scholarly journals Druggable genome in attention deficit/hyperactivity disorder and its co-morbid conditions. New avenues for treatment

Author(s):  
Tor-Arne Hegvik ◽  
Kai Waløen ◽  
Sunil K. Pandey ◽  
Stephen V. Faraone ◽  
Jan Haavik ◽  
...  

Abstract Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder with only symptomatic care available. Genome-wide association (GWA) studies can provide a starting point in the search for novel drug targets and possibilities of drug repurposing. Here, we explored the druggable genome in ADHD by utilising GWA studies on ADHD and its co-morbid conditions. First, we explored whether the genes targeted by current ADHD drugs show association with the disorder and/or its co-morbidities. Second, we aimed to identify genes and pathways involved in the biological processes underlying ADHD that can be targeted by pharmacological agents. These ADHD-associated druggable genes and pathways were also examined in co-morbidities of ADHD, as commonalities in their aetiology and management may lead to novel pharmacological insights. Strikingly, none of the genes encoding targets of first-line pharmacotherapeutics for ADHD were significantly associated with the disorder, suggesting that FDA-approved ADHD drugs may act through different mechanisms than those underlying ADHD. In the examined druggable genome, three loci on chromosomes 1, 4 and 12 revealed significant association with ADHD and contained nine druggable genes, five of which encode established drug targets for malignancies, autoimmune and neurodevelopmental disorders. To conclude, we present a framework to assess the druggable genome in a disorder, exemplified by ADHD. We highlight signal transduction and cell adhesion as potential novel avenues for ADHD treatment. Our findings add to knowledge on known ADHD drugs and present the exploration of druggable genome associated with ADHD, which may offer interventions at the aetiological level of the disorder.

2021 ◽  
Vol 11 (3) ◽  
pp. 166
Author(s):  
Luis Núñez-Jaramillo ◽  
Andrea Herrera-Solís ◽  
Wendy Verónica Herrera-Morales

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder in which patients present inattention, hyperactivity, and impulsivity. The etiology of this condition is diverse, including environmental factors and the presence of variants of some genes. However, a great diversity exists among patients regarding the presence of these ADHD-associated factors. Moreover, there are variations in the reported neurophysiological correlates of ADHD. ADHD is often treated pharmacologically, producing an improvement in symptomatology, albeit there are patients who are refractory to the main pharmacological treatments or present side effects to these drugs, highlighting the importance of developing other therapeutic options. Different non-pharmacological treatments are in this review addressed, finding diverse results regarding efficacy. Altogether, ADHD is associated with different etiologies, all of them producing changes in brain development, leading to the characteristic symptomatology of this condition. Given the heterogeneous etiology of ADHD, discussion is presented about the convenience of personalizing ADHD treatment, whether pharmacological or non-pharmacological, to reach an optimum effect in the majority of patients. Approaches to personalizing both pharmacological therapy and neurofeedback are presented.


CNS Spectrums ◽  
2020 ◽  
pp. 1-20 ◽  
Author(s):  
Greg W. Mattingly ◽  
Joshua Wilson ◽  
Leticia Ugarte ◽  
Paul Glaser

Abstract Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that manifests in childhood and can persist into adolescence and adulthood. Impairments associated with ADHD can impact quality of life, social interactions, and increase the risk of morbidity and mortality; however, for many patients, effective treatment can lessen these effects. Pharmacotherapy with stimulants or nonstimulants is recommended in conjunction with psychosocial therapy for most patients. Determining the optimal pharmacotherapy can be complex, and the clinician needs to consider many factors such as the patient’s age, comorbidities, and lifestyle. Furthermore, the needs of the patient with ADHD will change over time, with specific challenges to consider at each stage of life. A variety of Food and Drug Administration (FDA)-approved stimulant and nonstimulant formulations are available with different modes of delivery and durations of effect. This armamentarium of ADHD medications can be used to individualize ADHD treatment for each patient’s needs. This article combines current information from the literature and the first-hand experience of the authors to provide guidance on ADHD treatment options for patients of different ages and for some of the more common comorbidities.


2017 ◽  
Vol 23 (9-10) ◽  
pp. 916-929 ◽  
Author(s):  
E. Mark Mahone ◽  
Martha B. Denckla

AbstractThe behavior patterns of hyperactivity, impulsivity and inattention that would ultimately become recognized as Attention-Deficit Hyperactivity Disorder (ADHD) have been described for centuries. Nevertheless, in the past 35 years, advances in diagnostic methods, identification of biomarkers, and treatments have advanced at an exponential rate. ADHD is now recognized as the most common behavioral disorder of childhood, with risks extending well into adulthood for both males and females, leading to its identification as a significant public health issue. This historical neuropsychological review of ADHD emphasizes scientific highlights in the past 35 years related to ADHD, including the evolution of the diagnosis (from Hyperkinetic Reaction of Childhood to ADHD), influential theories (executive functions, cognitive-energetic, delay aversion), landmark treatment studies (Multimodal Treatment of ADHD [MTA] and Preschool ADHD Treatment Study [PATS]), and advances in brain mapping techniques (anatomic, functional, and resting state magnetic resonance imaging, diffusion tensor imaging). The review concludes by highlighting the challenges of studying and treating a heterogeneous neurodevelopmental disorder like ADHD, with emphasis on associated disorders and conditions (learning disabilities, sluggish cognitive tempo), special populations (girls, preschoolers, adults), and recommendations for scientific inquiry in the next 35 years. Neuropsychologists are well positioned to address the clinical and research challenges of the next generation of studies, especially involving advances in understanding the sexual dimor.phism, full developmental course, and dynamic risks associated with ADHD. (JINS, 2017, 23, 916–929)


2018 ◽  
Vol 35 (3) ◽  
pp. 247-249
Author(s):  
D. Murray ◽  
P. Devitt

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset in childhood. In Ireland adult ADHD treatment is drifting in an ad hoc manner into general adult psychiatric services. We propose this process should be halted in favour of a delivering a carefully planned adult ADHD service.


Author(s):  
Javier C. Vázquez ◽  
Ona Martin de la Torre ◽  
Júdit López Palomé ◽  
Diego Redolar-Ripoll

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity. Neurobiologically, ADHD impairments arise from abnormalities in different circuits involving the prefrontal cortex. In face of high rates of diagnosis, alternative/complementary pharmacological therapeutic approaches for ADHD are needed. Although the number of publications that study the potential effects of caf-feine consumption on ADHD treatment have been accumulating over the last years, and caffeine has recently been used in ADHD research in the context of animal models, an updated evi-dence-based systematic review on the effects of caffeine on ADHD-like symptoms in animal stud-ies is missing. To provide insight and value at the preclinical level, a systematic review based on PRISMA guidelines was performed for all publications available up to September 1, 2021. Caffeine treatment increases attention, improves learning, memory and olfactory discrimination, without altering blood pressure and body weight. These results are supported at the neuronal level. Nonetheless, the implication of caffeine in modulating ADHD-like symptoms of hyperactivity and impulsivity is contradictory, raising discrepancies that require further clarification. Our results strengthen the hypothesis that caffeine cognitive effects found in animal models could be trans-lated to human ADHD, particularly during adolescence.


2020 ◽  
Vol 10 (01) ◽  
pp. e97-e103
Author(s):  
Irene Rethemiotaki

AbstractAttention-deficit hyperactivity disorder (ADHD) is an increasingly recognized chronic neurodevelopmental disorder. This work aims at studying the prevalence and clinical characteristics of children with ADHD in the United States in the period between 2009 and 2018. Data from the National Health Interview Survey were analyzed by univariate and multivariate statistics to assess the role of socioeconomic factors in the development of ADHD. It has been studied 615,608 children, 51.2% male and 48.7% female. The prevalence of ADHD was 9.13%, with males predominating over females. The number of children with ADHD increased from 2009 to 2018 by 14.8%. As specified by multiple logistic regression analysis, males (odds ratio [OR] 2.38) who have neither mother nor father (OR 1.76) are twice as likely to have ADHD compared with their peers. In addition, family income (OR 1.40) and parent's education (OR 1.12) were significantly associated with ADHD. It has been highlighted the significance of deprivation of both family and financial comfort as primary indicators for ADHD in children. Moreover, children with ADHD were more likely to be males in the age group of 12 to 17.


2019 ◽  
Author(s):  
Paula Rovira ◽  
Ditte Demontis ◽  
Cristina Sánchez-Mora ◽  
Tetyana Zayats ◽  
Marieke Klein ◽  
...  

AbstractAttention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.


2018 ◽  
Vol 49 (1) ◽  
pp. 84-91 ◽  
Author(s):  
Elina Jokiranta-Olkoniemi ◽  
Keely Cheslack-Postava ◽  
Petteri Joelsson ◽  
Auli Suominen ◽  
Alan S. Brown ◽  
...  

AbstractBackgroundProbands with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for several psychiatric and neurodevelopmental disorders. The risk of these disorders among the siblings of probands has not been thoroughly assessed in a population-based cohort.MethodsEvery child born in Finland in 1991–2005 and diagnosed with ADHD in 1995–2011 were identified from national registers. Each case was matched with four controls on sex, place, and date of birth. The full siblings of the cases and controls were born in 1981–2007 and diagnosed in 1981–2013. In total, 7369 cases with 12 565 siblings and 23 181 controls with 42 753 siblings were included in the analyses conducted using generalized estimating equations.Results44.2% of the cases and 22.2% of the controls had at least one sibling diagnosed with any psychiatric or neurodevelopmental disorder (risk ratio, RR = 2.1; 95% CI 2.0–2.2). The strongest associations were demonstrated for childhood-onset disorders including ADHD (RR = 5.7; 95% CI 5.1–6.3), conduct and oppositional disorders (RR = 4.0; 95% CI 3.5–4.5), autism spectrum disorders (RR = 3.9; 95% CI 3.3–4.6), other emotional and social interaction disorders (RR = 2.7; 95% CI 2.4–3.1), learning and coordination disorders (RR = 2.6; 95% CI 2.4–2.8), and intellectual disability (RR = 2.4; 95% CI 2.0–2.8). Also, bipolar disorder, unipolar mood disorders, schizophrenia spectrum disorders, other neurotic and personality disorders, substance abuse disorders, and anxiety disorders occurred at increased frequency among the siblings of cases.ConclusionsThe results offer potential utility for early identification of neurodevelopmental and psychiatric disorders in at-risk siblings of ADHD probands and also argue for more studies on common etiologies.


Author(s):  
Pangajam Ponnuswamy ◽  
Ann Sarah Paul ◽  
Aneesha Brigitte Jose

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder most commonly found in childhood with its core symptoms manifesting as inattention, impulsiveness, and hyperactivity. As ADHD generates a substantial rate of burden to the society in terms of economic and medical resources used, priority is given to explore the risk factors that contributes towards the multifactorial origin of this disorder to offer possible preventive and therapeutic interventions. With heritability accounting for 75% to 80% of the variability seen in ADHD, the remaining are explained through environmental risk factors that are exposed during critical period of pre-, peri-, and postnatal development. Though literature on the risk factors have been mostly controversial, certain associations have been made with regards to ADHD pathophysiology.


2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Ilias Tachmazidis ◽  
Tianhua Chen ◽  
Marios Adamou ◽  
Grigoris Antoniou

AbstractAttention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that includes symptoms such as inattentiveness, hyperactivity and impulsiveness. It is considered as an important public health issue and prevalence of, as well as demand for diagnosis, has increased as awareness of the disease grew over the past years. Supply of specialist medical experts has not kept pace with the increasing demand for assessment, both due to financial pressures on health systems and the difficulty to train new experts, resulting in growing waiting lists. Patients are not being treated quickly enough causing problems in other areas of health systems (e.g. increased GP visits, increased risk of self-harm and accidents) and more broadly (e.g. time off work, relationship problems). Advances in AI make it possible to support the clinical diagnosis of ADHD based on the analysis of relevant data. This paper reports on findings related to the mental health services of a specialist Trust within the UK’s National Health Service (NHS). The analysis studied data of adult patients who underwent diagnosis over the past few years, and developed a hybrid approach, consisting of two different models: a machine learning model obtained by training on data of past cases; and a knowledge model capturing the expertise of medical experts through knowledge engineering. The resulting algorithm has an accuracy of 95% on data currently available, and is currently being tested in a clinical environment.


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