Dyslexia research at the turn of the 21st century:behavioural, neuroimaging and genetic findings

Behavioural studies have shown that dyslexics are a heterogeneous population and between-group comparisons are thus inadequate. Some subjects do not develop dyslexia despite having a deficit implicated in this disorder, which points to protective factors. Dyslexia co-occurs with ADHD, DCD, SLI, and SSD, so that future behavioural studies will need to screen and/or statistically control for other disorders. Studies of multiple cases of DPs with other developmental disorders are necessary. Neuroimaging findings show structural and/or functional brain abnormalities in language areas, V5/MT and the cerebellum. Future neuroimaging studies need to investigate the whole reading network and multiple cases. Six dyslexia risk genes have been found, mostly involved in neural migration, which may suggest dyslexia is a deficit of neuronal migration. However, it is not clear how these genes can restrict migration to specific brain areas. As a complex and heterogeneous disorder, dyslexia is likely to be associated with several mutated genes. ADHD and SSD are characterised by genetic risk factors which are partially shared with dyslexia, resulting in comorbidity. Future genetic studies need to focus on identifying other risk genes and pleiotropic genes involved in comorbidities, and linking genotypes implicated in dyslexia with brain structure. Any theory of dyslexia needs to take into account a multitude of risk and protective factors across behavioural, neural and genetic domains.

Personality profile of male adolescents with Tourette syndrome:a controlled study

Tourette syndrome is a neurodevelopmental disorder characterized by multiple tics and commonly associated with behavioral problems, especially obsessive-compulsive disorder and attention-deficit hyperactivity disorder (ADHD). The presence of specific personality traits has been documented in adult clinical populations with Tourette syndrome but has been underresearched in younger patients. We assessed the personality profiles of 17 male adolescents with Tourette syndrome and 51 age- and gender-matched healthy controls using the Minnesota Multiphasic Personality Inventory-Adolescent version, along with a standardized psychometric battery. All participants scored within the normal range across all Minnesota Multiphasic Personality Inventory-Adolescent version scales. Patients with Tourette syndrome scored significantly higher than healthy controls on the Obsessiveness Content Scale only (P = .046). Our findings indicate that younger male patients with Tourette syndrome do not report abnormal personality traits and have similar personality profiles to healthy peers, with the exception of obsessionality traits, which are likely to be related to the presence of comorbid obsessive compulsive symptoms rather than tics.

Why Most Biomedical Findings Echoed by Newspapers Turn Out to be False: The Case of Attention Deficit Hyperactivity Disorder

Context: Because positive biomedical observations are more often published than those reporting no effect, initial observations are often refuted or attenuated by subsequent studies. Objective: To determine whether newspapers preferentially report on initial findings and whether they also report on subsequent studies. Methods: We focused on attention deficit hyperactivity disorder (ADHD). Using Factiva and PubMed databases, we identified 47 scientific publications on ADHD published in the 1990s and soon echoed by 347 newspapers articles. We selected the ten most echoed publications and collected all their relevant subsequent studies until 2011. We checked whether findings reported in each ‘‘top 10’’ publication were consistent with previous and subsequent observations. We also compared the newspaper coverage of the ‘‘top 10’’ publications to that of their related scientific studies. Results: Seven of the ‘‘top 10’’ publications were initial studies and the conclusions in six of them were either refuted or strongly attenuated subsequently. The seventh was not confirmed or refuted, but its main conclusion appears unlikely. Among the three ‘‘top 10’’ that were not initial studies, two were confirmed subsequently and the third was attenuated. The newspaper coverage of the ‘‘top 10’’ publications (223 articles) was much larger than that of the 67 related studies (57 articles). Moreover, only one of the latter newspaper articles reported that the corresponding ‘‘top 10’’ finding had been attenuated. The average impact factor of the scientific journals publishing studies echoed by newspapers (17.1 n = 56) was higher (p,0.0001) than that corresponding to related publications that were not echoed (6.4 n = 56). Conclusion: Because newspapers preferentially echo initial ADHD findings appearing in prominent journals, they report on uncertain findings that are often refuted or attenuated by subsequent studies. If this media reporting bias generalizes to health sciences, it represents a major cause of distortion in health science communication.

It takes an institution's village to retain a student: A comprehensive look at two early warning system undergraduate retention programs and administrators' perceptions of students' experiences and the retention services they provide students in the early warning system retention programs

Institutions have implemented many campus interventions to address student persistence/retention, one of which is Early Warning Systems (EWS). However, few research studies show evidence of interventions that incorporate noncognitive factors/skills, and psychotherapy/psycho-educational processes in the EWS. A qualitative study (phenomenological interview and document analysis) of EWS at both a public and private 4-year Florida university was conducted to explore EWS through the eyes of the administrators of the ways administrators make sense of students' experiences and the services they provide and do not provide to assist students. Administrators' understanding of noncognitive factors and the executive skills subset and their contribution to retention and the executive skills development of at-risk students were also explored. Hossler and Bean's multiple retention lenses theory/paradigms and Perez's retention strategies were used to guide the study. Six administrators from each institution who oversee and/or assist with EWS for first time in college undergraduate students considered academically at-risk for attrition were interviewed. Among numerous findings, at Institution X: EWS was infrequently identified as a service, EWS training was not conducted, numerous cognitive and noncognitive issues/deficits were identified for students, and services/critical departments such as EWS did not work together to share students' information to benefit students. Assessment measures were used to identify students' issues/deficits; however, they were not used to assess, track, and monitor students' issues/deficits. Additionally, the institution's EWS did address students' executive skills function beyond time management and organizational skills, but did not address students' psychotherapy/psycho-educational processes. Among numerous findings, at Institution Y: EWS was frequently identified as a service, EWS training was not conducted, numerous cognitive and noncognitive issues/deficits were identified for students, and services/critical departments such as EWS worked together to share students' information to benefit students. Assessment measures were used to identify, track, and monitor students' issues/deficits; however, they were not used to assess students' issues/deficits. Additionally, the institution's EWS addressed students' executive skills function beyond time management and organizational skills, and psychotherapy/psycho-educational processes. Based on the findings, Perez's retention strategies were not utilized in EWS at Institution X, yet were collectively utilized in EWS at Institution Y, to achieve Hossler and Bean's retention paradigms. Future research could be designed to test the link between engaging in the specific promising activities identified in this research (one-to-one coaching, participation in student success workshops, academic contracts, and tutoring) and student success (e.g., higher GPA, retention). Further, because this research uncovered some concern with how to best handle students with physical and psychological disabilities, future research could link these same promising strategies for improving student performance for example among ADHD students or those with clinical depression.

La thérapie cognitive-comportementale dans le traitement du TDAH chez l'adulte: état des connaissances

Essai doctoral présenté à la Faculté des Arts et des Sciences en vue de l'obtention du grade de doctorat en psychologie clinique (D.psy.)

Management of adult attention deficit hyperactivity disorder in UK primary care: a survey of general practitioners

Background: Compared to existing literature on childhood attention deficit hyperactivity disorder (ADHD), little published adult data are available, particularly outside of the United States. Using General Practitioner (GP) questionnaires from the United Kingdom, this study aimed to examine a number of issues related to ADHD in adults, across three cohorts of patients, adults who received ADHD drug treatment in childhood/adolescence but stopped prior to adulthood; adults who received ADHD drug treatment in childhood/adolescence and continued treatment into adulthood and adults who started ADHD drug treatment in adulthood.Methods: Patients with a diagnosis of ADHD and prescribed methylphenidate, dexamfetamine or atomoxetine were identified using data from The Health Improvement Network (THIN). Dates when these drugs started and stopped were used to classify patients into the three cohorts. From each cohort, 50 patients were randomly selected and questionnaires were sent via THIN to their GPs.GPs returned completed questionnaires to THIN who forwarded anonymised copies to the researchers. Datasets were analysed using descriptive statistics.Results: Overall response rate was 89% (133/150). GPs stated that in 19 cases, the patient did not meet the criteria of that group; the number of valid questionnaires returned was 114 (76%). The following broad trends were observed: 1) GPs were not aware of the reason for treatment cessation in 43% of cases, 2) patient choice was the most common reason for discontinuation (56%), 3) 7% of patients who stopped pharmacological treatment subsequently reported experiencing ADHD symptoms, 4) 58% of patients who started pharmacological treatment for ADHD in adulthood received pharmacological treatment for other mental health conditions prior to the ADHD being diagnosed.Conclusion: This study presents some key findings relating to ADHD; GPs were often not aware of the reason for patients stopping ADHD treatment in childhood or adolescence. Patient choice was identified as the most common reason for treatment cessation. For patients who started pharmacological treatment in adulthood, many patients received pharmacological treatment for comorbidities before a diagnosis of ADHD was made.

Investigating the developmental and behavioral consequences of maternal immune activation on affected offspring

Maternal infection during pregnancy increases the risk of several neuropsychiatric disorders later in life, many of which have a component of dopaminergic (DA) dysfunction, including schizophrenia, autism spectrum disorders (ASD), and attention deficit hyperactivity disorder (ADHD). The majority of DA neurons are found in the adult midbrain; as such the midbrain is a key region of interest regarding these disorders. The literature is conflicting regarding the behavioral alterations following maternal immune activation (MIA) exposure, and the cellular and molecular consequences of MIA on the developing midbrain remain to be fully elucidated. Thus, this thesis aimed to establish the consequences of acute and mild MIA on offspring dopamine-related behaviors, as well as the associated cellular and molecular disturbances of MIA on offspring midbrains. We utilized a rat model of MIA using low dose (50μg/kg, I.P.) of LPS administered at different gestational ages. Our first study indicated that MIA at later gestational ages significantly increased pro-inflammatory IL-1β expression, and reduced HSD11B2 expression in the placenta, which is an important regulator of fetal development. In utero LPS exposure at later gestational ages also impaired the growth of neurons from affected offspring. This study identified key gestational stages during which MIA resulted in differential effects. We utilized these time points in subsequent studies, the next of which investigated neurobehavioral outcomes following MIA. Our results from that study showed that motor differences occurred in juvenile offspring following MIA at E16 only, and these differences were compensated for in adolescence. Then, there was a decline in motor behavior capabilities in adulthood, again only for animals exposed to MIA on E16 (and not E12). Furthermore, our results also demonstrated adolescent and adult offspring that were exposed to MIA at E12 had diminished responses to amphetamine in reward seeking behaviors. In our final study, we aimed to investigate the molecular and cellular changes following MIA which might explain these behavioral alterations. This final study showed a differential inflammatory response in fetal midbrains depending on gestational age of exposure as well as differential developmental alterations. For example, LPS exposure at E16 resulted in decreased VM neurosphere size after 7DIV and this was associated with an increased susceptibility to neurotoxic effects of pro-inflammatory cytokines for VM neurospheres and VM DA neurons treated in culture. In utero LPS exposure at E16 also reduced DA neuron count of fetal VM, measured by TH staining. However, there were no differences in DA neuron number in juvenile, adolescent, or adult offspring. Similarly, LPS exposure did not alter cell number or morphology of glial cells in the midbrains of affected offspring. In conclusion, this thesis indicated later rat pregnancy (E16) as vulnerable time for MIA to affect the development of the nigrostriatal pathway and subsequent behavioral outcomes, possibly implicating a role for MIA in increased risk for disorders associated with motor behavior, like PD. These effects may be mediated through alterations in the placenta and altered inflammatory mediators in the offspring brain. This thesis has also shown that MIA in earlier rat pregnancy (E12) results in altered mesocorticolimbic function, and in particular MIA on E12 resulted in a differential response to amphetamine in affected offspring, which may implicate a role for MIA in increasing the risk for disorders associated with this pathway, including drug tolerance and addiction.

Obstetric mode of delivery and child psychological development

Background/aims: Objective of the current thesis is to investigate the potential impact of birth by Caesarean section (CS) on child psychological development, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), behavioural difficulties and school performance. Structure/methods: Published literature to date on birth by CS, ASD and ADHD was reviewed (Chapter 2). Data from the UK Millennium Cohort Study (MCS) were analysed to determine the association between CS and ASD, ADHD and parent-reported behavioural difficulties (Chapter 3). The Swedish National Registers were used to further assess the association with ASD, ADHD and school performance (Chapters 4-6). Results: In the review, children born by CS were 23% more likely to be diagnosed with ASD after controlling for potential confounders. Only two studies reported adjusted estimates on the association between birth by CS and ADHD, results were conflicting and limited. CS was not associated with ASD, ADHD or behavioural difficulties in the UK MCS. In the Swedish National Registers, children born by CS were more likely to be diagnosed with ASD or ADHD. The association with elective CS did not persist when compared amongst siblings. There was little evidence of an association between birth by elective CS and poor school performance. Children born by elective CS had slight reduction in school performance. Conclusions: The lack of association with the elective CS in the sibling design studies indicates that the association in the population is most probably due to confounding. A small but significant association was found between birth by CS and school performance. However, the effect may have been due to residual confounding or confounding by indication and should be interpreted with caution. The overall conclusion is that birth by CS does not appear to have a causal relationship with the aspects of child psychological development investigated.

La thérapie cognitive-comportementale dans le traitement du TDAH chez l'adulte: état des connaissances

Essai doctoral présenté à la Faculté des Arts et des Sciences en vue de l'obtention du grade de doctorat en psychologie clinique (D.psy.)

Kärlek, till ett annorlunda barn : En litteraturstudie av bemötande och attityder gentemot familjer med diagnosbärande barn.

The issue of diagnosed children has been heavily debated in the media over the past decade. This study deals with the issue of diagnosis from a family perspective and utilizes a method of thematic analysis trough a literature review of four autobiographies that describes the parents experience of the diagnosis issue regarding attitudes and responses towards their children and family. The purpose is to create a greater understanding of the family situation and to explore new approaches and strategies to counter psychological affliction and exclusion in society. The results show a widespread exclusion based on the main themes, internal and external influences. These themes represent exclusion factors like for example inexperience in dealing with power bearing institutions such as schools and health facilities and creates few opportunities for socialization processes due to the child's disability, stigma. Both of these themes can be seen as a result of sensory deprivation. The attitudes and responses of society towards the stigma bearing child has a great negative impact on the families with diagnosed children.

Étiologie génétique et cognitive de l’association entre les habiletés en lecture et les dimensions du trouble déficitaire de l’attention avec ou sans hyperactivité (TDAH)

La présente thèse examine les associations entre les dimensions du TDAH et les habiletés en lecture sur les plans phénotypique, génétique et cognitif. En premier lieu, les associations entre les dimensions du TDAH (inattention et hyperactivité/impulsivité) et les habiletés en lecture (décodage et compréhension en lecture) chez des enfants au début du primaire (6-8 ans) ont été examinées. Les résultats révèlent des associations similaires. Toutefois, seules celles entre l’inattention et les habiletés en lecture demeurent après que l’hyperactivité/impulsivité, les symptômes de trouble du comportement et les habiletés non verbales aient été contrôlés. De plus, les associations entre l’inattention et les habiletés en lecture s’expliquent en grande partie par des facteurs génétiques. En second lieu, les associations entre les dimensions du TDAH et les habiletés en lecture (lecture de mots et exactitude/vitesse lors de la lecture d’un texte) ont été étudiées à 14-15 ans. Seule l’inattention demeure associée aux habiletés en lecture après que l’hyperactivité/impulsivité, les habiletés verbales et les habiletés non verbales aient été contrôlées. L’inattention et les habiletés en lecture sont aussi corrélées sur le plan génétique, mais ces corrélations deviennent non significatives lorsque les habiletés verbales sont contrôlées. En dernier lieu, des habiletés cognitives ont été étudiées comme mécanismes sous-jacents potentiels de l’association entre l’inattention et les habiletés en lecture (décodage et compréhension en lecture) à l’enfance. Il apparait que la conscience phonologique, la vitesse de dénomination de chiffres, le traitement temporel bimodal et le vocabulaire sont des médiateurs de l’association entre l’inattention et le décodage alors que la conscience phonologique, la vitesse de dénomination de chiffres et de couleurs et le vocabulaire sont des médiateurs de l’association entre l’inattention et la compréhension en lecture. De plus, des facteurs génétiques communs ont été observés entre certains médiateurs (conscience phonologique, vitesse de dénomination des chiffres et traitement temporel bimodal), l’inattention et le décodage. Somme toute, la présente thèse montre que des facteurs génétiques expliquent en partie ces associations à l’enfance et l’adolescence. Des médiateurs cognitifs sous-tendent ces associations, possiblement par des processus génétiques et environnementaux qui devront être précisés dans le futur.

Perfil Cognitivo e Perfil de Capacidades e Dificuldades de Crianças com Perturbações de Hiperatividade e Défice de Atenção (PHDA)

Apesar da Perturbação de Hiperatividade e Défice de Atenção (PHDA) ser uma das perturbações mais estudadas nos últimos anos, a definição da avaliação com vista ao seu diagnóstico está longe de ser consensual. Neste estudo quantitativo, transversal, foram avaliadas duas amostras de crianças com recurso à Escala de Inteligência de Wechsler para Crianças – III (WISCIII), duas amostras de pais com recurso ao Questionário de Capacidades e Dificuldades (Versão para pais) e duas amostras de professores com recurso ao Questionário de Capacidades e Dificuldades (Versão para professores). Os resultados demonstram que as crianças com PHDA apresentam um perfil cognitivo globalmente inferior ao das crianças sem diagnóstico de PHDA, mantendo no entanto, um Coeficiente Verbal (QIV) superior ao Coeficiente de Realização (QIR). Para o perfil de capacidades e de dificuldades, as crianças com esta perturbação demonstram genericamente dificuldades mais acentuadas do que as crianças sem PHDA. A multiplicidade de sintomas que caracterizam as crianças com esta perturbação, levam os investigadores a diferentes linhas de orientação. Desta forma, a definição de um perfil tipo para estas crianças poderá auxiliar na avaliação, no diagnóstico, na intervenção e na concordância entre os profissionais de saúde. / Despite Attention Deficit and Hyperactivity Disorder (ADHD) is one of the most studied disorders in the past years, the definition of the assessment for the purpose of diagnosis is far from consensual. In this quantitative and cross-finding study, two samples of children were assessed using the Wechsler Intelligence Scale for Children - III (WISC-III), two samples of parents were assessed using the Strengths and Difficulties Questionnaire (parent version) and two samples of teachers were assessed using Strengths and Difficulties Questionnaire (teacher version). The results show that children with ADHD have an overall lower cognitive profile in comparison to children without the diagnosis of ADHD, while maintaining a better Verbal Coefficient than the Performance Coefficient. In relation to the profile of strengths and difficulties, children with this disorder generally show more pronounced difficulties than children without ADHD. The multiplicity of symptoms that characterize children with this disorder, lead investigators to different guidelines. Thus, the definition of a profile type for these children may assist the assessment, the diagnosis, the intervention and the agreement among health professionals.

Omega-3 Fatty Acids are Related to Abnormal Emotion Processing in Adolescent Boys with Attention Deficit Hyperactivity Disorder

Background In addition to the core symptoms, attention deficit hyperactivity disorder (ADHD) is associated with poor emotion regulation. There is some evidence that children and young adults with ADHD have lower omega-3 levels and that supplementation with omega-3 can improve both ADHD and affective symptoms. We therefore investigated differences between ADHD and non-ADHD children in omega-3/6 fatty acid plasma levels and the relationship between those indices and emotion-elicited event-related potentials (ERPs). Methods Children/adolescents with (n=31) and without ADHD (n=32) were compared in their plasma omega-3/6 indices and corresponding ERPs during an emotion processing task. Results Children with ADHD had lower mean omega-3/6 and ERP abnormalities in emotion processing, independent of emotional valence relative to control children. ERP abnormalities were significantly associated with lower omega-3 levels in the ADHD group. Conclusions The findings reveal for the first time that lower omega-3 fatty acids are associated with impaired emotion processing in ADHD children.

Omega-3 Fatty Acids are Inversely Related to Callous and Unemotional Traits in Adolescent Boys with Attention Deficit Hyperactivity Disorder

A number of research studies have reported abnormal plasma fatty acid profiles in children with ADHD along with some benefit of n−3 to symptoms of ADHD. However, it is currently unclear whether (lower) long chain-polyunsaturated fatty acids (LC-PUFAs) are related to ADHD pathology or to associated behaviours. The aim of this study was to test whether (1) ADHD children have abnormal plasma LC-PUFA levels and (2) ADHD symptoms and associated behaviours are correlated with LC-PUFA levels. Seventy-two, male children with (n=29) and without a clinical diagnosis of ADHD (n=43) were compared in their plasma levels of LC-PUFA. Plasma DHA was higher in the control group prior to statistical correction. Callous–unemotional (CU) traits were found to be significantly negatively related to both eicosapentaenoic acid (EPA), and total omega-3 in the ADHD group. The findings unveil for the first time that CU and anti-social traits in ADHD are associated with lower omega-3 levels.

Validez de un modelo reducido de items del DSM-IV según respuesta de padres y profesores en el diagnóstico del Trastorno por Déficit de Atención con Hiperactividad Combinado

El objetivo es buscar un modelo reducido de síntomas del Trastorno por Déficit de Atención con Hiperactividad subtipo Combinado (TDAH-C), que presente adecuada validez de criterio para su diagnóstico. La metodología se basa en contexto de estudio epidemiológico. Muestra de 1095 casos entre 6 y 16 años [4.38 % TDAH-C]. Se realiza una selección de casos con primera fase psicométrica de sospecha TDAH-C que requiere que ADHD RS-IV, implementado por padres (PA) y profesores (PR), supere el PC 90. En la segunda fase, los casos seleccionados se evalúan mediante entrevista clínica modelo DISC-IV (DSM-IV) para confirmar TDAH-C. Se implementa regresión logística para buscar modelo parsimonioso de ítems que permita predecir TDAH-C. El modelo de ítems que permite predecir TDAH-C contiene 8 de los 36 ítems del ADHD RS-IV contestados por PA y PR. Considerando las odds ratio del modelo de regresión logística, los ítems del ADHD RS-IV seleccionados son los siguientes 15PR, 1PA, 16PR, 12PA, 17PA, 10PA, 14PA y 4PR. El modelo presenta validez de criterio para TDAH-C clínico (sensibilidad: 97.9 %. Especificidad: 93.8%. Razón de verosimilitud: 16.02). Es posible reducir la lista de síntomas de TDAH-C con buena validez de criterio, manteniendo los que proporcionan mayor discriminación entre TDAH-C y población general.