Cognitive-behavioural therapy in medication-treated adults with attention-deficit/hyperactivity disorder and co-morbid psychopathology:a randomized controlled trial using multi-level analysis

Background. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by high rates of co-morbid psychopathology. Randomized controlled trials of multimodal interventions, combining pharmacological and psychological treatments, have shown a robust treatment effect for ADHD symptoms but outcomes for co-morbid symptoms have been mixed. This may be accounted for by the type of intervention selected and/or by methodological problems including lack of follow-up and low power. The current study addressed these limitations in a parallel-group randomized controlled trial conducted in Iceland.  Method. A total of 95 adult ADHD patients who were already being treated with medication (MED) were randomly assigned to receive treatment as usual (TAU/MED) or 15 sessions of cognitive-behavioural therapy (CBT/MED) using the R&R2ADHD intervention which employs both group and individual modalities. Primary measures of ADHD symptoms and severity of illness, and secondary measures of anxiety, depression and quality of life were given at baseline, end of treatment and 3-month follow-up. Primary outcomes were rated by clinicians blind to treatment condition assignment.  Results. CBT/MED showed overall (combined outcome at end of treatment and 3-month follow-up) significantly greater reduction in primary outcomes for clinician-rated and self-rated ADHD symptoms. Treatment effect of primary outcomes was maintained at follow-up, which suggests robust and lasting findings. In contrast to the primary outcomes, the secondary outcomes showed significant improvement over time.  Conclusions. The study provides evidence for the effectiveness of R&R2ADHD and demonstrates that there are differential effects over time for ADHD symptoms versus co-morbid problems, the latter taking longer to show positive effects

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Association of HLA-DRB1 amino acid residues with giant cell arteritis: genetic association study, meta-analysis and geo-epidemiological investigation

Introduction: Giant cell arteritis (GCA) is an autoimmune disease commonest in Northern Europe and Scandinavia. Previous studies report various associations with HLA-DRB1*04 and HLA-DRB1*01; HLA-DRB1 alleles show a gradient in population prevalence within Europe. Our aims were (1) to determine which amino acid residues within HLA-DRB1 best explained HLA-DRB1 allele susceptibility and protective effects in GCA, seen in UK data combined in meta-analysis with previously published data, and (2) to determine whether the incidence of GCA in different countries is associated with the population prevalence of the HLA-DRB1 alleles that we identified in our meta-analysis. Methods: GCA patients from the UK GCA Consortium were genotyped by using single-strand oligonucleotide polymerization, allele-specific polymerase chain reaction, and direct sequencing. Meta-analysis was used to compare and combine our results with published data, and public databases were used to identify amino acid residues that may explain observed susceptibility/protective effects. Finally, we determined the relationship of HLA-DRB1*04 population carrier frequency and latitude to GCA incidence reported in different countries. Results: In our UK data (225 cases and 1378 controls), HLA-DRB1*04 carriage was associated with GCA susceptibility (odds ratio (OR) = 2.69, P = 1.5×10 −11 ), but HLA-DRB1*01 was protective (adjusted OR = 0.55, P = 0.0046). In meta-analysis combined with 14 published studies (an additional 691 cases and 4038 controls), protective effects were seen from HLA-DR2, which comprises HLA-DRB1*15 and HLA-DRB1*16 (OR = 0.65, P = 8.2×10 −6 ) and possibly from HLA-DRB1*01 (OR = 0.73, P = 0.037). GCA incidence (n = 17 countries) was associated with population HLA-DRB1*04 allele frequency (P = 0.008; adjusted R 2 = 0.51 on univariable analysis, adjusted R 2 = 0.62 after also including latitude); latitude also made an independent contribution. Conclusions: We confirm that HLA-DRB1*04 is a GCA susceptibility allele. The susceptibility data are best explained by amino acid risk residues V, H, and H at positions 11, 13, and 33, contrary to previous suggestions of amino acids in the second hypervariable region. Worldwide, GCA incidence was independently associated both with population frequency of HLA-DRB1*04 and with latitude itself. We conclude that variation in population HLA-DRB1*04 frequency may partly explain variations in GCA incidence and that HLA-DRB1*04 may warrant investigation as a potential prognostic or predictive biomarker

Capital controls and the resolution of failed cross-border banks: The case of Iceland

First published online December 6, 2013

Capital controls as a bargaining device: The case of Iceland

Iceland imposed strict capital controls when its banks failed in October 2008. Legacy problems and a large stock of carry-trade funds locked in by the controls hindered lifting them, but they also helped in resolving the banks. We formulate and calibrate a bargaining model describing the strategic interaction between Iceland and international investors. Outcomes indicate a judicious bargaining approach by Icelandic authorities which was ultimately successful and led to resolution by settlement. The results are robust to reasonable variations in parameter values and are consistent with outcomes in investment arbitration trials and anecdotal evidence from Icelandic case law