The Amphetamine Years is a history of psychostimulant drugs and their clinical applications in post-World War II American medicine. Comprising such well-known substances as the amphetamines (Benzedrine, Dexedrine), methylphenidate (Ritalin), and phenmetrazine (Preludin), this class of pharmaceuticals has been among the most widely consumed in the past half-century. Their therapeutic uses for a variety of indications such as depression, obesity, and attention-deficit/hyperactivity disorder (ADHD) in children, not to mention their relevance for a number of different medical specialties, reveals that psychostimulants have occupied an important, if underappreciated role in the practice of modern medicine. In this dissertation, I illuminate the various ways in which physicians, particularly psychiatrists, put these drugs to work in clinical practice. In short, I contend that physicians exploited the wide range of physiological and psychological effects of psychostimulants and made a place for them in different therapeutic settings, even ones characterized by competing views and theories about the workings of the human body and mind. My dissertation is distinguished by two prominent themes. First, I emphasize the clinician perspective as a vehicle for understanding the history of the psychostimulants, as well as related developments in psychiatry, pharmacotherapy, and the political economy of drugs, in the second half of the twentieth century. Scholars such Nicolas Rasmussen, David Courtwright, and Ilina Singh have elucidated the history of psychostimulants by emphasizing how pharmaceutical companies positioned their products in the medical marketplace. My dissertation takes a different, yet complimentary approach by studying clinicians, themselves, to further historical comprehension of the place of these pharmaceuticals within postwar medicine, society, and culture. Second, I advance the concept of "therapeutic versatility" to explain their historical trajectories. The complex set of psychological and physical effects these drugs produced made them ideal for a diverse range of therapeutic applications, which explains why they were embraced by many different medical specialties, why they were marketed by manufacturers for a variety of indications, and why they have enjoyed an enduring therapeutic lifespan, in spite of increasing efforts since the mid-1960s to regulate their availability and control their consumption. In addition to these two overarching themes, I advance five specific arguments in my dissertation. First, I contend that pharmaceutical markets were simultaneously created by the drug industry and clinicians. Pharmaceutical firms' efforts to develop markets for their products have been well documented by historians, but in my dissertation, I underscore the role also played by clinicians in discerning drugs' applications. Second, I argue that twentieth-century psychiatry's conception of illness and therapeutics may not be served best by strictly dividing its history along lines of institutional and outpatient treatment. Third, I demonstrate how the use of psychostimulants by analytically oriented psychiatrists during the 1950s complicates historical notions of paradigm shift from a psychodynamic to biological orientation. Psychotherapy and psychopharmacology were not competing paradigms; in practice, doctors often employed both. Fourth, I assert that an appreciation of psychiatrists' empirical and eclectic approaches to the use of drugs is necessary to comprehend the rise of psychiatric pharmacotherapy in the postwar era. Finally, I contend that in order to understand the relationship between medical applications of psychostimulants and their extramedical consumption, it is necessary to conceive of a plurality of distinct "amphetamine cultures," each characterized by a unique set of relationships between physician-prescribers, patient-consumers, pharmaceutical firms, and political authorities.

Succédant à une théorisation centrée sur le rôle des déficits des fonctions exécutives, les modèles contemporains du trouble déficit de l'attention / hyperactivité (TDAH) mettent en avant l’hétérogénéité d’une catégorie diagnostique impliquant des déficits neuropsychologiques, voies cérébrales et mécanismes étiopathogéniques multiples. En dépit de cette évolution, la majorité des études d'imagerie cérébrale des corrélats structurels du trouble menées à ce jour ont été conduites au niveau de la catégorie diagnostique, sans spécification supplémentaire. Cette approche comparant en moyenne un groupe de patients avec TDAH à un groupe de sujets sains a donné des résultats très variables d'une étude à l'autre, la comparaison inter-étude étant toutefois rendue difficile par la présence de facteurs confondants, tels que des différences en terme de régions d’intérêt examinées, de comorbidités acceptées chez les patients, de pourcentages de sujets masculins et féminins, de fenêtre d’âge sélectionnée, de méthodologie d'analyse ou encore de pourcentage de patients traités par méthylphénidate. Dans ce doctorat, nous nous sommes appuyés sur la morphométrie voxel-à-voxel pour isoler l’influence sur les volumes de matière grise de deux facteurs d’hétérogénéité intra-catégorielle dans le TDAH : le genre d’une part, et un polymorphisme génétique (Val158Met du gène Catéchol-O-méthyltransferase (COMT)) d’autre part ; ces deux facteurs présentant l’intérêt de moduler le risque associé de développer un trouble de type externalisé. Nous avons également comparé les volumes de matière grise d’enfants avec TDAH ayant reçu un traitement par méthylphénidate, de patients n'ayant jamais été exposé à la médication, et de sujet sains. Ces recherches expérimentales ont été inscrites dans une discussion plus générale de l’hétérogénéité des résultats de la littérature structurelle consacrée au TDAH et des sources neuropsychologiques de cette hétérogénéité. Dans notre étude des effets du genre sur les volumes de matière grise dans le TDAH, nous reportons pour la première fois une interaction entre genre et diagnostic, avec des corrélats structurels du trouble différents chez les garçons et les filles avec TDAH dans des régions de la ligne médiane du cerveau, impliquées à la fois dans la régulation émotionnelle et dans le fonctionnement du mode de réseau par défaut. Nous suggérons que ces différences structurelles pourraient contribuer aux différences de risque associé pour les troubles internalisés et externalisés présentées par les garçons et filles avec TDAH. Dans notre étude explorant l'influence du polymorphisme Val158Met sur les volumes de matière grise, nous mettons en évidence une modulation génétique des corrélats structurels du trouble : les sujets homozygotes pour l'allèle Val158, identifiés dans la littérature comme à risque pour le développement d'un trouble des conduites, présentent des volumes de matière grise supérieurs dans le noyau caudé comparativement aux sujets sains, tandis que les patients avec TDAH porteurs d'un allèle Met158 présentent des volumes de matière grise plus faibles dans le cortex préfrontal inférieur droit, une région cruciale pour les processus de contrôle attentionnel. Enfin, dans notre étude des corrélats structurels de l'exposition au méthylphénidate, nous reportons un effet potentiellement normalisateur du traitement sur les volumes de matière grise de l'insula et du pole temporal, des volumes de matière grise plus faibles chez les patients traités comparativement aux sujets sains dans le gyrus frontal moyen et dans le gyrus précentral, et une association entre volume de matière grise dans le nucleus accumbens gauche et durée d'exposition au méthylphénidate chez les sujets traités. (...) / Previous models of Attention Deficit / Hyperactivity Disorder (ADHD) such as Barkley’s or Brown’s conceptualized ADHD as essentially a developmental impairment of executive function. Against this view, it is now recognized that ADHD is a heterogeneous disorder, involving multiple deficits and multiple neuronal pathways. Despite this current theoretical framework, most structural brain imaging studies in ADHD have compared groups of children with ADHD with typically developing children, without trying to identify subgroups within the diagnostic category. This approach has yielded heterogeneous findings, possibly due to inter-studies variations in the type and number of comorbidities, the percentage of medicated participants included, the number of girls included, and/or methodological and statistical differences. Patients participating in these studies were also often exposed to methylphenidate, and potential medication effects on grey matter volumes are still unclear in certain brain regions such as the frontal lobe, despite a therapeutic action involving the preferential activation of catecholamine neurotransmission within the prefrontal cortex. In this thesis, we used voxel-based morphometry to study the influence of two important risk factors for the development of comorbid conditions in ADHD. The first of these two factors was gender, and the second a genetic polymorphism of the Catechol-O-methyltransferase gene known to put children with ADHD at risk for developing a conduct disorder (Val158Met). We also compared grey matter volumes in children with ADHD exposed to methylphenidate, never-medicated children with ADHD and typically developing children. These experimental studies were part of a more general discussion of ADHD neuropsychological and neurobiological heterogeneity. In our study exploring the influence of gender on the structural correlates of ADHD, we report for the first time a gender-by-diagnosis interaction, with grey matter volume differences in boys and girls with ADHD in midline cortical structures, involved in emotional regulation and part of the default mode network. We propose that these differences may contribute to explain why girls with ADHD more often develop inattentive and internalizing symptoms, whereas externalizing symptoms are predominant in boys with ADHD. In our study investigating the effects of Val158Met in ADHD, we report the first evidence of a COMT-related genetic modulation of ADHD-related grey matter volume alterations. Indeed, children with ADHD at higher risk for developing a conduct disorder (children homozygotes for the Val158 allele) presented increased grey matter volumes in the caudate nucleus when compared with typically developing children, whereas children carrying a Met158 allele presented with decreased grey matter volumes in the right inferior frontal cortex, a region known for its key role in attention. Finally, we measured grey matter volumes in medicated children with ADHD, never-medicated children with ADHD and typically developing children using both whole-brain voxel-based morphometry and automated tracing procedures in chosen regions of interest. We document potential methylphenidate-related grey matter volume normalization and deviation in previously unexplored frontal and temporal regions, and report a positive association between treatment history and grey matter volume in the nucleus accumbens, a key region for reward processing. Our first two experimental studies therefore contribute to a better understanding of the influence of important sources of within-category heterogeneity, while the third helps clarifying the potential confounding effect of medication exposure in previous structural brain imaging studies in ADHD.

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À ce jour, plusieurs études se sont penchées sur l’influence des comportements problématiques des enfants présentant un trouble déficitaire de l'attention avec ou sans hyperactivité (TDAH) sur les pratiques parentales (Chronis-Tuscano et al., 2008), mais peu de recherches se sont intéressées à la relation entre ce que pensent les parents et la façon dont ils se comportent avec leur enfant (Rudy & Grusec, 2006). L’objectif principal de cette thèse est d’étudier la relation entre les cognitions sociales des parents, les pratiques parentales et les caractéristiques comportementales de l’enfant présentant un TDAH. Une première étude examine la relation entre les cognitions sociales des parents (attributions causales, sentiment d’auto-efficacité parental (SAEP)), les caractéristiques comportementales de l’enfant (sous-type TDAH, symptômes concomitants) en lien avec les pratiques parentales utilisées. Cent dix familles dont l’enfant a un TDAH ont participé à l’étude. Les résultats indiquent que plus les parents ont un SAEP élevé, plus ils rapportent employer une discipline appropriée, une discipline verbale positive, des félicitations/récompenses et moins ils rapportent utiliser une discipline sévère/inconstante ou la punition physique. Les résultats montrent également que l’attribution des comportements de désobéissance de l’enfant soit à l’effort important du parent, soit au manque d’effort de l’enfant joue un rôle prédicteur en regard respectivement de l’utilisation d’une discipline verbale positive ou de l’utilisation d’une discipline sévère et inconstante par le parent. Par ailleurs, le fait de percevoir des symptômes d’opposition chez l’enfant TDAH prédit l’utilisation d’une discipline appropriée et d’une discipline verbale positive. Enfin, la présence de symptômes concomitants au TDAH prédit l’utilisation d’une discipline sévère et inconstante. L’objectif de la seconde étude est d’examiner le rôle des cognitions sociales des parents d’enfant ayant un TDAH en lien avec les pratiques parentales utilisées après leur participation à deux types d’intervention (programme d’entraînement aux habiletés parentales (PEHP) ou soutien téléphonique (ST)) comparativement à un groupe contrôle (GC). Les résultats suggèrent que dans certains cas, le SAEP ou les attributions causales prédisent différemment les pratiques parentales selon que les parents ont ou non participé à une intervention, mais il est prématuré de conclure que les cognitions sociales des parents d’enfant TDAH sont des modérateurs du changement des pratiques parentales. Les implications méthodologiques, conceptuelles et cliniques de ces deux études sont discutées. / Studies have confirmed that behavior of children with attention-deficit/hyperactivity disorder (ADHD) affects parents’ parenting practices (Chronis-Tuscano et al., 2008). However, only few studies have investigated the association between parental social cognition and parenting practices in parents of children with ADHD (Rudy & Grusec, 2006). The principal purpose of this thesis was to examine the association between parental social cognitions, parental practices and the behavioural characteristics of their child diagnosed with ADHD. The purpose of the first study was to examine the association between parental social cognitions (parental causal attributions, parental self-efficacy), behavioural characteristics of their child (ADHD subtypes, comorbidity symptoms) and parental practices. Multiple regressions indicate that parental self-efficacy is associated with more use of appropriate discipline, praise and incentives, positive verbal discipline, and less use of harsh and inconsistent discipline and physical punishment. Results also show that parental causal attributions for the child’s misbehaviour to their own efforts are a predictor of positive verbal discipline whereas parents’ causal attributions for the child’s misbehaviour to the child’s lack of efforts are a predictor of harsh and inconsistent discipline. Parents’ perception of their child’s oppositional symptom is a predictor of appropriate discipline and positive verbal discipline. Finally, the presence of comorbidity symptoms in ADHD children is a predictor of harsh and inconsistent discipline. The purpose of the second study was to examine the association between cognitions (self-efficacy, causal attributions) of parents of ADHD children about their child’s behavior and their parental practices following an intervention (parent training program (PTP), support phone call (SPC)) in comparison with a control group (CG). Multiple regressions indicated that in some instances parental self-efficacy and causal attributions were predictors of parenting practices after the intervention. However it would be premature to conclude to the moderating role of social cognitions with regard to parenting practices following an intervention. Clinical implications of these results are explored in the discussion.

Background: Iron deficiency (ID) is the most prevalent nutritional deficiency in the world. In children, both inadequate iron and fatty acid (FA) status have been found to have an effect on cognitive and behavioural function, including physical activity behaviour and attention deficit hyperactivity disorder (ADHD)–related behaviour. Aim: To investigate the effects of supplementation with iron and omega–3 fatty acids (n–3 FAs), alone and in combination, on spontaneous motor activity and ADHD–related behaviour in iron deficient primary school children in KwaZulu–Natal. An additional aim was to evaluate the use of the Actical accelerometer as a tool to assess physical activity behaviour. Methods: The study design was a 2x2 factorial, randomized, double–blind and placebo–controlled trial. Iron deficient school children aged six to ten years with or without mild anaemia were included in the study (n = 321). Subjects were randomly assigned to receive one of the following supplement combinations: (1) 420mg docosahexaenoic acid (DHA)/80 mg eicosapentaenoic acid (EPA) + 50mg of iron as ferrous sulphate (Fe); (2) 420mg DHA/80mg EPA + placebo; (3) 50mg of Fe + placebo; (4) placebo + placebo. Supplements were provided four times a week for a duration of 8.5 months (excluding school holidays). Physical activity of a subgroup of subjects (n=98) was recorded on four random school days at baseline, midpoint and endpoint (12 days in total) during three different time periods namely class time 1 (08h00-10h30), break time (10h30–11h00) and class time 2 (11h00–12h00). Classroom behaviour of study subjects was assessed by teachers at baseline and endpoint using the Conners’ Teacher Rating Scale–Revised: Short Forms (CTRS). Iron status indicators and red blood cell (RBC) FA composition were measured at baseline and endpoint. Treatment effects were assessed for activity and CTRS scores. Furthermore, the relationship between activity, CTRS scores and iron/FA status indicators was determined using bivariate correlation and multivariate linear regression analysis. Results: Overall activity of all subjects varied over time from baseline and midpoint to endpoint. A significant cycle x age interaction (P = 0.005) as well as a significant cycle x time period x gender interaction (P = 0.036) was observed on overall activity. There were no significant interactions of cycle or time period with treatment. However, there was a significant main effect of DHA/EPA supplementation for lower class time 1 activity at endpoint (P = 0.014). Biological markers indicating better or poorer iron status were positively and negatively associated with activity at break time, respectively. Subjects in the group receiving both iron and DHA/EPA supplements showed a significant improvement from baseline to endpoint on the cognitive problems/inattention subscale (P = 0.005) of the CTRS. Hyperactivity scores increased iv significantly from baseline to endpoint in all groups (P = 0.006). DHA (r = –.203; P = 0.040) and EPA (r = –.199; P = 0.044) content of RBC were negatively associated with activity at class time 1. No significant associations were observed between activity and CTRS scores at baseline. At endpoint, class time 1 activity was positively associated with all CTRS subscale scores except for the cognitive problems subscale, which only bordered significance (correlation, P = 0.051; regression, P = 0.073). Conclusions: These findings suggest that n–3 FA supplementation may have an influence on ADHD–related behaviour during class time. During school break time when subjects were allowed to move around freely, iron status was positively associated with spontaneous motor activity. Furthermore, the accelerometer might be a useful complimentary tool for assessing both classroom and break time activity behaviour in school children. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2012.

Background: Iron deficiency (ID) is the most prevalent nutritional deficiency in the world. In children, both inadequate iron and fatty acid (FA) status have been found to have an effect on cognitive and behavioural function, including physical activity behaviour and attention deficit hyperactivity disorder (ADHD)–related behaviour. Aim: To investigate the effects of supplementation with iron and omega–3 fatty acids (n–3 FAs), alone and in combination, on spontaneous motor activity and ADHD–related behaviour in iron deficient primary school children in KwaZulu–Natal. An additional aim was to evaluate the use of the Actical accelerometer as a tool to assess physical activity behaviour. Methods: The study design was a 2x2 factorial, randomized, double–blind and placebo–controlled trial. Iron deficient school children aged six to ten years with or without mild anaemia were included in the study (n = 321). Subjects were randomly assigned to receive one of the following supplement combinations: (1) 420mg docosahexaenoic acid (DHA)/80 mg eicosapentaenoic acid (EPA) + 50mg of iron as ferrous sulphate (Fe); (2) 420mg DHA/80mg EPA + placebo; (3) 50mg of Fe + placebo; (4) placebo + placebo. Supplements were provided four times a week for a duration of 8.5 months (excluding school holidays). Physical activity of a subgroup of subjects (n=98) was recorded on four random school days at baseline, midpoint and endpoint (12 days in total) during three different time periods namely class time 1 (08h00-10h30), break time (10h30–11h00) and class time 2 (11h00–12h00). Classroom behaviour of study subjects was assessed by teachers at baseline and endpoint using the Conners’ Teacher Rating Scale–Revised: Short Forms (CTRS). Iron status indicators and red blood cell (RBC) FA composition were measured at baseline and endpoint. Treatment effects were assessed for activity and CTRS scores. Furthermore, the relationship between activity, CTRS scores and iron/FA status indicators was determined using bivariate correlation and multivariate linear regression analysis. Results: Overall activity of all subjects varied over time from baseline and midpoint to endpoint. A significant cycle x age interaction (P = 0.005) as well as a significant cycle x time period x gender interaction (P = 0.036) was observed on overall activity. There were no significant interactions of cycle or time period with treatment. However, there was a significant main effect of DHA/EPA supplementation for lower class time 1 activity at endpoint (P = 0.014). Biological markers indicating better or poorer iron status were positively and negatively associated with activity at break time, respectively. Subjects in the group receiving both iron and DHA/EPA supplements showed a significant improvement from baseline to endpoint on the cognitive problems/inattention subscale (P = 0.005) of the CTRS. Hyperactivity scores increased iv significantly from baseline to endpoint in all groups (P = 0.006). DHA (r = –.203; P = 0.040) and EPA (r = –.199; P = 0.044) content of RBC were negatively associated with activity at class time 1. No significant associations were observed between activity and CTRS scores at baseline. At endpoint, class time 1 activity was positively associated with all CTRS subscale scores except for the cognitive problems subscale, which only bordered significance (correlation, P = 0.051; regression, P = 0.073). Conclusions: These findings suggest that n–3 FA supplementation may have an influence on ADHD–related behaviour during class time. During school break time when subjects were allowed to move around freely, iron status was positively associated with spontaneous motor activity. Furthermore, the accelerometer might be a useful complimentary tool for assessing both classroom and break time activity behaviour in school children. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2012.

Thèse (M.Ps.)--Université du Québec, 2002. / Document électronique également accessible en format PDF. CaQCU

The study proposes an ecosystemic approach as an intervention for attentional difficulties and heightened motor activity, traditionally known as AD/HD. A literature study of AD/HD is presented first as a psycho-educational frame of reference. The focus then shifts to the symtoms of AD/DH to move closer to the possible underlying causes of these symptoms. In doing so, the focus changes from AD/HD as a diagnosis to attentional difficulties and heightened motor activity as presenting symptoms. Attention and motor activity as constructs are investigated in terms of their neuro-anatomical, neuro-chemical and neuro-physiological aspects. Furthermore, neurodevelopment, physiological stress, neurodevelopmental delay, information processing systems, sensory-motor subsystems and integration as constructs are investigated to understand their role in attention and modulation of motor activity. The study of attention and motor activity and their associated neurological factors motivates an alternative, ecosystemic method of intervention. The proposed approach includes an investigation into internal and external biochemical ecosystems such as environmental pollutants, deficiencies of essential nutrients and genetic deficiencies of the immune system. Other aspects such as time, maturation and neurodevelopment are also considered as well as the gentle interplay between these aspects. The therapeutic intervention includes sound therapy, neurodevelopmental movement activities, EEG neurofeedback and nutrition. Experimental research with a sample population of 12 diagnosed grade 4 and 5 AD/HD learners over a 11 week period was conducted. Statistically significant improvements in aspects of attention were noted using 2 standardised instruments and verification through parent interviews in the first and second experimental groups. Statistically significant improvements were noted in aspects of motor activity (a decline in hyperactive behaviour) in the second experimental group with verification from teacher interviews. Additionally, children in the first experimental group improved significantly more than children in the control group with regards to mathematic skills. The second experimental group showed significant improvement with large effect sizes on reading, mathematic skills and spelling. In conclusion, the statistically significant results obtained with the proposed approach motivates implementation, with improvements in attention, motor activity control and academic performance as a prospect. / Psychology of Education / D. Ed.(Psychology of Education)