The diagnosis of mental disorders: the problem of reification

A pressing need for interrater reliability in the diagnosis of mental disorders emerged during the mid-twentieth century, prompted in part by the development of diverse new treatments. The Diagnostic and Statistical Manual of Mental Disorders (DSM), third edition answered this need by introducing operationalized diagnostic criteria that were field-tested for interrater reliability. Unfortunately, the focus on reliability came at a time when the scientific understanding of mental disorders was embryonic and could not yield valid disease definitions. Based on accreting problems with the current DSM-fourth edition (DSM-IV) classification, it is apparent that validity will not be achieved simply by refining criteria for existing disorders or by the addition of new disorders. Yet DSM-IV diagnostic criteria dominate thinking about mental disorders in clinical practice, research, treatment development, and law. As a result, the modernDSMsystem, intended to create a shared language, also creates epistemic blinders that impede progress toward valid diagnoses. Insights that are beginning to emerge from psychology, neuroscience, and genetics suggest possible strategies for moving forward

Understanding the Mind or Predicting Signal-Dependent Action? Performance of Children With and Without Autism on Analogues of the False-Belief Task

To evaluate the claim that correct performance on unexpected transfer false-belief tasks specifically involves mental-state understanding, two experiments were carried out with children with autism, intellectual disabilities, and typical development. In both experiments, children were given a standard unexpected transfer false-belief task and a mental-state-free, mechanical analogue task in which participants had to predict the destination of a train based on true or false signal information. In both experiments, performance on the mechanical task was found to correlate with that on the false-belief task for all groups of children. Logistic regression showed that performance on the mechanical analogue significantly predicted performance on the false-belief task even after accounting for the effects of verbal mental age. The findings are discussed in relation to possible common mechanisms underlying correct performance on the two tasks

Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits

Autism spectrum disorder (ASD) defines a group of common, complex neurodevelopmental disorders. Although the aetiology of ASD has a strong genetic component, there is considerable monozygotic (MZ) twin discordance indicating a role for non-genetic factors. Because MZ twins share an identical DNA sequence, disease-discordant MZ twin pairs provide an ideal model for examining the contribution of environmentally driven epigenetic factors in disease. We performed a genome-wide analysis of DNA methylation in a sample of 50 MZ twin pairs (100 individuals) sampled from a representative population cohort that included twins discordant and concordant for ASD, ASD-associated traits and no autistic phenotype. Within-twin and between-group analyses identified numerous differentially methylated regions associated with ASD. In addition, we report significant correlations between DNA methylation and quantitatively measured autistic trait scores across our sample cohort. This study represents the first systematic epigenomic analyses of MZ twins discordant for ASD and implicates a role for altered DNA methylation in autism

Spatial interactions in agent-based modeling

Agent Based Modeling (ABM) has become a widespread approach to model complex interactions. In this chapter after briefly summarizing some features of ABM the different approaches in modeling spatial interactions are discussed. It is stressed that agents can interact either indirectly through a shared environment and/or directly with each other. In such an approach, higher-order variables such as commodity prices, population dynamics or even institutions, are not exogenously specified but instead are seen as the results of interactions. It is highlighted in the chapter that the understanding of patterns emerging from such spatial interaction between agents is a key problem as much as their description through analytical or simulation means. The chapter reviews different approaches for modeling agents' behavior, taking into account either explicit spatial (lattice based) structures or networks. Some emphasis is placed on recent ABM as applied to the description of the dynamics of the geographical distribution of economic activities, - out of equilibrium. The Eurace@Unibi Model, an agent-based macroeconomic model with spatial structure, is used to illustrate the potential of such an approach for spatial policy analysis.Comment: 26 pages, 5 figures, 105 references; a chapter prepared for the book "Complexity and Geographical Economics - Topics and Tools", P. Commendatore, S.S. Kayam and I. Kubin, Eds. (Springer, in press, 2014

Simple mindreading abilities predict complex theory of mind: developmental delay in autism spectrum disorders

Theory of Mind (ToM) is impaired in individuals with Autism Spectrum Disorders (ASD). The aims of this study were to: i) examine the developmental trajectories of ToM abilities in two different mentalizing tasks in children with ASD compared to TD children; and ii) to assess if a ToM simple test known as Eyes-test could predict performance on the more advanced ToM task, i.e. Comic Strip test. Based on a sample of 37 children with ASD and 55 TD children, our results revealed slower development at varying rates in all ToM measures in children with ASD, with delayed onset compared to TD children. These results could stimulate new treatments for social abilities, which would lessen the social deficit in ASD

Impaired Prefrontal Hemodynamic Maturation in Autism and Unaffected Siblings

BACKGROUND: Dysfunctions of the prefrontal cortex have been previously reported in individuals with autism spectrum disorders (ASD). Previous studies reported that first-degree relatives of individuals with ASD show atypical brain activity during tasks associated with social function. However, developmental changes in prefrontal dysfunction in ASD and genetic influences on the phenomena remain unclear. In the present study, we investigated the change in hemoglobin concentration in the prefrontal cortex as measured with near-infrared spectroscopy, in children and adults with ASD during the letter fluency test. Moreover, to clarify the genetic influences on developmental changes in the prefrontal dysfunction in ASD, unaffected siblings of the ASD participants were also assessed. METHODOLOGY/PRINCIPAL FINDINGS: Study participants included 27 individuals with high-functioning ASD, age- and IQ-matched 24 healthy non-affected siblings, and 27 unrelated healthy controls aged 5 to 39 years. The relative concentration of hemoglobin ([Hb]) in the prefrontal cortex was measured during the letter fluency task. For children, neither the [oxy-Hb] change during the task nor task performances differed significantly among three groups. For adults, the [oxy-Hb] increases during the task were significantly smaller in the bilateral prefrontal cortex in ASD than those in control subjects, although task performances were similar. In the adult siblings the [oxy-Hb] change was intermediate between those in controls and ASDs. CONCLUSION/SIGNIFICANCE: Although indirectly due to a cross-sectional design, the results of this study indicate altered age-related change of prefrontal activity during executive processing in ASD. This is a first near-infrared spectroscopy study that implies alteration in the age-related changes of prefrontal activity in ASD and genetic influences on the phenomena

T.A. Ward

respectively). A combination of one habitat assessment and Proper Functioning Condition should be utilized to conduct a comprehensive assessment of riparian/stream health. Site characteristics, which were significantly associated with assessment outcomes included entrenchment ratio, substrate size, channel width to depth and slope. This presents a problem in that comparison of assessment outcomes across different streams and stream reaches are confounded by factors such as slope and substrate type, which may not always be indicative of riparian/stream health. The Rosgen Stream Morphology Classification system was used to successfully control for the effect of these site-specific effects on assessment outcome, allowing for comparison of riparian/stream health assessments across streams

Development of a High Intensity Neutron Source at the European Spallation Source: The HighNESS project

The European Spallation Source (ESS), presently under construction in Lund, Sweden, is a multidisciplinary international laboratory that will operate the world's most powerful pulsed neutron source. Supported by a 3M Euro Research and Innovation Action within the EU Horizon 2020 program, a design study (HighNESS) is now underway to develop a second neutron source below the spallation target. Compared to the first source, located above the spallation target and designed for high cold and thermal brightness, the new source will provide higher intensity, and a shift to longer wavelengths in the spectral regions of cold (2 /- 20 {\AA}), very cold (VCN, 10 /- 120 {\AA}), and ultra cold (UCN, > 500 {\AA}) neutrons. The core of the second source will consist of a large liquid deuterium moderator to deliver a high flux of cold neutrons and to serve secondary VCN and UCN sources, for which different options are under study. The features of these new sources will boost several areas of condensed matter research and will provide unique opportunities in fundamental physics. Part of the HighNESS project is also dedicated to the development of future instruments that will make use of the new source and will complement the initial suite of instruments in construction at ESS. The HighNESS project started in October 2020. In this paper, the ongoing developments and the results obtained in the first year are described.Comment: 10 pages, 10 figures, 14th International Topical Meeting on Nuclear Applications of Accelerators, November 30 to December 4, 2021, Washington, D

Social brain activation during mentalizing in a large autism cohort: the Longitudinal European Autism Project

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition with key deficits in social functioning. It is widely assumed that the biological underpinnings of social impairment are neurofunctional alterations in the “social brain,” a neural circuitry involved in inferring the mental state of a social partner. However, previous evidence comes from small-scale studies and findings have been mixed. We therefore carried out the to-date largest study on neural correlates of mentalizing in ASD. Methods: As part of the Longitudinal European Autism Project, we performed functional magnetic resonance imaging at six European sites in a large, well-powered, and deeply phenotyped sample of individuals with ASD (N = 205) and typically developing (TD) individuals (N = 189) aged 6 to 30 years. We presented an animated shapes task to assess and comprehensively characterize social brain activation during mentalizing. We tested for effects of age, diagnosis, and their association with symptom measures, including a continuous measure of autistic traits. Results: We observed robust effects of task. Within the ASD sample, autistic traits were moderately associated with functional activation in one of the key regions of the social brain, the dorsomedial prefrontal cortex. However, there were no significant effects of diagnosis on task performance and no effects of age and diagnosis on social brain responses. Besides a lack of mean group differences, our data provide no evidence for meaningful differences in the distribution of brain response measures. Extensive control analyses suggest that the lack of case-control differences was not due to a variety of potential confounders. Conclusions: Contrary to prior reports, this large-scale study does not support the assumption that altered social brain activation during mentalizing forms a common neural marker of ASD, at least with the paradigm we employed. Yet, autistic individuals show socio-behavioral deficits. Our work therefore highlights the need to interrogate social brain function with other brain measures, such as connectivity and network-based approaches, using other paradigms, or applying complementary analysis approaches to assess individual differences in this heterogeneous condition

Fatigue, reduced sleep quality and restless legs syndrome in Charcot-Marie-Tooth disease: a web-based survey

To investigate the prevalence of fatigue, daytime sleepiness, reduced sleep quality, and restless legs syndrome (RLS) in a large cohort of patients with Charcot-Marie-Tooth disease (CMT) and their impact on health-related quality of life (HRQoL). Participants of a web-based survey answered the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the Multidimensional Fatigue Inventory, and, if the diagnostic criteria of RLS were met, the International RLS Severity Scale. Diagnosis of RLS was affirmed in screen-positive patients by means of a standardized telephone interview. HRQoL was assessed by using the SF-36 questionnaire. Age- and sex-matched control subjects were recruited from waiting relatives of surgical outpatients. 227 adult self-reported CMT patients answered the above questionnaires, 42.9% were male, and 57.1% were female. Age ranged from 18 to 78 years. Compared to controls (n = 234), CMT patients reported significantly higher fatigue, a higher extent and prevalence of daytime sleepiness and worse sleep quality. Prevalence of RLS was 18.1% in CMT patients and 5.6% in controls (p = 0.001). RLS severity was correlated with worse sleep quality and reduced HRQoL. Women with CMT were affected more often and more severely by RLS than male patients. With regard to fatigue, sleep quality, daytime sleepiness, RLS prevalence, RLS severity, and HRQoL, we did not find significant differences between genetically distinct subtypes of CMT. HRQoL is reduced in CMT patients which may be due to fatigue, sleep-related symptoms, and RLS in particular. Since causative treatment for CMT is not available, sleep-related symptoms should be recognized and treated in order to improve quality of life