Screening and diagnostic assessment of neurodevelopmental disorders in a male prison

Purpose The purpose of this paper is to identify neurodevelopmental disorders and difficulties (NDD) in a male prison. The study used standardised tools to carry out screening and diagnostic assessment of the attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID). Design/methodology/approach The ADHD self-report scale, 20-item autism quotient and the Learning Disability Screening Questionnaire were used to screen 240 male prisoners. Prisoners who screened positive on one or more of these scales or self-reported a diagnosis of ADHD, ASD or ID were further assessed using the diagnostic interview for ADHD in adults, adapted Autism Diagnostic Observation Schedule and the Quick Test. Findings Of the 87 prisoners who screened positive for NDD and were further assessed, 70 met the study’s diagnostic criteria for ADHD, ASD or ID. Most of those with NDD (51 per cent) had previously gone unrecognised and a high proportion (51 per cent) were identified through staff- or self-referral to the study. Originality/value The study demonstrated that improving awareness and providing access to skilled, standardised assessment within a male prison can result in increased recognition and identification of NDD

Validation of the Mind Excessively Wandering Scale and the Relationship of Mind Wandering to Impairment in Adult ADHD.

OBJECTIVE: This study investigates excessive mind wandering (MW) in adult ADHD using a new scale: the Mind Excessively Wandering Scale (MEWS). METHOD: Data from two studies of adult ADHD was used in assessing the psychometric properties of the MEWS. Case-control differences in MW, the association with ADHD symptoms, and the contribution to functional impairment were investigated. RESULTS: The MEWS functioned well as a brief measure of excessive MW in adult ADHD, showing good internal consistency (α > .9), and high sensitivity (.9) and specificity (.9) for the ADHD diagnosis, comparable with that of existing ADHD symptom rating scales. Elevated levels of MW were found in adults with ADHD, which contributed to impairment independently of core ADHD symptom dimensions. CONCLUSION: Findings suggest excessive MW is a common co-occurring feature of adult ADHD that has specific implications for the functional impairments experienced. The MEWS has potential utility as a screening tool in clinical practice to assist diagnostic assessment

Antiphospholipid syndrome; its implication in cardiovascular diseases: a review

Antiphospholipid syndrome (APLS) is a rare syndrome mainly characterized by several hyper-coagulable complications and therefore, implicated in the operated cardiac surgery patient. APLS comprises clinical features such as arterial or venous thromboses, valve disease, coronary artery disease, intracardiac thrombus formation, pulmonary hypertension and dilated cardiomyopathy. The most commonly affected valve is the mitral, followed by the aortic and tricuspid valve. For APLS diagnosis essential is the detection of so-called antiphospholipid antibodies (aPL) as anticardiolipin antibodies (aCL) or lupus anticoagulant (LA). Minor alterations in the anticoagulation, infection, and surgical stress may trigger widespread thrombosis. The incidence of thrombosis is highest during the following perioperative periods: preoperatively during the withdrawal of warfarin, postoperatively during the period of hypercoagulability despite warfarin or heparin therapy, or postoperatively before adequate anticoagulation achievement. Cardiac valvular pathology includes irregular thickening of the valve leaflets due to deposition of immune complexes that may lead to vegetations and valve dysfunction; a significant risk factor for stroke. Patients with APLS are at increased risk for thrombosis and adequate anticoagulation is of vital importance during cardiopulmonary bypass (CPB). A successful outcome requires multidisciplinary management in order to prevent thrombotic or bleeding complications and to manage perioperative anticoagulation. More work and reporting on anticoagulation management and adjuvant therapy in patients with APLS during extracorporeal circulation are necessary

Genetic analysis of reaction time variability: room for improvement?

Background Increased reaction time variability (RTV) on cognitive tasks requiring a speeded response is characteristic of several psychiatric disorders. In attention deficit hyperactivity disorder (ADHD), the association with RTV is strong phenotypically and genetically, yet high RTV is not a stable impairment but shows ADHD-sensitive improvement under certain conditions, such as those with rewards. The state regulation theory proposed that the RTV difference score, which captures change from baseline to a rewarded or fast condition, specifically measures ‘state regulation'. By contrast, the interpretation of RTV baseline (slow, unrewarded) scores is debated. We aimed to investigate directly the degree of phenotypic and etiological overlap between RTV baseline and RTV difference scores. Method We conducted genetic model fitting analyses on go/no-go and fast task RTV data, across task conditions manipulating rewards and event rate, from a population-based twin sample (n=1314) and an ADHD and control sibling-pair sample (n=1265). Results Phenotypic and genetic/familial correlations were consistently high (0.72-0.98) between RTV baseline and difference scores, across tasks, manipulations and samples. By contrast, correlations were low between RTV in the manipulated condition and difference scores. A comparison across two different go/no-go task RTV difference scores (slow-fast/slow-incentive) showed high phenotypic and genetic/familial overlap (r=0.75-0.83). Conclusions Our finding that RTV difference scores measure largely the same etiological process as RTV under baseline condition supports theories emphasizing the malleability of the observed high RTV. Given the statistical shortcomings of difference scores, we recommend the use of RTV baseline scores for most analyses, including genetic analyse

Predictability of oppositional defiant disorder and symptom dimensions in children and adolescents with ADHD combined type

Background Oppositional defiant disorder (ODD) is frequently co-occurring with attention deficit hyperactivity disorder (ADHD) in children and adolescents. Because ODD is a precursor of later conduct disorder (CD) and affective disorders, early diagnostic identification is warranted. Furthermore, the predictability of three recently confirmed ODD dimensions (ODD-irritable, ODD-headstrong and ODD-hurtful) may assist clinical decision making. Method Receiver-operating characteristic (ROC) analysis was used in order to test the diagnostic accuracy of the Conners' Parent Rating Scale revised (CPRS-R) and the parent version of the Strength and Difficulties Questionnaire (PSDQ) in the prediction of ODD in a transnational sample of 1093 subjects aged 5-17 years from the International Multicentre ADHD Genetics study. In a second step, the prediction of three ODD dimensions by the same parent rating scales was assessed by backward linear regression analyses. Results ROC analyses showed adequate diagnostic accuracy of the CPRS-R and the PSDQ in predicting ODD in this ADHD sample. Furthermore, the three-dimensional structure of ODD was confirmed by confirmatory factor analysis and the CPRS-R emotional lability scale significantly predicted the ODD irritable dimension. Conclusions The PSDQ and the CPRS-R are both suitable screening instruments in the identification of ODD. The emotional lability scale of the CPRS-R is an adequate predictor of irritability in youth referred for ADH

The relationship between ADHD and key cognitive phenotypes is not mediated by shared familial effects with IQ

Background Twin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ. Method Multivariate familial models were run on data from 1265 individuals aged 6-18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice-delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI). Results Significant familial association (rF) was confirmed between cognitive performance and both ADHD (rF=0.41-0.71) and IQ (rF=−0.25 to −0.49). The association between ADHD and cognitive performance was largely independent (80-87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ. Conclusions The aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADH

Antiphospholipid Antibodies Bind ATP: A putative Mechanism for the Pathogenesis of Neuronal Dysfunction

Antiphospholipid antibodies (aPL) generated in experimental animals cross-react with ATP. We therefore examined the possibility that aPL IgG from human subjects bind to ATP by affinity column and an enzyme linked immunosorbent assay (ELISA). Sera with high levels of aPL IgG were collected from 12 patients with the antiphospholipid syndrome (APS). IgG fractions from 10 of 12 APS patients contained aPL that could be affinity-bound to an ATP column and completely eluted with NaCl 0.5 M. A significant (>50%) inhibition of aPL IgG binding by ATP 5 mM was found in the majority. Similar inhibition was obtained with ADP but not with AMP or cAMP. All the affinity purified anti-ATP antibodies also bound β2-glycoprotein-I (β2-GPI, also known as apolipoprotein H) suggesting that, similar to most pathogenic aPL, their binding depends on this serum cofactor. We further investigated this possibility and found that the binding of β2-GPI to the ATP column was similar to that of aPL IgG in that most was reversed by NaCl 0.5 M. Furthermore, addition of β2-GPI to aPL IgG significantly increased the amount of aPL binding to an ATP column. We conclude that aPL IgG bind ATP, probably through β2-GPI. This binding could interfere with the normal extracellular function of ATP and similar neurotransmitters

Randomised controlled trial of the short-term effects of OROS-methylphenidate on ADHD symptoms and behavioural outcomes in young male prisoners with attention-deficit/hyperactivity disorder (CIAO-II)

Background Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder, seen in 20–30% of young adult prisoners. Pharmacoepidemiological studies, a small randomised controlled trial and open trial data of methylphenidate suggest clinically significant reductions in ADHD symptoms, emotional dysregulation, disruptive behaviour and increased engagement with educational activities. Yet, routine treatment of ADHD in offenders is not yet established clinical practice. There is continued uncertainty about the clinical response to methylphenidate (MPH), a first-line treatment for ADHD, in offenders, who often present with an array of complex mental health problems that may be better explained by states of inattentive, overactive, restless and impulsive behaviours. To address this problem, we will conduct an efficacy trial to establish the short-term effects of osmotic-controlled release oral delivery system (OROS)-methylphenidate (Concerta XL), an extended release formulation of MPH, on ADHD symptoms, emotional dysregulation and behaviour. Methods This study is a parallel-arm, randomised, placebo-controlled trial of OROS-MPH on ADHD symptoms, behaviour and functional outcomes in young male prisoners aged 16–25, meeting Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria for ADHD. Participants are randomised to 8 weeks of treatment with OROS-MPH or placebo, titrated over 5 weeks to balance ADHD symptom improvement against side effects. Two hundred participants will be recruited with a 1:1 ratio of drug to placebo. The primary outcome is change in level of ADHD symptoms after 8 weeks of trial medication. Discussion Potential benefits include improvement in ADHD symptoms, emotional dysregulation, attitudes towards violence and critical incidents and increased engagement with educational and rehabilitation programmes. Demonstrating the efficacy and safety of MPH on ADHD symptoms and associated impairments may provide the data needed to develop effective healthcare pathways for a significant group of young offenders. Establishing efficacy of MPH in this population will provide the foundation needed to establish long-term effectiveness studies with the potential for demonstrating significant reductions in criminal behaviour and improved health-economic outcomes

Exome chip analyses in adult attention deficit hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. We performed an exome-wide scan of adult ADHD using the Illumina Human Exome Bead Chip, which interrogates over 250 000 common and rare variants. Participants were recruited by the International Multicenter persistent ADHD CollaboraTion (IMpACT). Statistical analyses were divided into 3 steps: (1) gene-level analysis of rare variants (minor allele frequency (MAF)<1%); (2) single marker association tests of common variants (MAFgreater than or equal to1%), with replication of the top signals; and (3) pathway analyses. In total, 9365 individuals (1846 cases and 7519 controls) were examined. Replication of the most associated common variants was attempted in 9847 individuals (2077 cases and 7770 controls) using fixed-effects inverse variance meta-analysis. With a Bonferroni-corrected significance level of 1.82E−06, our analyses of rare coding variants revealed four study-wide significant loci: 6q22.1 locus (P=4.46E−08), where NT5DC1 and COL10A1 reside; the SEC23IP locus (P=6.47E−07); the PSD locus (P=7.58E−08) and ZCCHC4 locus (P=1.79E−06). No genome-wide significant association was observed among the common variants. The strongest signal was noted at rs9325032 in PPP2R2B (odds ratio=0.81, P=1.61E−05). Taken together, our data add to the growing evidence of general signal transduction molecules (NT5DC1, PSD, SEC23IP and ZCCHC4) having an important role in the etiology of ADHD. Although the biological implications of these findings need to be further explored, they highlight the possible role of cellular communication as a potential core component in the development of both adult and childhood forms of ADHD