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PubMed1997

Recent advances in the identification of alpha1- and alpha2-adrenoceptor subtypes: therapeutic implications.

The cloning of multiple subtypes of both alpha1- and alpha2-adrenoceptors has renewed interest in the therapeutic application of agents interacting with these receptors. Effort has primarily been directed towards the design of uroselective alpha1-adrenoceptor antagonists for the treatment of benign prostatic hyperplasia (BPH). Evidence is accumulating for the involvement of a novel alpha1-adrenoceptor, designated as alpha1L-adrenoceptor, in alpha1-adrenoceptor-mediated smooth muscle contraction in prostatic and other urogenital tissues. While several antagonists showing a high degree of uroselectivity in animal models have been identified, their clinical superiority over the currently available alpha1-adrenoceptor antagonists has not yet been demonstrated. It is possible that the interaction with alpha1-adrenoceptors, as yet uncharacterised subtypes, at non-prostatic sites contributes to the therapeutic activity of this drug class in BPH. The alpha1-adrenoceptor subtypes involved in the control of vascular tone are currently being evaluated, and the profile of interaction with the various alpha1-adrenoceptor subtypes may play a key role in the efficacy of cardiovascular drugs such as carvedilol. Alpha2-adrenoceptor agonists are now being employed for a variety of therapeutic applications, most involving actions on receptors within the central nervous system (CNS). These agents are useful in the treatment of hypertension, glaucoma, opiate withdrawal and attention deficit hyperactivity disorder (ADHD), and as analgesics and adjuncts to general anaesthesia. While subtype selectivity has not yet been applied to the design of new alpha2-adrenoceptor agonists for these applications, recent gene mutation/knock-out experiments have identified the alpha2-subtypes involved in some of these actions, and optimisation of a therapeutic profile may be possible. Furthermore, the design of agents combining affinities for multiple adrenoceptor subtypes, or the combination of a specific adrenoceptor affinity profile with another pharmacological action, may offer advantages over molecules selective for an individual adrenoceptor subtype.

Journal Article↗

PubMedDate not supplied

[Epidemiological data about attention deficit hyperactivity disorder in a sample of Marabino children].

AIMS: This study reports the findings of a research project aimed at determining the rate of prevalence of attention deficit hyperactivity disorder (ADHD) in school aged children. PATIENTS AND METHODS: Different behavioural and cognitive measures were administered to a sample of children between 3 and 13 years of age obtained by means of a multistage sampling procedure that was stratified by socioeconomic and educational level. The sample was made up of 394 children; 33.25% (n = 131) were females and the remaining 66.75% (n = 263) males. The mean age of the sample was 7.64 years old (SD: 2.33). The assessment battery included the Conners Rating Scales adapted for parents and teachers, the abbreviated version of the Wechsler Intelligence Scale for Children (WISC III) and for Preschool children Revised (WPPSI R), several academic achievement scales, development history and DISC IV. RESULTS: The estimated prevalence of ADHD was 10.15%, and a figure of 2.03% was obtained for the hyperactive type, 0.51% for the inattentive subtype, and 7.61% for the combined subtype. Prevalence was higher for males, the ratio being 3:1. Subjects performance in the cognitive and academic measures was within the average interval. CONCLUSIONS: The prevalence of ADHD in our population oscillates around the average figures reported in other countries. This study confirms the prevalence of ADHD in the population of Venezuela, with a distribution of subtypes and in terms of gender similar to those reported in the literature.

Adolescent↗

PubMedDate not supplied

Attention deficit hyperactivity disorder: an update.

Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder, affecting 3% to 5% of school-aged children. Of the 3 subtypes--predominantly inattentive, predominantly hyperactive/impulsive, and a combined subtype--the latter is the most commonly represented group, accounting for 50% to 70% of all ADHD individuals. Stimulant medication is the cornerstone of management; however, stimulants with a short duration of action have been problematic for some patients. Recent technologic advances in delivery systems offer many patients the option of a once-daily dosage.

Age Distribution↗

PubMed2004

The distribution of symptoms of attention-deficit/hyperactivity disorder and oppositional defiant disorder in school age children in Turkey.

OBJECTIVE: The aim of this study was to determine the prevalence of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) in school age children in Sivas province centre and to examine the distribution of symptoms according to subtypes. METHOD: The study population was made up of 1425 children between the ages of 6 and 15 from eight primary schools selected by random sampling method in Sivas province centre. All students were given a questionnaire prepared according to DSMIV criteria that was completed by their parents or teachers. This form includes 18 symptoms of ADHD and eight symptoms of ODD. Student's t-test and variance analysis were used for statistical evaluation. RESULTS: A prevalence of 8.1% was found for ADHD in our study. According to subtypes, 32.2% of these were "inattentive", 40% were "hyperactive" and 27.8% were combined type. A prevalence of 11.5% was found for ODD. The boy/girl ratio was > 1 for both ADHD and ODD, and 52.2% of those with ADHD were established as having ODD at the same time. CONCLUSIONS: The prevalence of ADHD and ODD in primary school children was not considered to be small. Studies concerning the distribution of symptoms in different societies, cultures, and viewpoints and identification of children with this type of problem are beneficial for early diagnosis and prophylactic treatment.

Adolescent↗

PubMed2004

Comorbidity of generalized social anxiety disorder and depression in a pediatric primary care sample.

BACKGROUND: Comorbidity between adult social anxiety disorder and major depression is extensive. Considerably less information about this relationship is available among youth. METHODS: A randomly selected (from enrollees in a pediatric primary care clinic) sample of 190 families with children between the ages of 8 and 17 responded by mail to questionnaires assessing social anxiety, depression, and social functioning. Parents also completed a semi-structured telephone diagnostic interview about their child. RESULTS: The generalized type of social anxiety disorder was highly comorbid with major depression, generalized anxiety disorder, specific phobias, and ADHD, while little comorbidity was present for the nongeneralized subtype of social anxiety disorder. Logistic regression analyses indicated that generalized social anxiety disorder was the only anxiety disorder associated with an increased likelihood of major depression (OR=5.1). In all cases, social anxiety disorder had a significantly earlier age of onset than major depression. LIMITATIONS: This study relies on cross-sectional data and diagnoses are based on parent reporting of child behavior. CONCLUSIONS: Generalized social anxiety disorder is strongly associated with depressive illness in youth. Screening and treatment approaches that consider both social anxiety and depressive symptoms are necessary. Early intervention to treat social anxiety disorder may prevent later depressive disorders.

Adolescent↗

PubMed1997

Attention deficit disorder and conduct disorder: longitudinal evidence for a familial subtype.

BACKGROUND: An obstacle to the successful classification of attention deficit hyperactivity disorder (ADHD) is the frequently reported co-morbidity between ADHD and conduct disorder (CD). Prior work suggested that from a familial perspective, ADHD children with CD may be aetiologically distinct from those without CD. METHODS: Using family study methodology and three longitudinal assessments over 4 years, we tested hypotheses about patterns of familial association between ADHD, CD, oppositional defiant disorder (ODD) and adult antisocial personality disorder (ASPD). RESULTS: At the 4-year follow-up, there were 34 children with lifetime diagnoses of ADHD + CD, 59 with ADHD + ODD and 33 with ADHD only. These were compared with 92 non-ADHD, non-CD, non-ODD control probands. Familial risk analysis revealed the following: (1) relatives of each ADHD proband subgroup were at significantly greater risk for ADHD and ODD than relatives of normal controls; (2) rates of CD and ASPD were elevated among relatives of ADHD + CD probands only; (3) the co-aggregation of ADHD and the antisocial disorders could not be accounted for by marriages between ADHD and antisocial spouses; and (4) both ADHD and antisocial disorders occurred in the same relatives more often than expected by chance alone. CONCLUSIONS: These findings suggest that ADHD with and without antisocial disorders may be aetiologically distinct disorders and provide evidence for the nosologic validity of ICD-10 hyperkinetic conduct disorder.

Adolescent↗

PubMed2004

Family-based and case-control association studies of DRD4 and DAT1 polymorphisms in Chinese attention deficit hyperactivity disorder patients suggest long repeats contribute to genetic risk for the disorder.

Molecular genetic studies of attention deficit hyperactivity disorder (ADHD) have implicated the variable number of tandem repeat (VNTR) polymorphisms of two candidate genes, the dopamine D4 receptor (DRD4) and the dopamine transporter (DAT1). We sought to determine if these genes were relevant to the etiology of ADHD in China by using both family-based (N = 202 nuclear ADHD families) and case-control (N = 340 ADHD cases, and 226 controls) association study designs. Diagnoses and subtypes were ascertained according to Clinical Diagnostic Interview Scales (CDIS) using DSM-IV criteria. The repeat numbers at the DRD4 VNTR ranged from 2 to 6 repeats in the Han Chinese controls, with the most common being the 4-repeat (77%) and 2-repeat (19.4%) alleles. Neither the 7-repeat allele nor longer repeats were found. For the DAT1 VNTR, the repeat numbers ranged from 6 to 7 repeats and 9 to 11 repeats. The 10-repeat allele was the most frequent (90.7%). The long-repeat alleles of DRD4 (ranging from 4 to 6 repeats) and DAT1 (ranging from 11 to 12 repeats), were present more frequently in ADHD probands than controls (P < 0.05), although there was no significant allelic association when the alleles were analyzed separately from each other and there findings were not supported by within family tests of association. An exploratory stratification by gender suggests that long-repeat alleles of DRD4 and DAT1 may increase the risk for ADHD in Han Chinese children.

Adolescent↗

PubMed2006

Efficacy of retrospective recall of attention-deficit hyperactivity disorder symptoms: A twin study.

Attention-deficit hyperactivity disorder (ADHD) is currently recognized as a neurobiological, genetically based disorder in both children and adults. In this article we examine whether, by using a sample of middle-aged male twin veterans, the phenotypic characterization, prevalence, heritability and the longitudinal course of the illness is comparable to results observed in samples of children and adolescents. We evaluated the utility of adult reports of lifetime ADHD symptoms by examining the heritability of retrospectively reported childhood symptoms, using both symptom-based and discrete classification-based approaches, as well as examining the persistence of ADHD symptoms into adulthood for that subsample of individuals who were judged to possibly have ADHD as children. Our results showed prevalence rates that were approximately similar to those observed in other studies, demonstrable familiality, similar item endorsement patterns, a strong genetic association between hyperactive and inattentive subtypes, and a longitudinal decline in symptom severity. We concluded that while assessing ADHD in adult probands may be less accurate than with children or adolescents, since it demonstrates several characteristics in common with other assessment techniques it remains a viable diagnostic and research strategy, even with population samples.

Adult↗

PubMed2006

Attention deficit hyperactivity disorder: the childhood co-morbidity that most influences the disability burden in Tourette syndrome.

ADHD is a complex co-morbidity, as it is heteregeneous in terms of the clinical subtypes, but also in terms of the circuits involved and the level of involvement within those circuits. Specially focusing on the relationship of ADHD to TS, this author's studies have added some neurobehavioral and some anatomical magnetic resonance imaging evidence suggesting the ADHD occurring with TS, appears like "garden-variety" ADHD, at least in the matched research sample. The similarities of neuroanatomical findings in the TS plus ADHD and ADHD groups and their distinctness from neuroanatomical findings in childdren with "pure TS provide some parallels to the observed similarity of functional deficit in TS plus ADHD and ADHD alone groups and the relative lack of functional deficits in children with TS only. More specifically, the results of a decade of this author's research with the approximately 40% of children with TS who are free of ADHD indicate that they are entirely free of the motor control and executive control deficits of children with ADHD alone or TS plus ADHD, but they do have oculomotor control deficits in the initiation of prosaccades, regardless of their ADHD status. The neuroanatomical data in TS only is also of interest because it reflects increased white matter, particularly in the right frontal lobe and four out of five regions of the corps callosum, including the rostral portion most affiliated with the frontal lobes. It should be emphasized that almost everything summarized abouve is true for boys, whereas samples of girls grouped similarly have not yielded the same results.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

The dopamine transporter and attention-deficit/hyperactivity disorder.

The high incidence of attention-deficit/hyperactivity disorder (ADHD) and escalating use of ADHD medications present a compelling case for clarifying the pathophysiology of, and developing laboratory or radiologic tests for, ADHD. Currently, the majority of specific genes implicated in ADHD encode components of catecholamine signaling systems. Of these, the dopamine transporter (DAT) is a principal target of the most widely used antihyperactivity medications (amphetamine and methylphenidate); the DAT gene is associated with ADHD, and some studies have detected abnormal levels of the DAT in brain striatum of ADHD subjects. Medications for ADHD interfere with dopamine transport by brain-region- and drug-specific mechanisms, indirectly activating dopamine- and possibly norepinephrine-receptor subtypes that are implicated in enhancing attention and experiential salience. The most commonly used DAT-selective ADHD medications raise extracellular dopamine levels in DAT-rich brain regions. In brain regions expressing both the DAT and the norepinephrine transporter (NET), the relative contributions of dopamine and norepinephrine to ADHD pathophysiology and therapeutic response are obfuscated by the capacity of the NET to clear dopamine as well as norepinephrine. Thus, ADHD medications targeting DAT or NET might disperse dopamine widely and consign dopamine storage and release to regulation by noradrenergic, as well as dopaminergic neurons.

Adaptation, Physiological↗

PubMed2001

Attention deficit hyperactivity disorder with bipolar disorder in girls: further evidence for a familial subtype?

BACKGROUND: To clarify the nosologic status of girls with attention deficit hyperactivity disorder (ADHD) who also satisfy diagnostic criteria for bipolar disorder (BPD). METHODS: Using blind raters and structured psychiatric interviews, we examined 140 girls with ADHD, 122 non-ADHD comparisons and their 786 first degree relatives. Analyses tested specific hypotheses about the familial relationship between ADHD and bipolar disorder in girls. RESULTS: After stratifying our ADHD sample into those with and without BPD, we found that: (1) relatives of both ADHD subgroups were at significantly greater risk for ADHD than relatives of non-ADHD controls, (2) the two subgroups did not significantly differ in their relatives' risk for ADHD; (3) an elevated risk for bipolar disorder was observed among relatives when the proband child had BPD but not ADHD alone; (4) weak evidence of cosegregation between ADHD and BPD, and (5) no evidence of a trend for random mating between ADHD parents and those with mania. LIMITATIONS: Limitations of this study include the lack of direct interviewing of probands and the limited number of ADHD/BPD probands available. CONCLUSIONS: These findings extend to girls what was previously documented in boys and suggest that comorbid ADHD with BPD in girls is familially distinct from other forms of ADHD and may be related to what others have termed childhood onset BPD. Future work could determine if this subgroup has a characteristic course, outcome and response to treatment.

Adolescent↗

PubMed2002

Report from the third international meeting of the Attention-Deficit Hyperactivity Disorder Molecular Genetics Network.

Growing evidence of a genetic contribution to attention-deficit hyperactivity disorder (ADHD) has prompted investigators from around the world to convene annually to discuss ways of facilitating collaboration and sharing information about their work on this topic. The number of participants in the meeting has grown each year as a result of enthusiastic responses to each previous conference. This third annual meeting, held in Boston, began with presentations of ongoing and proposed collaborations. The status of Hypescheme, an operational criteria checklist developed in an effort to promote the reliable communication of information related to ADHD, was reviewed. A symposium was conducted to review current evidence for whether DSM-IV subtypes breed true. Finally, new data from individual research sites were presented. Despite recent advances, more work is needed to better characterize heritable aspects of the ADHD phenotype as well as the actual candidate genes themselves.

Attention Deficit Disorder with Hyperactivity↗

PubMed1997

[Hyperactivity at 18 months of age and attention-deficit hyperactivity disorder before entry to school--follow up study from 18 months to 6 years].

Forty children with the following behavior characteristic were selected by observing the attachment behavior between them and their parents at the time of developmental exam in a 18 months' health checkup. The behavior in question is; 18 month old children scurry away from their parent without looking back on parent's calls and without confirming parent's positions. Then all the examined 978 children including the children who had shown the above scurrying away behavior were prospectively followed until before the entry to school. At age six, 6 children were diagnosed of Mental Retardation, 4 of Pervasive Developmental Disorder, and 28 of Attention-Deficit Hyperactivity Disorder (ADHD). Now these results (especially the relationships between this scurrying away behavior at 18 months and ADHD before the entry to school) were analyzed statistically and discussed, then the next conclusions were derived. 1. This scurrying away behavior, especially the behavior without confirming parent's positions, is significantly related to ADHD before the entry to school. 2. This scurrying away behavior is one of the characteristic behaviors at 18 months in ADHD and corresponds to hyperactivity at 18 months. 3. The conduct of throwing a toy block is one of the behaviors that indicates impulsivity at 18 months, when children are requested to hand over a toy block in the developmental exam. 4. Through behavioral observation, ADHDs before the entry to school are categorized to 3 subtypes by presence or absence of this scurrying away behavior at 18 months or by presence or absence of aggressivity before the entry to school. 5. Among the 3 subtypes, the type with this scurrying away behavior and aggressivity before the entry is most necessary to be treated continuously from early childhood. Because it has impulsivity and speech delay since 18 months and untreatable behavioral problems in day nurseries or kindergartens, and therefore it might have Conduct Disorder or Learning Disorder in the future.

Aggression↗

PubMed2006

Attentional versus motor inhibition in adults with attention-deficit/hyperactivity disorder.

Faulty inhibition is theorized to be a central feature in attention-deficit/hyperactivity disorder (ADHD), but it remains unclear whether inhibitory impairments encompass both motoric and attentional domains. Further, characterization of inhibitory deficits in adults with ADHD is needed. We experimentally assessed adults who met diagnostic criteria for ADHD and a subgroup who had partially remitted. Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) subtype effects were also examined. Motoric inhibition was assessed with the antisaccade task, and attentional inhibition was assessed with the attentional blink (AB) task. Antisaccade results replicated prior findings of extended latencies and increased anticipatory saccades in ADHD. Errors, however, appeared to be epiphenomenal to ADHD as they were absent when symptoms had partially remitted. Anticipatory saccades appeared as potential core problems that remained even when symptoms had improved. Differential response patterns were found for predominantly inattentive and combined subtypes, with the latter showing increasing anticipatory movements with increasing fixation time. In the AB task, ADHD groups committed more errors but showed no convincing evidence of an abnormal blink. These results demonstrate clear effects on motoric inhibition but not attentional inhibition in adults with ADHD.

Adolescent↗

PubMed1997

Correspondence between DSM-III-R and DSM-IV attention-deficit/hyperactivity disorder.

OBJECTIVE: To evaluate the correspondence between DSM-III-R and DSM-IV definitions of attention-deficit/hyperactivity disorder (ADHD) in clinically referred children. Results of the field trials led to the hypothesis that there would be a strong correspondence between DSM-III-R and DSM-IV subtypes. METHOD: The sample consisted of all children and adolescents consecutively referred to a pediatric psychopharmacology clinic (N = 405). Children were comprehensively evaluated with structured diagnostic interviews assessing both DSM-III-R and DSM-IV ADHD. DSM-III-R symptoms were used to approximate DSM-IV subtypes. Kappa statistics and conditional probabilities were used to examine the correspondence between DSM-III-R and DSM-IV ADHD. RESULTS: Ninety-three percent of children who received a DSM-III-R diagnosis of ADHD also received a DSM-IV ADHD diagnosis. The kappa coefficient assessing the agreement between DSM-III-R and DSM-IV ADHD was .73 (z = 14.6, p < .0001). The kappa coefficient assessing the agreement between the DSM-III-R-approximated subtypes and the actual DSM-IV subtypes was .71 (z = 15, p < .0001). CONCLUSION: These results confirm previous findings and indicate that the change from DSM-III-R to DSM-IV results in minimal changes in case identification and provides support for diagnostic continuity between the two classification systems.

Adolescent↗

PubMed2004

Attention-deficit/hyperactivity disorder and the substance use disorders: the nature of the relationship, subtypes at risk, and treatment issues.

There is a strong literature supporting a relationship between ADHD and SUD. Clearly, ADHD adolescents with conduct or bipolar disorder as partof their clinical picture are at the highest risk for SUD. ADHD without comorbidity appears to confer an intermediate risk factor for SUD that appears to manifest in young adults and college students. Both family genetic and self-medication influences may be operational in the development and continuation of SUD in ADHD subjects: however, systematic data are lacking. Patients with ADHD and SUD require multi-modal intervention incorporating addiction and mental health treatment. Pharmacotherapy in individuals with ADHD and SUD needs to take into consideration abuse liability, potential drug interactions, and compliance concerns. Although the existing literature has provided important information on the relationship of ADHD and SUD, it also points to a number of areas in need of further study. The mechanism by which untreated ADHD leads toSUD and the risk reduction of ADHD treatment on later SUD, needs to be understood better. The influence of adequateness of treatment of ADHD on later SUD needs to be delineated. Given the prevalence and major morbidity and impairment caused by SUD and ADHD. prevention and treatment strategies for these patients need to be developed and evaluated further.

Adolescent↗

PubMed1997

Attention-deficit hyperactivity disorder with bipolar disorder: a familial subtype?

OBJECTIVE: To clarify the nosological status of children with attention-deficit hyperactivity disorder (ADHD) who also satisfy diagnostic criteria for bipolar disorder (BPD). METHOD: Blind raters and structured psychiatric interviews were used to examine 140 children with ADHD, a sample of 120 non-ADHD comparisons, and their 822 first-degree relatives. Data analyses tested specific hypotheses about the familial relationship between ADHD and BPD. RESULTS: After stratifying the ADHD sample into those with and without BPD, the authors found that (1) relatives of both ADHD subgroups were at significantly greater risk for ADHD than relatives of non-ADHD controls; (2) the two subgroups did not differ significantly from one another in their relatives' risk for ADHD; (3) a fivefold elevated risk for BPD was observed among relatives when the proband child had BPD but not when the proband had ADHD alone; (4) an elevated risk for major depression with severe impairment was found for relatives of ADHD + BPD probands; (5) both ADHD and BPD occurred in the same relatives more often than expected by chance alone; and (6) there was a trend for random mating between ADHD parents and those with mania. CONCLUSIONS: The data suggest that comorbid ADHD with BPD is familially distinct from other forms of ADHD and may be related to what others have termed childhood-onset BPD.

Adolescent↗

PubMed2002

Clinical implications of a link between fetal alcohol spectrum disorder and attention-deficit hyperactivity disorder.

OBJECTIVE: To provide an overview of the animal and human research literature on the link between fetal alcohol spectrum disorder (FASD) and attention-deficit hyperactivity disorder (ADHD). METHOD: We conducted a comprehensive literature review that addressed the history of, and current research on, fetal alcohol syndrome (FAS) and FASD, as well as that on ADHD in children. RESULTS: In animal and human research, there is emerging clinical, neuropsychological, and neurochemical evidence of a link between FASD and ADHD. CONCLUSIONS: The evidence of the link between these 2 conditions has implications for clinical management. The clinical quality of ADHD in children with FASD often differs from that of children without FASD. For children with FASD, ADHD is more likely to be the earlier-onset, inattention subtype, with comorbid developmental, psychiatric, and medical conditions. Children with FASD are commonly not mentally retarded but present complex learning disabilities, especially a mixed receptive-expressive language disorder with deficits in social cognition and communication (reminiscent of sensory aphasia and apraxia), working memory problems, and frequently, a mathematics disorder. Comorbid psychiatric conditions include anxiety, mood, conduct, or explosive disorders. As well, cardiac, renal, or skeletal problems are more likely to be present. Because these children have a disturbance in brain neurochemistry, or even brain structure (that is, in the corpus callosum), their response to standard psychostimulant medication can be quite unpredictable.

Animals↗