Validity of the Adult ADHD Self-Report Scale (ASRS) as a screener for adult ADHD in treatment seeking substance use disorder patients

Background: To detect attention deficit hyperactivity disorder (ADHD) in treatment seeking substance use disorders (SUD) patients, a valid screening instrument is needed. Objectives: To test the performance of the Adult ADHD Self-Report Scale V 1.1(ASRS) for adult ADHD in an international sample of treatment seeking SUD patients for DSM-IV-TR; for the proposed DSM-5 criteria; in different subpopulations, at intake and 1–2 weeks after intake; using different scoring algorithms; and different externalizing disorders as external criterion (including adult ADHD, bipolar disorder, antisocial and borderline personality disorder). Methods: In 1138 treatment seeking SUD subjects, ASRS performance was determined using diagnoses based on Conner's Adult ADHD Diagnostic Interview for DSM-IV (CAADID) as gold standard. Results: The prevalence of adult ADHD was 13.0% (95% CI: 11.0–15.0%). The overall positive predictive value (PPV) of the ASRS was 0.26 (95% CI: 0.22–0.30), the negative predictive value (NPV) was 0.97 (95% CI: 0.96–0.98). The sensitivity (0.84, 95% CI: 0.76–0.88) and specificity (0.66, 95% CI: 0.63–0.69) measured at admission were similar to the sensitivity (0.88, 95% CI: 0.83–0.93) and specificity (0.67, 95% CI: 0.64–0.70) measured 2 weeks after admission. Sensitivity was similar, but specificity was significantly better in patients with alcohol compared to (illicit) drugs as the primary substance of abuse (0.76 vs. 0.56). ASRS was not a good screener for externalizing disorders other than ADHD. Conclusions: The ASRS is a sensitive screener for identifying possible ADHD cases with very few missed cases among those screening negative in this population.

Monitoring of threo-methylphenidate enantiomers in oral fluid by capillary electrophoresis with head-column field-amplified sample injection

Threo-methylphenidate is a chiral psychostimulant drug widely prescribed to treat attention-deficit hyperactivity disorder in children and adolescents. An enantioselective CE-based assay with head-column field-amplified sample stacking for analysis of threo-methylphenidate enantiomers in liquid/liquid extracts of oral fluid is described. Analytes are electrokinetically injected across a short water plug placed at the capillary inlet and become stacked at the interface between plug and buffer. Enantiomeric separation occurs within a few minutes in a pH 3.0 phosphate/triethanolamine buffer containing 20 mg/mL (2-hydroxypropyl)-β-CD as chiral selector. The assay with six point multilevel internal calibration provides a linear response for each enantiomer in the 10-200 ng/mL concentration range, is simple, inexpensive, and reproducible, and has an LOQ of 5 ng/mL. It was applied to oral fluid patient samples that were collected up to 12 h after intake of an immediate release tablet and two different extended release formulations with racemic methylphenidate. Drug profiles could thereby be assessed in a stereoselective way. Almost no levorotary threo-methylphenidate enantiomer was detected after intake of the two extended release formulations, whereas this enantiomer was detected during the first 2.5 h after intake of the immediate release preparation. The noninvasive collection of oral fluid is an attractive alternative to plasma for the monitoring of methylphenidate exposure in the pediatric community.

Is excessive EEG beta activity associated with delinquent behavior in adult subjects with ADHD?

Objective: The attention deficit/hyperactivity disorder (ADHD) shows an increased prevalence in arrested offenders compared to the normal population. ADHD and delinquency seem to share some neurophysiological abnormalities. In recent studies, a subgroup of subjects with ADHD as well as delinquents displayed excessive EEG activity in the beta band compared to controls, which has been associated with antisocial behavior and aggression in ADHD children. The goal of the present study was to investigate whether delinquent behavior in ADHD is related to excessive beta activity. Methods: We compared the resting state EEGs (eyes closed and eyes open) of 13 non-delinquent and 13 delinquent subjects with ADHD and 13 controls regarding power spectra and topography of the EEG activity. Results: Offenders with ADHD showed more beta power mainly at frontal, central and parietal brain regions than non-delinquent subjects with ADHD. Conclusions: Excessive beta power may represent a risk-factor for delinquent behavior in adults with ADHD. Significance: The awareness of such risk-factors may be helpful in the assessment of the risk for delinquent behavior in a psychiatric context and may provide a neurobiological background for therapeutic interventions.

From nature versus nurture, via nature and nurture, to gene x environment interaction in mental disorders

It is now generally accepted that complex mental disorders are the results of interplay between genetic and environmental factors. This holds out the prospect that by studying G x E interplay we can explain individual variation in vulnerability and resilience to environmental hazards in the development of mental disorders. Furthermore studying G x E findings may give insights in neurobiological mechanisms of psychiatric disorder and so improve individualized treatment and potentially prevention. In this paper, we provide an overview of the state of field with regard to G x E in mental disorders. Strategies for G x E research are introduced. G x E findings from selected mental disorders with onset in childhood or adolescence are reviewed [such as depressive disorders, attention-deficit/hyperactivity disorder (ADHD), obesity, schizophrenia and substance use disorders]. Early seminal studies provided evidence for G x E in the pathogenesis of depression implicating 5-HTTLPR, and conduct problems implicating MAOA. Since then G x E effects have been seen across a wide range of mental disorders (e.g., ADHD, anxiety, schizophrenia, substance abuse disorder) implicating a wide range of measured genes and measured environments (e.g., pre-, peri- and postnatal influences of both a physical and a social nature). To date few of these G x E effects have been sufficiently replicated. Indeed meta-analyses have raised doubts about the robustness of even the most well studied findings. In future we need larger, sufficiently powered studies that include a detailed and sophisticated characterization of both phenotype and the environmental risk.

Orofacial dyskinesia induced by nasal Ritalin(R) (methylphenidate) sniffing: A rare case report from Switzerland

Ritalin® (methylphenidate) is an amphetamine-like prescription stimulant commonly used in the treatment of attention deficit hyperactivity disorder in children and adults. Recently, the recreational use of Ritalin has increased, particularly among young adults. Well-known symptoms of intoxication include signs of sympathetic nervous stimulation, such as agitation, anxiety, tachycardia, hypertension, headache, tremor, and dizziness. This case report describes oral dyskinesia as a rare presentation of Ritalin intoxication, with the review of pathophysiology and some epidemiological data.

Study design, baseline patient characteristics and intervention in a cross-cultural framework: results from the ADORE study

OBJECTIVE : To describe the methodology and to present the baseline findings of the Attention-deficit/hyperactivity Disorder Observational Research in Europe (ADORE) study, the primary objective of which is to describe the relationship between treatment regimen prescribed and quality of life of children with ADHD in actual practice. METHODS : In this 2-year prospective observational study, data on diagnosis, prescribed treatment and outcomes of ADHD were collected at seven time points by paediatricians and child psychiatrists on 1,573 children recruited in 10 European countries. The data presented here from the 1,478 patients included in the analyses describe the baseline condition, initial treatment regimen prescribed and quality of life of families with children with ADHD. RESULTS : Patients had a mean age of 9.0 years (SD 2.5) and 84% were male. Physicians diagnoses were made using DSM-IV (43 %), ICD-10 (32%) and both DSM-IV and ICD-10 (12 %). Mean age of awareness of a problem was 5.1 years, suggesting an average delay of approximately 4 years between awareness and diagnosis of ADHD. Baseline ADHD rating scale scores (physicianrated) indicated moderate to severe ADHD. Parent-rated SDQ scores were in agreement and suggested significant levels of co-existing problems. CGI-S, CGAS and CHIPCE scores also indicated significant impairment. Patients were offered the following treatments after the initial assessment: pharmacotherapy (25 %), psychotherapy (19 %), combination of pharmacotherapy and psychotherapy (25 %), other therapy (10 %) and no treatment (21 %). CONCLUSION : The ADORE study shows that ADHD is similarly recognised across 10 European countries and that the children are significantly impaired across a wide range of domains. In this respect, they resemble children described in previous ADHD samples.

Exploring the genetic link between RLS and ADHD

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder of childhood onset. Clinical and biological evidence points to shared common central nervous system (CNS) pathology of ADHD and restless legs syndrome (RLS). It was hypothesized that variants previously found to be associated with RLS in two large genome-wide association studies (GWA), will also be associated with ADHD. SNPs located in MEIS1 (rs2300478), BTBD9 (rs9296249, rs3923809, rs6923737), and MAP2K5 (rs12593813, rs4489954) as well as three SNPs tagging the identified haplotype in MEIS1 (rs6710341, rs12469063, rs4544423) were genotyped in a well characterized German sample of 224 families comprising one or more affected sibs (386 children) and both parents. We found no evidence for preferential transmission of the hypothesized variants to ADHD. Subsequent analyses elicited nominal significant association with haplotypes consisting of the three SNPs in BTBD9 (chi2 = 14.8, df = 7, nominal p = 0.039). According to exploratory post hoc analyses, the major contribution to this finding came from the A-A-A-haplotype with a haplotype-wise nominal p-value of 0.009. However, this result did not withstand correction for multiple testing. In view of our results, RLS risk alleles may have a lower effect on ADHD than on RLS or may not be involved in ADHD. The negative findings may additionally result from genetic heterogeneity of ADHD, i.e. risk alleles for RLS may only be relevant for certain subtypes of ADHD. Genes relevant to RLS remain interesting candidates for ADHD; particularly BTBD9 needs further study, as it has been related to iron storage, a potential pathophysiological link between RLS and certain subtypes of ADHD.

The International ADHD in Substance Use Disorders Prevalence (IASP) study: background, methods and study population

Attention deficit/hyperactivity disorder (ADHD) is an increasingly recognized comorbid condition in subjects with substance use disorders (SUDs). This paper describes the methods and study population of the International ADHD in Substance Use Disorders Prevalence (IASP) study. Objectives of the IASP are to determine the prevalence of ADHD in adult treatment seeking patients with SUD in different countries and SUD populations, determine the reliability and validity of the Adult ADHD Self-report Scale V 1.1 (ASRS) as ADHD screening instrument in SUD populations, investigate the comorbidity profile of SUD patients with and without ADHD, compare risk factors and protective factors in SUD patients with and without a comorbid diagnosis of ADHD, and increase our knowledge about the relationship between ADHD and the onset and course of SUD. In this cross-sectional, multi-centre two stage study, subjects were screened for ADHD with the ASRS, diagnosed with the Conner's Adult ADHD Diagnostic Interview for DSM-IV (CAADID), and evaluated for SUD, major depression, bipolar disorder, anti social personality disorder and borderline personality disorder. Three thousand five hundred and fifty-eight subjects from 10 countries were included. Of these 40.9% screened positive for ADHD. This is the largest international study on this population evaluating ADHD and comorbid disorders.

Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis.

BACKGROUND Panic disorder is characterised by the presence of recurrent unexpected panic attacks, discrete periods of fear or anxiety that have a rapid onset and include symptoms such as racing heart, chest pain, sweating and shaking. Panic disorder is common in the general population, with a lifetime prevalence of 1% to 4%. A previous Cochrane meta-analysis suggested that psychological therapy (either alone or combined with pharmacotherapy) can be chosen as a first-line treatment for panic disorder with or without agoraphobia. However, it is not yet clear whether certain psychological therapies can be considered superior to others. In order to answer this question, in this review we performed a network meta-analysis (NMA), in which we compared eight different forms of psychological therapy and three forms of a control condition. OBJECTIVES To assess the comparative efficacy and acceptability of different psychological therapies and different control conditions for panic disorder, with or without agoraphobia, in adults. SEARCH METHODS We conducted the main searches in the CCDANCTR electronic databases (studies and references registers), all years to 16 March 2015. We conducted complementary searches in PubMed and trials registries. Supplementary searches included reference lists of included studies, citation indexes, personal communication to the authors of all included studies and grey literature searches in OpenSIGLE. We applied no restrictions on date, language or publication status. SELECTION CRITERIA We included all relevant randomised controlled trials (RCTs) focusing on adults with a formal diagnosis of panic disorder with or without agoraphobia. We considered the following psychological therapies: psychoeducation (PE), supportive psychotherapy (SP), physiological therapies (PT), behaviour therapy (BT), cognitive therapy (CT), cognitive behaviour therapy (CBT), third-wave CBT (3W) and psychodynamic therapies (PD). We included both individual and group formats. Therapies had to be administered face-to-face. The comparator interventions considered for this review were: no treatment (NT), wait list (WL) and attention/psychological placebo (APP). For this review we considered four short-term (ST) outcomes (ST-remission, ST-response, ST-dropouts, ST-improvement on a continuous scale) and one long-term (LT) outcome (LT-remission/response). DATA COLLECTION AND ANALYSIS As a first step, we conducted a systematic search of all relevant papers according to the inclusion criteria. For each outcome, we then constructed a treatment network in order to clarify the extent to which each type of therapy and each comparison had been investigated in the available literature. Then, for each available comparison, we conducted a random-effects meta-analysis. Subsequently, we performed a network meta-analysis in order to synthesise the available direct evidence with indirect evidence, and to obtain an overall effect size estimate for each possible pair of therapies in the network. Finally, we calculated a probabilistic ranking of the different psychological therapies and control conditions for each outcome. MAIN RESULTS We identified 1432 references; after screening, we included 60 studies in the final qualitative analyses. Among these, 54 (including 3021 patients) were also included in the quantitative analyses. With respect to the analyses for the first of our primary outcomes, (short-term remission), the most studied of the included psychological therapies was CBT (32 studies), followed by BT (12 studies), PT (10 studies), CT (three studies), SP (three studies) and PD (two studies).The quality of the evidence for the entire network was found to be low for all outcomes. The quality of the evidence for CBT vs NT, CBT vs SP and CBT vs PD was low to very low, depending on the outcome. The majority of the included studies were at unclear risk of bias with regard to the randomisation process. We found almost half of the included studies to be at high risk of attrition bias and detection bias. We also found selective outcome reporting bias to be present and we strongly suspected publication bias. Finally, we found almost half of the included studies to be at high risk of researcher allegiance bias.Overall the networks appeared to be well connected, but were generally underpowered to detect any important disagreement between direct and indirect evidence. The results showed the superiority of psychological therapies over the WL condition, although this finding was amplified by evident small study effects (SSE). The NMAs for ST-remission, ST-response and ST-improvement on a continuous scale showed well-replicated evidence in favour of CBT, as well as some sparse but relevant evidence in favour of PD and SP, over other therapies. In terms of ST-dropouts, PD and 3W showed better tolerability over other psychological therapies in the short term. In the long term, CBT and PD showed the highest level of remission/response, suggesting that the effects of these two treatments may be more stable with respect to other psychological therapies. However, all the mentioned differences among active treatments must be interpreted while taking into account that in most cases the effect sizes were small and/or results were imprecise. AUTHORS' CONCLUSIONS There is no high-quality, unequivocal evidence to support one psychological therapy over the others for the treatment of panic disorder with or without agoraphobia in adults. However, the results show that CBT - the most extensively studied among the included psychological therapies - was often superior to other therapies, although the effect size was small and the level of precision was often insufficient or clinically irrelevant. In the only two studies available that explored PD, this treatment showed promising results, although further research is needed in order to better explore the relative efficacy of PD with respect to CBT. Furthermore, PD appeared to be the best tolerated (in terms of ST-dropouts) among psychological treatments. Unexpectedly, we found some evidence in support of the possible viability of non-specific supportive psychotherapy for the treatment of panic disorder; however, the results concerning SP should be interpreted cautiously because of the sparsity of evidence regarding this treatment and, as in the case of PD, further research is needed to explore this issue. Behaviour therapy did not appear to be a valid alternative to CBT as a first-line treatment for patients with panic disorder with or without agoraphobia.

German validation of the Conners Adult ADHD Rating Scales–self-report (CAARS-S) I: Factor structure and normative data

Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. Instruments for diagnosing ADHD in childhood are well validated and reliable, but diagnosis of ADHD in adults remains problematic. Attempts have been made to develop criteria specific for adult ADHD, resulting in the development of self-report and observer-rated questionnaires. To date, the Conners Adult ADHD Rating Scales (CAARS) are the international standard for questionnaire assessment of ADHD. The current study evaluates a German version of the CAARS self-report (CAARS-S).

Treatment of hyperactive children: increased efficiency through modifications of homeopathic diagnostic procedure

BACKGROUND: The rigorous test to which homeopathy was subject in our recent double-blind clinical trail of homeopathic treatment of attention deficit hyperactivity disorder (ADHD) necessitated optimized treatment meeting the highest standards. METHODS: Optimization was performed in three steps: (1) In successfully treated children, prescriptions leading to an insufficient response were analysed by a general questionnaire to identify unreliable symptoms. (2) Polarity analysis, a further development of Bönninghausen's concept of contraindications, was introduced in response to the frequently one-sided symptoms. This enabled us to use few but specific symptoms to identify the medicine whose genius symptoms exhibit the closest match to the patient's characteristic symptoms. (3) We investigated the influence of the primary perception symptoms on the result of the repertorization. Perception symptoms are not normally recorded during a patient interview even though they are among the most reliable facts related by the patients. At the same time we were able to improve the continuity of improvement of ADHD symptoms using liquid Q-potencies. RESULTS: Introducing the questionnaire, polarity analysis, and including perception symptoms, lead to an improvement in the success rate of the first prescription from 21% to 54%, of the fifth prescription from 68% to 84%.

Cerebellar disorders in childhood: cognitive problems

Over the last decade, increasing evidence of cognitive functions of the cerebellum during development and learning processes could be ascertained. Posterior fossa malformations such as cerebellar hypoplasia or Joubert syndrome are known to be related to developmental problems in a marked to moderate extent. More detailed analyses reveal special deficits in attention, processing speed, visuospatial functions, and language. A study about Dandy Walker syndrome states a relationship of abnormalities in vermis lobulation with developmental problems. Further lobulation or volume abnormalities of the cerebellum and/or vermis can be detected in disorders as fragile X syndrome, Downs's syndrome, William's syndrome, and autism. Neuropsychological studies reveal a relation of dyslexia and attention deficit disorder with cerebellar functions. These functional studies are supported by structural abnormalities in neuroimaging in these disorders. Acquired cerebellar or vermis atrophy was found in groups of children with developmental problems such as prenatal alcohol exposure or extreme prematurity. Also, focal lesions during childhood or adolescence such as cerebellar tumor or stroke are related with neuropsychological abnormalities, which are most pronounced in visuospatial, language, and memory functions. In addition, cerebellar atrophy was shown to be a bad prognostic factor considering cognitive outcome in children after brain trauma and leukemia. In ataxia teleangiectasia, a neurodegenerative disorder affecting primarily the cerebellar cortex, a reduced verbal intelligence quotient and problems of judgment of duration are a hint of the importance of the cerebellum in cognition. In conclusion, the cerebellum seems to play an important role in many higher cognitive functions, especially in learning. There is a suggestion that the earlier the incorrect influence, the more pronounced the problems.

Internet-Based Guided Self-Help for Several Anxiety Disorders: A Randomized Controlled Trial Comparing a Tailored With a Standardized Disorder-Specific Approach

Internet-delivered self-help with minimal therapist guidance has shown promising results for a number of diagnoses. Most of the evidence comes from studies evaluating standardized disorder-specific treatments. A recent development in the field includes transdiagnostic and tailored Internet-based treatments that address comorbid symptoms and a broader range of patients. This study evaluated an Internet-based tailored guided self-help treatment, which targeted symptoms of social anxiety disorder, panic disorder with or without agoraphobia, and generalized anxiety disorder. The tailored treatment was compared both with standardized disorder-specific Internet-based treatment and with a wait-list control group. Both active treatment conditions were based on cognitive-behavioral therapy and lasted for 8 weeks. A total of 132 individuals meeting diagnostic criteria for at least one of the anxiety disorders were randomly assigned to 1 of the 3 conditions. Both treatment groups showed significant symptom reductions as compared with the wait-list control group on primary disorder-unspecific measures of anxiety, depression, and general symptomatology and on secondary anxiety disorder-specific measures. Based on the intention-to-treat sample, mean between-group effect sizes were d = 0.80 for the tailored treatment and d = 0.82 for the standardized treatment, versus wait-list controls. Treatment gains were maintained at 6-month follow-up. No differences were found between the 2 active treatment conditions on any of the measures, including a telephone-administered diagnostic interview conducted at posttreatment. The findings suggest that both Internet-based tailored guided self-help treatments and Internet-based standardized treatments are promising treatment options for several anxiety disorders

Specific attentional impairments and complex visual hallucinations in eye disease

OBJECTIVE: To test the prediction by the Perception and Attention Deficit (PAD) model of complex visual hallucinations that cognitive impairment, specifically in visual attention, is a key risk factor for complex hallucinations in eye disease. METHODS: Two studies of elderly patients with acquired eye disease investigated the relationship between complex visual hallucinations (CVH) and impairments in general cognition and verbal attention (Study 1) and between CVH, selective visual attention and visual object perception (Study 2). The North East Visual Hallucinations Inventory was used to classify CVH. RESULTS: In Study 1, there was no relationship between CVH (n=10/39) and performance on cognitive screening or verbal attention tasks. In Study 2, participants with CVH (n=11/31) showed poorer performance on a modified Stroop task (p<0.05), a novel imagery-based attentional task (p<0.05) and picture (p<0.05) but not silhouette naming (p=0.13) tasks. Performance on these tasks correctly classified 83% of the participants as hallucinators or non-hallucinators. CONCLUSIONS: The results suggest that, consistent with the PAD model, complex visual hallucinations in people with acquired eye disease are associated with visual attention impairment.

DTI reveals hypothalamic and brainstem white matter lesions in patients with idiopathic narcolepsy

Symptomatic narcolepsy is often related to hypothalamic, pontine, or mesencephalic lesions. Despite evidence of disturbances of the hypothalamic hypocretin system in patients with idiopathic narcolepsy, neuroimaging in patients with idiopathic narcolepsy revealed conflicting results and there is limited data on possible structural brain changes that might be associated with this disorder.