Construct and diagnostic validities of the Free and Cued Selective Reminding Test in the alzheimer’s disease spectrum

The Free and Cued Selective Reminding Test (FCSRT) is a memory test that controls attention and acquisition, by providing category cues in the learning process. Because it enables an assessment of memory not confounded by normal age-related changes in cognition and a high accuracy on Alzheimer's disease (AD) evaluation, it has been suggested by the International Working Group on AD. Our aim was to assess the construct related validity of the FCSRT in the AD spectrum disorders.

Validity of the Brazilian Portuguese version of the bipolar spectrum diagnostic scale

OBJECTIVE: Bipolar spectrum disorders (BSDs) are prevalent and frequently unrecognized and undertreated. This report describes the development and validation of the Brazilian version of the bipolar spectrum diagnostic scale (B-BSDS), a screening instrument for bipolar disorders, in an adult psychiatric population. METHOD: 114 consecutive patients attending an outpatient psychiatric clinic completed the B-BSDS. A research psychiatrist, blind to the B-BSDS scores, interviewed patients by means of a modified version of the mood module of the Structured Clinical Interview for DSM-IV ("gold standard"). Subthreshold bipolar disorders were defined as recurrent hypomania without a major depressive episode or with fewer symptoms than those required for threshold hypomania. RESULTS: The internal consistency of the B-BSDS evaluated with Cronbach's alpha coefficient was 0.89 (95% CI; 0.86-0.91). On the basis of the modified SCID, 70 patients (61.4%) of the sample received a diagnosis of BSDs. A B-BSDS screening score of 16 or more items yielded: sensitivity of 0.79 (95% CI; 0.72-0.85), specificity of 0.77 (95% CI; 0.70-0.83), a positive predictive value of 0.85 (95% CI; 0.78-0.91) and a negative predictive value of 0.70 (95% CI; 0.63-0.75). CONCLUSION: The present data demonstrate that the B-BSDS is a valid instrument for the screening of BSDs.

Transmission disequilibrium of small CNVs in simplex autism.

We searched for disruptive, genic rare copy-number variants (CNVs) among 411 families affected by sporadic autism spectrum disorder (ASD) from the Simons Simplex Collection by using available exome sequence data and CoNIFER (Copy Number Inference from Exome Reads). Compared to high-density SNP microarrays, our approach yielded ∼2× more smaller genic rare CNVs. We found that affected probands inherited more CNVs than did their siblings (453 versus 394, p = 0.004; odds ratio [OR] = 1.19) and that the probands' CNVs affected more genes (921 versus 726, p = 0.02; OR = 1.30). These smaller CNVs (median size 18 kb) were transmitted preferentially from the mother (136 maternal versus 100 paternal, p = 0.02), although this bias occurred irrespective of affected status. The excess burden of inherited CNVs among probands was driven primarily by sibling pairs with discordant social-behavior phenotypes (p < 0.0002, measured by Social Responsiveness Scale [SRS] score), which contrasts with families where the phenotypes were more closely matched or less extreme (p > 0.5). Finally, we found enrichment of brain-expressed genes unique to probands, especially in the SRS-discordant group (p = 0.0035). In a combined model, our inherited CNVs, de novo CNVs, and de novo single-nucleotide variants all independently contributed to the risk of autism (p < 0.05). Taken together, these results suggest that small transmitted rare CNVs play a role in the etiology of simplex autism. Importantly, the small size of these variants aids in the identification of specific genes as additional risk factors associated with ASD.

Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature.

This study aimed to elucidate the observed variable phenotypic expressivity associated with NRXN1 (Neurexin 1) haploinsufficiency by analyses of the largest cohort of patients with NRXN1 exonic deletions described to date and by comprehensively reviewing all comparable copy number variants in all disease cohorts that have been published in the peer reviewed literature (30 separate papers in all). Assessment of the clinical details in 25 previously undescribed individuals with NRXN1 exonic deletions demonstrated recurrent phenotypic features consisting of moderate to severe intellectual disability (91%), severe language delay (81%), autism spectrum disorder (65%), seizures (43%), and hypotonia (38%). These showed considerable overlap with previously reported NRXN1-deletion associated phenotypes in terms of both spectrum and frequency. However, we did not find evidence for an association between deletions involving the β-isoform of neurexin-1 and increased head size, as was recently published in four cases with a deletion involving the C-terminus of NRXN1. We identified additional rare copy number variants in 20% of cases. This study supports a pathogenic role for heterozygous exonic deletions of NRXN1 in neurodevelopmental disorders. The additional rare copy number variants identified may act as possible phenotypic modifiers as suggested in a recent digenic model of neurodevelopmental disorders. © 2013 Wiley Periodicals, Inc.

Entrenament en atenció : Treball amb alumnat amb NEE

The purpose of this project was to analyze theattention span of students with mental retardation with Autism Spectrum Disorder (Asperger Syndrome) and with mild intellectual disabilities and behavioral disorders of an USEE class in a secondary school.

DSM-5: a collection of psychiatrist views on the changes, controversies, and future directions.

The recent release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by the American Psychiatric Association has led to much debate. For this forum article, we asked BMC Medicine Editorial Board members who are experts in the field of psychiatry to discuss their personal views on how the changes in DSM-5 might affect clinical practice in their specific areas of psychiatric medicine. This article discusses the influence the DSM-5 may have on the diagnosis and treatment of autism, trauma-related and stressor-related disorders, obsessive-compulsive and related disorders, mood disorders (including major depression and bipolar disorders), and schizophrenia spectrum disorders.

Mental disorders in offspring of parents with bipolar and major depressive disorders.

OBJECTIVES: There is limited information on the specificity of associations between parental bipolar disorder (BPD) and major depressive disorder (MDD) and the risk of psychopathology in offspring. The chief aim of the present study was to investigate the association between mood disorder subtypes in the two parents and mental disorders in the offspring. METHODS: A total of 376 offspring (aged 6.0-17.9 years; mean=11.5years) of 72 patients with BPD (139 offspring), 56 patients with MDD (110 offspring), and 66 controls (127 offspring) participated in a family study conducted in two university hospital centers in Switzerland. Probands, offspring, and biological co-parents were interviewed by psychologists blind to proband diagnoses, using a semi-structured diagnostic interview. RESULTS: Rates of mood and anxiety disorders were elevated among offspring of BPD probands (34.5% any mood; 42.5% any anxiety) and MDD probands (25.5% any mood; 44.6% any anxiety) as compared to those of controls (12.6% any mood; 22.8% any anxiety). Moreover, recurrent MDD was more frequent among offspring of BPD probands (7.9%) than those of controls (1.6%). Parental concordance for bipolar spectrum disorders was associated with a further elevation in the rates of mood disorders in offspring (64.3% both parents versus 27.2% one parent). CONCLUSIONS:   These findings provide unique information on the broad manifestations of parental mood disorders in their offspring. The earlier onset and increased risk of recurrent MDD in the offspring of parents with BPD compared to those of controls suggests that the episodicity characterizing BPD may emerge in childhood and adolescence.

IOWA Students with Autism: Who are they, how are they served, and are they achieving? October 2012

The Iowa Department of Education completed two studies in 2011-2012. The studies addressed several areas of need: (a) identifying students likely on the Autism Spectrum, (b) examining where large numbers of students on the Autism Spectrum are attending school, (c) evaluating the services being provided to students and the location of those services, (d) determining the extent to which services are evidence-based, (e) determining if services are sufficient to effect change needed to reach performance levels needed to access life opportunity, (f) understanding the kinds of problems being addressed through the Individualized Education Programs (IEPs) for the students identified, (g) examining the severity of behavior problems in the sample, and (h) examining academic proficiency and growth for students likely to be on the Autism Spectrum.

Iowa Autism Council By-Laws and Operating Procedures, Revised 2012

These By-laws and Operating Procedures are designed to guide the membership and work of the Iowa Autism Council. The Iowa Autism Council is a collaborative resource that envisions its role as an advocate for children and adults living with Autism Spectrum Disorder (autism and Asperger's and other conditions represented on the autism spectrum) and their families. As such, it is committed to representing individuals with diverse and changing educational needs. Iowa Autism Council (IAC) shall have, and will perform, functions and duties as specified by law. Responsibilities include offering advice, consultation, and recommendations to Governor Culver and the Iowa legislature regarding matters concerning the ASD population. The role of the Council members is to advise, not advocate, for an individual position. Advise means to inform, counsel, recommend, suggest or guide. To advocate means to plead for your case or position, to favor an individual case or argument. The advisory Council is to provide advice, based on facts and good judgment.

Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2.

Recent genetic studies have implicated a number of candidate genes in the pathogenesis of Autism Spectrum Disorder (ASD). Polymorphisms of CNTNAP2 (contactin-associated like protein-2), a member of the neurexin family, have already been implicated as a susceptibility gene for autism by at least 3 separate studies. We investigated variation in white and grey matter morphology using structural MRI and diffusion tensor imaging. We compared volumetric differences in white and grey matter and fractional anisotropy values in control subjects characterised by genotype at rs7794745, a single nucleotide polymorphism in CNTNAP2. Homozygotes for the risk allele showed significant reductions in grey and white matter volume and fractional anisotropy in several regions that have already been implicated in ASD, including the cerebellum, fusiform gyrus, occipital and frontal cortices. Male homozygotes for the risk alleles showed greater reductions in grey matter in the right frontal pole and in FA in the right rostral fronto-occipital fasciculus compared to their female counterparts who showed greater reductions in FA of the anterior thalamic radiation. Thus a risk allele for autism results in significant cerebral morphological variation, despite the absence of overt symptoms or behavioural abnormalities. The results are consistent with accumulating evidence of CNTNAP2's function in neuronal development. The finding suggests the possibility that the heterogeneous manifestations of ASD can be aetiologically characterised into distinct subtypes through genetic-morphological analysis.

Children at psychiatric risk and their families in Bucharest, in the context of 25 years of changes after December 89’ Romanian Revolution

The aim of the present dissertation was to capture a picture of child and adolescent mental health in Romania, in the context of almost 25 years of changes following the Romanian Revolution of December ’89. A three-part study was carried out in order to provide consistent answers to the pre-defined objectives: to appraise the development of child and adolescent mental health services in Romania (Part I), to explore the characteristics of clinically-referred patients in a Romanian child and adolescent psychiatry department (Part II), to examine the children’s mental health state and its connections with family functioning and associated risk factors (Part III). A multi-method research approach was used, comprising one qualitative analysis and two quantitative research studies. Part I consisted of a comparative qualitative analysis of the answers given by 10 mental health professionals at a 12-questions open ended interview about the current situation in child and adolescent mental health in Romania, on three topics: changes, challenges, solutions. Part II involved a descriptive quantitative analysis of certain variables (e.g. age, gender, primary diagnosis, co-morbidities, time of hospitalization) conducted on the patients who had been admitted to the Child and Adolescent Psychiatry Department at “Prof. Dr. Alexandru Obregia” Psychiatry Hospital, Bucharest in 1991 and in 2013. Part III was conducted on 342 subjects enrolled in two clinical groups and one school group, this study being performed through a cross-sectional analysis on multi-informant child and adolescent mental health problems and competencies (CBCL, YSR, SDQ P, SDQ SR) and their interrelation with household information (HQ) and family functioning (FAD). Outlining the results it can be stated that: 1) The CAMH System in Romania is definitely set on the path of reorganization, including a higher involvement of beneficiaries and of the community. 2) The characteristics of the admitted patients have changed significantly during the last almost 25 years since `89 December Revolution, under the influence of word wide trends in child psychiatry and of administrative aspects of the mental health network in Romania. 3) The rates of main diagnoses and co-morbidities confirm the reports in literature, with Autism Spectrum Disorder being the most frequent childhood psychiatric disorders in this study. 4) The children’s mental health problems in the psychiatry group are comparable to those reported for other clinical populations. 5) Significant score differences were observed according to various household features and also meaningful associations between a child’s clinical status and different aspects of family functioning. The Romanian Child and Adolescent Psychiatry has started to adopt the norms and standards of the European Union. In the 25 years that have elapsed after the 1989 Revolution, many changes have occurred in Romanian CAMH, but many unresolved issues have also risen. Therefore, the major contribution of this thesis is that it provides a coherent and updated overview of the present-day situation from three different perspectives- those of mental healthcare professionals, the one observed in clinical patients and the one reported by children’s families.

Decision support system for the diagnosis of schizophrenia disorders

Clinical decision support systems are useful tools for assisting physicians to diagnose complex illnesses. Schizophrenia is a complex, heterogeneous and incapacitating mental disorder that should be detected as early as possible to avoid a most serious outcome. These artificial intelligence systems might be useful in the early detection of schizophrenia disorder. The objective of the present study was to describe the development of such a clinical decision support system for the diagnosis of schizophrenia spectrum disorders (SADDESQ). The development of this system is described in four stages: knowledge acquisition, knowledge organization, the development of a computer-assisted model, and the evaluation of the system's performance. The knowledge was extracted from an expert through open interviews. These interviews aimed to explore the expert's diagnostic decision-making process for the diagnosis of schizophrenia. A graph methodology was employed to identify the elements involved in the reasoning process. Knowledge was first organized and modeled by means of algorithms and then transferred to a computational model created by the covering approach. The performance assessment involved the comparison of the diagnoses of 38 clinical vignettes between an expert and the SADDESQ. The results showed a relatively low rate of misclassification (18-34%) and a good performance by SADDESQ in the diagnosis of schizophrenia, with an accuracy of 66-82%. The accuracy was higher when schizophreniform disorder was considered as the presence of schizophrenia disorder. Although these results are preliminary, the SADDESQ has exhibited a satisfactory performance, which needs to be further evaluated within a clinical setting.

Benefits of Using Target Activities to Assist in Improvement of Striking in Striking and Fielding Games for Individuals with Autism: A Comparative Case Study

The purpose of the research study was to increase understanding about the potential benefits of combining target activities with striking-fielding games for individuals with high functioning autism spectrum disorder. A comparative case study was conducted to understand if target activities can assist in improving the skills of striking and throwing, aid the learning of tactics and add to current understanding of how certain teaching skills might be linked to the transfer between target and striking-fielding games. Data was collected through observations, student journals and interviews and were analyzed using both inductive and deductive methods. Results show an appearance of improvement in throwing, striking, bowling and badminton for overall skill levels. In regards to teaching skills, appropriate and effective teaching techniques, appropriate and effective equipment, dynamic of participants and student-instructors and consistency of attendance are vital. Future research should further look at the transferability to outdoor settings and interview the participants.

The lived experience of mothering a child with autism: a hermeneutic phenomenological understanding

Autism Spectrum Disorder is a complex developmental disorder with increasing prevalence. Despite the significant role of mothers, often seen as primary caregivers, there is limited understanding of this experience. The purpose of this study was to explore the everyday experience of mothers with children with autism. Accounts of lived experience were collected through research conversations with six mothers and analyzed using van Manen’s (1990) orientation to hermeneutic phenomenology. The main themes include: It Can’t Be Autism, The Womb is Extended, The Locus of Other, and The Womb is Now and is Forever. The findings suggest that mothers experienced a transformation from mother to mother with a child with autism; one that mirrors the transformation from woman to mother (Bergum, 1989). In this transformation, mothers move from suspicion of the potential diagnosis to acceptance that they are mothers with children whose needs define them and potentially, mothers whose wombs are forever extended.

Développement et fonctionnement des mécanismes de résonance motrice chez l'humain

La découverte dans le cerveau du singe macaque de cellules visuo-motrices qui répondent de façon identique à la production et la perception d’actes moteurs soutient l’idée que ces cellules, connues sous le nom de neurones-miroirs, encoderaient la représentation d’actes moteurs. Ces neurones, et le système qu’ils forment, constitueraient un système de compréhension moteur; par delà la simple représentation motrice, il est également possible que ce système participe à des processus de haut niveau en lien avec la cognition sociale. Chez l’humain adulte, des études d’imagerie récentes montrent d’importants chevauchements entre les patrons d’activité liés à l’exécution d’actes moteurs et ceux associés à la perception d’actions. Cependant, malgré le nombre important d’études sur ce système de résonance motrice, étonnamment peu se sont penchées sur les aspects développementaux de ce mécanisme, de même que sa relation avec certaines habiletés sociales dans la population neurotypique. De plus, malgré l’utilisation répandue de certaines techniques neurophysiologiques pour quantifier l’activité de ce système, notamment l’électroencéphalographie et la stimulation magnétique transcrânienne, on ignore en grande partie la spécificité et la convergence de ces mesures dans l’étude des processus de résonance motrice. Les études rassemblées ici visent à combler ces lacunes, c'est-à-dire (1) définir l’existence et les propriétés fonctionnelles du système de résonance motrice chez l’enfant humain, (2) établir le lien entre ce système et certaines habiletés sociales spécifiques et (3) déterminer la validité des outils d’investigation couramment utilisés pour mesurer son activité. Dans l’article 1, l’électroencéphalographie quantitative est utilisée afin de mesurer l’activité des régions sensorimotrices chez un groupe d’enfants d’âge scolaire durant la perception d’actions de la main. On y démontre une modulation de l’activité du rythme mu aux sites centraux non seulement lors de l’exécution de tâches motrices, mais également lors de l’observation passive d’actions. Ces résultats soutiennent l’hypothèse de l’existence d’un système de résonance motrice sensible aux représentations visuelles d’actes moteurs dans le cerveau immature. L’article 2 constitue une étude de cas réalisée chez une jeune fille de 12 ans opérée pour épilepsie réfractaire aux médicaments. L’électroencéphalographie intracrânienne est utilisée afin d’évaluer le recrutement du cortex moteur lors de la perception de sons d’actions. On y montre une modulation de l’activité du cortex moteur, visible dans deux périodes distinctes, qui se reflètent par une diminution de la puissance spectrale des fréquences beta et alpha. Ces résultats soutiennent l’hypothèse de l’existence d’un système de résonance motrice sensible aux représentations auditives d’actions chez l’enfant. L’article 3 constitue une recension des écrits portant sur les données comportementales et neurophysiologiques qui suggèrent la présence d’un système de compréhension d’action fonctionnel dès la naissance. On y propose un modèle théorique où les comportements d’imitation néonataux sont vus comme la résultante de mécanismes d’appariement moteurs non inhibés. Afin de mesurer adéquatement la présence de traits empathiques et autistique dans le but de les mettre en relation avec l’activité du système de résonance motrice, l’article 4 consiste en une validation de versions françaises des échelles Empathy Quotient (Baron-Cohen & Wheelwright, 2004) et Autism Spectrum Quotient (Baron-Cohen et al., 2001) qui seront utilisées dans l’article 5. Les versions traduites de ces échelles ont été administrées à 100 individus sains et 23 personnes avec un trouble du spectre autistique. Les résultats répliquent fidèlement ceux obtenus avec les questionnaires en version anglaise, ce qui suggère la validité des versions françaises. Dans l’article 5, on utilise la stimulation magnétique transcrânienne afin d’investiguer le décours temporel de l’activité du cortex moteur durant la perception d’action et le lien de cette activité avec la présence de traits autistiques et empathiques chez des individus normaux. On y montre que le cortex moteur est rapidement activé suivant la perception d’un mouvement moteur, et que cette activité est corrélée avec les mesures sociocognitives utilisées. Ces résultats suggèrent l’existence d’un système d’appariement moteur rapide dans le cerveau humain dont l’activité est associée aux aptitudes sociales. L’article 6 porte sur la spécificité des outils d’investigation neurophysiologique utilisés dans les études précédentes : la stimulation magnétique transcrânienne et l’électroencéphalographie quantitative. En utilisant ces deux techniques simultanément lors d’observation, d’imagination et d’exécution d’actions, on montre qu’elles évaluent possiblement des processus distincts au sein du système de résonance motrice. En résumé, cette thèse vise à documenter l’existence d’un système de résonance motrice chez l’enfant, d’établir le lien entre son fonctionnement et certaines aptitudes sociales et d’évaluer la validité et la spécificité des outils utilisés pour mesurer l’activité au sein de ce système. Bien que des recherches subséquentes s’avèrent nécessaires afin de compléter le travail entamé ici, les études présentées constituent une avancée significative dans la compréhension du développement et du fonctionnement du système de résonance motrice, et pourraient éventuellement contribuer à l’élaboration d’outils diagnostiques et/ou de thérapeutiques chez des populations où des anomalies de ce système ont été répertoriées.