Showing papers by "Stephen V. Faraone published in 2007"

Environmental risk factors for attention-deficit hyperactivity disorder

Abstract: Attention-deficit hyperactivity disorder (ADHD) is the most common cognitive and behavioural disorder diagnosed among school children. It is characterized by deficient attention and problem solving, along with hyperactivity and difficulty withholding incorrect responses. This highly prevalent disorder is estimated to affect 5–10% of children and in many cases, persists into adulthood, leading to 4% prevalence among adults. Converging evidence from epidemiologic, neuropsychology, neuroimaging, genetic and treatment studies shows that ADHD is a valid medical disorder. The majority of studies performed to assess genetic risk factors in ADHD have supported a strong familial nature of this disorder. Family studies have identified a 2- to 8-fold increase in the risk for ADHD in parents and siblings of children with ADHD. Various twin and adoption studies have also highlighted the highly genetic nature of ADHD. In fact the mean heritability of ADHD was shown to be 0.77, which is comparable to other neuropsychiatric disorders such as schizophrenia or bipolar disorder. However, several biological and environmental factors have also been proposed as risk factors for ADHD, including food additives/diet, lead contamination, cigarette and alcohol exposure, maternal smoking during pregnancy, and low birth weight. Many recent studies have specifically examined the relationships between ADHD and these extraneous factors. This review describes some of these possible risk factors. Conclusion: Although a substantial fraction of the aetiology of ADHD is due to genes, the studies reviewed in this article show that many environmental risk factors and potential gene–environment interactions also increase the risk for the disorder.

Cortical Thinning of the Attention and Executive Function Networks in Adults with Attention-Deficit/Hyperactivity Disorder

Abstract: Attention-deficit/hyperactivity disorder (ADHD) has been associated with structural alterations in brain networks influencing cognitive and motor behaviors. Volumetric studies in children identify abnormalities in cortical, striatal, callosal, and cerebellar regions. In a prior volumetric study, we found that ADHD adults had significantly smaller overall cortical gray matter, prefrontal, and anterior cingulate volumes than matched controls. Thickness and surface area are additional indicators of integrity of cytoarchitecture in the cortex. To expand upon our earlier results and further refine the regions of structural abnormality, we carried out a structural magnetic resonance imaging study of cortical thickness in the same sample of adults with ADHD (n = 24) and controls (n = 18), hypothesizing that the cortical networks underlying attention and executive function (EF) would be most affected. Compared with healthy adults, adults with ADHD showed selective thinning of cerebral cortex in the networks that subserve attention and EF. In the present study, we found significant cortical thinning in ADHD in a distinct cortical network supporting attention especially in the right hemisphere involving the inferior parietal lobule, the dorsolateral prefrontal, and the anterior cingulate cortices. This is the first documentation that ADHD in adults is associated with thinner cortex in the cortical networks that modulate attention and EF.

New models of collaboration in genome-wide association studies: the Genetic Association Information Network

Abstract: The Genetic Association Information Network (GAIN) is a public-private partnership established to investigate the genetic basis of common diseases through a series of collaborative genome-wide association studies. GAIN has used new approaches for project selection, data deposition and distribution, collaborative analysis, publication and protection from premature intellectual property claims. These demonstrate a new commitment to shared scientific knowledge that should facilitate rapid advances in understanding the genetics of complex diseases.

Behavioral inhibition in preschool children at risk is a specific predictor of middle childhood social anxiety: A five-year follow-up.

Abstract: Objective: Behavioral inhibition (BI) to the unfamiliar represents the temperamental tendency to exhibit fearfulness, reticence, or restraint when faced with unfamiliar people or situations. It has been hypoth- esized to be a risk factor for anxiety disorders. In this prospective longitudinal study, we compared the psychiatric outcomes in middle childhood of children evaluated at preschool age for BI. Method: The baseline sample consisted of 284 children ages 21 months to 6 years, including offspring at risk for anxiety (children of parents with panic disorder and/or major depression) and comparison offspring of parents without mood or major anxiety disorders. They had been assessed for BI using age-specific laboratory protocols. We reassessed 215 of the children (76.5%) at 5-year follow-up at a mean age of 9.6 years using structured diagnostic inter- views. Results: BI specifically predicted onset of social anxiety. The rate of lifetime social anxiety (DSM-IV social phobia or DSM-III-R avoidant disorder) was 28% versus 14% (odds ratio (OR) 2.37; 95% confidence interval (CI): 1.10-5.10) in inhibited versus noninhibited children. BI significantly predicted new onset of social phobia among children unaffected at baseline (22.2% vs 8.0% in inhibited versus noninhibited children (OR 3.15, 95% CI: 1.16-8.57). No other anxiety disorders were associated with BI. Conclusion: BI appears to be a temperamental antecedent to subsequent social anxiety in middle childhood. Children presenting with BI should be monitored for symptoms of social anxiety and may be good candidates for preventive cognitive behavioral strategies. (J Dev Behav Pediatr 28:225-233, 2007) Index terms: behavioral inhibition, social anxiety, high risk, childhood anxiety.

Stability of executive function deficits into young adult years : a prospective longitudinal follow-up study of grown up males with ADHD

Abstract: Objective: Although individuals with attention deficit-hyperactivity disorder (ADHD) commonly exhibit deficits in executive functions that greatly increase the morbidity of the disorder, all available information on the subject is cross sectional. Method: Males (n = 85) 9–22 years with ADHD followed over 7 years into young adulthood were assessed on measures of sustained attention/vigilance, planning and organization, response inhibition, set shifting and categorization, selective attention and visual scanning, verbal and visual learning, and memory. A binary definition of executive function deficits (EFDs) was defined based on a subject manifesting at least two abnormal tests 1.5 standard deviations from controls. Results: The majority of subjects maintained EFDs over time (kappa: 0.41, P < 0.001; sensitivity: 55%, specificity: 85%, positive predictive value: 69%, and negative predictive value: 75%). Conclusion: Considering the morbidity of EFDs, these findings stress the importance of their early recognition for prevention and early intervention strategies. EFDs are stable over time.

Axis I and II comorbidity in adults with ADHD.

Abstract: Ongoing debate over the validity of the attention-deficit/hyperactivity disorder (ADHD) construct in adulthood is fueled in part by uncertainty regarding implications of potentially extensive yet incompletely described comorbid Axis I and II psychopathology. Three hundred sixty-three adults ages 18 to 37 completed semistructured clinical interviews; informants were also interviewed, and best estimate diagnoses were obtained. Results were as follows: First, ADHD combined type (ADHD-C) had an excess of externalizing and internalizing Axis I disorders, suggesting a gradient-of-severity relationship between it and ADHD inattentive type (ADHD-I). Second, ADHD-C and ADHD-I did not differ in frequency of Axis II disorders. Third, however, ADHD overall was associated with increased rates of Axis II disorders, compared with rates in non-ADHD control participants, including both Cluster B (primarily borderline personality disorder) and Cluster C disorders. Fourth, ADHD incrementally accounted for clinician-rated global assessment of functioning scores above and beyond comorbid conditions or symptoms on either Axis I or Axis II. Results further inform nosology of ADHD in adults.

Confirmation that a specific haplotype of the dopamine transporter gene is associated with combined-type ADHD

Abstract: Introduction: One of the most prominent findings in genetics research on ADHD is the association with the 10-repeat-allele of a variable number tandem repeat (VNTR) in the 3'-untranslated region of the DA transporter gene. -- Despite a large number of positive reports the net-effect across studies is small with evidence for heterogeneity. -- One source of heterogeneity could arise if the 10-repeat allele tags a nearby functional variant (in partial linkage disequilibrium (LD) with the 10-repeat allele, with different levels of LD occurring in different populations) or interacts with another locus (additional DNA variants in DAT1 gene). Brookes et al., 2006 Arch. Gen. Psychiat., 63, 74-81 reported the association of ADHD with a sub-group of chromosomes, containing the 10-repeat-allele & the 3-repeat-allele of another VNTR in intron 8 a) The IMAGE final sample -- consisted of 998 families with 1,159 DSM-IV combined type probands. DNA from both parents available for 83.9% of cases, & 1 parent for 16.1% of cases. 93.5% were Ms, 61.5% had co-morbid oppositional defiant disorder & 23.2% conduct disorder. 76% of the sample was receiving medication for ADHD at the time of the research evaluations. Analysis was performed using the transmission disequilibrium test implemented in UNPHASED (www.hgmp.mrc.ac.uk/Registered/Options/unphased.html). b) We now report further replication of this finding (above)-- . with an overall odds ratio of 1.4 across our samples (P = 4.26 x 10-5, and haplotype-specific-P =6 x 10-7). (i.e., combination of 10-repeat allele with 3-repeat allele of a 30-bp VNTR located within intron 8 -- all other haplotype combinations are under-transmitted). c) These data-challenge -- meta-analyses suggesting there is no or little effect of DAT1 variation on risk for ADHD. Further investigation of functional variation across DAT1 is required.

Substance Use among ADHD Adults: Implications of Late Onset and Subthreshold Diagnoses

Abstract: Diagnosing ADHD in adults is difficult when the diagnostician cannot establish an onset prior to the DSM-IV criterion of age seven or if the number of symptoms does not achieve the DSM threshold for diagnosis. These diagnostic issues are an even larger concern for clinicians faced with adults with substance use disorders (SUD). The present study compared four groups of adults: full ADHD subjects who met all DSM-IV criteria for childhood onset ADHD, late onset ADHD subjects who met all criteria except the age at onset criterion, subthreshold ADHD subjects who did not meet full symptom criteria, and non-ADHD subjects who did not meet any of the above criteria. Diagnoses were by the Structured Clinical Interview for DSM-IV, and the Drug Use Severity Index (DUSI) was used for self-report of substance use. Cigarette and marijuana use was significantly greater in all ADHD groups relative to non-ADHD controls. Although usage rates of other drugs failed to reach significance, the ADHD groups were more likely to have used each drug (except alcohol) compared with the non-ADHD group. The late onset and full ADHD groups were more likely to have endorsed ever having a problem due to use of cigarettes, alcohol, or marijuana and reported more trouble resisting use of drugs or alcohol. The full ADHD group was more likely than the other groups to have reported "getting high" as their reason for using their preferred drug. Adults with ADHD have elevated rates of substance use and related impairment. Data about late onset ADHD provides further support for the idea that the DSM-IV age at onset criterion is too stringent. In contrast, subthreshold ADHD seems to be a milder form of the disorder, or perhaps a heterogeneous group of true ADHD cases and false positives.

Towards understanding the schizophrenia code: An expanded convergent functional genomics approach

Abstract: Identifying genes for schizophrenia through classical genetic approaches has proven arduous. Here, we present a comprehensive convergent analysis that translationally integrates brain gene expression data from a relevant pharmacogenomic mouse model (involving treatments with a psychomimetic agent - phencyclidine (PCP), and an anti-psychotic - clozapine), with human genetic linkage data and human postmortem brain data, as a Bayesian strategy of cross validating findings. Topping the list of candidate genes, we have three genes involved in GABA neurotransmission (GABRA1, GABBR1, and GAD2), one gene involved in glutamate neurotransmission (GRIA2), one gene involved in neuropeptide signaling (TAC1), two genes involved in synaptic function (SYN2 and KCNJ4), six genes involved in myelin/glial function (CNP, MAL, MBP, PLP1, MOBP and GFAP), and one gene involved in lipid metabolism (LPL). These data suggest that schizophrenia is primarily a disorder of brain functional and structural connectivity, with GABA neurotransmission playing a prominent role. These findings may explain the EEG gamma band abnormalities detected in schizophrenia. The analysis also revealed other high probability candidates genes (neurotransmitter signaling, other structural proteins, ion channels, signal transduction, regulatory enzymes, neuronal migration/neurite outgrowth, clock genes, transcription factors, RNA regulatory genes), pathways and mechanisms of likely importance in pathophysiology. Some of the pathways identified suggest possible avenues for augmentation pharmacotherapy of schizophrenia with other existing agents, such as benzodiazepines, anticonvulsants and lipid modulating agents. Other pathways are new potential targets for drug development. Lastly, a comparison with our earlier work on bipolar disorder illuminates the significant molecular overlap between schizophrenia and bipolar disorder.

Time reproduction in children with ADHD and their nonaffected siblings.

Abstract: Objective: Time reproduction is deficient in children with attention-deficit/hyperactivity disorder (ADHD). Whether this deficit is familial and could therefore serve as a candidate endophenotype has not been previously investigated. It is unknown whether timing deficits are also measurable in adolescent children with ADHD and nonaffected siblings. Method: These issues were investigated in 226 children with ADHD, 188 nonaffected siblings, and 162 normal controls ages 5 to 19. Children participated in a visual and auditory time reproduction task. They reproduced interval lengths of 4, 8, 12, 16, and 20 seconds. Results: Children with ADHD and their nonaffected siblings were less precise than controls, particularly when task difficulty was systematically increased. Time reproduction skills were familial. Time reproduction deficits were more pronounced in younger children with ADHD than in older children. Children with ADHD could be clearly dissociated from control children until the age of 9. After this age, group differences were somewhat attenuated, but were still present. Differences between nonaffected siblings and controls were constant across the age range studied. Deficits were unaffected by modality. Conclusions: Time reproduction may serve as a candidate endophenotype for ADHD, predominantly in younger children with (a genetic risk for) ADHD.

Is attention deficit hyperactivity disorder a valid diagnosis in the presence of high IQ? Results from the MGH Longitudinal Family Studies of ADHD.

Abstract: Background: The aim of this study was to assess the validity of diagnosing attention deficit/hyperactivity disorder (ADHD) in high IQ children and to further characterize the clinical features associated with their ADHD. Methods: We operationalized giftedness/high IQ as having a full scale IQ ≥120. We identified 92 children with a high IQ who did not have ADHD and 49 children with a high IQ that met diagnostic criteria for ADHD who had participated in the Massachusetts General Hospital Longitudinal Family Studies of ADHD. Results: Of our participants with ADHD and a high IQ, the majority (n = 35) met criteria for the Combined subtype. Relative to control participants, children with ADHD and high IQ had a higher prevalence rate of familial ADHD in first-degree relatives, repeated grades more often, had a poorer performance on the WISC-III Block Design, had more comorbid psychopathology, and had more functional impairments across a number of domains. Conclusions: Children with a high IQ and ADHD showed a pattern of familiality as well as cognitive, psychiatric and behavioral features consistent with the diagnosis of ADHD in children with average IQ. These data suggest that the diagnosis of ADHD is valid among high IQ children.

The effect of stimulant treatment for ADHD on later substance abuse and the potential for medication misuse, abuse, and diversion.

Abstract: Attention-deficit/hyperactivity disorder (ADHD) is known to be a strong risk factor for substance use disorders (SUD) in adolescence and in adulthood. Research shows that stimulant treatment does not increase the risk of SUD in adolescents or adults with ADHD but rather that stimulant treatments may have a protective effect. However, 2 in 10 youths with ADHD misuse their medication. Recent evidence suggests that slow uptake of medication in the brain allows for effective treatment without patients experiencing the euphoric qualities of immediate-release agents that lead to abuse or diversion. As a result, extended-release products and different formulations, such as lisdexamfetamine dimesylate (LDX), are less likely to be misused and diverted and may have lower abuse potential.

Effect of stimulant medications for attention-deficit/hyperactivity disorder on later substance use and the potential for stimulant misuse, abuse, and diversion.

Abstract: The objective of this article is to review literature about the effects of stimulant therapy on substance use disorders and the potential for misuse and diversion of stimulants. We reviewed published literature relevant to these objectives, and studies were selected if they were published or accepted for publication in peer-reviewed journals. Prospective longitudinal studies show that attention-deficit/hyperactivity disorder (ADHD) is a risk factor for subsequent substance use disorders. These studies also suggest that ADHD pharmacotherapy in childhood reduces the risk for substance use disorders. Misuse and diversion of prescribed stimulants occur among a minority of ADHD patients, especially those with conduct or substance use disorders. Long-acting stimulants may be less likely to be misused or diverted.

Predictors, clinical characteristics, and outcome of conduct disorder in girls with attention-deficit/hyperactivity disorder: a longitudinal study

Abstract: Background. Research on the overlap between attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) in males has provided useful information on the etiology, correlates, course, and nosology of this co-morbid condition. However, it is unclear how these results extend to females. Our aim was to examine the predictors, clinical characteristics, and functional outcome of CD in a sample of female youth with and without ADHD. Method. We conducted a blind, 5-year prospective longitudinal study of girls with (n= 140) and without (n= 122) ADHD, aged 6-18 years at baseline. At the 5-year follow-up, 123 (88 %) and 112 (92%) of the ADHD and control children respectively were reassessed at a mean age of 16·7 years. Psychiatric disorders were assessed using blind structured diagnostic interviews. Results. Baseline ADHD was a significant risk factor for lifetime CD throughout childhood and adolescence [hazard ratio (HR) 5·8, 95% confidence interval (CI) 2·9-11·5, p<0·001]. Among ADHD girls, childhood-onset (< 12 years) CD was predicted by paternal antisocial personality disorder (ASPD), while adolescent-onset CD (≥12 years) was predicted by family conflict. In addition, lifetime CD significantly predicted academic, psychiatric and sexual behavior problems in girls with ADHD at follow-up. Conclusions. ADHD is a significant risk factor for CD in girls. CD is associated with increased risk for academic, psychiatric and sexual behavior problems compared to ADHD girls without CD. Given that the therapeutic approaches indicated by ADHD and CD differ, these findings highlight the importance of improved efforts aimed at early identification and treatment of CD in girls with ADHD.

Stability of Executive Function Deficits in Girls with ADHD: A Prospective Longitudinal Followup Study into Adolescence

Abstract: Neuropsychological deficits in the executive system are major sources of morbidity in individuals with attention-deficit/hyperactivity disorder (ADHD) We conducted a 5-year longitudinal study of girls with (N = 140) and without (N = 122) ADHD, aged 6–18 years at baseline Neuropsychological functioning was assessed using standard neuropsychological testing assessing executive functions (EFs) Girls with ADHD were significantly more impaired than controls in all neuropsychological domains except set shifting Despite variability in the stability of individual domains of EFs, the majority (79%) of girls with ADHD that met the categorical definition of executive function deficits (EFDs, defined as two or more EF tasks impaired) at baseline continued to have EFDs at the five-year followup These findings document the stability of EFDs in girls with ADHD from childhood into adolescence

Can bipolar disorder-specific neuropsychological impairments in children be identified?

Abstract: This study examined neuropsychological deficits among children with bipolar disorder while attending to its comorbidity with attention-deficit/hyperactivity disorder (ADHD). Seventy-three unmedicated children (ages 6-17 years) with Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) bipolar disorder plus ADHD (BPD + ADHD) were compared with 102 unmedicated children with ADHD without bipolar disorder, and 120 children without bipolar disorder or ADHD. Ninety-four percent of participants were Caucasian, 58% were male, and 42% were female. On average participants were of middle to upper socioeconomic status. Participants were assessed with a comprehensive neuropsychological battery and measures of academic achievement, school failure, and special education placement. Participants with BPD + ADHD and with ADHD were impaired in interference control, verbal learning, and arithmetic achievement and had higher rates of special school services. Across all of the measures of neuropsychological functioning, the only difference observed between youths with BPD + ADHD and youths with ADHD was that youths with BPD + ADHD performed more poorly on one measure of processing speed. Thus, comorbidity with ADHD may account for many of the neuropsychological deficits observed in children with bipolar disorder.

Investigation of variation in SNAP-25 and ADHD and relationship to co-morbid major depressive disorder.

Abstract: Synaptosomal-associated protein of 25 kDa (SNAP-25), a protein involved in presynaptic neurotransmitter release, is a candidate gene for attention deficit/hyperactivity disorder (ADHD). Previous investigators have reported association initially with two single nucleotide polymorphisms (SNPs) (rs3746544, rs1051312) and their associated haplotypes. Subsequently, additional SNPs across the region were also reported to be associated with ADHD. We attempted to replicate these observations in a sample of 229 families with ADHD offspring by genotyping 61 SNPs spanning the region containing SNAP-25. A single SNP (rs3787283) which is in strong linkage disequilibrium (LD) with rs3746544 and rs1051312 (D′ = 0.89–0.94) resulted in a nominally significant association (P = 0.002). When we pooled our data with those from prior studies, results were modestly significant for rs3746544 (P = 0.048) and rs6077690 (P = 0.031). As an attempt to determine if specific ADHD-related phenotypes may be more relevant to SNAP-25 than the categorical diagnosis, we carried out exploratory subgroup analysis in our ADHD sample according to co-morbid status. We found the strongest association result in the ADHD patients with co-morbid major depressive disorder (MDD). Six SNPs were nominally associated with the ADHD and co-morbid MDD cases (P = 0.012–0.045). Furthermore, a haplotype block located 11 kb 3′ of the gene showed positive evidence for association with this phenotype (global P = 0.013). In conclusion, we report some evidence supporting the association of previously implicated SNPs (rs3746544, rs1051312) of SNAP-25 to ADHD. We further suggest that co-morbidity with MDD may enhance detection of the association between SNAP-25 and ADHD. © 2007 Wiley-Liss, Inc.

More evidence supports the association of PPP3CC with schizophrenia.

Abstract: Calcineurin is a calcium/calmodulin-dependent protein phosphatase composed of two subunits, a regulatory subunit of calcineurin B (CNB) and a catalytic subunit of calcineurin A (CNA). PPP3CC is the γ isoform of CNA located at the chromosome 8p21.3 region. To evaluate the association between PPP3CC and schizophrenia in the Taiwanese population, 10 single nucleotide polymorphism (SNP) markers across the gene were genotyped by the method of MALDI-TOF in 218 schizophrenia families with at least two affected siblings. One SNP (rs2272080) located around the exon 1 untranslated region was nominally associated with schizophrenia (P=0.024) and significantly associated with the expression of PPP3CC in lymphoblast cell line; the TT and TG genotype had significantly higher relative expression levels than the GG genotype (P=0.0012 and 0.015, respectively). In further endophenotype stratification, the single locus of rs2272080 and the haplotypes of both two-SNP haplotype (rs7833266–rs2272080) and seven-SNP haplotype (rs2461491–rs2469758–rs2461489–rs2469770–rs2449340–rs1482337–rs2252471) showed significant associations with the subgroup of schizophrenia with deficits of the sustained attention as tested by the continuous performance test (CPT, P<0.05) and the executive functioning as tested by the Wisconsin Card Sorting Test (WCST, P<0.05). The results suggest that PPP3CC gene may be a true susceptibility gene for schizophrenia.

An analysis of patient adherence to treatment during a 1-year, open-label study of OROS methylphenidate in children with ADHD.

Abstract: Objective: Treatment adherence is an important aspect of ADHD symptom management, but there are many factors that may influence adherence. Method: This analysis assessed adherence to OROS methylphenidate during a 1-year, open-label study in children. Adherence was defined as the number of days medication was taken divided by the number of days in the study and determined to be high if ≥75%. Possible clinical and demographic factors associated with adherence, including use of planned medication breaks, were assessed. Results: Mean adherence was 86.4%. It was 91.6% for the subgroup of patients who reported not taking planned medication breaks (n = 252) and 77.7% for the subgroup taking planned medication breaks (n = 155). Overall, 75% of patients showed high adherence. Older age, low starting dose, minority ethnic status, and fewer ADHD symptoms were associated with low adherence. Conclusion: Various factors were found to be associated with low adherence, and the results of this analysis provide guidance to...

Developmental trajectories of anxiety disorders in offspring at high risk for panic disorder and major depression.

Abstract: The objective of this study was to evaluate the longitudinal course of psychiatric disorders in children of parents with and without panic disorder and major depression as they transition through the period of risk from early to late childhood. Over a 5-year follow-up, we compared the course of psychiatric disorders in offspring of parents with panic disorder, major depression, or neither disorder. Subjects consisted of 233 offspring (from 151 families) with baseline and follow-up assessments. Subjects were comprehensively assessed with structured diagnostic interviews. Anxiety disorders at baseline were used to predict anxiety disorders and major depression at follow-up using stepwise logistic regression. Separation anxiety disorder significantly increased the risk for the subsequent development of specific phobia, agoraphobia, panic disorder, and major depression, even after parental panic and depression were covaried. Agoraphobia significantly increased the risk for subsequent generalized anxiety disorder. These findings suggest that separation anxiety disorder is a major antecedent disorder for the development of panic disorder and a wide range of other psychopathological outcomes, and that it increases the risk for subsequent psychopathology even among children already at high familial risk for anxiety or mood disorder.

Association between polymorphisms in serotonin transporter gene and attention deficit hyperactivity disorder in Chinese Han subjects.

Abstract: Prior work has shown reduced serotonin transmission to be associated with impulsivity and behavioral problems. The current study assessed the association between ADHD and two variants of the serotonin transporter gene: the 44-bp deletion/insertion polymorphism (5-HTTLPR) and the 17 bp-repeat polymorphism in intron 2 (STin2.VNTR). We hypothesized that ADHD phenotypes associated with impulsivity would show an association with these variants. Two-hundred and ninety-three ADHD trios were genotyped and analyzed using transmission disequilibrium test (TDT) analysis and haplotype analysis. We found no association between the STin2.VNTR and ADHD, but did find preferential transmission of the S allele of the 5-HTTLPR polymorphism (chi(2) = 5.751, P = 0.016) to probands with ADHD. Haplotype analysis found the L/10 haplotype was over-transmitted (chi(2) = 6.172, P = 0.013), while L/12 was under-transmitted to probands with ADHD (chi(2) = 4.866, P = 0.027).

A naturalistic study of the effects of pharmacotherapy on substance use disorders among ADHD adults.

Abstract: BackgroundStudies of adults with attention deficit hyperactivity disorder (ADHD) show an elevated prevalence of substance use disorders (SUDs) and the substance abuse literature shows that ADHD is elevated in substance users. Some researchers postulate that stimulant treatment of ADHD increases the risk for SUD in ADHD patients but follow-up studies suggest treatment protects patients from subsequent SUDs. This report uses retrospective data to assess the impact of prior ADHD pharmacotherapy on SUDs in 206 ADHD adults (n=79 late-onset ADHD, n=127 full ADHD) grouped by lifetime history of ADHD treatment (no treatment, past treatment, current and past treatment).MethodStructured Clinical Interview for DSM-IV (SCID) data were used to establish abuse and dependence, and Drug Use Screening Inventory (DUSI) responses were used to establish prevalence of use, preference for cigarettes, alcohol and drugs of abuse, complications from use, and motivation for use (get high, change mood, sleep better).ResultsNo differences were found in the prevalence of cigarette smoking, alcohol or drug abuse or dependence, as well as no significant differences in 1-month prevalence of any use or use more than 20 times. No differences were found in complications of drug or alcohol use across groups. Subjects with current treatment rated getting high as a motivating factor significantly more frequently than subjects in the past treatment group; this result lost significance when we included ADHD diagnostic category.ConclusionsOur results are consistent across substances and ADHD diagnoses, and support the hypothesis that pharmacotherapy does not cause subsequent SUDs.

Long-Term Effects of Methylphenidate Transdermal Delivery System Treatment of ADHD on Growth

Abstract: Objective: To examine the long-term effects of the methylphenidate transdermal system (MTS) on the growth of children being treated for attention-deficit/hyperactivity disorder. Method: Height, weight, and body mass index (BMI) were measured in 127 children ages 6 to 12 at longitudinal assessments for up to 36 months of treatment with MTS. These data were compared with norms provided by the Centers for Disease Control and Prevention. Results: MTS treatment was associated with small but significant delays in growth for height, weight, and BMI. The latter two indices were affected in a dose-dependent manner. Children who had not received prior stimulant therapy and children who entered the study with above-average height, weight, and BMI were most likely to experience growth deficits during the trial. Effects on all parameters of growth were most apparent during the first year of treatment, and attenuated over time. Conclusions: Consistent with prior studies of methylphenidate, our results suggest that treatment with MTS can lead to reductions in expected height, weight, and BMI that show some attenuation over the course of treatment. Growth of patients with attention-deficit/hyperactivity disorder treated with MTS should be closely monitored, but in this study, deficits in growth in relation to MTS treatment were not a significant clinical concern for most children.

A study of how socioeconomic status moderates the relationship between SNPs encompassing BDNF and ADHD symptom counts in ADHD families.

Abstract: Recent animal research suggests that brain-derived neurotrophic factor (BDNF), may mediate response to different environmental stimuli. In this paper, we evaluated the possible role of BDNF as a moderator of attention deficit hyperactivity disorder (ADHD) in the context of different socioeconomic classes. We genotyped ten single nucleotide polymorphisms (SNPs) in and around BDNF in 229 families and evaluate whether there are SNP-by-socioeconomic status (SES) interactions for attention deficit hyperactivity. We developed three quantitative phenotypes for ADHD from nine inattentive and nine hyperactive-impulsive symptoms that were used in SNP-by-SES interaction analyses using a new methodology implemented in the computer program PBAT. Findings were adjusted for multiple comparisons using the false discovery rate. We found multiple significant SNP-by-SES interactions using the inattentive symptom count. This study suggests that different SES classes may modify the effect of the functional variant(s) in and around BDNF to have an impact on the number of ADHD symptom counts that are observed. The two exons within BDNF represent potential functional variants that may be causing the observed associations.

A laboratory driving simulation for assessment of driving behavior in adults with ADHD: a controlled study

Abstract: Background It is now estimated that attention deficit-hyperactivity disorder (ADHD) afflicts at least 4% of adults in the United States and is associated with high levels of morbidity and functional impairment. One key area of dysfunction associated with ADHD is impaired motor vehicle operation. Our goal was to examine the association between ADHD and specific driving outcomes in a sample of adults using a driving simulator.