Snappy App: a mobile continuous performance test with physical activity measurement for assessing Attention Deficit Hyperactivity Disorder

A Continuous Performance Test (CPT) was incorporated into a smartphone application (App) to measure three symptom domains associated with Attention Deficit Hyperactivity Disorder (ADHD); attention, impulsivity and hyperactivity. The App was pilot tested on 11 healthy adults over three test-ing sessions. No differences in performance were found between testing ses-sions suggesting good test consistency. A decrement in performance over time was only found for one measure of attention and on one testing session. The CPT showed some sensitivity to ADHD-related symptoms where self-reported impulsive behaviour was related to the CPT measures of impulsivity and activi-ty. User acceptability was good although some design improvements were sug-gested. Further pilot testing of the App in a clinical population is needed

Overcoming the Metaphysics of Consciousness: Being/Artaud

Some recent theories of the mind have invoked the theatre as a metaphor to explain consciousness. This paper suggests that there is something irreducible to consciousness and that theatre can be an invaluable tool for exploring such subject matter. Rather than explain the mind through theory, performance practices can use immediate experience to investigate consciousness. Of course, Antonin Artaud’s ‘Theatre of Cruelty’ articulates the hope of apprehending consciousness through immediate experience, overcoming ‘literature’ and the alienating ossification of language. For Artaud, the ‘self’ has always been stolen at birth yet he suggests it can be returned through the theatre. The Theatre of Cruelty is an overcoming of the metaphysical obstructions of ‘being’. Martin Heidegger’s Being and Time also seeks to reveal the concept of 'Being' by destroying the historical misunderstanding of the term. Heidegger' claims that 'Dasein' (Being-there), the human subject, is maintained by a radical continuity with the world in which it exists. Because human subjects are 'absorbed' in the world of practical activity, projects and tasks, they tend to misrecognise themselves as a ‘thing’. But consciousness is not a ‘thing’ like other entities in the world. Such misrecognition is the fundamental error in what Heidegger calls metaphysics. My contention is that the Theatre of Cruelty is Artaud’s attempt at articulating a practical investigation of consciousness, resisting the metaphysical structures of language and logic and calling for the priority of ‘experience’. Cruelty is a return of the pre-theoretical, unspeakable words needed to explore the Being of consciousness. Such is an attempt to overcome the metaphysics of consciousness onstage.The conference was sponsored by A.D.S.A., the Department of Performance Studies, the School of Letters, Arts and Media, and the Faculty of Arts of the University of Sydney

A Fragmented Parallel Stream: The Bass Lines of Eddie Gomez in the Bill Evans Trio

Eddie Gomez was the bassist in the Bill Evans Trio for eleven years. His contribution to the group’s sound was considerable, but while there has been some recognition of his virtuoso solos in the trio there has been little academic interest in his bass lines. This essay examines bass lines from the album Since We Met, recorded in 1974 by Evans, Gomez and drummer Marty Morell. Analysis of the bass accompaniments to the piano solos on “Since We Met” and “Time Remembered” reveals that they form a fragmented two-feel. A traditional two-feel employs two notes to emphasise the first and third beats in bar of 4/4 time. In Gomez’s bass lines these two notes are frequently replaced with short rhythmic motifs. These motifs occur in a variety of forms and at different metric displacements that alternately propel and retard the forward motion of the music. Additionally, Gomez uses a wide range of register and varied articulations to create a richly diverse bass line. The resulting effect has often been interpreted as interactive or conversational with the soloist. However there is very little interaction between the bass line and Evans’ solo. The bass line is a parallel stream to the solo that energises and colours the music

Genetic Architecture of ADHD and Overlap With Other Psychiatric Disorders And Cognition-Related Phenotypes

Attention-deficit/hyperactivity disorder (ADHD) co-occurs with many other psychiatric disorders and traits. In this review, we summarize and interpret the existing literature on the genetic architecture of these comorbidities based on hypothesis-generating approaches. Quantitative genetic studies indicate that genetic factors play a substantial role in the observed co-occurrence of ADHD with many different disorders and traits. Molecular genetic correlations derived from genome-wide association studies and results of studies based on polygenic risk scores confirm the general pattern but provide effect estimates that are smaller than those from twin studies. The identification of the specific genetic variants and biological pathways underlying co-occurrence using genome-wide approaches is still in its infancy. The first analyses of causal inference using genetic data support causal relationships between ADHD and comorbid disorders, although bidirectional effects identified in some instances point to complex relationships. While several issues in the methodology and inferences from the results are still to be overcome, this review shows that the co-occurrence of ADHD with many psychiatric disorders and traits is genetically interpretable

Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder

The variability in phenotypic presentations and the lack of consistency of genetic associations in mental illnesses remain a major challenge in molecular psychiatry. Recently, it has become increasingly clear that altered promoter DNA methylation could play a critical role in mediating differential regulation of genes and in facilitating short-term adaptation in response to the environment. Here, we report the investigation of the differential activity of membrane-bound catechol-O-methyltransferase (MB - COMT) due to altered promoter methylation and the nature of the contribution of COMT Val158Met polymorphism as risk factors for schizophrenia and bipolar disorder by analyzing 115 post-mortem brain samples from the frontal lobe. These studies are the first to reveal that the MB - COMT promoter DNA is frequently hypomethylated in schizophrenia and bipolar disorder patients, compared with the controls (methylation rate: 26 and 29 versus 60; P = 0.004 and 0.008, respectively), particularly in the left frontal lobes (methylation rate: 29 and 30 versus 81; P = 0.003 and 0.002, respectively). Quantitative gene-expression analyses showed a corresponding increase in transcript levels of MB - COMT in schizophrenia and bipolar disorder patients compared with the controls (P = 0.02) with an accompanying inverse correlation between MB - COMT and DRD1 expression. Furthermore, there was a tendency for the enrichment of the Val allele of the COMT Val158Met polymorphism with MB - COMT hypomethylation in the patients. These findings suggest that MB - COMT over-expression due to promoter hypomethylation and/or hyperactive allele of COMT may increase dopamine degradation in the frontal lobe providing a molecular basis for the shared symptoms of schizophrenia and bipolar disorder. © Copyright 2006 Oxford University Press

Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic patients: A preliminary report

DNA methylation changes could provide a mechanism for DNA plasticity and dynamism for short-term adaptation, enabling a type of cell memory to register cellular history under different environmental conditions. Some environmental insults may also result in pathological methylation with corresponding alteration of gene expression patterns. Evidence from several studies has suggested that in schizophrenia and bipolar disorder, mRNA of the reelin gene (RELN), which encodes a protein necessary for neuronal migration, axonal branching, synaptogenesis, and cell signaling, is severely reduced in post-mortem brains. Therefore, we investigated the methylation status of the RELN promoter region in schizophrenic patients and normal controls as a potential mechanism for down regulation of its expression. Ten post-mortem frontal lobe brain samples from male schizophrenic patients and normal controls were obtained from the Harvard Brain Tissue Resources Center. DNA was extracted using a standard phenol-chloroform DNA extraction protocol. To evaluate differences between patients and controls, we applied methylation specific PCR (MSP) using primers localized to CpG islands flanking a potential cyclic AMP response element (CRE) and a stimulating protein-1 (SP1) binding site located in the promoter region. For each sample, DNA extraction, bisulfite treatment, and MSP were independently repeated at least four times to accurately determine the methylation status of the target region. Forty-three PCR trials were performed on the test and control samples. MSP analysis of the RELN promoter revealed an unmethylated signal in all reactions (43 of 43) using DNA from the frontal brain tissue, derived from either the schizophrenic patients or normal controls indicating that this region of the RELN promoter is predominantly unmethylated. However, we observed a distinct methylated signal in 73 of the trials (16 of 22) in schizophrenic patients compared with 24 (5 of 21) of controls. Thus, the hypermethylation of the CpG islands flanking a CRE and SP1 binding site observed at a significantly higher level (t = -5.07, P = 0.001) may provide a mechanism for the decreased RELN expression, frequently observed in post-mortem brains of schizophrenic patients. We also found an inverse relationship between the level of DNA methylation using MSP analysis and the expression of the RELN gene using semi-quantitative RT-PCR. Despite the small sample size, these studies indicate that promoter hypermethylation of the RELN gene could be a significant contributor in effecting epigenetic alterations and provides a molecular basis for the RELN gene hypoactivity in schizophrenia. Further studies with a larger sample set would be required to validate these preliminary observations. © 2005 Wiley-Liss, Inc

Psychiatric genomics: An update and an Agenda

The Psychiatric Genomics Consortium (PGC) is the largest consortium in the history of psychiatry. This global effort is dedicated to rapid progress and open science, and in the past decade it has delivered an increasing flow of new knowledge about the fundamental basis of common psychiatric disorders. The PGC has recently commenced a program of research designed to deliver “actionable” findings—genomic results that 1) reveal fundamental biology, 2) inform clinical practice, and 3) deliver new therapeutic targets. The central idea of the PGC is to convert the family history risk factor into biologically, clinically, and therapeutically meaningful insights. The emerging findings suggest that we are entering a phase of accelerated genetic discovery for multiple psychiatric disorders. These findings are likely to elucidate the genetic portions of these truly complex traits, and this knowledge can then be mined for its relevance for improved therapeutics and its impact on psychiatric practice within a precision medicine framework

Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Altres ajuts: Max Planck Society (Germany).The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes