Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that affects academic, social, and health functioning. The psychometric properties of measures commonly used in diagnostic settings to assess the constructs of attention, hyperactivity, and executive functioning, including concurrent and incremental validity with other commonly used measures, are not well-established. Additionally, these specific psychometric properties within ecological samples of children and adolescents presenting to community-based clinics is infrequent. The purpose of this dissertation was to describe a sample of children and adolescents presenting to a community-based mental health clinic and to test the concurrent and incremental validity of parent- and teacher-report questionnaires and neuropsychological measures of inattention, hyperactivity, and executive functioning. Participants included a consecutive sample of 597 youth aged six to eighteen years presenting to a community-based mental health clinic for a psychological assessment between 2010 and 2019. Measures included the BASC (2nd and 3rd editions), Conners 3 (long and short forms), BRIEF (1st and 2nd editions), D-KEFS, NEPSY-II, and CPT (2nd and 3rd editions). Approximately 50% of individuals were diagnosed with ADHD. Correlations between attention, hyperactivity, and executive function constructs on questionnaires were significantly and moderately-to-strongly correlated (Spearman’s  = .27-.82) to each other (e.g., BASC Hyperactivity and Conners Hyperactivity/Impulsivity subscales) and across parent and teacher forms (e.g., Conners Parent Inattention and Conners Teacher Inattention subscales). Constructs measured by neuropsychological tests were not significantly correlated to similar constructs measured by other neuropsychological measures or questionnaires (e.g., inhibition measured by NEPSY-II Response Set and BRIEF Inhibition subscale; Spearman’s  = .02-.38). Logistic regression analyses suggested that measures such as the BASC, BRIEF, NEPSY-II, and CPT do not clinically significantly increase prediction of ADHD diagnosis above and beyond the Conners 3. Results indicate convergence of information with potential redundancy in the assessment and diagnosis of ADHD across questionnaire measures and informants. Questionnaires and neuropsychological measures were not correlated, suggesting they measure different constructs or different aspects of the same construct. Results indicate that clinicians may sufficiently rely on questionnaires and reduce the number of other neuropsychological measures administered during a diagnostic assessment without significantly reducing diagnostic accuracy. However, the value of evidence of symptoms in multiple settings and converging information should still be considered.

Bakgrund: Fysioterapeutiska interventioner som exempelvis fysisk aktivitet har positiv effekt på flertalet symptom hos personer med ADHD. Dessa personer har även påvisad nedsatt motorisk kontroll och motorisk färdighet jämfört med neurotypiska personer. Trots påvisade positiva effekter nyttjas inte fysioterapeuters kompetens vid rehabilitering av ADHD. Syfte: Syftet var att kartlägga det aktuella kunskapsläget angående fysisk träning som fysioterapeutisk intervention för ökad motorisk färdighet och ökad motorisk kontroll hos personer med ADHD. Metod: En artikelsökning utfördes i databaserna Pubmed, PEDro, Cinahl, Web of Science och Scopus. Sökningen resulterade i elva relevanta artiklar varav fyra av dessa inkluderades. Referenslistor på inkluderade artiklar och review-studier granskades, vilket resulterade i ytterligare två inkluderade artiklar. Alla artiklar kvalitetsgranskades och sammanställdes i en resultattabell. Resultat: Fem artiklar, varav fyra av dessa med högt bevisvärde, visar att fysisk träning har signifikant effekt på motorisk färdighet. En artikel med högt bevisvärde indikerar att fysisk träning har signifikant effekt på motorisk kontroll. Effekten verkar inte bero på vilken typ av träning som utfördes, däremot visar en studie att högintensiv träning verkar ha bättre effekt på motorisk färdighet än lågintensiv. Konklusion: Fysisk träning verkar ha effekt på motorisk färdighet och motorisk kontroll hos personer med ADHD oavsett typ av träningsform. Högintensiv träning verkar ge bättre effekt på motorisk färdighet än lågintensiv. Brist på forskning inom området leder till svårigheter att dra tydliga slutsatser utifrån dessa resultat, därav behöver fler studier utföras.

Adhesion G-protein coupled receptors (GPCRs) are the second largest class of GPCRs, yet their functions and ligands remain predominantly unidentified. Polymorphisms in the gene encoding the adhesion GPCR latrophilin 3 (ADGRL3) have been associated with an increased risk for attention deficit hyperactivity disorder (ADHD) and substance use disorder (SUD) in various linkage and association studies. Disrupting the function of ADGRL3 homologs across mammalian and invertebrate model systems leads to changes in various dopaminergic phenotypes such as hyperactivity, sleep impairment, and changes in sensitivity to psychostimulants, suggesting that ADGRL3 contributes to behavior by modulating dopamine signaling. Here, I use behavioral and imaging studies to delineate an important role for Cirl, the Drosophila homolog of ADGRL3, in a recently characterized dopaminergic sleep circuit. Sleep impairment is a common symptom in both SUD and ADHD, and sleep studies are well established in Drosophila. Our work shows that fruit flies that carry a null mutation for Cirl are hyperactive and display a deficit in sleep that is enhanced by adult thermogenetic activation of dopamine neurons. Though Cirl displays high expression within dopamine neurons, conditional knockout of Cirl in dopamine neurons does not recapitulate sleep deficits seen in Cirl null flies, and specific rescue of Cirl in a knockout background does not ameliorate them. Intriguingly, activating dopamine neurons in Cirl null flies throughout development rescued the sleep deficits, indicating that this dopaminergic intervention induces lasting changes that can ameliorate lack of Cirl function. Imaging studies reveal that Cirl shows high expression in the central complex, which is involved in sleep and receives dense dopaminergic input. I demonstrate that Cirl functions within different populations of the central complex downstream of dopaminergic innervation to differentially affect night and daytime sleep through both dopaminergic and non-dopaminergic mechanisms. This work delineates a novel role for an adhesion GPCR in modulating sleep behavior, and further characterizes ADGRL3 as a potential therapeutic target for disorders characterized by dysregulation of dopaminergic neurotransmission.

Attention Deficit Hyperactivity Disorder, eller ADHD, är en neuropsykiatrisk funktionsnedsättning som kan ha stor inverkan på elevers skolgång. Den svenska skolans kompensatoriska uppdrag syftar dock till att bland annat minska diagnosernas påverkan på elevers skolgång med hjälp av olika stödinsatser så att elever ska kunna ta till sig utbildningen på bästa sätt. Detta kan ske på olika vis, men en faktor är de anpassningar som görs av lärare i undervisningen. Syftet med denna studie är att undersöka vilka anpassningar gymnasielärare har erfarenhet av att använda i sin undervisning i relation till ADHD, samt deras attityd till detta arbete. Data samlades in via inspelade semistrukturerade intervjuer som sedan transkriberades och analyserades med reflexiv tematisk analys. Samtliga moment genomfördes av båda författarna. I analysen framkom det att lärare genomför anpassningar som vi delade in i två huvudteman:individanpassningar och klassövergripande anpassningar. Detta beroende på om anpassningen endast var till nytta för individen eller om hela klassen kunde dra nytta av anpassningen. Det uppmärksammades även att lärarnas attityder formas av deras olika infallsvinklar och upplevelser till arbetet med anpassningar för elever med diagnoser som ADHD. Några av slutsatserna som framkom i studien är bland annat att gymnasielärare har erfarenhet av attanvända sig av en rad olika anpassningar, både för specifika individer men även anpassningar som gynnar hela klassen. Lärarnas attityd till arbetet med anpassningar är både komplext och varierande i relation till deras upplevelser och infallsvinklar till anpassningar.

Diverse clinical presentation in neurodevelopmental disorders (NDDs) leads to difficulty in matching individuals with effective treatments. Autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) are the two most prevalent neurodevelopmental disorders (NDDs), characterized by deficits in communication, social interactions, and behaviours. There is high within-diagnosis heterogeneity and striking overlap between diagnoses. The literature suggests that current diagnostic criteria do not align well with behaviour metrics. Therefore, identifying novel biomarkers underlying behaviour in NDDs may provide a reliable way to group individuals with similar behavioural phenotypes. This thesis examines how gut-immune biology is linked to clinical heterogeneity in children with NDDs. The first study used unsupervised machine learning to cluster typically developing (TD), ADHD, and ASD participants by their behaviour metrics in a diagnosis-agnostic approach. The results produced a six-cluster solution, five of which were a mix of all diagnostic categories. Further, gastrointestinal (GI) symptoms were mapped to the clusters, revealing a link between constipation, social communication deficits and restrictive-repetitive behaviours. The second study used hierarchical clustering to group TD and NDD participants based on a profile of gut and inflammatory markers. Participants clustered into two biotypes, both containing TD and NDD participants. Additionally, using regression analysis, novel markers were linked to anxiety. The third study evaluated the multisite biospecimen collection protocol of the Province of Ontario Neurodevelopmental Disorders (POND) Network. The final study used biospecimens collected from the POND network to phenotype peripheral blood mononuclear cells in TD and NDD participants. In NDD groups, monocyte and B cell activation markers were differentially expressed compared to TD. Overall, this thesis demonstrates that gut-immune mechanisms contribute to clinical heterogeneity in a subset of people and contribute to the search for biomarkers in NDDs. / Thesis / Doctor of Philosophy (PhD) / Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are diagnosed based on behavioural symptoms. However, symptoms can vary a lot from person to person, and some symptoms are shared between ASD and ADHD. Understanding the biological reasons for symptom differences between people can help pinpoint treatments which work best for an individual. This thesis looks at the role of the gut and immune system in ASD and ADHD. Blood samples and behaviour questionnaires were collected to study how immune cells, inflammation, and intestinal permeability shape behaviour symptoms. The results show that diagnosis is not the most accurate way to group people. Anxiety symptoms were different when people were grouped based on their inflammation levels. Also, specific immune cells appear to work differently in people with ASD and ADHD. These findings clarify some of the biology that affects behavioural symptoms in ASD and ADHD.

Introduction: Patients with autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) show more symptoms of ADHD. Since there are more adverse events caused by psychostimulants compared to non-psychostimulants, the use of a non-psychostimulant such as atomoxetine might prove more beneficial for younger patients and/or those with comorbid ADHD. Objective: The aim of this thesis is to determine the efficacy and tolerability of atomoxetine in ASD patients presenting with ADHD, by examining (a) differences in ADHD symptoms for participants receiving atomoxetine versus those receiving placebos, and (b) risk differences in adverse events between these participants. Methods: An electronic search of both PubMed.gov and ClinicalTrials.gov were conducted. To be deemed eligible, studies had to (a) be randomized, double-blind, placebo-controlled trials comparing atomoxetine with a placebo, (b) administer atomoxetine for at least 1 week, and (c) include data on either ADHD outcomes or adverse events. Effect sizes for ADHD outcomes were calculated using Cohen's d, whereas risk differences were calculated for adverse events. For each of these two meta-analyses, effect sizes were aggregated across studies using a random effects method. Results: Overall ADHD outcomes were better for participants who received atomoxetine than for participants who received placebo, =0.297. Participants who received atomoxetine also demonstrated better outcomes in terms of attention and hyperactivity-impulsivity symptoms, =0.345 and 0.393, respectively. Though there were more adverse events for patients taking atomoxetine than placebo, the results were not statistically significant. Discussion: This thesis extends the findings of previous meta-analyses of pharmacological treatments for ASD and ADHD, while addressing the concerns raised in the critique of existing meta-analyses presented in this thesis, e.g., limited studies, length of treatment weeks, and dichotomization of data. It provides evidence that atomoxetine improves ADHD symptoms, with an overall frequency of adverse events that did not sufficiently differ from placebo beyond chance.

No description available.

Prevalence rates for males and females with ADHD range from 2:1 to 9:1 depending on ADHD subtype and setting (APA, 2000). The purpose of the current study was to empirically review articles published between 2001-2010 from discipline-representative (psychology, pediatrics, and interdisciplinary) high- impact journals (JACP, JCCP, Pediatrics) to identify potential differences in the sampling or procedures of ADHD studies involving females and males. Results indicate females and minorities were both well represented across the three discipline-representative journals. However, no meaningful data were provided on minority ADHD females (0.04% of the overall N = 107,144 ADHD participants included in 212 studies). Recommendations to researchers and editors include a) increasing inclusion of minority ADHD females, b) requesting better documentation of overall inclusionary/exclusionary criteria, and c) increasing attention to potential biases in sampling procedures, referral practices, and data presentation approaches that hinder development of the literature concerning ADHD in minority females.

No description available.

No description available.