A mechanistic model of ADHD as resulting from dopamine phasic/tonic imbalance during reinforcement learning

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children. Although the involvement of dopamine in this disorder seems to be established, the nature of dopaminergic dysfunction remains controversial. The purpose of this study was to test whether the key response characteristics of ADHD could be simulated by a mechanistic model that combines a decrease in tonic dopaminergic activity with an increase in phasic responses in cortical-striatal loops during learning reinforcement. To this end, we combined a dynamic model of dopamine with a neurocomputational model of the basal ganglia with multiple action channels. We also included a dynamic model of tonic and phasic dopamine release and control, and a learning procedure driven by tonic and phasic dopamine levels. In the model, the dopamine imbalance is the result of impaired presynaptic regulation of dopamine at the terminal level. Using this model, virtual individuals from a dopamine imbalance group and a control group were trained to associate four stimuli with four actions with fully informative reinforcement feedback. In a second phase, they were tested without feedback. Subjects in the dopamine imbalance group showed poorer performance with more variable reaction times due to the presence of fast and very slow responses, difficulty in choosing between stimuli even when they were of high intensity, and greater sensitivity to noise. Learning history was also significantly more variable in the dopamine imbalance group, explaining 75% of the variability in reaction time using quadratic regression. The response profile of the virtual subjects varied as a function of the learning history variability index to produce increasingly severe impairment, beginning with an increase in response variability alone, then accumulating a decrease in performance and finally a learning deficit. Although ADHD is certainly a heterogeneous disorder, these results suggest that typical features of ADHD can be explained by a phasic/tonic imbalance in dopaminergic activity alone

Attention-Deficit/Hyperactivity Disorder and the Challenges of Close Friendship

Abstract Introduction: Much has been learned about the social rejection of children with Attention-Deficit Hyperactivity Disorder (ADHD) by their schoolmates. Although these group processes are clearly important, recent advances in theory and research have revealed the importance of close friendship. Method: In this paper, we review the current knowledge about the close friendships of children with ADHD. Results: Although children with ADHD tend to be excluded from close friendship, the data on the features of the friendships they do have are too limited and too flawed to permit conclusions about patterns of interaction between children with ADHD and their friends. Few data are actually available to indicate why children with ADHD have difficulty keeping the friends they do have. Conclusion: We conclude by briefly discussing some implications for pharmacological treatments and peer-relations interventions. Key words: Attention-Deficit Hyperactivity Disorder, close friendships, pharmacological treatment, peer-relations interventions Résumé Introduction: Il est désormais reconnu que les enfants avec un Trouble de déficit d'attention/hyperactivité (TDAH) soient rejetés par leurs pairs. Quoique ces processus de groupe soient importants, de récents développements théoriques et empiriques soulignent l'importance de l'amitié intime. Méthodologie: Dans cette revue de littérature, il est question de résumer les connaissances entourant les amitiés intimes des enfants avec TDAH. Résultats: Bien que les enfants avec TDAH aient tendance à ne pas avoir d'ami intime, les données sur les caractéristiques de leurs amitiés sont trop limitées pour permettre d'émettre des conclusions sur les patrons d'interaction entre ces enfants et leurs amis. Il existe actuellement peu de données indiquant la raison pour laquelle les enfants avec TDAH ont de la difficulté à conserver les amis qu'ils possè-dent. Conclusion: Nous terminons en discutant brièvement de certaines implications pour les traitements pharmacologiques et pour les interventions orientées vers les pairs. Mots clés: Trouble de déficit d'attention/hyperactivité; amitiés intimes; traitement pharmacologique; interventions orientées vers les pairs

The Quebec newborn twin study at 21

This paper is a revised and updated edition of a previous description of the Quebec Newborn Twin Study (QNTS), an ongoing prospective longitudinal follow-up of a birth cohort of twins born between 1995 and 1998 in the greater Montreal area, Québec, Canada. The goal of QNTS is to document individual differences in the cognitive, behavioral, and social-emotional aspects of developmental health across childhood, their early genetic and environmental determinants, as well as their putative role in later social-emotional adjustment, school, health, and occupational outcomes. A total of 662 families of twins were initially assessed when the twins were aged 6 months. These twins and their family were then followed regularly. QNTS now has 16 waves of data collected or planned, including 5 in preschool. Over the last 24 years, a broad range of physiological, cognitive, behavioral, school, and health phenotypes were documented longitudinally through multi-informant and multimethod measurements. QNTS also entails extended and detailed multilevel assessments of proximal (e.g., parenting behaviors, peer relationships) and distal (e.g., family income) features of the child’s environment. QNTS children and a subset of their parents have been genotyped, allowing for the computation of a variety of polygenic scores. This detailed longitudinal information makes QNTS uniquely suited for the study of the role of the early years and gene–environment transactions in development

A 2‐year dyadic longitudinal study of mothers' and fathers' marital adjustment when caring for a child with cancer

Objective Studies examining interrelationships within parental couples confronted with pediatric cancer are scarce. This study explored dyadic longitudinal associations between both partners' family functioning and mood at diagnosis, and marital adjustment 2 years later. Method Parents of children (n = 47 couples) with acute lymphoblastic leukemia (ALL) completed the Family Well‐Being Assessment and Profile of Mood States‐Bipolar Form at diagnosis, and the Locke–Wallace Marital Adjustment Test 2 years post diagnosis. Multilevel linear models using the actor–partner interdependence model (APIM) and controlling for baseline marital adjustment were conducted to evaluate within subject and dyadic longitudinal effects. Results For mothers, better marital adjustment 2 years post diagnosis was associated with perception of greater family support and less role conflict and role overload at diagnosis. For fathers, better marital adjustment 2 years post‐diagnosis was associated with perception of less role conflict, greater role ambiguity, and being more tired at diagnosis, as well as their partner's perception of less role conflict at diagnosis. Conclusions These findings highlight the importance of considering both partners' perspectives in understanding marital adjustment across treatment phases in parents of children with ALL. Early interventions for couples should be tailored to meet each partner's needs in order to foster resilience within the couple

Screening for distress in pediatric cancer survivors : a systematic comparison of one-step and two-step strategies to minimize detection errors

Background:Childhood cancer survivors should be routinelyscreened for psychological distress. However, existing screeningtools promoted by cancer care institutions, such as the DistressThermometer (DT) generate high rates of errors. The aim of thisstudy is to help refining strategies of screening psychologicaldistress in this population by exploring two-step methods com-bining the DT on step #1 with one question on step #2.Procedure:Data from 255 survivors of childhood acutelymphoblastic leukemia aged 13–40years were analyzed (38%13–18 years, 62% 19þyears, 53% females). We used the DTon step #1 and the individual emotion items from thePediatric Quality of Life Questionnaire (PedsQL) on step #2, todetect distress, depression and anxiety as measured by stand-ard instruments. We compared sensitivity, specificity, negativeand positive predictive values, Youden index, and clinical util-ity indices, in newly developed two-step strategies.Results:The best two-step strategies to screen anxious-depressive distress were DT 2 on step #1, with the item ofSadness on step #2, and DT 2 combined with the item ofConcerns. Two-step strategies outperformed the DT alone onthe correct identification of distressed survivors. However,two-step strategies did not outperform the DT used alone onthe correct detection of no distressed survivors. Results weresimilar when predicting depression or anxiety alone.Conclusion:Completing the DT with one single question onemotions from the PedsQL may minimize the number of par-ticipants falsely identified as distressed, which could be par-ticularly pertinent in resource-limited clinics

A mechanistic model of ADHD as resulting from dopamine phasic/tonic imbalance during reinforcement learning

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children. Although the involvement of dopamine in this disorder seems to be established, the nature of dopaminergic dysfunction remains controversial. The purpose of this study was to test whether the key response characteristics of ADHD could be simulated by a mechanistic model that combines a decrease in tonic dopaminergic activity with an increase in phasic responses in cortical-striatal loops during learning reinforcement. To this end, we combined a dynamic model of dopamine with a neurocomputational model of the basal ganglia with multiple action channels. We also included a dynamic model of tonic and phasic dopamine release and control, and a learning procedure driven by tonic and phasic dopamine levels. In the model, the dopamine imbalance is the result of impaired presynaptic regulation of dopamine at the terminal level. Using this model, virtual individuals from a dopamine imbalance group and a control group were trained to associate four stimuli with four actions with fully informative reinforcement feedback. In a second phase, they were tested without feedback. Subjects in the dopamine imbalance group showed poorer performance with more variable reaction times due to the presence of fast and very slow responses, difficulty in choosing between stimuli even when they were of high intensity, and greater sensitivity to noise. Learning history was also significantly more variable in the dopamine imbalance group, explaining 75% of the variability in reaction time using quadratic regression. The response profile of the virtual subjects varied as a function of the learning history variability index to produce increasingly severe impairment, beginning with an increase in response variability alone, then accumulating a decrease in performance and finally a learning deficit. Although ADHD is certainly a heterogeneous disorder, these results suggest that typical features of ADHD can be explained by a phasic/tonic imbalance in dopaminergic activity alone

Psychological risk in long-term survivors of childhood acute lymphoblastic leukemia and its association with functional health status : A PETALE cohort study

Background: Recent research has suggested that long-term pediatric cancer survivors were at risk of important physical and psychological morbidities. To date, we do not know to what extent functional health status contributes to psychological risk and which domains are most important. The aim of this study was to systematically explore which functional domain could explain anxiety, depression, and distress symptoms. Procedure: We used data available for 105 adolescents and 182 adults successfully treated for childhood acute lymphoblastic leukemia at two Canadian sites part of the PETALE cohort. Participants were ≥5 years postdiagnosis, aged 22 ± 6 years, 52% female, and 49% acute lymphoblastic leukemia high-risk status. The contribution of health functional status (15D/16D questionnaires) to self-reported anxiety, depression, and distress (Beck scales and distress thermometer) was evaluated using adjusted logistic regression models. Results: Prevalence rates found for mild-severe anxiety, depression, and distress were 14%, 21%, and 30% among adolescents and 27%, 20%, and 19% among adults. Frequent health domains associated with psychological risk were sleeping and breathing in adolescents, and vitality/fatigue, discomfort/symptoms, mental function, and sleeping in adults. Mental function was systematically associated with psychological risk across age groups (median OR = 10.00, 95% CI 3.01-33.71). Exploratory mediation bootstrapping analyses suggested that the effect on psychological risk of overall health status and mental function problems was partly explained by social/work/school functioning. Conclusion: The results identified important functional health domains that could be targeted for interventions preventing psychological risk: vitality/fatigue, discomfort/symptoms, sleeping, and mental function issues. Health domains probably affect mood partly by limiting social/work/school functioning

Contributing factors of unmet needs among young adult survivors of childhood acute lymphoblastic leukemia with comorbidities

Purpose: This study aimed to: (1) describe the domains and levels of unmet needs of young adult survivors of childhood acute lymphoblastic leukemia (cALL) with comorbidities, and (2) to explore the factors associated with higher levels of unmet needs. Unmet need was considered as supportive care needs not met. Methods: The most vulnerable cALL survivors from the PETALE study cohort completed the Short-Form Survivor Unmet Needs Survey, the Brief Pain Inventory and the 15D instrument of health-related quality of life. Demographic and clinical information, including comorbidities, were obtained from medical records or self-reporting. The participants' needs and contributing factors to their needs were evaluated using nonparametric tests. Results: Of the 72 participants, 9 (13%) reported moderate/high levels of overall unmet needs. “Worry about earning money” (56%) and “Dealing with feeling tired” (51%) were the most frequent unmet needs (all levels combined). The factors associated significantly with any domain of unmet needs were: having a comorbidity, reporting altered functional health status, high ALL risk status, pain, age (<26 years), and having previously received psychological support. Conclusion: A minority of young adult survivors of cALL with comorbidities interviewed reported moderate/high levels of unmet needs. However, financial concerns and emotional health and relationship are the two domains of greatest need. Survivors with altered health condition are most at risk of experiencing moderate/high levels of unmet needs. If confirmed in larger samples, interventions should target modifiable contributors of unmet needs such as physical health and comfort, fatigue, and emotional health