ADHD Combined Subtype Research Articles

Disturbed structural connectivity is related to inattention and impulsivity in adult attention deficit hyperactivity disorder

Inattention and impulsivity are the most prominent clinical features of attention deficit hyperactivity disorder (ADHD) in adulthood. Structural and functional neuroimaging studies of subjects with ADHD have demonstrated abnormalities in several brain areas, including fronto-striatal and fronto-cerebellar networks. Mostly, these studies were based on volumetric measurements and have been conducted in children. We investigated white matter (WM) integrity and correlation with measures of attention and impulsivity in adult patients with ADHD adopting diffusion tensor imaging (DTI). N = 37 (21 males) never-medicated adult patients with ADHD combined subtype and N = 34 (16 males) healthy controls were investigated. ADHD diagnosis (DSM-IV) was assessed with clinical interviews and rating scales, subjects also underwent a large neuropsychological test battery including tests of attention and impulsivity. DTI was acquired, and group differences of fractional anisotropy (FA) and mean diffusivity (MD) as well as correlation analyses with measures of attentional performance and impulsivity were calculated using voxel-based analyses. In adult patients with ADHD, we found reduced FA as well as higher MD bilaterally in orbitomedial prefrontal WM and in the right anterior cingulate bundle, while elevated FA was present bilaterally in temporal WM structures. Measures of attention were correlated with DTI parameters in the right superior longitudinal fasciculus, whereas measures of impulsivity were correlated with FA in right orbitofrontal fibre tracts. This is the first DTI study demonstrating disturbed structural connectivity of the frontal-striatal circuitry in adult patients with ADHD. Moreover, a direct correlation between WM integrity and measures of attention and impulsivity is shown.

Attentional Control Activation Relates to Working Memory in Attention-Deficit/Hyperactivity Disorder

Attentional control difficulties in individuals with attention-deficit/hyperactivity disorder (ADHD) might reflect poor working memory (WM) ability, especially because WM ability and attentional control rely on similar brain regions. The current study examined whether WM ability might explain group differences in brain activation between adults with ADHD and normal control subjects during attentional demand. Participants were 20 adults with ADHD combined subtype with no comorbid psychiatric or learning disorders and 23 control subjects similar in age, IQ, and gender. The WM measures were obtained from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-Revised. Brain activation was assessed with functional magnetic resonance imaging (fMRI) while performing a Color-Word Stroop task. Group differences in WM ability explained a portion of the activation in left dorsolateral prefrontal cortex (DLPFC), which has been related to the creation and maintenance of an attentional set for task-relevant information. In addition, greater WM ability predicted increased activation of brain regions related to stimulus-driven attention and response selection processes in the ADHD group but not in the control group. The inability to maintain an appropriate task set in young adults with combined type ADHD, associated with decreased activity in left DLPFC, might in part be due to poor WM ability. Furthermore, in individuals with ADHD, higher WM ability might relate to increased recruitment of stimulus-driven attention and response selection processes, perhaps as a compensatory strategy.

Cortical Gray Matter in Attention-Deficit/Hyperactivity Disorder: A Structural Magnetic Resonance Imaging Study

ObjectivePrevious studies have shown smaller brain volume and less gray matter in children with attention-deficit/hyperactivity disorder (ADHD). Relatively few morphological studies have examined structures thought to subserve inhibitory control, one of the diagnostic features of ADHD. We examined one such region, the pars opercularis, predicting a thinner cortex of the inferior frontal gyrus (IFG) in children with ADHD.MethodStructural images were obtained from 49 children (24 control; 25 ADHD combined subtype) aged 9 though 15 years. Images were processed using a volumetric pipeline to provide a fully automated estimate of regional volumes of gray and white matter. A further analysis using FreeSurfer provided measures of cortical thickness for each lobe, and for 13 regions in the frontal lobe.ResultsRelative to controls, children with ADHD had smaller whole brain volume and lower gray matter, but not white matter, volumes in all lobes. An analysis of frontal regions showed a significant interaction of group by region. Planned contrasts showed bilateral thinner cortex in the pars opercularis in children with ADHD.ConclusionsChildren with ADHD showed both diffuse and regional gray matter abnormalities. Consistent with its putative role in response inhibition, the cortex of the pars opercularis was thinner in children with ADHD who, as expected, had significantly poorer inhibitory performance on a Go/No-go task. These differences held for both hemispheres raising the possibility that a developmental abnormality of IFG might drive development of inhibition difficulties.

The use of biofeedback, CES, brain mapping and neurofeedback with youth who have sexual behavior problems.

Introduction During the early part of this decade, an increasing number of researchers, practitioners, and clinicians, within the field of assessing and treating sexually abusive and sexually aggressive behavior, among others, have begun to address the impact of trauma on the brain, especially in young people with sexual behavior problems, Teicher (2007), Creeden, (2006), Bengis & Cunningam (2006). This information and knowledge also has direct application to those young people who also have histories of abuse and/or neglect, Ziegler, (2005), Ogden, Minton, & Pain, (2006). In particular the professionals listed above and others have addressed the impact on youth with sexual behavior problems and those who have been sexually abused. This is important because many young people with sexual behavior problems have a history of abuse and neglect. Teicher, (2008), notes that exposure to childhood abuse, particularly childhood sexual abuse, is a risk factor for development of impulse control disorders, and can lead to a cycle of violence and perpetration. Exposure to early stress can exert enduring effects on brain development that may underlie many of the consequences of exposure to sexual abuse. Research indicates there are negative effects of childhood sexual abuse on development of the hippocampus, corpus callosum, prefrontal cortex and visual cortex. Martin Kafka, MD, Clinical Associate Professor of Psychiatry at Harvard Medical School notes, that the following are risk factors for sexual recidivism in adult males: negative states, disorder, ADHD combined subtype, PTSD, Conduct Disorder, and BiPolar Dysthymic Disorder. Kafka notes that 10-15% of males with anxiety and/or depression had sexual risk taking behaviors; and that mood and anxiety disorders may be so common among sexual offenders, that these conditions and their associated effects are not distinctly identified as correlated with recidivism. Trauma and Its Impact on the Brain Trauma resulting from early childhood abuse and neglect impacts the brain in a variety of ways. The Training & Research Institute, Inc. in Albuquerque, NM (2004) notes that childhood physical, emotional, sexual abuse and neglect can cause antisocial behavior by over-excitation of the limbic system; the primitive midbrain region that regulates memory and emotion, and the prefrontal cortex; which is associated with judgment, consequential thinking, and moral reasoning. They note, for example: 1) The left hemisphere is responsible for regulation and oversight of logical responses to a situation; and control and mediation of emotional responses generated by the right hemisphere. The impact of childhood abuse or neglect results in diminished control of emotional response, resulting in poor or inappropriate reactions to emotional situations, angry outbursts, selfdestructive or suicidal impulses, paranoia, psychosis, and a tendency to pursue intense ultimately unstable relationships. 2) The prefrontal cortex is the internal editor of emotional states, consequential thinking, moral reasoning, and reactions to emotional crisis. The impact of childhood abuse or neglect results in increased potential for depression and delinquent and criminal behavior. 3) The corpus collosum creates communication between the right and left hemispheres. The impact of childhood abuse or neglect results in a significantly smaller corpus collosum, causing nonintegrated, inappropriate responses to everyday situations. 4) The temporal lobes regulate emotions and verbal memory. The impact of childhood abuse or neglect results in poor modulation of emotions, and an increased chance for temporal lobe epilepsy. 5) The hippocampus (part of the limbic system) is responsible for the formulation and retrieval of verbal and emotional memories. …

PW01-112 - Prevalence of ADHD in school children in Athens. Association of ADHD subtypes with clinical impairment

ObjectivesThe aim of this study was to explore the prevalence of Attention Deficit Hyperactivity Disorder (ADHD) and social and academic impairment in 6-11 year-old children residents of Athens, Greece.MethodsFollowing the DSM-IV diagnostic criteria, the study combined information from teachers for 603 elementary school children following grades first to sixth. A 2-stage screening process was employed including the standardized ADHD test and the Teacher Report Form (TRF).ResultsAmong 603 children, 36 (6.0%) met the study criteria for ADHD. The estimated prevalence was 8% for boys and 3.8% for girls (p=0.028). The most prevalent subtype of ADHD was the Combined type (3.8%), followed by ADHD- Inattentive (1.7%) and Hyperactive-Impulsive type (0,5%). Gender differences were observed in the prevalence of ADHD-Combined subtypes (p=0.003). Statistical significant differences were observed between ADHD subtypes and gender (p=0.047). ADHD-Combined type was associated with greater impairment in both academic and social domains, where ADHD-Inattentive subtype showed a higher academic, but lower social impairment. The ADHD-Hyperactive-impulsive children were not significantly impaired in their academic functioning, while social functioning resulted moderately impaired.ConclusionsThe prevalence of ADHD among schoolchildren in Athens and the risk factors are comparable to those reported in several epidemiological studies worldwide. Impairment in social and academic functioning seems to be strongly associated with the subtype of ADHD. Further research into the association between ADHD symptoms and impairment is warrant.

Platelet monoamine oxidase activity in children with attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable developmental disorder characterized by symptoms of impulsivity, hyperactivity and/or inattention, and associated with structural and biochemical abnormalities in cortical and limbic structures innervated by dopamine, noradrenalin and serotonin. The enzyme monoamine oxidase, type B (MAO-B), is expressed in platelets, and metabolizes endogenous amines. Its activity has been proposed to represent a peripheral marker of various traits and forms of psychopathology. This study evaluated platelet MAO activity with a spectrofluorimetric method in 72 boys and 12 girls with predominantly hyperactive, predominantly inattentive, and combined subtype of ADHD (DSM-IV criteria), and in 64 control children. The results showed significantly lower platelet MAO activity in children with hyperactive, inattentive, and combined subtype of ADHD than in control children. There was no significant association between platelet MAO activity and gender or age. The limitation of the study was in the small sample of girls with ADHD ( N = 12), and in the determination of only one peripheral marker. In line with hypotheses of lower platelet MAO activity in different types of psychopathology, children with different subtypes of ADHD had significantly lower platelet MAO-B activity than control children.

Characteristics of Placebo Responders in Pediatric Clinical Trials of Attention-Deficit/Hyperactivity Disorder

Objective Understanding placebo response is a prerequisite to improving clinical trial methodology. Data from placebo-controlled trials of atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) were analyzed to identify demographic and clinical characteristics that might predict placebo response in future clinical trials. Method Data were pooled across 731 placebo-treated pediatric patients who participated in 10 acute, randomized, placebo-controlled trials. Responder status was based on empirically derived thresholds of change on the total score of the ADHD Rating Scale with minimal and robust response defined as 25% or greater and 40% or greater decrease, respectively. Study design characteristics, including randomization ratio, dose, and titration strategy, and patient demographic and clinical characteristics were examined as potential predictors of placebo response. Results Inattentive subtype, lack of previous stimulant treatment, presence of comorbid tics and nonwhite ethnicity were associated with robust placebo response. A subset analysis of patients completing 6 weeks of treatment (to eliminate the effects of early dropout) identified inattentive subtype and lack of previous stimulant experience as significant predictors of robust placebo response. Conclusions Placebo response is less likely in subjects with combined-subtype ADHD who are not stimulant-naive. Limiting ADHD clinical trials to this more restricted subject group is likely to maximize treatment differences. However, because this is not always possible or desirable, identifying other methods of mitigating placebo response is essential.

Maternal Ratings of Attention Problems in ADHD: Evidence for the Existence of a Continuum

ObjectiveTo investigate whether items assessing attention problems provide evidence of quantitative differences or categorically distinct subtypes of attention problems (APs) and to investigate the relation of empirically derived latent classes to DSM-IV diagnoses of subtypes of attention-deficit/hyperactivity disorder (ADHD), for example, combined subtype, predominantly inattentive type, and predominantly hyperactive/impulsive type. MethodData on attention problems were obtained from maternal ratings on the Child Behavior Check List (CBCL). Latent class models, which assume categorically different subtypes, and factor mixture models, which permit severity differences, are fitted to data obtained from Dutch boys at age 7 (N = 8,079), 10 (N = 5,278), and 12 years (N = 3,139). The fit of the different models to the data is compared to decide which model, and hence, which corresponding interpretation of AP, is most appropriate. Next, ADHD diagnoses are regressed on latent class membership in a subsample of children. ResultsAt all the three ages, models that distinguish between three mainly quantitatively different classes (e.g., mild, moderate, and severe attention problems) provide the best fit to the data. Within each class, the CBCL items measure three correlated continuous factors that can be interpreted in terms of hyperactivity/impulsivity, inattentiveness/dreaminess, and nervous behavior. The AP severe class contains all of the subjects diagnosed with ADHD–combined subtype. Some subjects diagnosed with ADHD–predominantly inattentive type are in the moderate AP class. ConclusionsFactor mixture analyses provide evidence that the CBCL AP syndrome varies along a severity continuum of mild to moderate to severe attention problems. Children affected with ADHD are at the extreme of the continuum. These data are important for clinicians, research scholars, and the framers of the DSM-V as they provide evidence that ADHD diagnoses exist on a continuum rather than as discrete categories. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(11):1085–1093.

Recognition and referral of girls with Attention Deficit Hyperactivity Disorder: case vignette study

Compared with boys, girls with Attention Deficit Hyperactivity Disorder (ADHD) are under-recognized. Parents commonly discuss concerns with teachers, who play an important role in the recognition and referral of children with ADHD. We investigated whether the predominating subtype of symptomatology influences teacher recognition of affected girls. A total of 212 teachers from 40 randomly selected primary schools in England participated in a postal questionnaire study. The questionnaire consisted of a case vignette (based on DSM-IV criteria) describing a girl with either combined or predominantly inattentive subtype ADHD. Each school received an equal number of each type of vignette for distribution. Further questions elicited teachers' conceptualization of the girl's difficulties and need for specialist referral, their views on treatment modalities and demographic data. Most (98%) teachers recognized the presence of a problem but mainly conceptualized the girl's behaviour as reflecting attentional (89%) or emotional (62%) difficulties. Teachers were less likely to correctly identify a girl with inattentive than combined subtype ADHD (14% vs. 43%) or recommend clinical referral (50% vs. 59%) for her. Few (15%) teachers thought that medication might be helpful for a girl meeting diagnostic criteria for ADHD. Teachers are able to recognize ADHD-related behaviours and impairments but conceptualize these as reflecting attentional or emotional difficulties rather than as relating to a disorder (ADHD). Teachers' conceptualization of ADHD and views about medication are important factors that could affect accurate recognition and referral. Improving teachers' knowledge about ADHD, especially the inattentive subtype, could assist in tackling gender-related barriers to care.

Comorbidity in Adults with Attention-Deficit Hyperactivity Disorder

To examine the prevalence of comorbid Axis I (current and lifetime) and II disorders in adult men and women with attention-deficit hyperactivity disorder (ADHD). Adult patients (n = 447; 266 men, 181 women) received comprehensive assessments for ADHD and Axis I and II disorders. Adults were aged between 17 and 74 years. Among the patients diagnosed with ADHD (n = 335), there were those with ADHD inattentive subtype (ADHD-I) (n = 199), hyperactive-impulsive subtype (ADHD-H) (n = 24), or combined ADHD subtype (ADHD-C) (n = 112). Chi-square and logistic regression analyses were performed to examine associations between adults with and without ADHD on Axis I and II disorders. Adults with ADHD, compared with those without ADHD, had higher rates of Axis I (46.9% and 27.31%) and Axis II (50.7% and 38.2%) disorders. Adults with ADHD-C were more likely to have mood disorder, anxiety, conduct disorder, and substance use disorder as well as obsessive-compulsive personality disorder, passive-aggressive personality disorder, depressive personality disorder, narcissistic personality disorder, and borderline personality disorder (BPD). Men with ADHD were more likely to have antisocial personality disorder and had higher rates of current drug abuse than women with ADHD. Women with ADHD had higher rates of past and current panic disorder, and past anorexia and bulimia. Women with ADHD were more likely to have BPD than men with ADHD. Adults with ADHD have very high rates of comorbid Axis I and II disorders, with differences found between men and women on certain comorbid disorders.

Is Overactivity a Core Feature in ADHD? Familial and Receiver Operating Characteristic Curve Analysis of Mechanically Assessed Activity Level

ObjectiveSymptoms of overactivity form part of the DSM-IV criteria for the combined or hyperactive-impulsive subtypes of attention-deficit/hyperactivity disorder (ADHD); yet little data exist that would quantify the nature of the overactivity component. We aimed to quantify the ability of four different measures of motion sensor data, taken from actigraphs, and the intraindividual variability (IIV) in these measures, to distinguish ADHD cases from controls. Furthermore, we aimed to investigate the degree of shared familial influences on these measures and the ADHD diagnosis. MethodReceiver operating characteristic analysis and multivariate structural equation modeling were used on actigraph data collected during a cognitive testing session in a sample of 116 ADHD combined-type probands, 119 of their siblings, and 218 control siblings (age range 6–18 years). ResultsThree measures of actigraph data—the number of movements made, the magnitude of these movements, and the IIV in the magnitude of movements—yielded an area under the curve of up to 0.8, indicating an ability to distinguish between cases and controls. The latter two of these measures showed significant shared familial vulnerability with an ADHD diagnosis, with high ADHD-actigraph familial correlations. ConclusionsThe actigraph data support the DSM-IV conceptualization of including overactivity as one of the core features within ADHD combined subtype. The magnitude of movements made, and the IIV of these movements, may be suitable candidates for future molecular genetic studies seeking to identify polymorphisms associated with the risk for ADHD. Further research should investigate if these findings generalize to a more naturalistic, homelike setting.

Sleep disorders in children with Attention-Deficit/Hyperactivity Disorder (ADHD) recorded overnight by video-polysomnography

Objective To outline specific sleep disturbances in different clinical subsets of Attention Deficit/Hyperactivity Disorder (ADHD) and to confirm, by means of nocturnal video-polysomnography (video-PSG), a variety of sleep disorders in ADHD besides the classically described periodic leg movement disorder (PLMD), restless legs syndrome (RLS) and sleep related breathing disorder (SRBD). Methods Fifty-five ADHD children (47 M, 8F; mean age = 8.9y) were included: 16 had Inattentive and 39 Hyperactive/Impulsive or Combined ADHD subtype. Behavior assessment by Conners and SNAP-IV Scales, a structured sleep interview and a nocturnal video-PSG were administered. Results Most children/parents reported disturbed, fragmentary sleep at night; complaints were motor restlessness (50%), sleep walking (47.6%), night terrors (38%), confusional arousals (28.5%), snoring (21.4%), and leg discomfort at night associated with RLS (11.9%). There is a significant difference ( p value <0.05 or <0.001) in almost all the studied sleep variables between ADHD children and controls. International RLS Rating Scale scoring, Periodic Limb Movements during Sleep (PLMS) and Wake (PLMW) indexes, hyperactivity and opposition scores and ADHD subtype appear related. Different sleep disorders seem to address specific ADHD phenotypes and correlate with severity of symptoms as in sleep related movement disorders occurring in Hyperactive/Impulsive and Combined ADHD subtypes. Besides, an abnormality of the arousal process in slow wave sleep with consequent abnormal prevalence of disorders of arousal possibly enhanced by SRBD has also been detected in 52% of our sample. Conclusions This study underlines the opportunity to propose and promote the inclusion of sleep studies, possibly by video-PSG, as part of the diagnostic screening for ADHD. This strategy could address the diagnosis and treatment of different specific ADHD phenotypic expressions that might be relevant to children’s symptoms and contribute to ADHD severity.

Priming sentence production in adolescents and adults with attention-deficit/hyper-activity disorder.

Theoretical accounts of attention-deficit/hyperactivity disorder (ADHD) posit a prominent role for problems in response inhibition (Nigg 2006). A key avenue for impulsivity in children with ADHD is inappropriate language expression. In this study, we sought to determine whether poor inhibitory control affects language production in adolescents and adults with ADHD. One hundred and ninety-five participants (13-35 years old; 65% male) were presented with two pictures and a verb, and their task was to form a sentence. If deficits in response inhibition affect language production, then participants with ADHD should be more likely than non-ADHD controls to begin speaking before having formulated a plan that will allow a grammatical continuation. The results showed that the ADHD-combined subtype, in particular, was more likely to produce an ungrammatical sequence. Effects were not moderated by age or gender. These data suggest that response suppression deficits in ADHD adversely affect the basic processes of sentence formation.

Social Functioning in Predominantly Inattentive and Combined Subtypes of Children With ADHD

Objective: The objective of this study was to compare the social functioning of children with the Combined (CB) and Predominantly Inattentive (PI) subtypes of Attention Deficit/Hyperactivity Disorder (ADHD), controlling for comorbidity and medication-status, which may have confounded the results of previous research. Method: Parents and teachers of rigorously diagnosed unmedicated children with PI or CB subtypes of ADHD, and typical comparison children, rated them on the multidimensional Social Skills Rating Scale (SSRS). Results: After co-varying for oppositionality and anxiety, social impairment was substantial and equivalent in both ADHD groups whether rated by parent or teacher. In addition, when rated by teacher, the nature of the deficits varied by subtype: Children with PI were impaired in assertiveness, whereas children with CB were deficient in self-control. These findings indicate that AD/HD subtypes differ in the nature of their social dysfunction independent of comorbidity and highlight the need for interventions to target their divergent needs.

Reflective and impulsive reactions in ADHD subtypes

Research on different subtypes of attention deficit hyperactivity disorder (ADHD) yielded inconsistent results regarding the nature of cognitive deficits. Whereas some studies report significant differences between subtypes, others fail to report these differences. In fact, the majority of studies in the field of ADHD does not differentiate between subtypes at all. The present study adopted the cognitive task of negating valence to compare the DSM-defined ADHD combined subtype (ADHD-C; n = 25), the inattentive subtype (ADHD-I; n = 25) and the control group (n = 30). As a main result, children with ADHD-C showed significant impairments compared to children with ADHD-I and the control group on conscious responses-driven by executive function, as well as on unconscious associative tasks. Medical treatment with stimulants positively influenced cognitive performance, although to a different extent for subgroups. The results are discussed in the context of current theories of ADHD and imply indications for further research in this field.

Better efficacy for the osmotic release oral system methylphenidate among poor adherents to immediate‐release methylphenidate in the three ADHD subtypes

To determine factors for switching to osmotic release oral system methylphenidate (OROS-MPH) among poor adherents to immediate-release methylphenidate (IR-MPH); and to compare the efficacy of OROS-MPH on the three attention-deficit/hyperactivity disorder (ADHD) subtypes in a multi-site prospective observational study in Taiwan. The sample included 240 children with ADHD, aged 6-16 years, who were poor adherents to IR-MPH, 137 of whom were switched to OROS-MPH. The child psychiatrists diagnosed the Diagnostic Statistical Manual of Mental Disorders (4th edition) ADHD subtypes and assessed the medical history, adherence, side-effects, global ADHD severity, and family/school effectiveness. Parents reported their child's behavioral symptoms. The determinants for an OROS-MPH switch were higher dosage, shorter treatment and thrice-daily administration of IR-MPH, and more severe inattention symptoms. Hyperactivity and oppositional symptoms were greater in the ADHD combined and hyperactive-impulsive subtypes than the inattentive subtype. Switching to OROS-MPH significantly improved behavioral symptoms and family/school measures, and this was most evident in the ADHD-combined group, followed by the ADHD-inattentive group. Inattention influenced not only academic performance, but also overall classroom behaviors and the parent-child relationship, with the latter two also influenced by oppositional symptoms. This study suggests better efficacy for the OROS-MPH among poor adherents to IR-MPH; however, its effectiveness varied across the three ADHD subtypes (ClinicalTrials.gov number NCT00460720).

Platelet Serotonin Concentration in Children with Attention-Deficit/Hyperactivity Disorder

Background: Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric disorder highly prevalent in children. The neurobiology of ADHD is still not clear, but is assumed to be related to disturbances in catecholaminergic and serotonergic (5-hydroxytryptamine, 5-HT) systems. Peripheral indices of central 5-HT function were shown in recent studies to be lower, unaltered, or increased in ADHD. Methods: The study determined platelet 5-HT concentration in 84 medication-free 9-year-old (range 4–14 years) boys and girls with DSM-IV diagnosis of ADHD, subdivided according to the different symptoms (inattention, hyperactivity, and impulsivity) and clinical ADHD subtypes (predominantly hyperactive, predominantly inattentive, and combined subtype), and in 30 age- and sex-matched healthy controls. Results: Children with ADHD had similar platelet 5-HT concentrations to control children. Platelet 5-HT concentration did not differ between boys and girls, or between children with a hyperactive, inattentive, or combined subtype of ADHD. In children with ADHD there was a significant positive correlation between platelet 5-HT concentration and impulsive symptoms, but not with symptoms of inattention or hyperactivity.Platelet 5-HT concentration wassignificantly higher in impulsive compared to non-impulsive children with ADHD. Conclusion: The data provide preliminary evidence that increased platelet 5-HT concentration might be a trait marker predictive of impulsivity in ADHD.

Efficacy and safety of atomoxetine as add-on to psychoeducation in the treatment of attention deficit/hyperactivity disorder

The primary objective of this study was to assess the impact of atomoxetine in combination with psychoeducation, compared with placebo and psychoeducation, on health-related quality of life (HRQL) in Swedish stimulant-naïve pediatric patients with attention deficit/hyperactivity disorder (ADHD). HRQL results will be presented elsewhere. Here, psychoeducation as well as efficacy and safety of the treatment are described. A total of 99 pediatric ADHD patients were randomized to a 10-week double-blind treatment with atomoxetine (49 patients) or placebo (50 patients). Parents of all patients received four sessions of psychoeducation. Atomoxetine was dosed up to approximately 1.2 mg/kg day (< or = 70 kg) or 80 mg/day (> 70 kg). Improvement of ADHD symptoms was evaluated using the ADHD rating scale (ADHD-RS) and clinical global impression (CGI) rating scales. Safety was assessed based on adverse events (AEs). The study population was predominantly male (80.8%) and diagnosed with the combined ADHD subtype (77.8%). The least square mean (lsmean) change from baseline to endpoint in total ADHD-RS score was -19.0 for atomoxetine patients and -6.3 for placebo patients, resulting in an effect size (ES) of 1.3 at endpoint. Treatment response (reduction in ADHD-RS score of > or = 25 or > or = 40%) was achieved in 71.4 or 63.3% of atomoxetine patients and 28.6 or 14.3% of placebo patients. The lsmean change from baseline to endpoint in CGI-Severity was -1.8 in the atomoxetine group compared with -0.3 in the placebo group. The difference between treatments in CGI-Improvement at endpoint was -1.4 in favor of atomoxetine. No serious AEs occurred. The safety profile of atomoxetine was in line with the current label. Atomoxetine combined with psychoeducation was superior to placebo and psychoeducation in ADHD core symptoms improvement. The large ES might be a result of including stimulant-naïve patients only, but also may indicate a positive interaction between atomoxetine treatment and psychoeducation, possibly by increased compliance.

Motor function may differentiate attention deficit hyperactivity disorder from early onset bipolar disorder

BackgroundDifferentiating between bipolar spectrum disorder (BD) and attention deficit hyperactivity disorder (ADHD) in childhood and adolescence is difficult because the clinical presentation is influenced by ongoing neural development, causing considerable symptom overlap. Motor problems and neurological soft signs have been associated with ADHD for decades. Little is known about motor skills in BD. Here we assess the diagnostic accuracy of neuromotor deviations in differentiating ADHD from BD in clinical practice. We also investigate if these deviations exist in concurrent ADHD and BD, thus indicating true comorbidityMethods64 patients 6-18 years (31 girls, 33 boys) fulfilling the diagnostic criteria of BD, ADHD combined subtype (ADHD-C) or comorbid BD and ADHD-C, were compared using an age-standardized neuromotor test; NUBU. Categorical variables were analyzed using cross table with two-tailed chi square test or Fisher's exact test when appropriate. Continuous variables were analyzed by Kruskal-Wallis test and, if significant, Mann-Whitney U test and ROC plots.ResultsThe ADHD-C group and the comorbid ADHD-C and BD group both showed significantly more neurological soft signs (p less than 0.01) and lower mean static coordination percentile (p less than 0.01) than the BD group. The positive predictive value of NUBU in the diagnosis of ADHD-C with or without concurrent BD was 89% (80-95) for total soft signs and 87% (79-95) for static coordination below the 7.5 percentile.ConclusionAn age-standardized neuromotor test battery may promote diagnostic accuracy in differentiating ADHD from BD in clinical practice, and help evaluating whether symptoms of ADHD in children who have BD reflect symptom overlap or real comorbidity. This may have important implications for everyday diagnostic work.

The association between children's ADHD subtype and parenting stress and parental symptoms

Objective. To investigate the association between two attention deficit/hyperactivity disorder (ADHD) subtypes—combined and inattentive subtypes—and parental stress in a Taiwanese population. Method. One hundred and nine children with ADHD were interviewed using the MINI Kid questionnaire. The children were divided into combined and inattentive subtypes. The level of parenting stress was measured with the self-report Parenting Stress Index and Parental Symptom Scale (Symptom Check List, SCL-90). The data were used to identify child and parental risk factors. Results. Combined subtype was highly associated with parental stress. Parents of children in this group were significantly younger, had a poorer understanding of ADHD, and had significantly higher levels of marital discord, parenting stress, parental symptoms, and life stress (all P<0.05). Multivariate analysis revealed that age of mother, child with comorbidity diagnosis, and parents with poor understanding of ADHD were significantly associated with the combined subtype relative to inattentive subtype (all P<0.05). Conclusion. The combined subtype of ADHD is associated with more parental psychopathology and stress than the inattentive subtype and the presence of combined subtype may indicate that such a child is at greater risk than the inattentive subtype for comorbid conditions such as oppositional defiant disorder and conduct disorder.