Mit dieser Studie sollte untersucht werden, ob ein Genexpressionsunterschied zwi- schen heterogenen erwachsenen ADHS-Patienten und gesunden Kontrollen besteht und eine Behandlung mit Methylphenidat kurz- oder langfristige Genexpressionsunter- schiede hervorruft. Außerdem war von Interesse, ob ein sich ein möglicher Behand- lungseffekt durch MPH zwischen ADHS- und Kontrollgruppe unterscheidet. Dazu wurde ein peripheres Zellmodell mit EBV-modifizierten Lymphoblasten von ADHS-Patienten und Kontrollen gewählt, deren RNA für die weiteren Versuche genutzt wurde. In Vor- versuchen sollte die Verwendung von MPH für die Versuchsmodellbedingungen opti- miert werden. In der vorliegenden Arbeit konnte anhand der Parameter Zellkonzentration und Zellgröße kein zelltoxischer Effekt von MPH in Konzentrationen bis 100 ng/µl ermittelt werden. Die Proben zeigten durchschnittlich sehr gute RNA-Konzentrationen (354 ng/µL), eine gute RNA-Qualität und nur leichte Verunreinigungen. Die hypothesenfreien Microarray-Untersuchung zeigte zum Zeitpunkt t4 und unter MPH-Behandlung 163 Gene an der Grenze zu statistischem Signifikanzniveau. Die aus den ersten 138 (p < 0,00139, korrigiert für multiples Testen p = 0,06) ausgewählten Genen ATXN1, GLUT3, GUCY1B3, HEY1, MAP3K8 und NAV2 zeigten in der anschließen- den qRT-PCR außer bei GUCY1B3 (zu allen Zeiten eine höhere Expression bei ADHS; p- Werte der aufsteigenden Zeitpunkte 0,002; 0,089; 0,027; 0,055 und 0,064) keine signi- fikanten Gruppenunterschiede zwischen ADHS-Probanden und Kontrollen. Allerdings konnten bei ATXN1, GLUT3, HEY1, MAP3K8 und NAV2 statistisch relevante Behandlungseffekte durch MPH beobachtet werden. Sie unterschieden sich in beiden Gruppen. Kurzzeiteffekte (innerhalb 1 bzw. 6h) traten ausschließlich bei der ADHS- Gruppe, Langzeiteffekte (2 Wochen) nur bei Kontrollen auf. Bei ADHS-Zellen wurde zum Zeitpunkt t1 die Expression von ATXN1 (p = 0,012) und NAV2 (p = 0,001) unter MPH erhöht. Eine signifikant geringerer kurzfristiger Genexpressionsanstieg zeigte sich bei MAP3K8 (p = 0,005). Im dynamischen Verlauf zeigte sich eine signifikante Genexpressi- onssteigerung innerhalb von einer Woche (t3) bei ATXN1 (p= 0,057) und HEY1 (0,042). Bei Kontrollzellen führte die MPH-Behandlung zu signifikanten Genexpressionsunter- schieden zum Zeitpunkt t4 bei GLUT3 ((p = 0,044) und MAP3K8 (p = 0,005) und im dy- namischen Verlauf zu höheren Expressionsanstiegen innerhalb von zwei Wochen (t4) bei GLUT3 (p = 0,033) und MAP3K8 (p = 0,005). Zumindest in dem untersuchten Gen GUCY1B3 gibt es also Expressionsunterschiede zwischen ADHS- und Kontrollgruppe. Methylphenidat beeinflusst die Genexpression in peripheren Zellen, obwohl seine Hauptwirkung im zentralen Nervensystem erzielt wird. Ob es sich dabei um eine Wirkung oder Nebenwirkung handelt, bleibt offen. Es gibt sowohl lang- als auch kurzfristige Genexpressionsveränderungen, wobei die kurzfristi- gen bei ADHS, die langfristigen in der Kontrollgruppe detektiert wurden. Damit unter- scheidet sich der Effekt von MPH auf die Genexpression peripherer Zellen zwischen ADHS und Kontrollgruppe. Die untersuchten Gene beeinflussen unterschiedliche Signalwege. Besonders hervor- zuheben sind das Dopaminsystem, der Notch- und NO-Signalweg. Da die Genprodukte jeweils nur ein Element längerer Signalkaskaden darstellen und oft auch mit mehreren Wegen interagieren, ist es schwer, direkte und indirekte Wirkungen von MPH zu unter- scheiden. Es gibt allerdings Hinweise, dass die untersuchten Gene sowie deren Verän- derung durch MPH im präfrontalen Kortex, dem limbischen System, Basalganglien und Kleinhirnarealen und dem aufsteigenden retikulären aktivierenden System (ARAS) eine wichtige Rollen spielen. Dies äußert sich schon in der embryonalen Hirnentwicklung, neuronalen Differenzierung und Synapsenbildung und hat Einfluss auf Aufmerksamkeit, Gedächtnis, Lernen, motorische Kontrolle und Emotionen. Diese Ergebnisse müssen nun in einer größeren Stichprobe validiert werden. Somit könnten einige Effekte, die hier als nominal bezeichnet wurden, in einer größeren Stichprobe signifikante Werte erreichen, während andere Unterschiede evtl. auch ver- schwinden könnten. Außerdem sollte berücksichtigt werden, dass nicht alle ADHS- Patienten auf eine Behandlung mit MPH ansprechen. Es ist also sinnvoll, eine Subgrup- penanalyse zwischen MPH-Resondern und Non-Respondern durchzuführen. In weiteren Untersuchungen ist es notwendig, Behandlungseffekte durch MPH in neu- ronalen Zelllinien zu untersuchen, da ADHS primär eine Störung des zentralen Nerven- systems darstellt, welches auch therapeutisch von MPH angesteuert wird. / We investigated the impact of MPH treatment on gene expression levels of lymphoblastoid cells derived from adult ADHD patients and healthy controls by hypothesis-free, genome-wide microarray analysis. Significant findings were subsequently confirmed by quantitative Real-Time PCR (qRT PCR) analysis. RESULTS: The microarray analysis from pooled samples after correction for multiple testing revealed 138 genes to be marginally significantly regulated due to MPH treatment, and one gene due to diagnosis. By qRT PCR we could confirm that GUCY1B3 expression was differential due to diagnosis. We verified chronic MPH treatment effects on the expression of ATXN1, HEY1, MAP3K8 and GLUT3 in controls as well as acute treatment effects on the expression of NAV2 and ATXN1 specifically in ADHD patients. CONCLUSIONS: Our preliminary results demonstrate MPH treatment differences in ADHD patients and healthy controls in a peripheral primary cell model. Our results need to be replicated in larger samples and also using patient-derived neuronal cell models to validate the contribution of those genes to the pathophysiology of ADHD and mode of action of MPH.

Adolescent and young adult males are at a higher risk for traumatic brain injury (TBI) compared to the general population. Diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) is also more prevalent for males in these age groups. The most commonly prescribed medication for ADHD is methylphenidate (MPH). Based on the increase in the number of new diagnoses of ADHD and the number of children who continue taking MPH into adulthood, it is important to evaluate how chronic or acute MPH administered prior to injury may influence recovery following TBI. In both studies, cognitive abilities of male Sprague-Dawley rats were assessed on post-injury using the Morris Water Maze. There was no effect of chronic MPH treatment on cognitive outcome following TBI. In contrast, acute MPH pre-treatment improved cognitive outcome as measured by the MWM. The MPH + injury group reached sham-injury levels on days 4 and 5 in the MWM.

Background: In 1998 the Wits Faculty of Health Science began to offer a master’s programme in public health, through the School of Public Health, called the Master of Public Health. (MPH). The aim of the degree is to prepare “professionals to play leadership roles in the management, improvement and evaluation of health and the health care system” and to respond “to the needs of the people of South Africa and the African continent in their various living and working conditions”. Eight objectives have been set for the degree and these will be gone into in detail. Admission requirements to the programme are a bachelor’s degree of a minimum of four years duration in dentistry, medicine, nursing, occupational therapy, physiotherapy, etc. The programme can be offered on a full- or part-time basis. The following core modules are offered: Primary Health Care & Social Context of Health; Health Measurement I & II; Environmental & Occupational Health; Public Health Law & Health Systems Integration; Health Policy &Policy Analysis; Health Systems & Decentralization; Health Management Theory & Practice; Epidemiology; Health Care Financing etc. The primary motivation for this study was to determine the level of satisfaction of MPH graduates with the degree that they studied. Methods: The study was a cross-sectional study design. It was a survey that entailed using a pretested interview schedule or questionnaire. The study population was all MPH graduates up until June 2007 (N = 80). The participants were contacted telephonically or by e-mail by the researcher. The initial idea was to interview the participants telephonically, but most preferred to have the prepared interview schedule e-mailed to them. A Pilot Study (using 8 students) was conducted before commencement of the actual study. The pilot study revealed that the study questionnaire, although long and cumbersome, was do-able. A sample of 70 graduates was used and of these, 60 responded i.e. response rate of 86%. The researcher e-mailed the interview schedule and the information sheet which explained what the study was about and also made it clear that even if they had initially agreed to participate, they could still opt out if they later changed their minds. The information sheet further explained that their participation would be kept strictly anonymous, only codes would be used. The data gathering sheet (questionnaire) is in two parts: Part One is the “Course Evaluation” and Part Two is the “Value of the Masters in Public Health to Your Career”. Under Part One the candidates gave their views on the following: the content of various courses or modules offered; the teaching methods applied by the School; academic quality; administrative support; and research report support. Questions in each of these subsections were such that a rating on a scale of 1 to 5 (5 being excellent and 1 poor) had to be given and next to the score (rating) the candidate could also give a comment to explain the rating or how they felt about what was asked. At the end of each of the subsections are a number of open-ended questions that gave the candidate more scope for further written or verbal input. Similarly, Part Two has a rating on a scale of 1 to 5 (5 being extremely valuable and 1 less valuable) in terms of the value the particular course or module mentioned in the career of the graduate. There is also a “comment” portion accompanying every question. And at the end of this part are six open-ended questions aimed at eliciting more qualitative information based on the experiences of graduates post graduation and specifically focusing on the working environment. One very important question in this section is: “Would you or have you recommended this masters programme to others”. There are only two possible answers to this question: “Yes” – which signifies satisfaction with the programme, and “No” – which signifies unhappiness with the programme. It is a very important question in gauging client satisfaction. Results: On a rating of 1 to 5 (1 being poor whilst 5 is excellent the top rated modules were rated as follows under course evaluation: (i) Primary Health Care & Social Context of Health: All respondents (60 i.e. 100%) rated this module and gave it a rating of 4.13 (83%) (ii) Health Policy and Policy Analysis: Although 40 (67%) out of 60 people responded to this question, they gave it a rating of 4.25 (85%) (iii) Project Management for Public Health Practitioners: It was given a 4.27 (85%) rating by 44 (73%) out of 60 participants. (iv) Management in Health and Health Services: This module was given a rating of 3.83 (77%) by 58 (97%) out of 60 participants and (v) Introduction to Management in Theory and Practice: It was rated at 3.82 (76%) by 32 (53%) of the 60 participants. The same top-rated above modules were rated as follows under “Value of the Masters in Public Health (MPH) to your career” i.e. Part II of the questionnaire. (i)Primary Health Care & Social Context of Health: 3.26 (65%) as rated by 46 (77%) out 60 participants. (ii) Health Policy and Policy Analysis: 3.96 (79%) by 46 (77%) respondents out of 60. (iii) Project Management for Public Health Practitioners: 3.26 (65%) as rated by 46 (77%) out 60 participants. (iv) Management in Health and Health Services: 3.96 (79%) by 54 (90%) out of 60 participants. Discussion: Various laudable written comments made by participants about each module have been captured and recorded. These will be seen later. (i) Primary Health Care & Social Context of Health: This module received a very high from all the participants of the research study. The concepts of Primary Health Care and Social Context of Health have clearly been taught and grasped. (ii) Health Policy and Policy Analysis: This was the track that most graduates followed. It helped graduates understand and be able to analyse various policy issues in their respective organizations. Emphasis has not only been laid on policy formulation but also on policy implementation. (iii) Project Management for Public Health Practitioners: This module scored a very high rating under course evaluation. There is a perception that some public health services could be run as projects in an endeavour to increase efficiency. (iv) Management in Health and Health Services: A number of the students who come from the public health sector to do MPH are in management positions already, although they may not have a formal management qualification. Those who are not in management positions are preparing themselves to go into management positions in future. This module is of great assistance in preparing them for careers in management. The study has revealed that 98% of participants have stated that they would or have recommended the Wits MPH to others. And 80% of the participants have also stated that there has been a positive change in their careers since acquiring the MPH qualification.

O Transtorno de Déficit de Atenção/Hiperatividade (TDAH) é comum em adultos e caracteriza-se por sintomas persistentes de desatenção, hiperatividade e impulsividade. Clinicamente, o TDAH é um fenótipo bastante heterogêneo e, frequentemente, encontra-se associado a diversos outros transtornos psiquiátricos. A contribuição genética é substancial no TDAH e diversos genes de pequeno efeito têm sido associados com o desenvolvimento do transtorno. O metilfenidato (MPH) representa o principal agente farmacológico usado no tratamento e seu mecanismo de ação parece envolver a potencialização da transmissão catecolaminérgica no córtex pré-frontal. Estudos farmacogenéticos têm investigado o papel de diversas variantes genéticas, principalmente em sistemas de neurotransmissão, na resposta ao tratamento com MPH. No entanto, esses estudos têm focado quase que exclusivamente no tratamento de crianças com TDAH. No presente trabalho foi investigada a associação entre 17 polimorfismos genéticos, em nove genes candidatos (DAT1, ADRA2A, 5-HTT, HTR1B, TPH2, DBH, DRD4, COMT e SNAP25), e a resposta ao tratamento com MPH. A amostra foi composta de 165 adultos com TDAH, diagnosticados de acordo com os critérios do DSM-IV. A gravidade dos sintomas dos pacientes foi avaliada antes e após um mês de uso de MPH através da aplicação das subescalas SNAP-IV e da escala CGI-S. Também avaliamos uma amostra de 136 dependentes de álcool e 237 controles, em um estudo de associação envolvendo o gene HTR1B. A resposta ao MPH foi analisada através de avaliações categórica e dimensional da redução nos sintomas após o uso de MPH. Foi observada uma redução significativa nos escores de gravidade total dos sintomas após o tratamento, sendo que 83% dos pacientes foram classificados como respondedores e 17% como não respondedores. Interpretamos a dificuldade de identificar variantes genéticas envolvidas na resposta ao tratamento como o reflexo da complexidade clínica e etiológica do TDAH. Exemplo disso é o fato de que o gene HTR1B, que apresenta resultados positivos para associação com o TDAH em meta-análises e em um estudo com crianças da nossa população, não se mostrou associado com o TDAH em adultos ou com a resposta ao MPH, mas sim com o alcoolismo nesse estudo. Novas investigações, em amostras maiores, serão necessárias para que seja alcançado maior sucesso nos estudos farmacogenéticos envolvendo o MPH ou outros fármacos no tratamento do TDAH. / Attention deficit/hyperactivity disorder (ADHD) has a high prevalence in adults and it is characterized by pervasive symptoms of inattention, hyperactivity and impulsivity. Clinically, ADHD is a very heterogeneous disorder frequently associated with other psychiatric conditions. The genetic contribution in ADHD is substantial and several genes of small effect have been associated with ADHD susceptibility. Methylphenidate (MPH) is the primary agent used in pharmacological intervention for ADHD. Its mechanism of action is believed to potentiate catecholamine transmission in the pre-frontal cortex. Pharmacogenetic studies have been investigating the role of genetic variants in the response to the treatment with MPH. However, previous studies have focused almost exclusively in the treatment of children with ADHD. In this study, we investigated the association between 17 polymorphisms, in 9 candidate genes (DAT1, ADRA2A, 5- HTT, HTR1B, TPH2, DBH, DRD4, COMT and SNAP25), and the response to MPH. The sample comprised 165 adults with ADHD diagnosed according to DSMIV criteria. We also evaluated a sample of 136 alcohol dependents and 237 control subjects, in an association study involving the HTR1B gene. The response to MPH was assessed by both categorical and dimensional approaches through the SNAP-IV sub-scales and the CGI-S scale, applied at the beginning and after the 30th day of treatment. We detected a significant reduction in SNAP-IV total scores during the follow-up period. According to the categorical definition of MPH response, 83% of the patients were classified as responders and 17% were classified as non-responders. Our results indicated that none of the investigated variants showed significant effects on the MPH response. We interpret the difficulty of identifying genetic variants involved in response to treatment as a reflection of the clinical and etiological complexity of ADHD. For example, we did not find association of the HTR1B gene with ADHD nor with treatment response to MPH in our adult sample, but it was in fact associated with alcohol dependence. However, this gene has previously shown positive results for association with children ADHD in meta-analysis and also in a study with children of the same population of the current work. More investigations with larger sample sizes will be need to achieve greater success in pharmacogenetic studies involving the MPH or other drugs used in the treatment of ADHD.

O Transtorno de Déficit de Atenção/Hiperatividade (TDAH) é comum em adultos e caracteriza-se por sintomas persistentes de desatenção, hiperatividade e impulsividade. Clinicamente, o TDAH é um fenótipo bastante heterogêneo e, frequentemente, encontra-se associado a diversos outros transtornos psiquiátricos. A contribuição genética é substancial no TDAH e diversos genes de pequeno efeito têm sido associados com o desenvolvimento do transtorno. O metilfenidato (MPH) representa o principal agente farmacológico usado no tratamento e seu mecanismo de ação parece envolver a potencialização da transmissão catecolaminérgica no córtex pré-frontal. Estudos farmacogenéticos têm investigado o papel de diversas variantes genéticas, principalmente em sistemas de neurotransmissão, na resposta ao tratamento com MPH. No entanto, esses estudos têm focado quase que exclusivamente no tratamento de crianças com TDAH. No presente trabalho foi investigada a associação entre 17 polimorfismos genéticos, em nove genes candidatos (DAT1, ADRA2A, 5-HTT, HTR1B, TPH2, DBH, DRD4, COMT e SNAP25), e a resposta ao tratamento com MPH. A amostra foi composta de 165 adultos com TDAH, diagnosticados de acordo com os critérios do DSM-IV. A gravidade dos sintomas dos pacientes foi avaliada antes e após um mês de uso de MPH através da aplicação das subescalas SNAP-IV e da escala CGI-S. Também avaliamos uma amostra de 136 dependentes de álcool e 237 controles, em um estudo de associação envolvendo o gene HTR1B. A resposta ao MPH foi analisada através de avaliações categórica e dimensional da redução nos sintomas após o uso de MPH. Foi observada uma redução significativa nos escores de gravidade total dos sintomas após o tratamento, sendo que 83% dos pacientes foram classificados como respondedores e 17% como não respondedores. Interpretamos a dificuldade de identificar variantes genéticas envolvidas na resposta ao tratamento como o reflexo da complexidade clínica e etiológica do TDAH. Exemplo disso é o fato de que o gene HTR1B, que apresenta resultados positivos para associação com o TDAH em meta-análises e em um estudo com crianças da nossa população, não se mostrou associado com o TDAH em adultos ou com a resposta ao MPH, mas sim com o alcoolismo nesse estudo. Novas investigações, em amostras maiores, serão necessárias para que seja alcançado maior sucesso nos estudos farmacogenéticos envolvendo o MPH ou outros fármacos no tratamento do TDAH. / Attention deficit/hyperactivity disorder (ADHD) has a high prevalence in adults and it is characterized by pervasive symptoms of inattention, hyperactivity and impulsivity. Clinically, ADHD is a very heterogeneous disorder frequently associated with other psychiatric conditions. The genetic contribution in ADHD is substantial and several genes of small effect have been associated with ADHD susceptibility. Methylphenidate (MPH) is the primary agent used in pharmacological intervention for ADHD. Its mechanism of action is believed to potentiate catecholamine transmission in the pre-frontal cortex. Pharmacogenetic studies have been investigating the role of genetic variants in the response to the treatment with MPH. However, previous studies have focused almost exclusively in the treatment of children with ADHD. In this study, we investigated the association between 17 polymorphisms, in 9 candidate genes (DAT1, ADRA2A, 5- HTT, HTR1B, TPH2, DBH, DRD4, COMT and SNAP25), and the response to MPH. The sample comprised 165 adults with ADHD diagnosed according to DSMIV criteria. We also evaluated a sample of 136 alcohol dependents and 237 control subjects, in an association study involving the HTR1B gene. The response to MPH was assessed by both categorical and dimensional approaches through the SNAP-IV sub-scales and the CGI-S scale, applied at the beginning and after the 30th day of treatment. We detected a significant reduction in SNAP-IV total scores during the follow-up period. According to the categorical definition of MPH response, 83% of the patients were classified as responders and 17% were classified as non-responders. Our results indicated that none of the investigated variants showed significant effects on the MPH response. We interpret the difficulty of identifying genetic variants involved in response to treatment as a reflection of the clinical and etiological complexity of ADHD. For example, we did not find association of the HTR1B gene with ADHD nor with treatment response to MPH in our adult sample, but it was in fact associated with alcohol dependence. However, this gene has previously shown positive results for association with children ADHD in meta-analysis and also in a study with children of the same population of the current work. More investigations with larger sample sizes will be need to achieve greater success in pharmacogenetic studies involving the MPH or other drugs used in the treatment of ADHD.

O Transtorno de Déficit de Atenção/Hiperatividade (TDAH) é comum em adultos e caracteriza-se por sintomas persistentes de desatenção, hiperatividade e impulsividade. Clinicamente, o TDAH é um fenótipo bastante heterogêneo e, frequentemente, encontra-se associado a diversos outros transtornos psiquiátricos. A contribuição genética é substancial no TDAH e diversos genes de pequeno efeito têm sido associados com o desenvolvimento do transtorno. O metilfenidato (MPH) representa o principal agente farmacológico usado no tratamento e seu mecanismo de ação parece envolver a potencialização da transmissão catecolaminérgica no córtex pré-frontal. Estudos farmacogenéticos têm investigado o papel de diversas variantes genéticas, principalmente em sistemas de neurotransmissão, na resposta ao tratamento com MPH. No entanto, esses estudos têm focado quase que exclusivamente no tratamento de crianças com TDAH. No presente trabalho foi investigada a associação entre 17 polimorfismos genéticos, em nove genes candidatos (DAT1, ADRA2A, 5-HTT, HTR1B, TPH2, DBH, DRD4, COMT e SNAP25), e a resposta ao tratamento com MPH. A amostra foi composta de 165 adultos com TDAH, diagnosticados de acordo com os critérios do DSM-IV. A gravidade dos sintomas dos pacientes foi avaliada antes e após um mês de uso de MPH através da aplicação das subescalas SNAP-IV e da escala CGI-S. Também avaliamos uma amostra de 136 dependentes de álcool e 237 controles, em um estudo de associação envolvendo o gene HTR1B. A resposta ao MPH foi analisada através de avaliações categórica e dimensional da redução nos sintomas após o uso de MPH. Foi observada uma redução significativa nos escores de gravidade total dos sintomas após o tratamento, sendo que 83% dos pacientes foram classificados como respondedores e 17% como não respondedores. Interpretamos a dificuldade de identificar variantes genéticas envolvidas na resposta ao tratamento como o reflexo da complexidade clínica e etiológica do TDAH. Exemplo disso é o fato de que o gene HTR1B, que apresenta resultados positivos para associação com o TDAH em meta-análises e em um estudo com crianças da nossa população, não se mostrou associado com o TDAH em adultos ou com a resposta ao MPH, mas sim com o alcoolismo nesse estudo. Novas investigações, em amostras maiores, serão necessárias para que seja alcançado maior sucesso nos estudos farmacogenéticos envolvendo o MPH ou outros fármacos no tratamento do TDAH. / Attention deficit/hyperactivity disorder (ADHD) has a high prevalence in adults and it is characterized by pervasive symptoms of inattention, hyperactivity and impulsivity. Clinically, ADHD is a very heterogeneous disorder frequently associated with other psychiatric conditions. The genetic contribution in ADHD is substantial and several genes of small effect have been associated with ADHD susceptibility. Methylphenidate (MPH) is the primary agent used in pharmacological intervention for ADHD. Its mechanism of action is believed to potentiate catecholamine transmission in the pre-frontal cortex. Pharmacogenetic studies have been investigating the role of genetic variants in the response to the treatment with MPH. However, previous studies have focused almost exclusively in the treatment of children with ADHD. In this study, we investigated the association between 17 polymorphisms, in 9 candidate genes (DAT1, ADRA2A, 5- HTT, HTR1B, TPH2, DBH, DRD4, COMT and SNAP25), and the response to MPH. The sample comprised 165 adults with ADHD diagnosed according to DSMIV criteria. We also evaluated a sample of 136 alcohol dependents and 237 control subjects, in an association study involving the HTR1B gene. The response to MPH was assessed by both categorical and dimensional approaches through the SNAP-IV sub-scales and the CGI-S scale, applied at the beginning and after the 30th day of treatment. We detected a significant reduction in SNAP-IV total scores during the follow-up period. According to the categorical definition of MPH response, 83% of the patients were classified as responders and 17% were classified as non-responders. Our results indicated that none of the investigated variants showed significant effects on the MPH response. We interpret the difficulty of identifying genetic variants involved in response to treatment as a reflection of the clinical and etiological complexity of ADHD. For example, we did not find association of the HTR1B gene with ADHD nor with treatment response to MPH in our adult sample, but it was in fact associated with alcohol dependence. However, this gene has previously shown positive results for association with children ADHD in meta-analysis and also in a study with children of the same population of the current work. More investigations with larger sample sizes will be need to achieve greater success in pharmacogenetic studies involving the MPH or other drugs used in the treatment of ADHD.

Autism Spectrum Disorder (ASD), previously known as Pervasive Development Disorder (PDD) is a developmental disorder present from early childhood. Children diagnosed with ASD commonly exhibit symptoms of ADHD resulting in increased severity of symptoms and impairment of functioning. This group of children is frequently treated with methylphenidate which has been recommended by some but criticised by others. This systematic review aims to explore the effect of methylphenidate treatment on symptoms of ASD, functioning and adverse effects  Six articles were extracted from five different databases (Medline, Psych INFO, PubMed, Scopus, and Web of Science) and chosen based on a pre-determined inclusion and exclusion criteria. The results show that MPH treatment may be successful as an intervention for some children with ASD showing ADHD symptoms while other children are very susceptible to adverse effects with some being unable to tolerate the treatment. The chosen studies provided limited acknowledgement of the effect on functioning making it an important focus for future research. It is important that professionals are aware of the negative effects MPH might cause to ensure a positive outcome and well-being for children with this disorder. There is a need for further understanding of the connection between ASD and ADHD with additional exploration of possible moderators such as IQ, dose size and level of functioning.

Introduktion: ADHD är en uppmärksamhet -och hyperaktiv störning, där 90 % i Sverige behandlas med det farmakologiska läkemedlet Metylfenidat (MPH). En stor andel med ADHD utvecklar psykiatrisk komorbiditet i form av psykisk ohälsa (frånvaro av mentalt välbefinnande). Patofysiologin hur MPH påverkar hjärnan är okänd och behandlingsformen har diskuterats som bristfällig på grund av förekommande bieffekter. Fysisk aktivitet har föreslagits som ett hälsosammare behandlingsalternativ, då evidens visat att fysisk aktivitet kan förbättra ADHD-symptom och samsjuklighet av psykisk ohälsa. Det finns inga studier som undersökt hur individer med ADHD upplever nuvarande- och önskar behandling. Syftet med denna studie blev därför att undersöka upplevda erfarenheter av ADHD och hur det farmakologiska läkemedlet MPH och fysisk aktivitet upplevs ha påverkat diagnosens symptom och individernas psykiska hälsa samt att ta reda på vilken behandling individerna önskar utifrån deras livserfarenheter. Metoden utgick från ett fenomenologiskt ramverk med hjälp av en deskriptiv kvalitativ tvärsnittsstudie, där data extraherades genom en innehållsanalys med en induktiv ansats. Urvalet selekterades genom snöbollsurval, där inklusionskriteriet var att deltagarna blivit diagnostiserad med ADHD och har erfarenheter av MPH och fysisk aktivitet. Resultatet visade att symptom för ADHD var problematik med koncentration-, hyperaktivitet-, uppmärksamhet- och systematiska svårigheter, där symptom försämrat den psykiska hälsan. Det framgick att både MPH och fysisk aktivitet effektiviserade symptom mot koncentration, hyperaktivitet och uppmärksamhet, varav KBT (kognitiv beteendeterapi) förbättrade systematiska svårigheter. Vidare bidrog MPH med fysiska, mentala och beteendeföränderliga bieffekter som försämrade den psykiska hälsan. Fysisk aktivitet visade däremot förbättra den psykiska hälsan, där inaktivitet framgick som en central nackdel för förvärring av symptom och psykisk hälsa. Deltagarnas önskan var att behandling bör uppföljas och baseras på en överenskommelse som anpassas efter individuella svårigheter och hälsotillstånd. Slutsatsen med studien kom fram till att behandlas med fysisk aktivitet i kombination med KBT skulle vara hälsosammare som första behandling mot samtliga ADHD-symptom och psykisk hälsa. I andra hand var det deltagarnas önskan att applicera MPH vid akut behov, och är därav förslag att forska fram MPH som engångsbehandling som kan användas vid inaktiva tillstånd. Studien kom fram till att inkludering av fler idrottsvetenskapliga tjänster till vård och skola behövs för mer kompetens om vikten av fysisk aktivitet för individer som har ADHD. / Introduction: ADHD is an attention-deficit/hyperactivity disorder, where 90% in Sweden is treated with the pharmacological drug Methylphenidate (MPH). People diagnosed with ADHD develop often psychiatric comorbidity in form of mental illness. The pathophysiology behind how MPH influence the brain is unknown and the treatment have been discussed as deficient due to side effects. Physical activity has been suggested as a healthier treatment option, as evidence shows that physical activity can improve ADHD-symptoms and comorbidity of mental illness. There are no studies that have invastigate how individuals with ADHD experience current- and desired treatment. The aim of this study was therefore to investigate the experiences of having ADHD and how the pharmacological treatment MPH and physical activity has affected the symptoms and mental health, and also find out what treatment the individuals want based on their life experiences. The method was derived from a phenomenological framework using a descriptive qualitative cross-sectional study. Data was analyzed with an inductive approach using an interpretive analysis. Participants was recruited through a snowball selection, where the inclusion criteria stated that participants been diagnosed with ADHD and have experience of MPH and physical activity. The results showed that the frequent occurring symptoms of ADHD were difficulties with concentration-, hyperactivity-, attention- and systematic symptoms, where symptoms had shown a negative effect on the mental health. It appeared that both MPH and physical activity made symptom improvement against concentration-, hyperactivity- and attention difficulties, while CBT (Cognitive Behavioral Therapy) improved systematic difficulties. MPH contributed to side effects that affected physiological-, psychological- and behavioral aspects, which all were perceived to have a negative influence on mental health. In contrast, physical activity improved mental health and showed no evidence of side effects, except when physical activity was absent from daily life. Inactivity appeard to be a central disadvantage for worsening symptoms and mental health. The participants desired that their treatment should be tailored to individual difficulties and health condition in a collaborative way and with follow-up from the health care worker. The study concluded that physical activity in combination with CBT would be a healthier as first treatment option to reduce symptoms of ADHD and improve mental heatlh. Additionally, the participants desired treatment with MPH in form of single doses for urgent need, and it is therefore to suggest development of such treatment option. Furthermore, the study proposes more services for sport science within healthcare and schools for containing applicable knowledge in physical activity for dose with ADHD.