Reward dysfunction in AD/HD

Adult attention-deficit/hyperactivity disorder (ADHD) has a population prevalence of 5%. However, its prevalence is much higher in mental health and substance use treatment settings. It is associated with significant physical and psychiatric morbidity, as well as social, occupational, and legal consequences. Adult ADHD is considered to be a part of the externalizing spectrum with which it shares both homotypic comorbidity and heterotypic continuity across the lifespan. This is attributable to a shared genetic basis, which interacts with environmental risk factors such as nutritional deficiencies and psychosocial adversity to bring about epigenetic changes...

Individuals with attention deficit hyperactivity disorder (ADHD) often show poor planning and poor organization of tasks and activities which has been related to reduced memory for delayed intentions (prospective memory) and procrastination-in addition to other cognitive or motivational factors. This study set out to bring the fields of prospective memory and procrastination research together and to explore possible relations between the two constructs in ADHD. Twenty-nine adults with ADHD and 24 healthy controls performed several laboratory-based and real-life prospective memory tasks and filled in questionnaires measuring their symptom severity and procrastination behaviour...

Research on motivational processes in attention deficit/hyperactivity disorder (ADHD) focuses on reward. Studies with punishment are limited and findings mixed. This study evaluated the effects of punishment on response allocation in Japanese children with and without ADHD. Thirty-four children meeting DSM-IV criteria for ADHD and 59 typically developing control-group children completed an operant task in which they choose between playing two simultaneously available games. Reward was arranged symmetrically across the games under concurrent variable interval schedules...

Attention-deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders of childhood and previous studies indicate the dopamine system plays a major role in ADHD pathogenesis. Two environmental exposures independently associated with dopaminergic dysfunction and ADHD risk include exposure to deltamethrin, a pyrethroid insecticide, and chronic stress. We hypothesized that combined neurodevelopmental exposure to both deltamethrin and corticosterone (CORT), the major stress hormone in rodents, would result in additive changes within the dopamine system...

The precise regulation of synaptic dopamine (DA) content by the dopamine transporter (DAT) ensures the phasic nature of the DA signal, which underlies the ability of DA to encode reward prediction error, thereby driving motivation, attention, and behavioral learning. Disruptions to the DA system are implicated in a number of neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD) and, more recently, Autism Spectrum Disorder (ASD). An ASD-associated de novo mutation in the SLC6A3 gene resulting in a threonine to methionine substitution at site 356 (DAT T356M) was recently identified and has been shown to drive persistent reverse transport of DA (i...

KCNJ6, encoding a potassium channel subunit, regulates the excitability of dopaminergic neurons and is expressed in attention-deficit/hyperactivity disorder (ADHD)-relevant brain regions. As a potential ADHD risk gene, KCNJ6, therefore, may contribute to the endophenotypic variation of the disorder. The impact of two SNPs, rs7275707 and rs6517442, both located in the transcriptional control region of KCNJ6, on reporter gene expression was explored in cultured cells. The KCNJ6 variants were then tested for association with ADHD and personality traits in a family-based sample (165 affected children) and an adult case-control sample (450 patients, 426 controls)...

Methylphenidate (MPH) is the leading drug for treatment of attention deficit/hyperactivity disorder (ADHD), yet its underlying neuronal mechanisms are still unclear. Here, we use a dynamical brain networks approach to explore the effects of cognitive effort and MPH on ADHD subjects. Electroencephalography data were recorded from 19 ADHD subjects and 18 controls during a Go/No-Go Task. ADHD subjects completed the task twice a day over 2 days. The second session was administered post-ingestion of placebo/MPH (alternately)...

Many adolescents have difficulty regulating their impulses and become prone to externalizing problems (e.g., attention-deficit/hyperactivity disorder [ADHD], oppositional defiant disorder [ODD], and conduct disorder [CD]) and other adverse consequences. Using multimethod data from a longitudinal study of Mexican-origin youth (N = 674), assessed annually from age 10 to 16, we examined the relations between effortful control and ADHD, ODD, and CD symptoms over time. Bivariate latent growth curve models showed negative correlations between the trajectories of effortful control and ADHD, ODD, and CD, indicating that steeper decreases in effortful control were related to steeper increases in ADHD, ODD, and CD symptoms...

OBJECTIVE: Although poor sleep is often reported in adolescents with attention-deficit/hyperactivity disorder (ADHD), prior studies have been correlational. This study investigated whether sleep duration is causally linked to sleepiness, inattention, and behavioral functioning in adolescents with ADHD. METHOD: A total of 72 adolescents (aged 14-17 years) entered a 3-week sleep protocol using an experimental crossover design. The protocol included a phase stabilization week, followed in randomized counterbalanced order by 1 week of sleep restriction (6...

ADHD is associated with altered dopamine regulated reinforcement learning on prediction errors. Despite evidence of categorically altered error processing in ADHD, neuroimaging advances have largely investigated models of normal reinforcement learning in greater detail. Further, although reinforcement leaning critically relies on ventral striatum exerting error magnitude related thresholding influences on substantia nigra (SN) and dorsal striatum, these thresholding influences have never been identified with neuroimaging...

Adhesion G protein-coupled receptor L3 (ADGRL3, LPHN3) has putative roles in neuronal migration and synapse function. Various polymorphisms in ADGRL3 have been linked with an increased risk of attention deficit/hyperactivity disorder (ADHD). In this study, we examined the characteristics of Adgrl3-deficient mice in multiple behavioural domains related to ADHD: locomotive activity, impulsivity, gait, visuospatial and recognition memory, sociability, anxiety-like behaviour and aggression. Additionally, we investigated the effect of Adgrl3-depletion at the transcriptomic level by RNA-sequencing three ADHD-relevant brain regions: prefrontal cortex (PFC), hippocampus and striatum...

The prevalence of anxiety disorders in patients with Attention Deficit/Hyperactivity Disorder (ADHD) is around 15-40%, three times higher than in the general population. The dopaminergic system, classically associated with ADHD, interacts directly with the adenosinergic system through adenosine A2A receptors (A2A ) and dopamine D2 receptors (D2 ) forming A2A -D2 heterodimers. Both dopaminergic and adenosinergic systems are implicated in anxiety disorders. Therefore, the aims of this study were: a) to investigate the main effects of ADORA2A and DRD2 gene variants on anxiety disorders in an ADHD sample of children and adolescents; b) to test potential synergism between ADORA2A and DRD2 genes on the same outcome; c) to explore ADORA2A variants functionality using an in silico approach...

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder persisting in adulthood in 40-60% of cases. Clinical and neuroimaging studies suggest that patients affected by both drug addiction and ADHD show higher rates of craving for drug than patients without ADHD. We designed a pilot open-label study to investigate the effects of ADHD on craving for heroin in methadone maintenance therapy patients. METHOD: Patients were recruited from outpatient facilities in an addiction treatment unit in the municipality of Alba, Italy...

Impulsive-compulsive behaviours like pathological gambling or hypersexuality are a frequent side effect of dopamine replacement therapy in patients with Parkinson's disease. Multiple imaging studies suggest a significant reduction of presynaptic dopamine transporters in the nucleus accumbens to be a predisposing factor, reflecting either a reduction of mesolimbic projections or, alternatively, a lower presynaptic dopamine transporter expression per se. Here, we aimed to test the hypothesis of fewer mesolimbic projections as a risk factor by using dopamine synthesis capacity as a proxy of dopaminergic terminal density...

The dopaminergic neural system plays a crucial role in motor regulation as well as regulation of anxiety-related behaviors. Although rats with neonatal dopamine depletion exhibit motor hyperactivity and have been utilized as animal models of attention deficit hyperactivity disorder, characterization of their behavior under anxiogenic conditions is lacking. In the present study, we investigated behavioral responses to anxiogenic stimuli in young adult rats with neonatal dopamine depletion using the open field (OF), elevated plus maze (EPM), and light/dark (L/B) box tests...

Impulsivity is a transdiagnostic feature of a range of externalizing psychiatric disorders. Preclinical work links reduced ventral striatal dopamine transporter (DAT) availability with heightened impulsivity and novelty seeking. However, there is a lack of human data investigating the relationship between DAT availability, particularly in subregions of the striatum, and the personality traits of impulsivity and novelty seeking. Here we collected PET measures of DAT availability (BPND ) using the tracer 18 F-FE-PE2I in 47 healthy adult subjects and examined relations between BPND in striatum, including its subregions: caudate, putamen, and ventral striatum (VS), and trait impulsivity (Barratt Impulsiveness Scale: BIS-11) and novelty seeking (Tridimensional Personality Questionnaire: TPQ-NS), controlling for age and sex...

Cognitive control, the ability to orchestrate behavior in accord with our goals, depends on the prefrontal cortex. These cognitive functions are heavily influenced by the neuromodulator dopamine. We review here recent insights exploring the influence of dopamine on neuronal response properties in prefrontal cortex (PFC) during ongoing behaviors in primates. This review suggests three major computational roles of dopamine in cognitive control: (i) gating sensory input, (ii) maintaining and manipulating working memory contents, and (iii) relaying motor commands...

Attention deficit and hyperactivity disorder (ADHD) is characterized by impaired levels of hyperactivity, impulsivity, and inattention. Adenosine and endocannabinoid systems tightly interact in the modulation of dopamine signaling, involved in the neurobiology of ADHD. In this study, we evaluated the modulating effects of the cannabinoid and adenosine systems in a tolerance to delay of reward task using the most widely used animal model of ADHD. Spontaneous Hypertensive Rats (SHR) and Wistar-Kyoto rats were treated chronically or acutely with caffeine, a non-selective adenosine receptor antagonist, or acutely with a cannabinoid agonist (WIN55212-2, WIN) or antagonist (AM251)...

The aim of this study was to compare impulsivity levels, as assessed by a continuous performance test (CPT), and the correlations between baseline CPT performance and response to methylphenidate (MPH), as assessed by the conjunctive CPT (CCPT), in children with only Diagnostic and Statistical Manual of Mental Disorders, 5th ed. attention-deficit hyperactivity disorder with no oppositional defiant disorder (ADHD/noODD) or with comorbid ODD (ADHD/ODD). Fifty-three children and adolescents were included in the study (ADHD/noODD group, n = 25, 12 women/13 men and ADHD/ODD group, n = 28, eight females/20 males)...

Methylphenidate (MPD) is a psychostimulant used for the treatment of ADHD and works by increasing the bioavailability of dopamine (DA) in the brain. As a major source of DA, the ventral tegmental area (VTA) served as the principal target in this study as we aimed to understand its role in modulating the acute and chronic MPD effect. Forty-eight male Sprague-Dawley rats were divided into control, sham, electrical lesion, and 6-OHDA lesion groups. Given the VTA's implication in the locomotive circuit, three locomotor indices-horizontal activity, number of stereotypy, and total distance-were used to measure the animals' behavioral response to the drug...