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Objective: Examining the joint effect of two functional variants in two dopamine-related genes (DRD3 and COMT) on ADHD-relevant behaviors under three experimental conditions (EC). Method: 362 children with ADHD were assessed by parents and teachers during a week of baseline evaluation, followed by 1 week of MPH and placebo, administered in a double-blind crossover design. Results: Statistically significant 3-way (DRD3 -by- COMT -by-EC; p =.004) and 2-way interactions (COMT by EC; p =.002) were observed on Conners'-Teachers scores. Children with the COMT Met/Met genotype had lower scores at baseline and on placebo compared to the other genotype groups. Furthermore, stratifying the children according to their COMT genotypes helped to detect statistically significant and biologically meaningful effects of DRD3 genotype. Conclusions: These findings suggest that COMT and DRD3 genetic variants may together play a role in ADHD symptomatology and response to treatment through gene-gene interaction. [ABSTRACT FROM AUTHOR]

Physical activity experiences of 12 age-matched boys with and without attention-deficit hyperactivity disorder (ADHD) were explored by converging information from Test of Gross Motor Development-2 assessments and semistructured interviews. The knowledge-based approach and the inhibitory model of executive functions, a combined theoretical lens, enabled the description of similarities and differences in experiences that emerged during interviews. Skill assessments indicated boys with ADHD were not as proficient movers as their peers without ADHD. Thematic analysis revealed that boys with ADHD reported playing with friends, paid little attention to detail, possessed superficial knowledge about movement skills, and expressed many negative feelings about physical activity. Task-specific interventions and a wider range of mixed methods research are recommended for future research studies in ADHD. [ABSTRACT FROM AUTHOR]

Alterations in catecholamine signaling and cortical morphology have both been implicated in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). However, possible links between the two remain unstudied. Here, we report exploratory analyses of cortical thickness and its relation to striatal dopamine transmission in treatment-naïve adults with ADHD and matched healthy controls. All participants had one magnetic resonance imaging (MRI) and two [11C]raclopride positron emission tomography scans. Associations between frontal cortical thickness and the magnitude of d-amphetamine-induced [11C]raclopride binding changes were observed that were divergent in the two groups. In the healthy controls, a thicker cortex was associated with less dopamine release; in the ADHD participants the converse was seen. The same divergence was seen for baseline D2/3 receptor availability. In healthy volunteers, lower D2/3 receptor availability was associated with a thicker cortex, while in the ADHD group lower baseline D2/3 receptor availability was associated with a thinner cortex. Individual differences in cortical thickness in these regions correlated with ADHD symptom severity. Together, these findings add to the evidence of associations between dopamine transmission and cortical morphology, and suggest that these relationships are altered in treatment-naïve adults with ADHD. [ABSTRACT FROM AUTHOR]

Attention Deficit/Hyperactivity Disorder (ADHD) has been associated with atypical patterns of neural activity measured by electroencephalography (EEG). However, the identification of EEG diagnostic biomarkers has been complicated by the disorder's heterogeneity. The objective of this review was to synthesize the literature investigating EEG variation in patients diagnosed with ADHD, addressing the following questions: 1) Are the diagnostic ADHD subtypes associated with different EEG characteristics? 2) Are EEG measures correlated with ADHD traits and/or symptom severity? and 3) Do classification techniques using EEG measures reveal different clinical presentations of ADHD? Outcomes highlight the potential for electrophysiological measures to provide meaningful insights into the heterogeneity of ADHD, although direct translation of EEG biomarkers for diagnostic purposes is not yet supported. Key measures that show promise for the discrimination of existing ADHD subtypes and symptomatology include: resting state and task-related modulation of alpha, beta and theta power, and the event-related N2 and P3 components. Prescriptions are discussed for future studies that may help to bridge the gap between research and clinical application. • Electrophysiology provides meaningful insight into the heterogeneity of ADHD. • Attentional, inhibitory control, and resting tasks are compared in ADHD subtypes. • Power spectrum and event-related potential analyses are related to ADHD symptoms. • EEG shows promise for the discovery of novel subgroups of ADHD. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Both genetic and environmental factors have been implicated in the etiology of attention-deficit/hyperactivity disorder ( ADHD). We had previously suggested that exposure to maternal smoking during pregnancy ( MSDP) may be a valid basis for delineating a distinct subtype of ADHD, where children exposed to MSDP present with a more severe clinical picture. Here, we examine the psychopathology of parents in this group, to better understand the etiology of ADHD. Methods Using the Family Interview for Genetic Studies in a sample of 514 families of children with ADHD, we collected data pertaining to lifetime parental psychopathology. Families were stratified based on maternal smoking during the complete gestational period. The frequency of different disorders was compared using the χ2 statistic. Results In the group where mothers smoked during pregnancy, both parents were significantly more likely to have antisocial personality disorder, and problems with alcohol and drug abuse. Mothers had a significantly higher frequency of major depressive disorder ( MDD), while fathers showed a trend for both MDD and bipolar disorder. Conclusions Based on the pattern of psychopathology in parents of children exposed to MSDP, as well as earlier reports of the severe clinical, behavioral, and cognitive phenotype in these children, combined with the large body of epidemiological evidence, we propose that these children present a distinct subtype of ADHD with comorbid conduct disorder. Furthermore, we propose that MSDP may be a proxy measure to help delineate this subtype. [ABSTRACT FROM AUTHOR]

Background: Physical educators suggested that they are not well-informed about behaviors of children with disabilities, especially attention-deficit hyperactivity disorder (ADHD). Children with ADHD represent a significant number of students in school systems worldwide who often experience difficulties in performing fundamental movement skills. Reasons for these challenging movement behaviors are not clearly understood. There were no significant effects of stimulant medication on performance of the Test of Gross Motor Development-2 (TGMD-2) for 22 children with ADHD. Six boys with ADHD possessed superficial content knowledge about physical activity (PA) participation. Poor movement skills may be related to a mismatch between content knowledge and specific skill performance, which can be problematic at individual skill levels. Purpose: To explore how children with ADHD regulate PA participation by listening to PA stories. Participants and setting: Ten children with ADHD participated in this study. They were identified by qualified child psychiatrists from an ADHD clinic at a major mental health institute in a large urban Canadian city. Research design: A concurrent mixed methods design explored the PA experiences of the children. The qualitative data were given a higher priority. Data collection: The quantitative research component was individualized assessments of fundamental movement skills with the TGMD-2 and Movement Assessment Battery for Children-2. The qualitative research component included: (1) PA self-reporting where each child recorded daily experiences for a two week period and (2) concurrent scrapbook interviews that enhanced participant recall/reflection to generate rich discussions about individual PA experiences. Data analysis: Quantitative skill assessments provided movement-related descriptions of participants. Individual skill levels were labeled with normative test descriptors linked to each respective assessment instrument. These qualitized descriptors were mixed with interview data only after all movement skill assessments and scrapbook interviews were completed. Interviews were transcribed verbatim and a within group thematic analysis was conducted. Findings: Many of the children demonstrated movement skill problems on both tests but skill performance was worse on the TGMD-2. Three qualitative themes emerged. The participants with ADHD spoke about their PA experiences in many different individual physical activities (play theme) and various settings (context theme). All children expressed personal wishes to be included in PA with other children in the community. A range of perceived self-regulatory behaviors emerged for planning PA (organization theme). The findings suggest some of the children with ADHD chose and organized their own PA while other children performed PA that was immediately in front of them with minimal organization of their PA behaviors. Conclusions: Children with ADHD told PA stories that many children without disabilities would tell. However, many of the children with the disorder described experiences related to exclusion from PA. They also lacked conceptual understanding of the purpose and goals related to general participation in various PA. Physical education teacher interventions, leisure counseling and community-based participatory research projects in PA are among the recommendations discussed for children with ADHD. [ABSTRACT FROM AUTHOR]

Objective Attention-deficit/hyperactivity disorder (ADHD) is an etiologically complex heterogeneous behavioral disorder. Several studies have reported that ADHD subjects are more likely to be overweight/obese and that this comorbidity may be due to shared genetic factors. The objective of this study is to explore the association between ADHD and FTO, a gene strongly associated with obesity in genome-wide studies. Design and Methods One tag SNP (single-nucleotide polymorphism, rs8050136, risk allele A) in the FTO gene was selected and its association with ADHD was tested. Family-based association tests (FBATs) were conducted with the categorical diagnosis of ADHD as well as behavioral and cognitive phenotypes related to ADHD. Furthermore, stratified FBAT analyses based on maternal smoking during pregnancy (MSDP) status were conducted. Results Statistically significant associations were observed between rs8050136 and several of the traits tested in the total sample. These associations were stronger when the analysis was restricted to children who were not exposed to MSDP. Conclusions These exploratory results suggest the involvement of the FTO SNP rs8050136 in modulating the risk for ADHD, particularly in those children who were not exposed to MSDP. If confirmed, they may explain, at least in part, the complex links between obesity and ADHD. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Service learning (SL) is a collaborative relationship between university professors, their students, and community partners who combine academic learning and active participation to address community issues. Previous studies in SL and physical education teacher education (PETE) found SL projects increased opportunities for learning and applying pedagogical methods, prepared PETE students to teach children from diverse backgrounds, and promoted an understanding of individual teaching responsibilities. Given the number of PETE university programs in SL emerged over the past decade, minimal research has supported the specific use of SL in PETE.  It was suggested that PETE programs provided content knowledge and pedagogical strategies to deal effectively with immediate instructional challenges but paid less attention to anticipate future challenges through student teaching experiences. A SL project for children with attention-deficit hyperactivity disorder (ADHD) was designed which enabled PETE students to learn how to manage behavior while teaching physical education. Purpose: To explore the experiences of PETE students in a SL project for children with ADHD. Participants and setting: Four female and two male PETE students were the participants in this study which investigated their project experiences in SL at a major mental health institute in a large urban Canadian city. Research design: A phenomenological approach was used to describe the lived experiences of PETE students in the SL project. Data gathering: Individual semi-structured interviews were conducted and videotaped to acquire rich and deep knowledge of PETE students’ SL experience. Each student was requested to bring unit plans, lesson plans, written reflections, and final term papers to enhance the interview process. Data analysis: Each interview was transcribed verbatim and a line-by-line thematic analysis was performed. Findings: Three higher-order themes emerged from thematic analysis. The ‘where have I been’ theme suggested past teaching and community work experiences shaped decisions to become physical educators. The ‘it's all about caring’ theme involved reduction of stigma linked to teaching children with ADHD and merging theory and practice through application of instructional models and deliberate lesson plans. The ‘teaching to play’ theme revealed various benefits linked to PETE student participation in SL and challenges inherent with team teaching. Conclusions: Future research recommendations include capturing the experiences of other participants in the SL project for children with ADHD to gain much greater insight into the whole SL experience and help to shape future projects. Much research remains to be performed in SL and adapted physical education (APE) or local community recreation centers where students from allied health disciplines could participate together. A variety of different qualitative research approaches were also recommended to explore participant experiences in SL projects. Similar SL projects, conducted in multidisciplinary environments, may also be exciting new venues for PETE programs. Finally, the participants’ stories led us to suggest that SL is a contemporary pedagogy that addresses calls  for the development of caring pedagogies that prepare future teachers for the realities and challenges of a changing world. [ABSTRACT FROM PUBLISHER]

Introduction: Evidence from epidemiological studies has consistently shown an association between maternal smoking during pregnancy (MSDP) and attention-deficit/hyperactivity disorder (ADHD). The objective of this study is to test the hypothesis that children with ADHD exposed to MSDP show a distinctive clinical and neurocognitive profile when compared with unexposed children. Methods: Four hundred and thirty-six children diagnosed with ADHD were stratified by exposure to MSDP and compared with regard to severity of illness, comorbidity, IQ, and executive function as assessed by a battery of neuropsychological tests. All comparisons were adjusted for socioeconomic status, ethnicity, mother’s age at child’s birth, and maternal alcohol consumption during pregnancy. Results: Exposed children had more severe behavioral problems with greater externalizing symptoms and more conduct and oppositional defiant disorder items, lower verbal IQ, and a sluggish cognitive profile on the Continuous Performance Test (CPT). Linear regression analyses revealed a dose-response relationship between the average number of cigarettes smoked per day during pregnancy and verbal IQ, CPT omission errors T score and several other clinical variables. Conclusions: These results suggest that MSDP is associated with a more severe form of ADHD, characterized by more severe clinical manifestations and poorer neuropsychological performance. This phenotypic signature associated with MSDP may help to identify a more homogenous subgroup of children with ADHD. [ABSTRACT FROM AUTHOR]

Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex and heterogeneous childhood disorder that often coexists with other psychiatric and somatic disorders. Recently, a link between ADHD and body weight dysregulation has been reported and often interpreted as impaired self-regulation that is shared between the two conditions. The objective of this study is to investigate the relation between body weight/BMI and cognitive, emotional and motor characteristics in children with ADHD. Methods: 284 ADHD children were stratified by weight status/BMI according to WHO classification and compared with regard to their neurocognitive characteristics, motivational style, and motor profile as assessed by a comprehensive battery of tests. All comparisons were adjusted for demographic characteristics of relevance including, socioeconomic status (SES). Results: Both Obese and overweight ADHD children exhibited significantly lower SES compared to normal weight ADHD children. No significant differences were observed between the three groups with regards to their neurocognitive, emotional and motor profile. Conclusions: Our findings provide evidence that differences in weight/BMI are not accounted for by cognitive, motivational and motor profiles. Socio-economic characteristics are strongly associated with overweight and obesity in ADHD children and may inform strategies aimed at promoting healthier weight. [ABSTRACT FROM AUTHOR]

Background: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous behavioral disorder, complex both in etiology and clinical expression. Both genetic and environmental factors have been implicated, and it has been suggested that gene-environment interactions may play a pivotal role in the disorder. Recently, a significant association was reported between ADHD and LPHN3 (which codes for latrophilin 3), and replicated in independent samples. Methods: We have examined the association between tag single nucleotide polymorphisms (SNPs) in LPHN3 within the region previously implicated in ADHD. Family based association tests (FBAT) were conducted ( n = 380 families) with the categorical diagnosis of ADHD, behavioral and cognitive phenotypes related to ADHD, and response to treatment (given a fixed dose of methylphenidate, 0.5 mg/day). Stratified FBAT analyses, based on maternal smoking and stress during pregnancy, was conducted. Results: Whereas limited association was observed in the total sample, highly significant interaction between four LPHN3 tag SNPs (rs6551665, rs1947274, rs6858066, rs2345039) and maternal stress during pregnancy was noted. Analysis conducted in the sub-group of mothers exposed to minimal stress during pregnancy showed significant associations with ADHD, behavioral and cognitive dimensions related to ADHD, as well as treatment response. Although extensive association was observed with the candidate SNPs, the findings are partially inconsistent with previously published results with the opposite alleles over-transmitted in these studies. Conclusions: These results provide evidence for the interaction between a genetic and environmental factor independently shown to be associated with ADHD. If confirmed in independent large studies, they may present a step forward in unraveling the complex etiology of ADHD. [ABSTRACT FROM AUTHOR]

Background: Pharmacologic and animal studies have strongly Implicated the noreplnephrine transporter (NET) in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We conducted a family-based study, with stratification based on sex and subtype, to test the association between 30 tag single-nucleotide polymorphisms (SNPs) within the gene encoding NET (SLC6A2) and ADHD. Methods: Family-based association tests were conducted with the categorical diagnosis of ADHD, as well as quantitative phenotypes of clinical relevance (Conners Global Index for Teachers and Parents, and Child Behavior Checklist measures). Sliding window haplotype analysis was conducted with screening based on conditional power using PBAT. Results: A previously reported association with rs3785143 was confirmed in this study. Further, extensive association was observed with haplotype blocks, with a differential pattern observed based on sex and subtype. The 5' region of the gene (encompassing haplotype block 1 and including a functional promoter SNP, rs28386840) showed an association with ADHD in girls (irrespective of subtype). A different region of the gene (distributed around haplotype block 2) was associated with distinct behavioural phenotypes in boys. These findings are correlated with previously reported functional studies of gene variants in SLC6A2. Limitations: The most important limitation of the study is the small size of the groups resulting from the stratification based on sex followed by subtype. Conclusion: The results obtained in this family-based study suggest that haplotype blocks within different regions of SLC6A2 show differential association with the disorder based on sex and subtype. These associations may have been masked in previous studies when tests were conducted with pooled samples. [ABSTRACT FROM AUTHOR]

As a relatively large body of research has been published up to now, it may be informative to explore whether the use of endophenotypes has produced consistent findings in attention-deficit hyperactivity disorder (ADHD). We reviewed the results of genetic studies investigating associations between putative susceptibility genes for ADHD and neuropsychological traits relevant for this disorder. A PubMed database search identified 47 studies. Most of them ( n = 36) examined a single candidate gene, while seven studies examined two or three genes and only four studies examined 10 genes or more. The most investigated genes were DRD4, DAT1, COMT, MAOA, and DBH. Regarding DRD4, association of high reaction time variability with the 7-R allele absence appears to be the most consistent result. Speed of processing, set shifting, and cognitive impulsiveness were less frequently investigated, but seem to be altered in the 7-R allele carriers. Regarding DAT1, majority of studies reported negative results indicating that this gene may have a modulating effect rather than direct influence on cognitive functioning. The other genes were investigated in fewer studies, and the reported findings need to be replicated. The principal methodological issues that could represent confounding factors and may explain conflicting results are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Background: A history of childhood symptoms of inattention–hyperactivity is often reported in first episode psychosis (FEP) as is cannabis use. In the general population childhood ADHD predicts future cannabis use but the relationship has not been tested in FEP. Method: Parents of patients with a first episode of psychosis (n=75) retrospectively assessed their affected child for symptoms of early-life disorders, namely, attention deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD) using the Child Behaviour Checklist (CBCL). Assessments were made prospectively of cannabis use over two years following a FEP and of SCID diagnosis of cannabis-use disorder. Results: Childhood hyperactivity–inattention symptoms predicted inability to maintain abstinence from cannabis following treatment (Wald=8.4, p=.004) and lifetime cannabis-use diagnosis (Wald=5.3, p=.022) in a logistic regression controlling for relevant covariates including symptoms of CD and ODD from ages 12 to 18. When the symptom of inattention was considered in place of the hyperactivity–inattention syndrome it predicted cannabis-use diagnosis (Wald=6.4, p=.011) and persistent abstinence from cannabis (Wald=5.3, p=.021). Symptoms of CD and ODD did not predict cannabis use when hyperactivity–inattention symptoms were controlled for. Conclusions: Symptoms of childhood inattention–hyperactivity predict subsequent cannabis use in FEP. [Copyright &y& Elsevier]

Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Animal models of ADHD suggest that the paradoxical calming effect of methylphenidate on motor activity could be mediated through its action on serotonin transmission. In this study, we have investigated the relationship between the 5-HTTLPR polymorphism in the serotonin transporter gene (SLC6A4) and the response of ADHD relevant behaviors with methylphenidate treatment. Methods: Patients between ages 6-12 (n = 157) were assessed with regard to their behavioral response to methylphenidate (0.5 mg/kg/day) using a 2-week prospective within-subject, placebo-controlled (crossover) trial. The children were then genotyped with regard to the triallelic 5-HTTLPR polymorphism in the SLC6A4 gene. Main outcome measure: Conners' Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) at baseline and at the end of each week of treatment with placebo and methylphenidate. For both outcome measurements, we used a mixed model analysis of variance to determine gene, treatment and gene × treatment interaction effects. Results: Mixed model analysis of variance revealed a gene × treatment interaction for CGI-Parents but not for CGITeachers. Children homozygous for the lower expressing alleles (s+lG = s') responded well to placebo and did not derive additional improvement with methylphenidate compared to children carrying a higher expressing allele (lA). No genotype main effects on either CGI-Parents or CGI-teachers were observed. Conclusions: A double blind placebo-controlled design was used to assess the behavioral effects of methylphenidate in relation to the triallelic 5-HTTLPR polymorphism of the SLC6A4 gene in children with ADHD. This polymorphism appears to modulate the behavioral response to methylphenidate in children with ADHD as assessed in the home environment by parents. Further investigation is needed to assess the clinical implications of this finding. Trial Registration: ClinicalTrials.gov NCT00483106 [ABSTRACT FROM AUTHOR]

Copyright of Journal of Psychiatry & Neuroscience is the property of CMA Impact Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

It has been suggested that the symptoms of attention-deficit/hyperactivity disorder (ADHD), including inattention and/or hyperactivity/impulsivity, translate into deficits in task-oriented behavior or problem-focused activity. The frontosubcortical dopamine pathway has been implicated in ADHD. One of the key modulators of extracellular dopamine levels in the prefrontal cortex is catechol-O-methyltransferase (COMT). The objective of this study was to examine the association of the COMT Val108/158Met polymorphism with (1) task-oriented behavior in children with ADHD, and (2) response of this behavior given methylphenidate (MPH) treatment. Children of Caucasian ethnicity, having ADHD (n=188), were assessed using the Restricted Academic Situation Scale (RASS). The RASS uses a simulated academic environment within the research clinic, to assess the child's ability for independent, sustained orientation to an assignment of math problems. Each child was administered placebo and MPH (0.5 mg/kg in a divided b.i.d. dose), each for a 1-week period, in a randomized, double-blind, crossover trial. On day 3 of the respective treatment week, the child was administered placebo/MPH in the clinic, and the acute change in behavior (before and 1 h after treatment) was evaluated on the RASS. Analysis was carried out using mixed model analysis of variance. Significant main effects of COMT genotype (F2,184=5.12, p=0.007) and treatment (F1,184=44.26, p<0.001) on task-oriented behavior were observed. However, no genotype by treatment interaction was observed. These results suggest that the COMT Val108/158Met polymorphism modulates task-oriented behavior, but it does not modulate the response of this behavior with MPH treatment.Neuropsychopharmacology (2008) 33, 3069–3077; doi:10.1038/npp.2008.85; published online 25 June 2008 [ABSTRACT FROM AUTHOR]

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a heterogeneous disorder from both clinical and pathogenic viewpoints. Executive function deficits are considered among the most important pathogenic pathways leading to ADHD and may index part of the heterogeneity in this disorder. Methods: To investigate the relationship between the dopamine transporter gene (SLC6A3) 3'- UTR VNTR genotypes and executive function in children with ADHD, 196 children diagnosed with ADHD were sequentially recruited, genotyped, and tested using a battery of three neuropsychological tests aimed at assessing the different aspects of executive functioning. Results: Taking into account a correction for multiple comparisons, the main finding of this study is a significant genotype effect on performances on the Tower of London (F = 6.902, p = 0.009) and on the Wechsler Intelligence Scale for Children, Third Edition (WISC-III) Freedom From Distractibility Index (F = 7.125, p = 0.008), as well as strong trends on Self Ordered Pointing Task error scores (F = 4,996 p = 0.026) and WISC-III Digit Span performance (F = 6.28, p = 0.023). Children with the 9/10 genotype exhibited, on average, a poorer performance on all four measures compared to children with the 10/10 genotype. No effect of genotype on Wisconsin Card Sorting Test measures of performance was detected. Conclusion: Results are compatible with the view that SLC6A3 genotype may modulate components of executive function performance in children with ADHD. [ABSTRACT FROM AUTHOR]

We sought to test the hypothesis that the variable number of tandem repeat (VNTR) polymorphism in the 3′-untranslated region (3′-UTR) of the SLC6A3 gene modulates behavior in children with ADHD and/or behavioral response to methylphenidate (MPH). One hundred and fifty-nine children with AHDH (6–12 years) were assessed with regard to the Conners’ Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) and the response of these behaviors to MPH (0.5 mg/kg/day) using a 2-week prospective within-subject (crossover) trial. Based on CGI-Parents, the profile of behavioral response to MPH as compared to placebo was not parallel in the three groups of children separated according to their genotype in the 3′-UTR VNTR polymorphism of SLC6A3, as indicated by a significant (p=0.017) genotype by treatment two-way interaction. Individuals having the 9/10 and 10/10 genotypes displayed a significant positive response to MPH as opposed to those homozygous for the 9-repeat allele. No genotype or genotype by treatment interaction was observed for CGI-Teachers. These findings support a role for the DAT gene 3′-UTR VNTR polymorphism in modulating the response of some behavioral dimensions to MPH in children with ADHD. They also suggest the presence of genetic heterogeneity that could be indexed by the quality of behavioral response to MPH.Neuropsychopharmacology (2007) 32, 1370–1376. doi:10.1038/sj.npp.1301240; published online 25 October 2006 [ABSTRACT FROM AUTHOR]

Previous research has suggested that there may be overlap between schizophrenia and attention-deficit hyperactivity disorder (ADHD). The relationship between schizotypal personality traits, ADHD features and polymorphisms was evaluated in dopamine-related genes. Thirty-one healthy, Caucasian men completed the Rust Inventory of Schizotypal Cognitions (RISC) and the ADHD Self-Report Scale (ASRS). Catechol-O-methyltransferase (COMT) Val158Met, dopamine receptors of the D3 type (DRD3) Ser9Gly, DRD4 variable number of tandem repeats (VNTR), and SLC6A3 VNTR polymorphisms were analyzed. RISC score was correlated with ASRS score ( r = 0.54, P = 0.003). COMT Met homozygotes had higher ASRS scores than Val homozygotes ( P = 0.005). These findings are consistent with evidence of overlap between schizophrenia and ADHD and support an involvement of COMT genotype in ADHD features. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Psychiatry & Neuroscience is the property of CMA Impact Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Psychiatry & Neuroscience is the property of CMA Impact Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: An association has been observed between the catechol-O-methyltransferase (COMT) gene, the predominant means of catecholamine catabolism within the prefrontal cortex (PFC), and neuropsychological task performance in healthy and schizophrenic adults. Since several of the cognitive functions typically deficient in children with Attention Deficit Hyperactivity Disorder (ADHD) are mediated by prefrontal dopamine (DA) mechanisms, we investigated the relationship between a functional polymorphism of the COMT gene and neuropsychological task performance in these children. Methods: The Val108/158 Met polymorphism of the COMT gene was genotyped in 118 children with ADHD (DSM-IV). The Wisconsin Card Sorting Test (WCST), Tower of London (TOL), and Self-Ordered Pointing Task (SOPT) were employed to evaluate executive functions. Neuropsychological task performance was compared across genotype groups using analysis of variance. Results: ADHD children with the Val/Val, Val/Met and Met/Met genotypes were similar with regard to demographic and clinical characteristics. No genotype effects were observed for WCST standardized perseverative error scores [F2,97 = 0.67; p > 0.05], TOL standardized scores [F2,99 = 0.97; p > 0.05], and SOPT error scores [F2,108 = 0.62; p > 0.05]. Conclusions: Contrary to the observed association between WCST performance and the Val108/ 158 Met polymorphism of the COMT gene in both healthy and schizophrenic adults, this polymorphism does not appear to modulate executive functions in children with ADHD. [ABSTRACT FROM AUTHOR]

Objective: To review the results of genetic studies investigating dopamine-related genes in attention-deficit hyperactivity disorder (ADHD). Data sources: Papers (association/linkage, meta-analyses and animal model studies) were identified through searches of the PubMed database and systematically reviewed. Data synthesis: Consistent results from molecular genetic studies are pointing strongly to the possible link between 2 specific genes, the dopamine transporter (SLC3A6) and the dopamine receptor 4 (DRO4), and ADHD. Conclusions: The implication of SLC6A3 and DRD4 genes in ADHD appears to be one of the most replicated in psychiatric genetics and strongly suggests the involvement of the brain dopamine systems in the pathogenesis of ADHD. However, more work is required to further these findings by genotype-to-phenotype correlations and identify the functional allelic variants/mutations that are responsible for these associations. The role of other dopamine genes, which may have smaller effects than SLC6A3 and ORD4, needs also to be determined. [ABSTRACT FROM AUTHOR]

Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental psychiatric disorder. Genome-wide association studies (GWAS) have identified several loci associated with ADHD. However, understanding the biological relevance of these genetic loci has proven to be difficult. Here, we conduct an ADHD transcriptome-wide association study (TWAS) consisting of 19,099 cases and 34,194 controls and identify 9 transcriptome-wide significant hits, of which 6 genes were not implicated in the original GWAS. We demonstrate that two of the previous GWAS hits can be largely explained by expression regulation. Probabilistic causal fine-mapping of TWAS signals prioritizes KAT2B with a posterior probability of 0.467 in the dorsolateral prefrontal cortex and TMEM161B with a posterior probability of 0.838 in the amygdala. Furthermore, pathway enrichment identifies dopaminergic and norepinephrine pathways, which are highly relevant for ADHD. Overall, our findings highlight the power of TWAS to identify and prioritize putatively causal genes. A recent GWAS reported 12 genetic loci for attention deficit/hyperactivity disorder (ADHD). Here, Liao et al. perform transcriptomic imputation using these data and 12 brain-relevant tissues from GTEx and CMC to identify 9 genes associated with ADHD by TWAS, 3 of which had not yet been reported for ADHD. [ABSTRACT FROM AUTHOR]

The article describes the case of a 25-year-old man with attention-deficit/hyperactivity disorder (ADHD) with comorbid bipolar disorder (BD). Topics mentioned include the efficacy and tolerability of medication use in the treatment of ADHD comorbid with BD, psychostimulants with antipsychotics as a good therapeutic approach, and use of clonidine in treatment of manic episodes.

A letter to the editor is presented in response to the article "Preferential transmission of paternal alleles at risk genes in attention-deficit/hyperactivity disorder," by Z. Hawi, R. Segurado, J. Conroy, K. Sheehan, N. Lowe, A. Kirley, D. Shields, M. Fitzgerald, L. Gallagher and M. Gill in the December 2005 issue of the journal.

The article focuses on the case of an 8-year old child named G.R. who manifests difficulties of attention and learning. It cites that the conducted investigations on the deficiency show that his achievements in the Continuous Performance Task are in clinical range. Further, the cited case of G.R. indicates diagnostic attention deficit disorder due to clear evidences of symptoms.

• While maternal smoking during pregnancy (MSDP) is established as a risk factor for ADHD, the mechanisms underlying this association are not well understood. • We investigated the effect of MSDP on cortical brain structures in children with ADHD. • A significant effect of MSDP on structural MRI parameters was detected when using an epigenetic signature instead of maternal recall. Maternal smoking during pregnancy (MSDP) is considered a risk factor for ADHD. While the mechanisms underlying this association are not well understood, MSDP may impact the developing brain in ways that lead to ADHD. Here, we investigated the effect of prenatal smoking exposure on cortical brain structures in children with ADHD using two methods of assessing prenatal exposure: maternal recall and epigenetic typing. Exposure groups were defined according to: (1) maternal recall (+MSDP: n = 24; −MSDP: n = 85) and (2) epigenetic markers (EM) (+EM: n = 14 −EM: n = 21). CIVET-1.1.12 and RMINC were used to acquire cortical brain measurements and perform statistical analyses, respectively. The vertex with highest significance was tested for association with Continuous Performance Test (CPT) dimensions. While no differences of brain structures were identified between +MSDP and –MSDP, +EM children (n = 10) had significantly smaller surface area in the right orbitofrontal cortex (ROFc), middle temporal cortex (RTc) and parahippocampal gyrus (RPHg) (15% FDR) compared to -EM children (n = 20). Cortical surface area in the RPHg significantly correlated with CPT commission errors T-scores. This study suggests that molecular markers may better define exposure to environmental risks, as compared to human recall. [ABSTRACT FROM AUTHOR]

Objective: To assess the sensitivity of scales (Conners' Global Index Parent and Teacher form [CGI-P, CGI-T], Clinical Global Impression Scale [CGI], Continuous Performance Test [CPT], and Restricted Academic Situation Scale [RASS]) in evaluating improvement in symptomatology with methylphenidate in different Attention Deficit Hyperactivity Disorder (ADHD) subtypes. Method: Four hundred and ninety children (309 with ADHD Combined/Hyperactive [ADHD-CH] and 181 with ADHD Inattentive subtype [ADHD-I]) participated in a two week double-blind placebo-controlled crossover methylphenidate trial. Results: CGI-P showed small effect size for ADHD-I and medium effect size for the ADHD-CH subtype. CGI-T showed medium effect size for ADHD-I and large effect size for ADHD-CH subtype. CGI and RASS showed large effect size while CPT showed medium effect size for both subtypes. Conclusion: Acute behavioural assessments by clinicians (CGI, RASS) are better at detecting improvement with medication in all subtypes than parent or teacher reports (CGI-P, CGI-T). CGI-T is better than CGI-P for ADHD-I in detecting change in symptomatology as there is a greater demand for attention at school. [ABSTRACT FROM AUTHOR]

Highlights • There is evidence that neurodevelopmental disorders overlap. Yet it is unclear how etiological pathways intersect. • SNPs identified in non-ADHD GWAS showed association with multiple dimensions related to ADHD. • Here we attempt to tease apart the heterogeneity in the phenotype, and understand its genetic underpinnings. • Results are presented as preliminary findings as they provide insight into cross-disorder associations. Abstract Several epidemiological and genetic studies have provided evidence of an overlap between neurodevelopmental disorders. However, the details of the etiological pathways remain to be elucidated. In this study, we garnered the findings of previous GWAS, conducted with schizophrenia and bipolar disorder. We conducted an exploratory study to examine the association between these SNPs and quantitative clinical/ behavioural/ cognitive/ structural brain parameters, as well as response to treatment with a fixed dose of methylphenidate, in a relatively large sample of children with ADHD. Family-based association tests were conducted with nine tag SNPs with 602 nuclear families. In addition, structural magnetic resonance imaging (sMRI) was conducted in a subset of children with ADHD (n = 76). Of the 9 tag SNPs examined, rs1602565 showed a significant association with ADHD, several dimensional measures and response to treatment. An association was also observed between rs1006737 (CACNA1C) and performance IQ. In addition, significant reductions in cortical thickness measurements were observed with the risk allele in rs1006737. These results provide preliminary evidence for putative shared genetic vulnerability between childhood ADHD and other neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Maternal smoking during pregnancy is the most commonly cited risk factor for ADHD. While the causal relation between this factor and ADHD is debated, several lines of evidence suggest that it modulates the severity of ADHD, particularly through higher association with conduct disorder (CD). We hypothesized that maternal smoking during pregnancy may be associated with differential methylation in selected genes in children with ADHD. DNA extracted from peripheral blood was used to examine methylation between 25 children exposed, and 22 children not exposed to maternal smoking during pregnancy. Three genes ( AHRR , CYP1A1 , GFI 1) were selected based on previous results observed in the general population. Regression analysis was conducted between methylation levels in these candidate genes and: (a) total number of ADHD and CD symptoms; (b) birth weight. Significant differences in methylation were observed in each of the candidate genes between children exposed and not exposed to maternal smoking during pregnancy. Methylation at the selected sites showed significant association with specific phenotypes. Significant correlations were observed between methylation within AHRR and number of CD symptoms; GFI 1 and number of ADHD symptoms and GFI 1 and birth weight. These initial results may have important clinical implications if confirmed in a larger independent sample. [ABSTRACT FROM AUTHOR]

Objective: ADHD and asthma are prevalent conditions in childhood, with complex pathophysiology involving geneticenvironmental interplay. The study objective is to examine the prevalence of asthma in our ADHD population and explore factors that may increase the risk of developing asthma in children with ADHD. Methods: We retrospectively analyzed the presence of maternal stress during pregnancy and history of asthma in 201 children diagnosed with ADHD. Results: Chi-square analysis indicated significant higher presence of asthma in our ADHD sample compared to Quebec children, x2(1, N = 201) = 15.37, P<0.001. Only prematurity and stress during pregnancy significantly predicted asthma in a logistic regression model, x2(2)=23.70, P<0.001, with odds ratios of 10.6 (95% CI: 2.8-39.5) and 3.2 (95% CI: 1.4-7.3), respectively. Conclusion: Children with ADHD have a higher prevalence of asthma than the general Quebec pediatric population. Children with ADHD born prematurely and/or those whose mothers experienced stress during pregnancy have a significantly increased risk of developing asthma. The study highlights the importance of potentially offering social and psychological support to mothers who experienced stress during pregnancy and/or are at risk of delivering prematurely. [ABSTRACT FROM AUTHOR]

Objective: Maternal stress during pregnancy (MSDP) has been linked to a decrease in Intelligence Quotient (IQ) in the general population. The purpose of this study is to first examine the association between MSDP and IQ in children with Attention-Deficit/Hyperactivity Disorder (ADHD) and second, to confirm, in a large sample, the link between MSDP and ADHD behavioral symptomatology. Methods: Four hundred ten children diagnosed with ADHD, ages six to 12, were consecutively recruited from the ADHD clinic and day hospital at the Douglas Institute from 1999 to 2013. IQ was assessed using the WISC III and IV. Symptom severity was evaluated using the Child Behavior Checklist (CBCL) and Connor's Global Index for Parents (CGI-P) and Teachers (CGI-T). Results: No significant effect of MSDP on full scale IQ was observed, but MSDP had a significant effect on CBCL and CGI scores. Elevated MSDP was significantly associated with increased CBCL internalizing scores (β=4.2, p<.01), CBCL externalizing scores (β=1.9, p=.04), CGI-P restless-impulsive scores (β=2.6, p=.01), CGI-P emotional lability scores (β=3.1, p=.02), and CGI-T restless-impulsive (β=2.2, p=.05) and emotional lability (β=3.4, p=.04) scores. MSDP increased the variance explained of ADHD symptomatology even after controlling for various factors (i.e. familial income, parental education, smoking and drinking during pregnancy, gender and age). Conclusion: The study demonstrates that in children with ADHD, MSDP does not have an impact on IQ but rather on ADHD symptomatology, highlighting the importance of potentially offering psychological and social support to mothers who experience stress during pregnancy. [ABSTRACT FROM AUTHOR]

Case control studies suggest a relationship between maternal stress during pregnancy and childhood ADHD. However, maternal smoking, parenting style and parental psychiatric disorder are possible confounding factors. Our objective was to control for these factors by using an intra-familial design, and investigate gene-environment interactions. Methods: One hundred forty two children, ages 6 to 12, (71 with ADHD, and their 71 non-ADHD siblings) participated in the intra-familial study design. A larger sample of ADHD children (N=305) was genotyped for DAT1 and DRD4 to examine gene-environment interactions. Symptom severity was evaluated using the Child Behavior Checklist (CBCL) and the Conners' Global Index for Parents (CGI-P). The Kinney Medical and Gynecological Questionnaire was used to report stressful events during pregnancies. Results: Logistic regression indicated that mothers were more likely to have experienced high stress during pregnancy of their ADHD child compared to that of the unaffected sibling (OR: 6.3, p=.01). In the larger sample, DRD4 7/7 genotype was associated with increased symptom severity in the high stress pregnancy (p=.01). Conclusions: Maternal stress during pregnancy was associated with the development of ADHD symptomatology after controlling for family history of ADHD and other environmental factors. This association could partly be mediated through the DRD4 genotype. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Attention-deficit/hyperactivity disorder (ADHD) is often associated with reduced IQ and high levels of externalizing behavior (EB). This study tested if DRD4 7-repeat allele and DAT1 10-repeat allele homzygosity interact in modulating correlations between IQ and EB in affected boys. Methods: Boys (n =130) between 6 and 12 years of age diagnosed with ADHD were included in the study. IQ and EB were assessed by WISC-III and Child Behavioral Checklist, respectively. The 40 bp variable number tandem repeat (VNTR) of the DAT1 gene and the 48 bp VNTR of the DRD4 gene polymorphisms were genotyped and 4 subgroups were defined by the presence/absence of the DRD4 7-repeat allele and by the presence/absence of the DAT1 10/10 genotype. Correlation coefficients were compared using the Fisher''s Z transformation and regression lines by a Potthoff analysis. Results: In the total sample, all correlation coefficients between EB score and IQ were non significant. Also, no differences in IQ were observed between the 4 genotype groups. However, different pattern of correlations between IQ and EB score appeared. In boys carrying no or only one genetic risk, IQ and EB score were uncorrelated while in children carrying both risk factors, negative and significant correlations emerged. Notably, correlation of EB to verbal IQ was strong (r =−0.71) and highly significant (P <0.01) in boys carrying both risk alleles. All pair-wise comparisons of correlation coefficients were significant for EB–verbal IQ correlation. Test of coincidence of regression lines did not show significant differences. Conclusions: A specific domain of IQ, namely the verbal quotient is highly correlated to the level of EB in boys with ADHD carrying both dopaminergic risk genotypes. Further investigations are required to replicate these results and determine specificity to ADHD. [Copyright &y& Elsevier]

Tryptophan hydroxylase 2 (TPH2) is a key enzyme in the biosynthesis of serotonin in the brain. This study aims to investigate the role of a functional variant in TPH2 (rs17110747) in the pathophysiology of ADHD. This variant has been implicated in mood disorders in recent meta-analysis. This study uses a comprehensive approach that combines association testing and pharmaco-dynamic evaluation of behaviour, in a large sample of children with ADHD (n = 570). The association between various ADHD relevant traits and rs17110747 was analyzed using family-based association tests (FBAT). Children were assessed by parents, teachers and research staff under three experimental conditions (EC): baseline, placebo, and methylphenidate using a double-blind placebo-controlled crossover trial. FBAT analysis conducted in a sample stratified based on sex of the proband, showed that there was a highly significant overtransmission of the G allele from parents to affected girls. In addition, significant association with several behavioral and cognitive dimensions of ADHD was observed only when the proband was female. Further, girls with the G/G genotype (rs17110747) had greater response to placebo when evaluated by parents. These results suggest that there may be a complex association of TPH2 in the etiology of ADHD, with a sex-specific effect. • Family-based association tests show specific findings with TPH2 and girls with ADHD. • Sex-specific effect is observed with behaviour and cognitive dimensions. • Differential association also observed with treatment response in girls. • Appears that there may be different etiological pathways in girls with ADHD. • Results may inform sex-specific pharmacological interventions. [ABSTRACT FROM AUTHOR]

Objective: To examine whether COMT (catechol-O-methyltransferase) polymorphism modulates aspects of sleep in children diagnosed with attention-deficit/hyperactivity disorder (ADHD).Method: Nightly sleep actigraphic recordings during a double-blind, placebo-controlled, crossover clinical study (1 week of 0.5 mg/kg MPH; 1 week of placebo) were obtained for 34 children, 7.4 to 12 years old, diagnosed with ADHD (DSM-IV). Diagnosis was generated by the Diagnostic Interview Schedule for Children and was confirmed by multidisciplinary consensus.Results: Children who were Val allele carriers had poorer sleep continuity compared with children with the Met-Met genotype while receiving a placebo and while receiving methylphenidate.Conclusions: The findings of the present study support the hypothesis that sleep disturbances in children with ADHD are related to the underlying pathophysiology of the disorder. [ABSTRACT FROM AUTHOR]

Objective: To compare the pattern of familial aggregation of psychopathology in children who are good responders (GR) to methylphenidate (MPH) versus those who are poor responders (PR).Method: A total of 118 clinically referred children ages 6 to 12 years, diagnosed with ADHD participated in a double-blind, placebo-controlled, randomized 2-week crossover trial of MPH from 1999 to 2004. A low dose of 0.5 mg/kg of body weight of MPH divided in two equal doses was used. Family history was obtained by interviewing at least one key historian relative of each subject using Family Interview for Genetic Studies. Information was collected on 342 first-degree and 1,151 second-degree relatives of children with attention-deficit/hyperactivity disorder.Results: Forty-four subjects showed mild or no improvement (PR) and 74 showed moderate or very much improvement (GR) on MPH over placebo. First-degree relatives of GR subjects were at significantly higher risk of attention-deficit/hyperactivity disorder than the relatives of PR subjects (p<.05). Second-degree relatives of the GR were at significantly higher risk of antisocial personality disorder compared to the relatives of PR subjects (p<.05).Conclusions: The significantly higher presence of attention-deficit/hyperactivity disorder in the first-degree relatives and of antisocial personality disorder in the second-degree relatives of GR children suggests that this group may, at least partially, be distinct from the PR group on the basis of genetic determinants. [ABSTRACT FROM AUTHOR]

Objective: Sleep disturbances appear as a comorbid condition in children with attention-deficit/hyperactivity disorder. The aim of this study was to investigate the relationship of activity levels during sleep and therapeutic response to methylphenidate (MPH). Method: Nightly sleep actigraphic recordings during a double-blind, placebo-controlled, cross- over clinical study (1-week of 0.5 mg/kg MPH; 1-week of placebo) were obtained on 44 children, 6 to 12 years old, diagnosed with attention-deficit/hyperactivity disorder (DSM-IV). Results: Significant (p c .005) differences between the conditions were found in several software-computed parameters: sleep onset latency (MPH, 39.3 minutes; placebo, 28.2 minutes), sleep efficiency (MPH, 78.0%; placebo, 80.4%), total sleep time (MPH, 7 hours; 57 minutes; placebo, 8 hours, 16 minutes). No significant differences on any of these measures were found among the 26 subjects who showed a moderate or large global improvement on MPH over placebo compared with 18 subjects who showed mild or no clinical improvement. Conclusions: MPH, given twice daily, induces a slight but significant sleep disturbance. Motor activity levels during sleep did not differentiate children who responded to MPH from those who did not respond. This suggests that responders to MPH treatment do not experience greater sleep disturbances than nonresponders, at least at the dose studied. [ABSTRACT FROM AUTHOR]

This exploratory study aims to determine whether the change in systolic blood pressure (sBP) after acute methylphenidate (MPH) administration (ΔBP MPH) is associated with the neurocognitive response to MPH in the Conners Continuous Performance Test (CPT) in 513 children with ADHD (aged 6 to 12 years old). We noted that higher increases in sBP were associated with larger improvement in CPT performance with MPH. In the univariate regression model, the ΔBP MPH accounted for an additional 2% of the variance in the change in CPT-Overall Index (OI) after controlling for covariates (p <.001). Linear regression analysis also indicated that ΔBP MPH significantly contributed to predict a change in omission errors, reaction time, and reaction time variability (p <.001, p <.01, p =.001, respectively), but not in commission errors or detectability index (d'). Participants with a clinically meaningful sBP increase of at least 5 mmHg (n = 191) improved by 4.8 points on the CPT-OI score (p <.001), compared to an improvement of only 0.6 points for participants whose sBP declined by at least 5 mmHg (n = 121). In conclusion, larger sBP increases after MPH administration were associated with greater enhancement in CPT performance. These results could be useful in informing MPH dosing in clinical practice. • Examined response to methylphenidate (MPH) treatment in children with ADHD. • Change in systolic blood pressure (sBP) noted after MPH treatment. • Higher increases in sBP were associated with larger improvement in attention. • Higher increases in sBP were also associated with better clinical response. [ABSTRACT FROM AUTHOR]