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Psychiatric comorbidity and functioning in clinically referred preschool children and school-age youths with ADHD.

OBJECTIVE: Although the literature documents that attention-deficit/hyperactivity disorder (ADHD) commonly onsets prior to age 6, little is known about the disorder in preschool children. We evaluated the clinical characteristics, psychiatric comorbidity, and functioning of preschool children and school-age youths with ADHD referred to a pediatric psychiatric clinic for evaluation. METHOD: Structured psychiatric interviews assessing lifetime psychopathology by DSM-III-R criteria were completed with parents about their children. Family, social, and overall functioning were also assessed at intake. RESULTS: We identified 165 children with ADHD aged 4 to 6 years (preschool children) and 381 youths aged 7 to 9 years (school-age) with ADHD. Despite being younger, preschool children had similar rates of comorbid psychopathology compared with school-age youths with ADHD. There was an earlier onset of ADHD and co-occurring psychopathology in the preschool children compared to school-age youths. Both preschool children and school-age youths had substantial impairment in school, social, and overall functioning. CONCLUSIONS: The results of this study suggest that despite being significantly younger, clinically referred preschool children with ADHD are reminiscent of school-age youths with ADHD in the quality of ADHD, high rates of comorbid psychopathology, and impaired functioning. Follow-up of these clinically referred preschool children with ADHD to evaluate the stability of their diagnoses, treatment response, and their long-term outcome are necessary.

Attention Deficit Disorder with Hyperactivity↗

A systematic evaluation of ADHD and comorbid psychopathology in a population-based twin sample.

OBJECTIVE: Clinical and population samples demonstrate that attention-deficit/hyperactivity disorder (ADHD) occurs with other disorders. Comorbid disorder clustering within ADHD subtypes is not well studied. METHOD: Latent class analysis (LCA) examined the co-occurrence of DSM-IV ADHD, oppositional defiant disorder (ODD), conduct disorder (CD), and depression symptoms in a population twin sample. The authors fit separate models for ADHD and comorbid disorder symptoms. Twin concordance ratios (monozygotic versus dizygotic) were compared examining genetic influence on class membership. RESULTS: LCA of ADHD symptoms resulted in seven classes including inattentive, combined, and hyperactive subtypes in 1,616 subjects. The few ADHD symptoms (53.4%) and severe inattentive (12.3%) classes were most frequent. LCA of ODD, CD, and depression symptoms in 1,587 subjects revealed five classes including ODD (19.4%), depression (14.5%), and two composite classes: ODD/CD (6.9%) and ODD/CD/depression (7.2%). Internalizing and externalizing comorbid disorders were present across all ADHD subtypes. Odds ratios (ORs) for twin concordance indicate genetic influence on severe inattentive (OR = 4.18; 95% confidence interval [CI], 1.52-11.53) and combined (OR = 5.25; 95% CI, 1.32-20.78) ADHD classes and ODD (OR = 1.49; 95% CI, 0.70-3.17), ODD/CD (OR = 3.32; 95% CI, 0.57-19.28), and ODD/CD/depression (OR = 1.20; 95% CI, 0.30-4.77) classes. CONCLUSIONS: Internalizing and externalizing disorders did not cluster differentially within ADHD subtypes. LCA may provide a more precise characterization of comorbidity with ADHD.

Adolescent↗

Characteristics of adolescents and young adults with ADHD who divert or misuse their prescribed medications.

OBJECTIVE: Little is known about the risks and characteristics of attention-deficit/hyperactivity disorder (ADHD) patients who misuse or divert their stimulant medications. As part of a 10-year longitudinal study of youths with ADHD, the authors evaluated medication diversion or misuse at the last follow-up period. METHOD: Structured psychiatric interviews for diagnosis and a self-report questionnaire regarding medication use in medicated subjects with ADHD compared with controls without ADHD receiving psychotropics for non-ADHD treatment were employed. RESULTS: Of 98 subjects receiving psychotropic medications (mean age of 20.8 +/- 5 years), 55 (56%) were ADHD subjects and 43 (44%) were controls receiving medications for other purposes. The authors found that 11% of the ADHD group reported selling their medications compared with no subjects in the control group (z = 0.00, p <.05). An additional 22% of the ADHD group reported misusing their medications compared with 5% of the control subjects (z = 1.7 p =.09) and that those with conduct or substance use disorders accounted for the misuse and diversion. A minority of subjects reported escalating their doses and concomitant use with alcohol and drugs. CONCLUSIONS: The data indicate that the majority of ADHD individuals, particularly those without conduct or substance use disorders, use their medications appropriately. The authors' findings also highlight the need to monitor medication use in ADHD individuals with conduct and/or substance use disorders and to carefully select agents with a low likelihood of diversion or misuse in this group.

Adolescent↗

Collaborative analysis of DRD4 and DAT genotypes in population-defined ADHD subtypes.

BACKGROUND: It has been proposed that some of the variability in reporting of associations between attention deficit hyperactivity disorder (ADHD) and candidate genes may result from mixing of genetically heterogeneous forms of ADHD using DSM-IV criteria. The goal of the current study is to test whether population-based ADHD subtypes defined by latent class analysis help resolve issues of variable findings across individual gene association studies. METHODS: Three studies which had previously reported no associations between polymorphisms of the DRD4 and DAT genes and DSM-IV defined ADHD were reanalyzed using population-based and DSM-IV defined ADHD subtypes. RESULTS: Across studies no significant associations were found for either DRD4 or DAT polymorphisms using DSM-IV ADHD subtypes. In contrast, a significant association was found between the combined data set for the 440 base pair 3' DAT VNTR polymorphism and population-defined severe combined ADHD (OR=1.25, p=.01). A marginally significant association was also found between the 7 repeat DRD4 allele and population-defined severe combined ADHD. CONCLUSION: Use of alternative population-based defined ADHD subtypes may help resolve some of the variable results presented for candidate gene association studies in ADHD.

Adolescent↗

Racial and ethnic differences in ADHD and LD in young school-age children: parental reports in the National Health Interview Survey.

OBJECTIVES: Racial and ethnic disparities have been documented for many physical health outcomes in children. Less is known, however, about disparities in behavioral and learning disorders in children. This study uses data from a national health survey to examine racial and ethnic differences in identified attention deficit hyperactivity disorder (ADHD) and learning disability (LD). METHODS: The 1997-2001 National Health Interview Surveys obtained information from parents about the health and sociodemographic characteristics of children. Using these data, prevalence rates of identified ADHD and/or LD were estimated for Hispanic, African American, and white children 6-11 years of age. Racial and ethnic differences in health conditions, income, and insurance coverage were examined as possible explanations for disparities in parental reports of ADHD and LD, as well as the use of any prescription medication among children with ADHD. RESULTS: Hispanic and African American children, compared to white children, had parental reports of identified ADHD without LD less often, and adjustments for the confounding variables-birthweight, income, and insurance coverage-did not eliminate these differences. Hispanic and African American children, compared to white children, also had parental reports of ADHD with LD less often after adjustments for the effects of confounding variables. By contrast, after adjustments for confounding variables, Hispanic and African American children were as likely as white children to have LD without ADHD. Among children with ADHD, use of any prescription medication was reported less often for Hispanic and African American children than white children. These disparities in medication use persisted after adjustments for confounding variables. CONCLUSIONS: The prevalence of ADHD and the use of any prescription medication among children with ADHD differed among Hispanic, African American, and white children. These disparities could not be explained by racial and ethnic differences in other health conditions and sociodemographic variables.

Attention Deficit Disorder with Hyperactivity↗

Attention-deficit hyperactivity disorder (ADHD).

Approaches to the diagnosis and treatment of attention-deficit hyperactivity disorder (ADHD) are undergoing a major change as a result of information from studies on the genetics of ADHD and the use of new neuroimaging technologies. Moreover, pharmacogenomics, although still in its infancy, will provide a basis for much more sophisticated treatment strategies for ADHD, particularly once more information is available about the genetics of ADHD. Even at this point in time, there is some pertinent information available that, although not ready for application in clinical settings, nonetheless provides a broader perspective for the clinician. In terms of etiology, ADHD is a neuropsychiatric disorder. There is a genetic basis in about 80% of the cases, involving a number of different genes, and in about 20% of the cases, ADHD is the result of an acquired insult to the brain. Some individuals likely have both genetic and acquired forms. Although medication works well in many cases of ADHD, optimal treatment of ADHD requires integrated medical and behavioral treatment. The family plays a crucial role in the management of children with ADHD. Because there is often a very high degree of comorbidity between ADHD and learning disabilities, teachers also have a great deal to contribute in the day-to-day management of these children. Early recognition and treatment prevent the development of more serious psychopathology in adolescence and adulthood.

Attention Deficit Disorder with Hyperactivity↗

Reexamining the familial association between asthma and ADHD in girls.

The objective of this study is to further evaluate the association between asthma and ADHD, addressing issues of familiality in female probands. A case control study of referred ADHD proband girls, controls, and relatives are used. Participants include 140 ADHD proband girls and 122 non-ADHD comparisons, with 417 and 369 first-degree biological relatives, respectively. Relatives are stratified into four groups according to proband ADHD and asthma status. The authors compare rates of asthma and ADHD in relatives. ADHD does not increase the risk for asthma in probands. Patterns of familial aggregation are mostly consistent with independent transmission of ADHD and asthma in families of girl probands. The results extend to female probands' previously reported findings that asthma and ADHD are independently transmitted in families. These findings further support the conclusion that ADHD symptoms should not be dismissed as part of asthma symptomatology or a consequence of its treatment.

Adult↗

Children with ADHD and depression: a multisource, multimethod assessment of clinical, social, and academic functioning.

Although ADHD and depression are common comorbidities in youth, few studies have examined this particular clinical presentation. To address method bias limitations of previous research, this study uses multiple informants to compare the academic, social, and clinical functioning of children with ADHD, children with ADHD and depression, and children without ADHD, all derived from a large community sample. High levels of comorbid depression are found in children with ADHD. Children withADHDand depression are more depressed and anxious than their non-depressed ADHDcounterparts but do not have more extreme levels of ADHD or aggression. The association between depression and ADHD does not appear to be epiphenomenal, that is, related to a shared association with anxiety or externalizing symptoms. Finally, children with ADHD and depression display more impairment in social and academic functioning compared to controls. Although social impairment is greater in children with ADHD and depression than in children with only ADHD, conduct problems are not.

Achievement↗

Training attention-switching ability in adults with ADHD.

OBJECTIVE: Children with ADHD show attention-switching impairment. The present study assessed attention-switching ability in adults with ADHD, the extent to which this ability can be improved via targeted training, and the degree to which training extends to novel tasks of attention-switching. METHOD: Adults with ADHD (n = 16) and adults without ADHD (n = 18) were divided into training and non-training groups. Training groups performed six blocks of four different attention-switching tasks, while non-training groups completed non-switching, "filler" tasks. Lastly, the four groups were tested on two novel attention-switching tasks. RESULTS: Adults with ADHD showed impaired attention-switching, relative to non-ADHD adults, but training significantly improved attention-switching in both ADHD and non-ADHD training groups. Finally, training effects transferred to new tasks of attention-switching. CONCLUSION: Adults with ADHD show attention-switching impairments, but deficits may be ameliorated with short-term, targeted training. Research has implications for cognitive training in ADHD.

Adult↗

Deficient social problem-solving in boys with ODD/CD, with ADHD, and with both disorders.

OBJECTIVE: To study social problem-solving skills in psychiatrically defined aggressive boys, starting from Dodge's social information-processing model. METHOD: Videotaped stimuli of problematic social situations and questions were presented to elicit responses that indicate boys' social problem-solving skills (encoding and interpretation of social cues, generation of possible responses, evaluation of responses, self-efficacy evaluation, and response selection). Boys aged 7 to 12 years with oppositional defiant or conduct disorder (ODD/CD) (n = 48), attention-deficit hyperactivity disorder (ADHD) (n = 27), and both disorders (ODD/CD + ADHD) (n = 29) were involved as well as a normal control group (n = 37) and a psychiatric control group with internalizing disorders (n = 23). RESULTS: When compared with normal controls, boys with ADHD, with ODD/CD, and with ODD/CD + ADHD encoded fewer social cues and generated fewer responses. Boys with ODD/CD and with ODD/CD + ADHD moreover were more confident in their ability to enact an aggressive response than normal controls. When ODD/CD boys and ODD/CD + ADHD boys were given the opportunity to select a response from various types of responses shown, they selected an aggressive response more often than normal controls. Thus, in ADHD boys social problem-solving was affected only in encoding and in the generation of responses, whereas in ODD/CD and ODD/CD + ADHD boys social problem-solving was affected throughout the process. CONCLUSION: For the further study of social problem-solving in aggressive children, it is essential to differentiate between children with ADHD and children with ODD/CD and ODD/CD + ADHD.

Aggression↗

Diagnosis and treatment of ADHD in adults in primary care.

The prevalence rate of adult attention-deficit/hyperactivity disorder (ADHD) indicates that 4.5% of adults continue to exhibit ADHD from childhood. Most adult sufferers of ADHD have not been properly diagnosed or treated. The majority of adults with ADHD exhibit at least 1 comorbid psychiatric disorder, such as major depressive disorder, anxiety disorder, personality disorder, substance abuse disorder, or bipolar disorder. In many instances, such a disorder may offer the first clue to diagnosing an adult with ADHD. Comorbidities may, however, confound a proper ADHD diagnosis, so it is important to look for and establish an early (childhood) and persistent (lifelong) history of inattention or hyperactivity. The use of available standardized ADHD rating scales and checklists will then help the physician to differentiate between ADHD and other comorbid psychiatric disorders commonly seen in primary care. At present, there is no universally accepted and efficient standardized assessment tool for identifying adult ADHD in primary care. However, the Adult Self-Report Scale Screener may represent such a tool and may be used with ease in a busy office setting. Using such strategies, primary care providers are still able and encouraged to identify and treat adults with ADHD.

Adult↗

Impact of ADHD and its treatment on substance abuse in adults.

Attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance abuse in adults. Additional psychiatric comorbidity increases this risk. ADHD is associated with different characteristics of substance abuse: substance abuse transitions more rapidly to dependence, and lasts longer in adults with ADHD than those without ADHD. Self-medication may be a factor in the high rate of substance abuse in adults with ADHD. While previous concerns arose whether stimulant therapy would increase the ultimate risk for substance abuse, recent studies have indicated that pharmacologic treatment appears to reduce the risk of substance abuse in individuals with ADHD. When treating adults with ADHD and substance abuse, clinicians should assess the relative severity of the substance abuse, the symptoms of ADHD, and any other comorbid disorders. Generally, stabilizing or addressing the substance abuse should be the first priority when treating an adult with substance abuse and ADHD. Treatment for adults with ADHD and substance abuse should include a combination of addiction treatment/psychotherapy and pharmacotherapy. The clinician should begin pharmacotherapy with medications that have little likelihood of diversion or low liability, such as bupropion and atomoxetine, and, if necessary, progress to the stimulants. Careful monitoring of patients during treatment is necessary to ensure compliance with the treatment plan.

Adult↗

Polymorphism of DRD2 gene and ADHD.

OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) is a prevalent childhood disorder. Evidence from the family and twin studies suggest that ADHD is familiar and highly heritable. Association studies are frequently used for the searching of markers responsible for genetic basis of ADHD. We investigated TaqI polymorphism of the dopamine receptor D2 (DRD2) in relationship with ADHD. The association between TaqI A polymorphism of DRD2 gene and ADHD has previously been published. DESIGN: We used the association study to test the relationship between TaqI A polymorphism of DRD2 gene and ADHD on groups of ADHD boys and control boys. SETTING: For DNA isolation, buccal tissue was used. PCR with restriction analysis of PCR products was used for genotyping. RESULTS: We found statistically different genotypic and allelic frequencies (p < 0.008, p < 0.002, respectively) of DRD2 polymorphism between two studied groups of boys. MAIN FINDINGS: According to our results we suppose that polymorphism TaqI A of DRD2 gene is involved in the pathogenesis of childhood ADHD in male subjects. Allele A1 and genotype A1A1 in male subjects is associated with ADHD. CONCLUSIONS: Our study confirmed the relationship between TaqI A polymorphism of DRD2 gene and ADHD published previously.

Adolescent↗

Disentangling the overlap between Tourette's disorder and ADHD.

OBJECTIVE: To identify similarities and differences in neuropsychiatric correlates in children with Tourette's syndrome (TS) and those with ADHD. METHOD: The sample consisted of children with Tourette's syndrome with ADHD (N = 79), children with Tourette's syndrome without ADHD (N = 18), children with ADHD (N = 563), psychiatrically referred children (N = 212), and healthy controls (N = 140). RESULTS: Disorders specifically associated with Tourette's syndrome were obsessive compulsive disorder (OCD) and simple phobias. Rates of other disorders, including other disruptive behavioral, mood, and anxiety disorders, neuropsychologic correlates, and social and school functioning were indistinguishable in children with Tourette's and ADHD. However, children with Tourette's syndrome plus ADHD had more additional comorbid disorders overall and lower psychosocial function than children with ADHD. CONCLUSIONS: These findings confirm previously noted associations between Tourette's syndrome and OCD but suggest that disruptive behavioral, mood, and anxiety disorders as well as cognitive dysfunctions may be accounted for by comorbidity with ADHD. However, Tourette's syndrome plus ADHD appears to be a more severe condition than ADHD alone.

Adolescent↗

Instability of the DSM-IV Subtypes of ADHD from preschool through elementary school.

CONTEXT: The DSM-IV definition of attention-deficit/hyperactivity disorder (ADHD) distinguished 3 subtypes that had not been extensively studied. OBJECTIVE: To determine whether the ADHD subtypes are stable enough over time to be valid. DESIGN: Longitudinal study with a greater-than 89% retention rate in 7 assessments over 8 years. SETTING: Outpatient clinics. PARTICIPANTS: Volunteer sample of 118 4- to 6-year-olds who met DSM-IV criteria for ADHD, including impairment in 2 settings in at least 1 assessment. MAIN OUTCOME MEASURE: Meeting DSM-IV criteria for the subtypes of ADHD during years 2 through 8. RESULTS: The number of children who met criteria for ADHD declined over time, but most persisted. Children who met criteria for the combined subtype (CT, n = 83) met criteria for ADHD in more subsequent assessments than children in the predominantly hyperactive-impulsive subtype (HT, n = 23). Thirty-one (37%) of 83 CT children and 6 (50%) of 12 children in the predominantly inattentive subtype (IT) met criteria for a different subtype at least twice in the next 6 assessments. Children of the HT subtype were even more likely to shift to a different subtype over time, with HT children who persisted in ADHD mostly shifting to CT in later assessments. The subtypes exhibited consistently different mean levels of hyperactive-impulsive symptoms during years 2 through 8 that corresponded with their initial subtype classifications, but initial subtype differences in inattention symptoms diminished in later years. CONCLUSIONS: In younger children, the CT and IT may be stable enough to segregate groups for research, but they seem too unstable for use in the clinical assessment of individual children. Children rarely remain in the HT classification over time; rather, they sometimes desist from ADHD but mostly shift to CT in later years. Using continuous ratings of hyperactivity-impulsivity symptoms as a diagnostic qualifier should be considered as an alternative to classifying nominal subtypes of ADHD in DSM-V.

Attention Deficit Disorder with Hyperactivity↗

Association of DRD4 in children with ADHD and comorbid conduct problems.

Recent family and twin study findings suggest that ADHD when comorbid with conduct problems may represent a particularly familial and heritable form of ADHD. Although several independent groups have shown association between the DRD4 7 repeat allele and ADHD, others have failed to replicate this finding. Previous TDT analyses of UK and Eire samples had also been negative. We set out to further examine the role of DRD4 but selecting a subgroup of children with ADHD and comorbid conduct problems. Families were recruited from Manchester, Ireland, Birmingham and London clinics. From these, 67 children who fulfilled diagnostic criteria for ADHD and who displayed conduct disorder symptoms were selected. TDT analysis, which had previously yielded negative results for the total sample, showed evidence of association between DRD4 and "ADHD with conduct problems" (7 repeat allele-24 transmissions, 13 non-transmissions; one-tailed P=0.05). These results provide further support for the role of DRD4 in ADHD. Furthermore, these results when considered together with family and twin study findings, suggest that those children with ADHD and comorbid conduct problems may be particularly informative for molecular genetic studies of ADHD. Further work is needed to examine these phenotype issues.

Adolescent↗

Co-occurrence of ADHD and low IQ has genetic origins.

Previous studies show that the symptoms of attention deficit hyperactivity disorder (ADHD) and lower intelligence quotient (IQ) covary in children. We investigated the aetiology of this association in a large population-based sample of 5-year-old twins. The twins were individually assessed on an IQ test, and data on ADHD symptoms were obtained from mother interviews and teacher ratings. Confirming previous studies, the phenotypic correlation between ADHD symptom scores and IQ was -0.3 and, in a categorical analysis, children with a Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) ADHD research diagnosis obtained IQ scores nine points lower, on average, than comparison children. We show here that the co-occurrence of ADHD and lower IQ has genetic origins: 86% of the association between ADHD symptom scores and IQ, and 100% of the association between ADHD diagnosis and IQ, was accounted for by genetic influences that are shared by ADHD and IQ. Some candidate genes for ADHD could also contribute to variation in IQ or vice versa.

Analysis of Variance↗

Family-based association study of the serotonin transporter gene polymorphisms in Korean ADHD trios.

The dopamine (DA) system has been implicated in attention deficit hyperactivity disorder (ADHD) based on pharmacologic evidence. Because of an interaction between the serotonin (5-HT) and DA systems, the serotonin transporter gene (SLC6A4) has been considered as a candidate ADHD susceptibility gene. Two common polymorphisms, 5-HTTLPR and the intron 2 VNTR, have been studied for association in ADHD, with both positive (increased frequency of long allele of 5-HTTLPR and decreased frequency of 12 repeats of the intron 2 VNTR) and negative findings. However, there has not been an association study in an East Asian ADHD population. In this study, we examined the genotypes of these two polymorphisms in 126 Korean ADHD families and investigated linkage disequilibrium (LD) between SLC6A4 and ADHD, using the transmission disequilibrium test (TDT) and haplotype analysis. Additionally, association with quantitative measures of inattention, hyperactivity-impulsivity, and overall severity was tested using logistic regression and QTDT analysis. TDT of both polymorphisms and haplotype analysis failed to detect LD. However, after excluding ADHD NOS subtype, TDT revealed nominally significant LD between 5-HTTLPR and ADHD (chi2 = 4.9, P = 0.036). QTDT revealed positive association between 12 repeats of the intron 2 VNTR and attention (P = 0.031), but case-control and TDT logistic regression analyses were negative. These markers have low heterozygosity in the Korean population, which would be expected to reduce the power of association. This result suggests that future studies should include more polymorphic markers and subjects to thoroughly investigate a potential association between SLC6A4 and ADHD in the Korean population.

Attention Deficit Disorder with Hyperactivity↗