV patients affected by Adult ADHD. Temperament and Character Inventory (TCI) scores were included as covariates in the analysis to distinguish the contribution of personality traits from the contribution of the nicotinic genes under investigation. Smoking status was determined from the medical history questionnaire, and there were 35 current smokers and 55 non-smokers. Single marker associations and the CHRNA7-CHRFAM7A interaction were calculated by logistic regression, considering the 113 bp and the -2 bp deletion in a dominant model. No association of these genes with smoking was observed. Similarly, no significant interaction between the genes was observed in the logistic model. However, Persistence score of the TCI was significantly associated with smoking status. Further investigation on the hypothesis of the molecular interaction between CHRNA7 and CHRFAM7A genes is warranted.

To examine the unity and diversity of inattention and hyperactivity/impulsivity symptom domains of Attention-Deficit/Hyperactivity Disorder (ADHD) in a clinical sample of adolescents with ADHD. Parents and adolescents were administered a semi-structured diagnostic interview, the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL), to assess adolescent ADHD. Data from 201 parent interviews and 189 adolescent interviews were examined. Four potential factor structures for the 18 ADHD symptoms were tested using confirmatory factor analysis: two models with correlated factors and two bifactor models. A bifactor model with two specific factors best accounted for adolescent symptoms, according to both parent and adolescents' reports. Replication of these findings from behavioral rating scales completed for this sample by parents and teachers indicates that the findings are not method- or informant-specific. The results suggest that there is an important unitary component to ADHD symptoms and separable dimensional traits of Inattention and Hyperactivity/Impulsivity.

Performance-based measures and ratings of executive functions were examined in a sample of adolescents with attention deficit/hyperactivity disorder (ADHD) and comparison controls. Performance-based measures of executive function included inhibition, working memory, set shifting, and planning, and ratings of these same executive functions were completed by parents and teachers. Adolescents with ADHD demonstrated lower executive function performance than controls and displayed elevated ratings on the executive function ratings by parents and teachers. Significant associations were obtained between the performance-based measures and the parent and teacher ratings, but each measure was not uniquely associated with its respective scale on the rating scales. When performance-based measures and ratings were examined as predictors of ADHD status, the parent and teacher ratings entered as significant predictors of ADHD status. Further commonality analyses indicated that performance-based measures accounted for little unique variance in predicting ADHD status and also displayed little overlap with the behavioral ratings. These findings highlight the diagnostic utility of behavioral ratings of executive function in predicting ADHD status; however, behavioral ratings should not be assumed to be a proxy for performance on measures of executive function in clinical practice.

Childhood attention deficit hyperactivity disorder (ADHD) symptomatology persists in a substantial proportion of cases into adult life. ADHD is highly heritable but the etiology of ADHD is complex and heterogeneous, involving both genetic and non-genetic factors. In the present article we analyzed the influence of both genetics and adverse life events on severity of ADHD symptoms in 110 adult ADHD patients. Subjects were genotyped for the norepinephrine transporter (NET), the catechol-O-methyltransferase (COMT), the serotonin transporter promoter polymorphism (SERTPR) and the more rare A/G variant within SERTPR. Three main outcomes were obtained: (1) adverse events showed a small but positive correlation with current ADHD severity; (2) NET, COMT and the A/G variant within SERTPR were not associated with ADHD severity; (3) taking into account stressors, the long (L) SERTPR variant showed a mild effect on ADHD, being associated with an increased severity, particularly as regard affective dysregulations; on the other hand, in subjects exposed to early stressors, it showed a protective effect, as compared to the short (S) variant. In conclusion, our data support the role of environmental factors in adult ADHD symptomatology. SERTPR may be involved in some features of the illness and act as a moderator of environmental influences in ADHD., (Copyright 2008 Wiley-Liss, Inc.)

Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder with a large genetic component that has been shown to persist into adulthood in 30-60% of childhood ADHD cases. Adult ADHD confers an increased risk of ADHD in relatives when compared to childhood ADHD, possibly due to a greater genetic liability than the childhood form. Brain-derived neurotrophic factor (BDNF) is a neurotrophin expressed in the brain throughout life and is involved in survival, differentiation, and synaptic plasticity of several neuronal systems including dopaminergic pathways. Mammalian LIN-7 homolog is selectively expressed in specific neuronal populations and is involved in the postsynaptic density of neuronal synapses. LIN-7 is also a positional candidate, as it lies immediately downstream of BDNF. We tested for association between five BDNF polymorphisms, two LIN-7 polymorphisms and adult ADHD. The sample consisted of 80 trios comprised of an adult ADHD proband and their biological parents and an independent sample of 121 adult ADHD cases and a corresponding number of sex, age, and ethnically matched controls (total 201 probands). Allelic and haplotype association was found between both BDNF and adult ADHD, and LIN-7 and adult ADHD. HapMap indicates BDNF and LIN-7 occur in different haplotype blocks, though some linkage disequilibrium exists between the SNPs in these adjacent genes. Further investigations into the pathologic mechanisms of BDNF and LIN-7 in adult ADHD are required., (2008 Wiley-Liss, Inc.)

Several lines of evidence from neuroimaging, pharmacology and genetics support the involvement of the dopaminergic system in the etiology of Attention Deficit Hyperactivity Disorder (ADHD). Previous candidate gene studies have investigated the association between a dinucleotide (CA)(n) repeat polymorphism, located 18.5 kb from the start codon of the DRD5 gene, and ADHD. Association between the 148 bp allele and ADHD has been reported in some studies, however replication of the finding has not been consistent. We tested for an association between the (CA)(n) repeat and adult ADHD in a sample comprised of 119 families with adult ADHD probands and 88 unrelated adult ADHD cases with a corresponding number of controls matched for age, ethnicity and sex. In the family sample we found a non-significant trend for association between the 148 bp allele and ADHD (Z=1.91, p=0.055). An excess of non-transmissions was detected for the 150 and 152bp alleles (Z=-2.26, p=0.023; Z=-2.20, p=0.028). Quantitative analysis performed using the Brown Attention Deficit Disorder Scale (BADDS) showed association between the 150 bp allele and lower total score (p=0.011), and lower effort (p=0.008), activation (p=0.008) and attention (p=0.01) cluster scores. We did not replicate association findings in the case-control group, likely due to the lack of statistical power of this sample. Our findings add to the literature suggesting DRD5 (CA)(n) repeat has a modest effect in modulating susceptibility to adult ADHD but further studies are required.

Objective: The objective of the study was to measure both seasonal mood change and circadian preference, and their clinical and neuropsychological correlates, in adults with ADHD during the fall/winter months., Method: Twenty-nine adults with attention-deficit/hyperactivity disorder (ADHD) were assessed in the fall/winter season using self-report measures of ADHD, mood, seasonality, and circadian preference. Neuropsychological tests were also completed. Correlations between chronobiologic variables and clinical/neuropsychological measures were performed., Results: Consistent with prior work in adult ADHD, high rates of seasonal depression were reported in this sample. Based on the morningness-eveningness questionnaire, which assesses circadian preference 11 (40.7%, N = 27) subjects were designated as evening types and only 5 (18.5%) as morning types, a distribution highly discrepant with general population studies. Later circadian preference, independent of seasonality, was strongly correlated with both self-reported symptoms of ADHD and neuropsychological deficits, including impulsive responding and poor target discrimination. None of these findings was attributable to state depression., Conclusions: In the fall/winter period, a mood-independent delay in circadian phase may contribute significantly to core pathology in many adults with ADHD. These findings establish a potential target for chronobiologic treatments such as light therapy in this complex population.

Objective: The purpose of this study was to evaluate the comparative efficacy and safety of a novel long-duration multilayer-release (MLR) methylphenidate (MPH) formulation and immediate-release (IR) MPH in attention-deficit/hyperactivity disorder (ADHD) children., Patients and Methods: This study was a randomized, double-blind, crossover comparison of once-daily MLR and twice-daily IR-MPH in home and school settings in children with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of ADHD. Patients completed a 1-week baseline followed by two active medication titration phases. Each phase of treatment was 1-4 weeks of titration with an additional stable dose week. The final dose was based on efficacy and adverse events for each patient. Efficacy measures included Clinical Global Impressions (CGI) and Conners' Parent and Teacher Rating Scales (CPRS and CTRS). The Clinical Assessment of Side Effects (CASE) scale assessed frequency of adverse events., Results: Of the 90 enrolled patients, aged 6.4-17.5 years, 79 (88%) completed the study. Stable daily doses were 32.0 and 32.5 mg for MLR and IR-MPH, respectively. All efficacy parameters were significantly improved from baseline. A total of 73.2% and 81.0% of patients on MLR and IR-MPH were rated as "much" or "very much improved" on the CGI. A total of 77.4% and 81.1% of patients were normalized on the CPRS-R and 78.9 and 90.4% of patients were normalized on the CTRS-R for MLR and IR-MPH, respectively. The mean CASE score was not different from baseline for either treatment.

Background: To investigate the effects of methylphenidate (MPH) on components of working memory (WM) in attention-deficit hyperactivity disorder (ADHD) and determine the responsiveness of WM measures to MPH., Methods: Participants were a clinical sample of 50 children and adolescents with ADHD, aged 6 to 16 years old, who participated in an acute randomized, double-blind, placebo-controlled, crossover trial with single challenges of three MPH doses. Four components of WM were investigated, which varied in processing demands (storage versus manipulation of information) and modality (auditory-verbal; visual-spatial), each of which was indexed by a minimum of two separate measures., Results: MPH improved the ability to store visual-spatial information irrespective of instrument used, but had no effects on the storage of auditory-verbal information. By contrast, MPH enhanced the ability to manipulate both auditory-verbal and visual-spatial information, although effects were instrument specific in both cases., Conclusions: MPH effects on WM are selective: they vary as a function of WM component and measurement.

Objective: To evaluate the efficacy and safety of a new biphasic multilayer-release (MLR) methylphenidate formulation in a double-blind, placebo-controlled crossover study of adults with attention-deficit/hyperactivity disorder (ADHD)., Method: Adults 18 to 60 years of age with a DSM-IV diagnosis of ADHD entered a no-medication baseline week and were then randomly assigned to once-daily MLR methylphenidate or matching placebo. Patients were titrated to optimal effect over 1 to 3 weeks followed by 2 weeks of treatment on a stable dose. The same titration protocol was repeated with the alternate treatment. Clinical Global Impressions scale (CGI) and Conners' Adult ADHD Rating Scales (Self-rated, CAARS-S, and Observer-rated, CAARS-O) were collected at weekly clinic visits. The study was conducted between October 2003 and April 2004., Results: Fifty patients were randomly assigned to treatment, and 39 were analyzed in a per-protocol population (23 men, 16 women; mean age = 37.9 years). CGI-Improvement scores of subjects taking MLR methylphenidate were significantly improved compared with placebo (Global Improvement: 2.6 vs. 3.7; p = .0015). MLR methylphenidate produced improvements over placebo on the ADHD Index T scores of the CAARS-S (12.2 vs. 5.4 [change from baseline score]; p = .0083) and the CAARS-O (10.9 vs. 6.6 [change from baseline score]; p = .1404). The most frequent adverse events for MLR methylphenidate and placebo were headache (26% and 24%, respectively), anorexia (22% and 6%), insomnia (22% and 8%), nervousness (20% and 4%), and nausea (16% and 8%). There were no serious adverse events., Conclusions: Once-daily MLR methylphenidate produces significant improvements in ADHD symptoms and situational behavior in adult patients with ADHD, with a prolonged duration of effect and minimal side effects, thus having the potential to improve compliance and, therefore, treatment outcomes in routine clinical use.

Background: Dopaminergic neurotransmission is implicated in externalizing behavior problems, such as aggression and hyperactivity. Externalizing behavior is known to be negatively associated with cognitive ability. Activation of dopamine D4 receptors appears to inhibit the functioning of the prefrontal cortex, a brain region implicated in cognitive ability. The 7-repeat allele of the dopamine D4 receptor gene produces less efficient receptors, relative to other alleles, and this may alter the effects of dopamine on cognitive function., Objective: To examine the influence of a polymorphism in the third exon of the dopamine D4 receptor gene on the association between externalizing behavior and IQ., Design: In 1 community sample and 2 clinical samples, the presence or absence of the 7-repeat allele was examined as a moderator of the association between externalizing behavior and IQ; the strength of this effect across samples was estimated meta-analytically., Patients: Eighty-seven boys from a longitudinal community study, 48 boys referred clinically for aggression, and 42 adult males diagnosed with attention-deficit/hyperactivity disorder., Main Outcome Measures: IQ scores and observer ratings of externalizing behavior were taken from existing data sets., Results: Among individuals lacking the 7-repeat allele, externalizing behavior was negatively correlated with IQ (mean r = -0.43; P<.001). Among individuals having at least 1 copy of the 7-repeat allele, externalizing behavior and IQ were uncorrelated (mean r = 0.02; P = .45). The difference between these correlations was significant (z = -2.99; P<.01)., Conclusions: Allelic variation of the dopamine D4 receptor gene appears to be a genetic factor moderating the association between externalizing behavior and cognitive ability. This finding may help to elucidate the adaptive value of the 7-repeat allele.

Objective: In adults with attention-deficit/ hyperactivity disorder (ADHD), a delayed sleep/ activity rhythm and/or seasonal mood symptoms may contribute significantly to core pathology and disability. This study examined whether a chronobiologically based treatment, i.e., morning bright light therapy (LT), might have utility as an adjunctive treatment for adult ADHD in the fall/ winter period., Method: Twenty-nine adults with DSM-IV ADHD were administered a standard 3-week open trial of LT during the fall or winter months. Primary outcome measures included percentage reduction on the Brown Adult ADD Scale and the Conners' Adult ADHD Scale. Secondary measures were decrease in depression scores according to the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorder version; improvements on various neuropsychological tests; and shift toward an earlier circadian preference as measured by the Horne-Ostberg Morningness-Eveningness questionnaire. Regression analyses determined which variables at baseline best predicted improvement on a given outcome measure and which variables changed in parallel with one another. The study was conducted from November 2003 through February 2004., Results: Morning bright light therapy was associated with a significant decrease in both subjective and objective measures of core ADHD pathology, improved mood symptoms, and a significant phase advance in circadian preference. Multiple regression showed that the shift toward an earlier circadian preference with LT was the strongest predictor of improvement on both subjective and objective ADHD measures. Neither baseline global seasonality scores nor baseline depression scores strongly predicted LT effects on most measures of ADHD., Conclusion: These findings suggest that during the fall/winter period, LT may be a useful adjunct in many adults with ADHD. Strikingly, the strongest correlate of improvement in core ADHD pathology was a phase advance in circadian preference rather than alleviation of comorbid seasonal affective disorder, suggesting important clinical benefits of LT beyond the treatment of seasonal affective disorder.

Reading comprehension is a very complex task that requires different cognitive processes and reading abilities over the life span. There are fewer studies of reading comprehension relative to investigations of word reading abilities. Reading comprehension difficulties, however, have been identified in two common and frequently overlapping childhood disorders: reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD). The nature of reading comprehension difficulties in these groups remains unclear. The performance of four groups of adolescents (RD, ADHD, comorbid ADHD and RD, and normal controls) was compared on reading comprehension tasks as well as on reading rate and accuracy tasks. Adolescents with RD showed difficulties across most reading tasks, although their comprehension scores were average. Adolescents with ADHD exhibited adequate single word reading abilities. Subtle difficulties were observed, however, on measures of text reading rate and accuracy as well as on silent reading comprehension, but scores remained in the average range. The comorbid group demonstrated similar difficulties to the RD group on word reading accuracy and on reading rate but experienced problems on only silent reading comprehension. Implications for reading interventions are outlined, as well as the clinical relevance for diagnosis.

Numerous family, twin and adoption studies have reported a strong genetic component for attention deficit hyperactivity disorder (ADHD). In addition, an extensive amount of literature has implicated abnormalities of the dopaminergic system. In view of this evidence, genes that influence dopaminergic transmission have become prime candidates for molecular genetic investigations of ADHD. There are currently three studies (Daly et al., 1999; Roman et al., 2002; Wigg et al., 2002) that have found an association between the dopamine beta-hydroxylase gene (DBH) TaqI 2 allele and childhood ADHD. As such, we tested for association of the DBH TaqI 2 allele in two independent samples of patients with the persistent variant of ADHD. These consisted of 97 nuclear families, and 112 adult cases with controls carefully matched according to gender, age and ethnicity. Transmission Disequilibrium Test analysis revealed weak over-transmission of the 2 allele (35 transmissions versus 27 non-transmissions; chi2 = 1.03, 1 degree of freedom, P=0.31). The case-control sample did not support previous findings since the 2 allele was more frequent in our control sample (137 versus 116; chi2 = 3.63, 1 degree of freedom, P=0.057). Taken together, these results do not provide support for a role of the DBH TaqI marker in our persistent ADHD samples.

Attention deficit hyperactivity disorder (ADHD) is a chronic psychiatric condition in children and follow up studies have indicated that one to two thirds of patients continue to suffer from ADHD during late adolescence and adulthood. Pharmacological interventions, such as the new selective noradrenergic reuptake inhibitor, atomoxetine, suggest the adrenergic system as candidate in ADHD. We examined for the presence of linkage disequilibrium between the alpha 2C adrenergic receptor (ADRA2C) microsatellite polymorphism upstream of the ADRA2C gene and adult ADHD in a sample of nuclear families. We also present new information on the genomic organization of the ADRA2C locus. The microsatellite polymorphism was typed in 128 small families and analyzed using the Transmission Disequilibrium Test (TDT). There was no preferential transmission of any allele. These findings exclude a strong effect of this ADRA2C marker on risk for ADHD in our sample of adult proband families., (Copyright 2004 Wiley-Liss, Inc.)

Attention deficit hyperactivity disorder (ADHD) is a prevalent psychiatric condition in children and follow-up studies have indicated that one to two thirds of patients continue to suffer from ADHD during late adolescence and adulthood. The mechanism of action of the new selective noradrenergic reuptake inhibitor, atomoxetine, efficacious in the treatment of ADHD symptoms, suggests that the norepinephrine transporter (NET) may be involved in ADHD. The aim of this study was to investigate for the presence of linkage disequilibrium between the MnlI RFLP in the NET gene and adult ADHD in a sample of nuclear families. The MnlI polymorphism was typed in 128 trios and analyzed using the transmission disequilibrium test (TDT). There was no preferential transmission of either allele (chi(2) = 0.209, df = 1, P = 0.647)., (Copyright 2003 Wiley-Liss, Inc.)

Numerous lines of evidence have shown that attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder, whether it is considered as a category or a dimension. We tested for an association between the dopamine transporter gene (DAT1) and ADHD considering the disorder as categorical as well as a continuous trait. Genotypes for the DAT1 variable number of tandem repeat (VNTR) alleles, along with Brown Attention Deficit Disorder Scale (BADDS) and Wender Utah Rating Scale (WURS) scores were available for 152 adult ADHD patients. In 72 of these patients DNAs from at least one parent were accessible to perform a family-based analysis (FBAT). The mean quantitative trait values of the whole sample of singleton patients were compared among the specific genotype groups using ANOVA. The family-based analysis did not reveal any association between DAT1 alleles and ADHD either when it was considered as a dichotomous trait (Z = 0.16, p =.86) or as a continuous trait (Wender Scale Z = -1.67, p =.09; Brown ADD Scale Z = 0.28, p =.77). No significant differences were detected in the mean symptom scores among the specific genotype groups. The results from our study do not support a major role for the DAT1 VNTR alleles in our sample of adult ADHD. In view of several positive reports in child ADHD, more work is required to elucidate the potential role of the DAT1 VNTR as a risk factor in ADHD.

Convincing data support the hypothesis that genetic factors are involved in the etiology of attention-deficit hyperactivity disorder (ADHD). Various lines of evidence have shown that the dopamine system plays a crucial role in the pathophysiology of ADHD. The dopamine D3 receptor gene (DRD3) represents a promising candidate to examine in ADHD. Animal studies have shown that DRD3 mRNA is highly expressed in the ventral striatum suggesting an involvement of this receptor in the control of motor behaviour. Manipulation of DRD3 in rodents has led to a mouse model with nonfunctional D3 receptors that displays hyperactive behaviour in various environmental conditions. Furthermore, administration of 7-OH-DPAT, a dopaminergic agonist that binds preferentially to D3 receptors exerts an inhibitory effect on locomotor activity while D3 antagonists induce hyperactivity. Among various polymorphisms described for DRD3, the BalI polymorphism is most interesting because it codes for an aminoacid substitution in the N-terminus of the receptor. The receptor products of the two alleles (Ser/Gly) exhibit differential affinity for dopamine. To determine if DRD3 Ser9/Gly is involved in the susceptibility to ADHD we genotyped 39 adults with ADHD and their respective parents (trios). Adult ADHD represents a promising phenotype for studying the genetic component of the disorder. In fact, a recent family study has shown that relatives of adult ADHD patients have a higher rate of ADHD compared to relatives of children with ADHD suggesting a stronger genetic component for the adult version. The results of genotyping in the 39 trios analyzed with the transmission disequilibrium test showed no excess of transmission for DRD3 MscI/BalI alleles (chi(2) = 0.360; df = 1; P = 0.54). This result, although from a relatively small sample, indicates that it is unlikely that DRD3 is playing a major role in the etiology of ADHD in our sample.

Attention deficit hyperactivity disorder (ADHD) is a prevalent psychiatric condition in children and follow up studies have indicated that 22-33% of patients continue to suffer from ADHD during late adolescence and adulthood. The action of psychostimulant drugs may be determined by additional mechanisms beyond the dopamine transporter and receptors. We are exploring new methodology for discovering these mechanisms. For example, in Drosophila, such an additional determinant of psychostimulant action could be protein kinase G (PKG) that affects food-search behavior. Here we initiated studies with the human homologue of PKG, the PRKG1 gene. The aim of this study was to investigate for the presence of linkage disequilibrium between the protein kinase G gene (PRKG1) and adult ADHD in a sample of nuclear families. Genotyping data for the C2276T polymorphism were analyzed using the Transmission Disequilibrium Test (TDT). Sixty three nuclear families were informative for the TDT on C2276T polymorphism, which showed no preferential transmission of either allele (chi-square = 0.778, df = 1, p = 0.316). These findings exclude a direct involvement of this genetic marker of the Protein kinase G gene in the pathogenesis of ADHD.