Characterising resting-state functional connectivity in a large sample of adults with ADHD

AbstractAttention-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 1.5T 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

An evaluation of DSM-III-R and ICD-10 benzodiazepine dependence criteria using Rasch modelling

Abstract Aims. To evaluate the homogeneity of the elements of the Substance Dependence Syndrome (SDS) as applied to benzodiazepines (BZD

The Beck Depression Inventory (BDI-II) and a single screening question as screening tools for depressive disorder in Dutch advanced cancer patients

Item does not contain fulltextPURPOSE: 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.1 februari 201

Enlarged striatal volume in adults with ADHD carrying the 9-6 haplotype of the dopamine transporter gene DAT1

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

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (<50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, <50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters

Transfer of toxic substances from feed to food Transferência de substâncias tóxicas de alimentos para animais para alimentos para humanos

The title may raise questions about definitions of the terms used. The more obvious ones are: 1) What is transfer? 2) How to define toxic; and 3) How to define feed or food. A more underlying question is how to measure the substances we are interested in. The (often) chemical methods used, are not always sensitive or specific enough. Sometimes, biologically based methods are used which detect a biological response, but seldom identify the compound responsible for that. Transfer is often not quantified in absolute terms but expressed in concentrations in feed and food. Mass balance between intake and excretion are quite rare as a steady state situation of residues in the animal is sometimes not obtained. Toxicity is mostly dependent on the concentration of the substance involved and even substances presumed to be innocent. Feed does certainly include the materials provided to the animal but also include the soil in which they walk and graze? Animals will consume some of the soil and it might contain considerable amounts of unwanted substances. Food certainly includes meat, milk and eggs and probably liver and kidney. But does also include intestine, spleen, testicles or even bone? Analytical methods may give wrong results if not applied properly and with adequate background knowledge. The recent episode of melamine in milk powder has been a very tragic wake-up call in this respect. Based on 35 years of carry-over studies with farm animals and data from the literature, a number of these points will be discussed.O título deste artigo pode levantar algumas questões a respeito dos termos adotados. As mais óbvias são: 1) O que é transferência? 2) Como definir tóxico? 3) Como definir alimento para animais e para humanos? Uma questão mais destacada é como medir as substâncias nas quais nós estamos interessados. Os métodos químicos frequentemente usados, nem sempre apresentam sensibilidade ou são suficientemente específicos para os metabólitos que desejamos. Algumas vezes, métodos com base biológica são usados, os quais detectam uma resposta biológica, mas não a identidade da substância responsável pela resposta. Transferência frequentemente não é quantificada em termos absolutos, mas expressa em concentração no alimento. Os balanços de massa entre ingestão e excreção são raros, e assim as condições de estabilização dos resíduos no animal muitas vezes não são obtidas. A toxicidade é dependente principalmente da concentração da substância envolvida e até mesmo da concentração da substância presumida como não tóxica. Entre os alimentos fornecidos aos animais pelo produtor se inclui outros materiais, como solo por exemplo. Animais que consomem solo podem ingerir quantidades consideráveis de substâncias não desejáveis. Alimentos para humanos certamente incluem carne, leite e ovos, e provavelmente fígado e rins. Mas incluem também intestino, pulmão, testículos, ou mesmo osso? Os métodos analíticos podem dar resultados errados se não aplicados corretamente e com conhecimento. O recente episódio da melamina no leite em pó foi uma trágica ocorrência que reforça a atenção dos pesquisadores. Baseado em nossos estudos de mais de 35 anos sobre contaminação cruzada e de dados de literatura, vários destes pontos destacados serão discutidos