Search

Background: There is a high need for evidence-based psychosocial treatments for adult attention-deficit hyperactivity disorder (ADHD) to offer alongside treatment as usual (TAU). Mindfulness-based cognitive therapy (MBCT) is a promising psychosocial treatment. This trial investigated the efficacy of MBCT + TAU v. TAU in reducing core symptoms in adults with ADHD. Methods: A multicentre, single-blind, randomised controlled trial (ClinicalTrials.gov: NCT02463396). Participants were randomly assigned to MBCT + TAU (n = 60), an 8-weekly group therapy including meditation exercises, psychoeducation and group discussions, or TAU only (n = 60), which reflected usual treatment in the Netherlands and included pharmacotherapy and/or psychoeducation. Primary outcome was ADHD symptoms rated by blinded clinicians. Secondary outcomes included self-reported ADHD symptoms, executive functioning, mindfulness skills, self-compassion, positive mental health and general functioning. Outcomes were assessed at baseline, post-treatment, 3- and 6-month follow-up. Post-treatment effects at group and individual level, and follow-up effects were examined. Results: In MBCT + TAU patients, a significant reduction of clinician-rated ADHD symptoms was found at post-treatment [ M difference = −3.44 (−5.75, −1.11), p = 0.004, d = 0.41]. This effect was maintained until 6-month follow-up. More MBCT + TAU (27%) than TAU participants (4%) showed a ⩽30% reduction of ADHD symptoms (p = 0.001). MBCT + TAU patients compared with TAU patients also reported significant improvements in ADHD symptoms, mindfulness skills, self-compassion and positive mental health at post-treatment, which were maintained until 6-month follow-up. Although patients in MBCT + TAU compared with TAU reported no improvement in executive functioning at post-treatment, they did report improvement at 6-month follow-up. Conclusions: MBCT might be a valuable treatment option alongside TAU for adult ADHD aimed at alleviating symptoms. [ABSTRACT FROM AUTHOR]

Background: Adults with attention deficit hyperactivity disorder (ADHD) often present with a lifelong pattern of core symptoms that is associated with impairments of functioning in daily life. This has a substantial personal and economic impact. In clinical practice there is a high need for additional or alternative interventions for existing treatments, usually consisting of pharmacotherapy and/or psycho-education. Although previous studies show preliminary evidence for the effectiveness of mindfulness-based interventions in reducing ADHD symptoms and improving executive functioning, these studies have methodological limitations. This study will take account of these limitations and will examine the effectiveness of Mindfulness Based Cognitive Therapy (MBCT) in further detail. Methods/design: A multi-centre, parallel-group, randomised controlled trial will be conducted in N = 120 adults with ADHD. Patients will be randomised to MBCT in addition to treatment as usual (TAU) or TAU alone. Assessments will take place at baseline and at three, six and nine months after baseline. Primary outcome measure will be severity of ADHD symptoms rated by a blinded clinician. Secondary outcome measures will be self-reported ADHD symptoms, executive functioning, mindfulness skills, self-compassion, positive mental health and general functioning. In addition, a cost-effectiveness analysis will be conducted. Discussion: This trial will offer valuable information about the clinical and cost-effectiveness of MBCT in addition to TAU compared to TAU alone in adults swith ADHD. [ABSTRACT FROM AUTHOR]

Persons with and without autism process sensory information differently. Differences in sensory processing are directly relevant to social functioning and communicative abilities, which are known to be hampered in persons with autism. We collected functional magnetic resonance imaging data from 25 autistic individuals and 25 neurotypical individuals while they performed a silent gesture recognition task. We exploited brain network topology, a holistic quantification of how networks within the brain are organized to provide new insights into how visual communicative signals are processed in autistic and neurotypical individuals. Performing graph theoretical analysis, we calculated two network properties of the action observation network: 'local efficiency', as a measure of network segregation, and 'global efficiency', as a measure of network integration. We found that persons with autism and neurotypical persons differ in how the action observation network is organized. Persons with autism utilize a more clustered, local-processing-oriented network configuration (i.e. higher local efficiency) rather than the more integrative network organization seen in neurotypicals (i.e. higher global efficiency). These results shed new light on the complex interplay between social and sensory processing in autism. [ABSTRACT FROM AUTHOR]

The aim of the present study was to compare the possible dependence potential of antidepressants (ADs) to benzodiazepines (BZDs). The Schedules for Clinical Assessment in Neuropsychiatry (SCAN), the Benzodiazepine Dependence Self-Report Questionnaire (Bendep-SRQ) and the Symptom Checklist-90 (SCL-90) were administered to 70 psychiatric outpatient BZD users and 54 psychiatric outpatient AD users. Significantly more Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised (DSM-III-R) as well as International Classification of Disease, Tenth Edition (ICD-10) past year (PY) and lifetime (LT) dependence diagnoses were made in the BZD group than in the AD group. Bendep-SRQ scale scores for Problematic Use, Preoccupation and Lack of Compliance were significantly higher in the BZD group than in the AD group. The BZD group also had a higher rating on the Withdrawal scale, but this difference was not statistically significant. According to DSM-III-R and ICD-10 criteria ADs do have some dependence liability in psychiatric outpatients, but clearly to a lesser extent than BZDs. Further research is needed to differentiate the dependence potential among the various classes of ADs. [Copyright &y& Elsevier]

In this study on 99 outpatients who were being treated for alcohol and/or drug dependence and also using benzodiazepines (BZDs), prevalence rates of DSM-III-R and ICD-10 substance dependence diagnoses were ascertained and scalability, reliability and validity of the scales of the Benzodiazepine Dependence Self-Report Questionnaire (Bendep-SRQ) were assessed. The latter properties were investigated by Rasch analyses, discriminability coefficients, test–retest coefficients and factor analyses. BZD dependence was found to be a prevalent additional diagnosis. The psychometric findings appear to support the use of the Bendep-SRQ at outpatient addiction centers, which could contribute to a more differentiated treatment for poly-substance dependence. [ABSTRACT FROM AUTHOR]

Presents a study on the benzodiazepines Substance Dependence Syndrome by Rasch modelling. Information on the Rasch scaling model; Details on the subjects used in the study; Method in which the study was conducted; Details on the findings; Conclusions reached.

The actions and feelings questionnaire (AFQ) provides a short, self-report measure of how well someone uses and understands visual communicative signals such as gestures. The objective of this study was to translate and cross-culturally adapt the AFQ into Dutch (AFQ-NL) and validate this new version in neurotypical and autistic populations. Translation and adaptation of the AFQ consisted of forward translation, synthesis, back translation, and expert review. In order to validate the AFQ-NL, we assessed convergent and divergent validity. We additionally assessed internal consistency using Cronbach's alpha. Validation and reliability outcomes were all satisfactory. The AFQ-NL is a valid adaptation that can be used for both autistic and neurotypical populations in the Netherlands. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Mindfulness-Based Cognitive Therapy v. treatment as usual in adults with ADHD: a multicentre, single-blind, randomised controlled trial" which was published in 28 February, 2018 issue of the perodical.

Primary caregivers experience consequences from being in close contact to a person with autism spectrum disorder (ASD). This study used the Involvement Evaluation Questionnaire to explore the level of consequences of 104 caregivers involved with adults with High Functioning ASD (HF-ASD) and compared these with the consequences reported by caregivers of patients suffering from depression and schizophrenia. Caregivers involved with adults with an HF-ASD experience overall consequences comparable to those involved with patients with depression or schizophrenia. Worrying was the most reported consequence. More tension was experienced by the caregivers of ASD patients, especially by spouses. More care and attention for spouses of adults with an HF-ASD appears to be needed. [ABSTRACT FROM AUTHOR]

Background: Benzodiazepines are widely used in the treatment of anxiety disorders and sleep disturbances, but negative cognitive side effects have been reported after long-term use. Studies on the cognitive effects of long-term benzodiazepine use to date have typically included small samples and limited cognitive assessments.Objectives: This study examined cognitive performance on four cognitive domains in long-term benzodiazepine users, compared to normative data. Furthermore, it was examined whether sex, age, benzodiazepine dose, and state and trait anxiety moderated cognitive functioning in long-term benzodiazepine users.Methods: Neuropsychological tests targeting different cognitive domains were administered to 92 patients with long-term benzodiazepine use who were accepted for enrolment into a benzodiazepine discontinuation programme in an academic hospital. Test scores were compared to a large normative data sample.Results: Of the long-term benzodiazepine users, 20.7% could be classified as cognitively impaired across all domains, with the largest effects found in the domains processing speed and sustained attention, and an overall worse performance in women, an effect which appears to be moderated by state anxiety. No effects of age or benzodiazepine dose were found.Conclusions: These results extend those of earlier studies on benzodiazepine effects on specific cognitive domains. This study implies an overall detrimental cognitive effect in long-term benzodiazepine users rather than specific effects. Therefore, long-term benzodiazepine use should be avoided, and once present, tailored interventions aimed at tapering benzodiazepines are warranted. [ABSTRACT FROM AUTHOR]

Background: Atomoxetine treatment is associated with improvements in functional outcomes in patients with attention-deficit/hyperactivity disorder (ADHD), although relationships between improvements in these outcomes and reductions in ADHD symptoms have not been comprehensively investigated in adults.Objectives: The aim of this study was to assess relationships between functional outcomes and ADHD symptoms (primary objective), and to assess time courses of changes in functional outcomes from baseline to weeks 10 and 24 (secondary objective).Methods: We analyzed data pooled from seven Eli Lilly-sponsored placebo-controlled trials of atomoxetine in adults with ADHD that had Conners' Adult ADHD Rating Scales-Investigator Rated: Screening Version (CAARS-Inv:SV) total scores and functional outcome data at baseline and at week 10. Two trials also had these data at week 24. Patients were included in these pooled analyses if they had a CAARS-Inv:SV total score at baseline and at one or more post-baseline visits at weeks 10 or 24, or had post-baseline scores that would allow missing scores at weeks 10 or 24 to be imputed. To address the primary objective, changes in functional outcomes during treatment with atomoxetine versus placebo were assessed using last observation carried forward (LOCF) analysis of covariance (ANCOVA) and mixed-effects model repeated measures (MMRM) analysis, and correlations between score changes in CAARS-Inv:SV total and functional outcomes were assessed using Spearman's rank correlation coefficient (r) at weeks 10 and 24. The secondary objective was addressed using MMRM.Results: At baseline, patients generally had moderately severe or worse ADHD symptoms (based on CAARS-Inv:SV total scores) and impaired functional outcomes (based on Adult ADHD Quality-of-Life [AAQoL], Behavior Rating Inventory of Executive Function-Adult Version [BRIEF-A], Sheehan Disability Scale [SDS], and 36-item Short-Form Health Survey [SF-36] scores). These baseline characteristics were comparable in the atomoxetine and placebo groups. For atomoxetine versus placebo, statistically significant improvements were detected in AAQoL total and subscores at weeks 10 and 24, and in BRIEF-A Self-Report scores at week 10, but not in BRIEF-A Informant Report or SDS scores at week 10 (no BRIEF-A or SDS data were available at week 24), and not in SF-36 at weeks 10 or 24. All functional improvements were gradual. During treatment with atomoxetine, there were moderate correlations between reductions in CAARS-Inv:SV total scores and increases in AAQoL total and subscores at weeks 10 and 24 (r range -0.58 to -0.39; n = 394-545), and also with reductions in BRIEF-A Self-Report at week 10 (r = 0.49; n = 256). With placebo, moderate correlations were also found between reductions in CAARS-Inv:SV total scores and increases in AAQoL total and subscores at weeks 10 and 24 (r range -0.56 to -0.28; n = 321-542), and with reductions in BRIEF-A Self-Report at week 10 (r = 0.49; n = 271). However, correlations between changes in CAARS-Inv:SV and BRIEF-A Informant at week 10 were low for atomoxetine-treated patients (r = 0.25; n = 65), moderate with placebo (r = 0.42; n = 72), and there were low/no correlations between changes in CAARS-Inv:SV and functional outcome rating scales that are not specific to ADHD; that is, for atomoxetine-treated patients, SDS total r = 0.19 (n = 32 at week 10) and SF-36 r range - 0.20 to -0.01 (n = 51 at week 10, n = 183 at week 24).Conclusions: Atomoxetine-treated adult patients experienced improvements in functional outcomes (AAQoL and BRIEF-A Self-Report) that correlated with reductions in ADHD symptoms. Although atomoxetine improved both the ADHD symptoms and functional outcomes, the correlation between symptoms and functional outcomes was low to moderate, suggesting that they measure overlapping but different aspects of the disorder. Hence, clinicians should assess not just ADHD symptoms, but also the functional impairments. [ABSTRACT FROM AUTHOR]

This study investigated processing of emotion words in autism spectrum disorders (ASD) using reaction times and event-related potentials (ERP). Adults with (n = 21) and without (n = 20) ASD performed a lexical decision task on emotion and neutral words while their brain activity was recorded. Both groups showed faster responses to emotion words compared to neutral, suggesting intact early processing of emotion in ASD. In the ERPs, the control group showed a typical late positive component (LPC) at 400-600 ms for emotion words compared to neutral, while the ASD group showed no LPC. The between-group difference in LPC amplitude was significant, suggesting that emotion words were processed differently by individuals with ASD, although their behavioral performance was similar to that of typical individuals. [ABSTRACT FROM AUTHOR]

Highlights: [•] Mindfulness-based cognitive therapy (MBCT) suggests enacting comparable neurophysiological effects related to attention and self-regulation as pharmacological treatments for ADHD. [•] Enhanced error-positivity (Pe) amplitudes indexing error saliency/awareness were associated with ameliorated inattention symptoms. [•] Increased NoGo-P3 amplitude reflecting greater inhibitory control correlated with attenuated hyperactivity/impulsivity symptomatology. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorders (ASDs) are associated with auditory hyper- or hyposensitivity; atypicalities in central auditory processes, such as speech-processing and selective auditory attention; and neural connectivity deficits. We sought to investigate whether the low-level integrative processes underlying sound localization and spatial discrimination are affected in ASDs. Methods: We performed 3 behavioural experiments to probe different connecting neural pathways: 1) horizontal and vertical localization of auditory stimuli in a noisy background, 2) vertical localization of repetitive frequency sweeps and 3) discrimination of horizontally separated sound stimuli with a short onset difference (precedence effect). Results: Ten adult participants with ASDs and 10 healthy control listeners participated in experiments 1 and 3; sample sizes for experiment 2 were 18 adults with ASDs and 19 controls. Horizontal localization was unaffected, but vertical localization performance was significantly worse in participants with ASDs. The temporal window for the precedence effect was shorter in participants with ASDs than in controls. Limitations: The study was performed with adult participants and hence does not provide insight into the developmental aspects of auditory processing in individuals with ASDs. Conclusion: Changes in low-level auditory processing could underlie degraded performance in vertical localization, which would be in agreement with recently reported changes in the neuroanatomy of the auditory brainstem in individuals with ASDs. The results are further discussed in the context of theories about abnormal brain connectivity in individuals with ASDs. [ABSTRACT FROM AUTHOR]

Background: Attention-deficit/hyperactivity disorder (ADHD) is characterized by problems in directing and sustaining attention. Recent findings suggest that alpha oscillations (8–12 Hz) are crucially involved in gating information between brain regions when allocating attention. The current study investigates whether aberrant modulation of alpha oscillations contributes to attention problems in ADHD patients. Methods: Magnetoencephalographic signals were recorded in adults with ADHD (n = 17) and healthy control subjects (n = 18) while they performed a visuospatial attention task. Cues directed attention to the left or right visual hemifield with an 80% validity with respect to the upcoming target. Results: Unlike the control group, subjects with ADHD showed a higher accuracy for invalidly cued right targets compared with invalidly cued left targets (p = .04). This coincided with an inability of the ADHD subjects to sustain the posterior hemispheric alpha lateralization in the period before the target for the left cue condition (p = .011). Furthermore, the control group showed a strong correlation between the degree of alpha lateralization and the magnitude of the cueing effect assessed in terms of accuracy (r s = .71, p = .001) and reaction times (r s =−.81, p<.001). These correlations were absent in the ADHD group. Conclusions: Our results demonstrate that subjects with ADHD have a failure in sustaining hemispheric alpha lateralization when cued to the left, resulting in an attentional bias to the right visual hemifield. These findings suggest that aberrant modulations of alpha oscillations reflect attention problems in ADHD and might be related to the neurophysiological substrate of the disorder. [Copyright &y& Elsevier]

Heightened attention towards negative information is characteristic of depression. Evidence is emerging for a negative attentional bias in Autism spectrum disorder (ASD), perhaps driven by the high comorbidity between ASD and depression. We investigated whether ASD is characterised by a negative attentional bias and whether this can be explained by comorbid (sub) clinical depression. Participants (n = 116) with current (CD) or remitted depression (RD) and/or ASD, and 64 controls viewed positively and negatively valenced (non-)social pictures. Groups were compared on three components of visual attention using linear mixed models. Both CD individuals with and without ASD, but not remitted depressed and never-depressed ASD individuals showed a negative bias, suggesting that negative attentional bias might be a depressive state-specific marker for depression in ASD. [ABSTRACT FROM AUTHOR]

Abstract: Attention-deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD) are frequently comorbid. To contribute to a better understanding of the associations regularly found between ADHD and BPD, on the one hand, and the developmental pathways for these disorders, on the other hand, latent class analyses (LCA) were undertaken to identify classes differing in profiles of childhood symptoms of ADHD and adult symptoms of ADHD and BPD. Diagnostic interviews with 103 female outpatients meeting the criteria for ADHD and/or BPD were used to assess current DSM-IV symptoms; childhood symptoms of ADHD were assessed in parent interviews. The latent classes were examined in relation to the DSM-IV conceptualizations of ADHD and BPD. And relations between childhood and adult classes were examined to hypothesize about developmental trajectories. LCA revealed an optimal solution with four distinct symptom profiles: only ADHD symptoms; BPD symptoms and only ADHD symptoms of hyperactivity; BPD symptoms and ADHD symptoms of inattention and hyperactivity; BPD symptoms and ADHD symptoms of inattention, hyperactivity and impulsivity. All patients with BPD had some ADHD symptoms in both adulthood and childhood. Hyperactivity was least discriminative of adult classes. Adult hyperactivity was not always preceded by childhood hyperactivity; some cases of comorbid ADHD and BPD symptoms were not preceded by significant childhood ADHD symptoms; and some cases of predominantly BPD symptoms could be traced back to combined symptoms of ADHD in childhood. The results underline the importance of taking ADHD diagnoses into account with BPD. ADHD classification subtypes may not be permanent over time, and different developmental pathways to adult ADHD and BPD should therefore be investigated. [Copyright &y& Elsevier]

Deficits in multiple neuropsychological domains and specific personality profiles have been observed in attention-deficit/hyperactivity disorder (ADHD). In this study we investigated whether personality traits are related to neurocognitive profiles in adults with ADHD. Neuropsychological performance and Five Factor Model (FFM) personality traits were measured in adults with ADHD (n = 133) and healthy controls (n = 132). Three neuropsychological profiles, derived from previous community detection analyses, were investigated for personality trait differences. Irrespective of cognitive profile, participants with ADHD showed significantly higher Neuroticism and lower Extraversion, Agreeableness, and Conscientiousness than healthy controls. Only the FFM personality factor Openness differed significantly between the three profiles. Higher Openness was more common in those with aberrant attention and inhibition than those with increased delay discounting and atypical working memory / verbal fluency. The results suggest that the personality trait Openness, but not any other FFM factor, is linked to neurocognitive profiles in ADHD. ADHD symptoms rather than profiles of cognitive impairment have associations with personality traits. [ABSTRACT FROM AUTHOR]

Attention Deficit Hyperactivity Disorder (ADHD) is characterized by poor cognitive control/attention and hypofunctioning of the dorsal anterior cingulate cortex (dACC). In the current study, we investigated for the first time whether real-time fMRI neurofeedback (rt-fMRI) training targeted at increasing activation levels within dACC in adults with ADHD leads to a reduction of clinical symptoms and improved cognitive functioning. An exploratory randomized controlled treatment study with blinding of the participants was conducted. Participants with ADHD (n = 7 in the neurofeedback group, and n = 6 in the control group) attended four weekly MRI training sessions (60-min training time/session), during which they performed a mental calculation task at varying levels of difficulty, in order to learn how to up-regulate dACC activation. Only neurofeedback participants received continuous feedback information on actual brain activation levels within dACC. Before and after the training, ADHD symptoms and relevant cognitive functioning was assessed. Results showed that both groups achieved a significant increase in dACC activation levels over sessions. While there was no significant difference between the neurofeedback and control group in clinical outcome, neurofeedback participants showed stronger improvement on cognitive functioning. The current study demonstrates the general feasibility of the suggested rt-fMRI neurofeedback training approach as a potential novel treatment option for ADHD patients. Due to the study’s small sample size, potential clinical benefits need to be further investigated in future studies. Trial Registration: [ABSTRACT FROM AUTHOR]

The dopamine transporter gene, DAT1 ( SLC6A3), has been studied extensively as a candidate gene for attention-deficit/hyperactivity disorder (ADHD). Different alleles of variable number of tandem repeats (VNTRs) in this gene have been associated with childhood ADHD (10/10 genotype and haplotype 10-6) and adult ADHD (haplotype 9-6). This suggests a differential association depending on age, and a role of DAT1 in modulating the ADHD phenotype over the lifespan. The DAT1 gene may mediate susceptibility to ADHD through effects on striatal volumes, where it is most highly expressed. In an attempt to clarify its mode of action, we examined the effect of three DAT1 alleles (10/10 genotype, and the haplotypes 10-6 and 9-6) on bilateral striatal volumes (nucleus accumbens, caudate nucleus, and putamen) derived from structural magnetic resonance imaging scans using automated tissue segmentation. Analyses were performed separately in three cohorts with cross-sectional MRI data, a childhood/adolescent sample (NeuroIMAGE, 301 patients with ADHD and 186 healthy participants) and two adult samples (IMpACT, 118 patients with ADHD and 111 healthy participants; BIG, 1718 healthy participants). Regression analyses revealed that in the IMpACT cohort, and not in the other cohorts, carriers of the DAT1 adult ADHD risk haplotype 9-6 had 5.9 % larger striatum volume relative to participants not carrying this haplotype. This effect varied by diagnostic status, with the risk haplotype affecting striatal volumes only in patients with ADHD. An explorative analysis in the cohorts combined ( N = 2434) showed a significant gene-by-diagnosis-by-age interaction suggesting that carriership of the 9-6 haplotype predisposes to a slower age-related decay of striatal volume specific to the patient group. This study emphasizes the need of a lifespan approach in genetic studies of ADHD. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood psychiatric disorder that often persists into adulthood. While several studies have identified altered functional connectivity in brain networks during rest in children with ADHD, few studies have been performed on adults with ADHD. Existing studies have generally investigated small samples. We therefore investigated aberrant functional connectivity in a large sample of adult patients with childhood-onset ADHD, using a data-driven, whole-brain approach. Adults with a clinical ADHD diagnosis (N = 99) and healthy, adult comparison subjects (N = 113) underwent a 9-minute resting-state fMRI session in a 1.5 T MRI scanner. After elaborate preprocessing including a thorough head-motion correction procedure, group independent component analysis (ICA) was applied from which we identified six networks of interest: cerebellum, executive control, left and right frontoparietal and two default-mode networks. Participant-level network maps were obtained using dual-regression and tested for differences between patients with ADHD and controls using permutation testing. Patients showed significantly stronger connectivity in the anterior cingulate gyrus of the executive control network. Trends were also observed for stronger connectivity in the cerebellum network in ADHD patients compared to controls. However, there was considerable overlap in connectivity values between patients and controls, leading to relatively low effect sizes despite the large sample size. These effect sizes were slightly larger when testing for correlations between hyperactivity/impulsivity symptoms and connectivity strength in the executive control and cerebellum networks. This study provides important insights for studies on the neurobiology of adult ADHD; it shows that resting-state functional connectivity differences between adult patients and controls exist, but have smaller effect sizes than existing literature suggested. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) in childhood is characterized by gray and white matter abnormalities in several brain areas. Considerably less is known about white matter microstructure in adults with ADHD and its relation with clinical symptoms and cognitive performance. In 107 adult ADHD patients and 109 gender-, age- and IQ-matched controls, we used diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) to investigate whole-skeleton changes of fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). Additionally, we studied the relation of FA and MD values with symptom severity and cognitive performance on tasks measuring working memory, attention, inhibition, and delay discounting. In comparison to controls, participants with ADHD showed reduced FA in corpus callosum, bilateral corona radiata, and thalamic radiation. Higher MD and RD were found in overlapping and even more widespread areas in both hemispheres, also encompassing internal and external capsule, sagittal stratum, fornix, and superior lateral fasciculus. Values of FA and MD were not associated with symptom severity. However, within some white matter clusters that distinguished patients from controls, worse inhibition performance was associated with reduced FA and more impulsive decision making was associated with increased MD. This study shows widespread differences in white matter integrity between adults with persistent ADHD and healthy individuals. Changes in RD suggest aberrant myelination as a pathophysiological factor in persistent ADHD. The microstructural differences in adult ADHD may contribute to poor inhibition and greater impulsivity but appear to be independent of disease severity. [ABSTRACT FROM AUTHOR]

Background: Response time variability (RTV) is consistently increased in patients with attention-deficit/hyperactivity disorder (ADHD). A right-hemispheric frontoparietal attention network model has been implicated in these patients. The 3 main connecting fibre tracts in this network, the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and the cingulum bundle (CB), show microstructural abnormalities in patients with ADHD. We hypothesized that the microstructural integrity of the 3 white matter tracts of this network are associated with ADHD and RTV. Methods: We examined RTV in adults with ADHD by modelling the reaction time distribution as an exponentially modified Gaussian (ex-Gaussian) function with the parameters μ, σ and, the latter of which has been attributed to lapses of attention. We assessed adults with ADHD and healthy controls using a sustained attention task. Diffusion tensor imaging--derived fractional anisotropy (FA) values were determined to quantify bilateral microstructural integrity of the tracts of interest. Results: We included 100 adults with ADHD and 96 controls in our study. Increased τ was associated with ADHD diagnosis and was linked to symptoms of inattention. An inverse correlation of τ with mean FA was seen in the right SLF of patients with ADHD, but no direct association between the mean FA of the 6 regions of interest with ADHD could be observed. Limitations: Regions of interest were defined a priori based on the attentional network model for ADHD and thus we might have missed effects in other networks. Conclusion: This study suggests that reduced microstructural integrity of the right SLF is associated with elevated τ in patients with ADHD. [ABSTRACT FROM AUTHOR]

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high heritability. At least 30% of patients diagnosed in childhood continue to suffer from ADHD during adulthood and genetic risk factors may play an essential role in the persistence of the disorder throughout lifespan. To date, genome-wide association studies (GWAS) of ADHD have been completed in seven independent datasets, six of which were pediatric samples and one on persistent ADHD using a DNA-pooling strategy, but none of them reported genome-wide significant associations. In an attempt to unravel novel genes for the persistence of ADHD into adulthood, we conducted the first two-stage GWAS in adults with ADHD. The discovery sample included 607 ADHD cases and 584 controls. Top signals were subsequently tested for replication in three independent follow-up samples of 2104 ADHD patients and 1901 controls. None of the findings exceeded the genome-wide threshold for significance (PGC<5e−08), but we found evidence for the involvement of the FBXO33 (F-box only protein 33) gene in combined ADHD in the discovery sample (P=9.02e−07) and in the joint analysis of both stages (P=9.7e−03). Additional evidence for a FBXO33 role in ADHD was found through gene-wise and pathway enrichment analyses in our genomic study. Risk alleles were associated with lower FBXO33 expression in lymphoblastoid cell lines and with reduced frontal gray matter volume in a sample of 1300 adult subjects. Our findings point for the first time at the ubiquitination machinery as a new disease mechanism for adult ADHD and establish a rationale for searching for additional risk variants in ubiquitination-related genes. [ABSTRACT FROM AUTHOR]

Abstract: This study examined whether cognitive measures of response inhibition derived from the AX-CPT are able to differentiate between adult attention deficit/hyperactivity disorder (ADHD), borderline personality disorder (BPD), and healthy controls (HC). Current DSM-IV-TR symptoms of ADHD and BPD were assessed by structured diagnostic interviews, and parent developmental interviews were used to assess childhood ADHD symptoms. Patients (14 ADHD, 12 BPD, 7 ADHD and BPD, and 37 HC) performed the AX-CPT. Seventy percent of AX-CPT trials were target (AX) trials, creating a bias to respond with a target response to X probes in the nontarget (AY, BX, BY) trials. On BX trials, context, i.e. the non-‘A’ letter, must be used to inhibit this prepotent response tendency. On AY trials context actually causes individuals to false alarm. The effects of ADHD and BPD on AX-CPT outcome were tested using two-way ANOVA. BPD was associated with higher percentage of errors across the task and more errors and slower responses on BX trials, whereas ADHD was associated with slower responses on AY trials. The findings suggest response inhibition problems to be present in both ADHD and BPD, and patients with BPD to be particularly impaired due to poor context processing. [Copyright &y& Elsevier]

Abstract: Children with attention-deficit/hyperactivity disorder (ADHD) have smaller volumes of total brain matter and subcortical regions, but it is unclear whether these represent delayed maturation or persist into adulthood. We performed a structural MRI study in 119 adult ADHD patients and 107 controls and investigated total gray and white matter and volumes of accumbens, caudate, globus pallidus, putamen, thalamus, amygdala and hippocampus. Additionally, we investigated effects of gender, stimulant treatment and history of major depression (MDD). There was no main effect of ADHD on the volumetric measures, nor was any effect observed in a secondary voxel-based morphometry (VBM) analysis of the entire brain. However, in the volumetric analysis a significant gender by diagnosis interaction was found for caudate volume. Male patients showed reduced right caudate volume compared to male controls, and caudate volume correlated with hyperactive/impulsive symptoms. Furthermore, patients using stimulant treatment had a smaller right hippocampus volume compared to medication-naïve patients and controls. ADHD patients with previous MDD showed smaller hippocampus volume compared to ADHD patients with no MDD. While these data were obtained in a cross-sectional sample and need to be replicated in a longitudinal study, the findings suggest that developmental brain differences in ADHD largely normalize in adulthood. Reduced caudate volume in male patients may point to distinct neurobiological deficits underlying ADHD in the two genders. Smaller hippocampus volume in ADHD patients with previous MDD is consistent with neurobiological alterations observed in MDD. [Copyright &y& Elsevier]

Abstract: Attention deficit/hyperactivity disorder (ADHD) is a highly heritable disorder and several genes increasing disease risk have been identified. The dopamine transporter gene, SLC6A3/DAT1, has been studied most extensively in ADHD research. Interestingly, a different haplotype of this gene (formed by genetic variants in the 3′ untranslated region and intron 8) is associated with childhood ADHD (haplotype 10-6) and adult ADHD (haplotype 9-6). The expression of DAT1 is highest in striatal regions in the brain. This part of the brain is of interest to ADHD because of its role in reward processing is altered in ADHD patients; ADHD patients display decreased striatal activation during reward processing. To better understand how the DAT1 gene exerts effects on ADHD, we studied the effect of this gene on reward-related brain functioning in the area of its highest expression in the brain, the striatum, using functional magnetic resonance imaging. In doing so, we tried to resolve inconsistencies observed in previous studies of healthy individuals and ADHD-affected children. In a sample of 87 adult ADHD patients and 77 healthy comparison subjects, we confirmed the association of the 9-6 haplotype with adult ADHD. Striatal hypoactivation during the reward anticipation phase of a monetary incentive delay task in ADHD patients was again shown, but no significant effects of DAT1 on striatal activity were found. Although the importance of the DAT1 haplotype as a risk factor for adult ADHD was again demonstrated in this study, the mechanism by which this gene increases disease risk remains largely unknown. [Copyright &y& Elsevier]

Purpose: Depression is highly prevalent in advanced cancer patients, but the diagnosis of depressive disorder in patients with advanced cancer is difficult. Screening instruments could facilitate diagnosing depressive disorder in patients with advanced cancer. The aim of this study was to determine the validity of the Beck Depression Inventory (BDI-II) and a single screening question as screening tools for depressive disorder in advanced cancer patients. Methods: Patients with advanced metastatic disease, visiting the outpatient palliative care department, were asked to fill out a self-questionnaire containing the Beck Depression Inventory (BDI-II) and a single screening question 'Are you feeling depressed?' The mood section of the PRIME-MD was used as a gold standard. Results: Sixty-one patients with advanced metastatic disease were eligible to be included in the study. Complete data were obtained from 46 patients. The area under the curve of the receiver operating characteristics analysis of the BDI-II was 0.82. The optimal cut-off point of the BDI-II was 16 with a sensitivity of 90% and a specificity of 69%. The single screening question showed a sensitivity of 50% and a specificity of 94%. Conclusions: The BDI-II seems an adequate screening tool for a depressive disorder in advanced cancer patients. The sensitivity of a single screening question is poor. [ABSTRACT FROM AUTHOR]

Objective: Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder. The NOS1 gene encoding nitric oxide synthase is a candidate gene for ADHD and has been previously linked with impulsivity. In the present study, the authors investigated the effect of a functional variable number of tandem repeats (VNTR) polymorphism in NOS1 (NOS1 exon 1f-VNTR) on the processing of rewards, one of the cognitive deficits in ADHD. Method: A sample of 136 participants, consisting of 87 adult ADHD patients and 49 healthy comparison subjects, completed a reward-related impulsivity task. A total of 104 participants also underwent functional magnetic resonance imaging during a reward anticipation task. The effect of the NOS1 exon 1f-VNTR genotype on reward-related impulsivity and reward-related ventral striatal activity was examined. Results: ADHD patients had higher impulsivity scores and lower ventral striatal activity than healthy comparison subjects. The association between the short allele and increased impulsivity was confirmed. However, independent of disease status, homozygous carriers of the short allele of NOS1, the ADHD risk genotype, demonstrated higher ventral striatal activity than carriers of the other NOS1 VNTR genotypes. Conclusions: The authors suggest that the NOS1 genotype influences impulsivity and its relation with ADHD is mediated through effects on this behavioral trait. Increased ventral striatal activity related to NOS1 may be compensatory for effects in other brain regions. [ABSTRACT FROM AUTHOR]

Abstract: While autism is one of the most intensively researched psychiatric disorders, little is known about reasoning skills of people with autism. The focus of this study was on defeasible inferences, that is inferences that can be revised in the light of new information. We used a behavioral task to investigate (a) conditional reasoning and (b) the suppression of conditional inferences in high-functioning adults with autism. In the suppression task a possible exception was made salient which could prevent a conclusion from being drawn. We predicted that the autism group would have difficulties dealing with such exceptions because they require mental flexibility to adjust to the context, which is often impaired in autism. The findings confirm our hypothesis that high-functioning adults with autism have a specific difficulty with exception-handling during reasoning. It is suggested that defeasible reasoning is also involved in other cognitive domains. Implications for neural underpinnings of reasoning and autism are discussed. [Copyright &y& Elsevier]