Etiology Of Attention Deficit Hyperactivity Disorder Research Articles

Birth Order and Number of Siblings in Attention Deficit Hyperactivity Disorder: A Case Control Study

Aim: Studies addressing the etiology of Attention Deficit Hyperactivity Disorder (ADHD) in recent years have focused on family and birth-related factors.This study aimed to examine the relationship between Attention Deficit Hyperactivity Disorder (ADHD) and birth order and number of siblings. Method: A total of 239 participants, 135 children diagnosed with ADHD and 104 healthy children, were included in the study. All participants were evaluated through DSM-5-based psychiatric examinations, and their sociodemographic data forms were obtained. Conners’ Parent Rating Scale-Revised Short form (CPRS-RS) was also applied to the case group in order to determine the severity of ADHD symptoms. The findings were then compared using statistical methods. Results: No significant difference was observed between the individuals with ADHD and the healthy controls in terms of birth order or number of siblings (p= 0.252 and p= 0.222, respectively). A significant positive correlation was determined in the ADHD group between birth order and hyperactivity and oppositional subscales (r= 0.212, p= 0.022 and r= 0.231, p= 0.012, respectively). A significant positive correlation was also determined in the ADHD group between number of siblings and the oppositional subscale (r= 0.237, p= 0.009). Conclusions:In our study, no significant difference was observed between the ADHD and control groups in terms of birth order or number of siblings.It was observed that hyperactivity and defiance symptoms increased as birth order increased in children diagnosed with ADHD. Oppositional findings also increased in line with the number of siblings.We think that these findings should be taken into consideration in future research on ADHD.

The detect consensus report on Attention Deficit/Hyperactivity Disorder and its management among Turkish children and adolescents (Detect: consensus report on ADHD among Turkish youth).

Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most common and heritable neurodevelopmental disorders which may last through the life-span. A consensus report on diagnosis and management of ADHD among Turkish youth was prepared previously. However, the participants as well as the management options were rather limited and developments in the past decade necessitated a revision and update of the consensus. Therefore, this review aims to summarize the consensus among Child and Adolescent Psychiatrists from Türkiye on the nature and management of pediatric ADHD. For those aims, the etiology of ADHD, diagnostic and evaluation process, epidemiology, developmental presentations, differential diagnoses and comorbidities, course/outcome and pharmacological as well as non-pharmacological management options were reviewed and suggestions for clinical practice are presented. Since ADHD is a chronic disorder with wide-ranging effects on functionality that is frequently accompanied by other mental disorders, a multidimensional therapeutic approach is recommended. However, since the disorder has neurobiological basis, pharmacotherapy represents the mainstay of treatment. Additional therapies may include psychosocial therapy, behavioral therapy, school-based therapeutic approaches, and family education. This review provides recommendations for ADHD at the national and global levels. It contains information about ADHD that will contribute to and facilitate clinicians' decision-making processes. It is advisable to consider this guideline in clinical practice.

The Prevalence of Risk Factors Among Children Diagnosed With Attention-Deficit/Hyperactivity Disorder, Aged 4-17 Years: A Cross-Sectional Study.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder commonly observed in children. Although the etiology of ADHD is still unclear, many risk factors have been shown to increase the prevalence of ADHD, such as genetics, environmental factors, socioeconomic status, maternal smoking, and low birth weight. The current cross-sectionalstudy aimed to assess the prevalence of several risk factors associated with ADHD-diagnosed children aged 4-17 years using parent-reported data. An observational cross-section study was conducted between December 2022 and February 2023 using a self-constructed questionnaire that we sent to parents whose children were diagnosed with ADHD. The questionnaire included socioeconomic information (income, gender, parent education, number of children), child information (age, ADHD type, academic achievement), pregnancy and neonatal period (smoking status, gestation age, mode of delivery, child weight), and if there is a history of ADHD in the family. A total of 306 parents responded to the questionnaire. The majority of our study population was males (77.8%). The combined type, which includes symptoms of both hyperactivity and inattention, represented 70% of the population in our study, which is higher than the inattention type (23%) and the hyperactivity type (6%). The prevalence of several risk factors known to be associated with ADHD, such as family income, parental education, complications during pregnancy, and the low birth weight of the child, were also reported. To the best of our knowledge, this is the first study that examines the frequency of risk factors among children diagnosed with ADHD in Saudi Arabia. The study revealed that males are more likely to be diagnosed with ADHD than females. We also found that the combined type is the most diagnosed ADHD among children. Furthermore, there are no significant differences in the prevalence of the risk factors during the gestational or neonatal period among ADHD-diagnosed children. Therefore, a large-scale prospective study is needed to aid in evaluating the frequency and significance of various risk factors among diagnosed children.

Inflammation and emotion regulation: a narrative review of evidence and mechanisms in emotion dysregulation disorders.

Emotion dysregulation (ED) describes a difficulty with the modulation of which emotions are felt, as well as when and how these emotions are experienced or expressed. It is a focal overarching symptom in many severe and prevalent neuropsychiatric diseases, including bipolar disorders (BD), attention deficit/hyperactivity disorder (ADHD), and borderline personality disorder (BPD). In all these disorders, ED can manifest through symptoms of depression, anxiety, or affective lability. Considering the many symptomatic similarities between BD, ADHD, and BPD, a transdiagnostic approach is a promising lens of investigation. Mounting evidence supports the role of peripheral inflammatory markers and stress in the multifactorial aetiology and physiopathology of BD, ADHD, and BPD. Of note, neural circuits that regulate emotions appear particularly vulnerable to inflammatory insults and peripheral inflammation, which can impact the neuroimmune milieu of the central nervous system. Thus far, few studies have examined the link between ED and inflammation in BD, ADHD, and BPD. To our knowledge, no specific work has provided a critical comparison of the results from these disorders. To fill this gap in the literature, we review the known associations and mechanisms linking ED and inflammation in general, and clinically, in BD, ADHD, and BD. Our narrative review begins with an examination of the routes linking ED and inflammation, followed by a discussion of disorder-specific results accounting for methodological limitations and relevant confounding factors. Finally, we critically discuss both correspondences and discrepancies in the results and comment on potential vulnerability markers and promising therapeutic interventions.

Glutamate receptor genetic variants affected peripheral glutamatergic transmission and treatment induced improvement of Indian ADHD probands

Attention deficit hyperactivity disorder (ADHD), a childhood-onset neurobehavioral disorder, often perturbs scholastic achievement and peer-relationship. The pivotal role of glutamate (Glu) in learning and memory indicated an influence of Glu in ADHD, leading to the exploration of Glu in different brain regions of ADHD subjects. We for the first time analyzed GluR genetic variations, Glu levels, as well as expression of Glu receptors (GluR) in the peripheral blood of eastern Indian ADHD probands to find out the relevance of Glu in ADHD prognosis. After obtaining informed written consent for participation, peripheral blood was collected for analyzing the genetic variants, Glu level, and expression of target genes. Since ADHD probands are often treated with methylphenidate or atomoxetine for providing symptomatic remediation, we have also tested post-therapeutic improvement in the ADHD trait scores in the presence of different GluR genotypes. Two variants, GRM7 rs3749380 “T” and GRIA1 rs2195450 “C”, exhibited associations with ADHD (P ≤ 0.05). A few GluR genetic variants showed significant association with higher trait severity, low IQ, lower plasma Glu level, down-regulated GluR mRNA expression, and poor response to medications. This indicates that down-regulated glutamatergic system may have an effect on ADHD etiology and treatment efficacy warranting further in-depth investigation.

An Examination of the Relationship Between Exposure to Bisphenol A and Attention-Deficit/Hyperactivity Disorder in Children and Adolescents.

Exposure to environmental toxic agents in the prenatal and/or postnatal periods may play in the acquired development of attention-deficit/hyperactivity disorder (ADHD) in groups with genetic risks. Bisphenol A (BPA) is a widely used industrial chemical with neurotoxic effects. This study examined the relationship between exposure to BPA and clinical ADHD. This cross-sectional, case-controlled clinical study compared 45 drug-naive children and adolescents with ADHD and 30 healthy controls in terms of serum BPA levels. Psychiatric comorbidities in the ADHD group were determined using the "Schedule for Affective Disorders and Schizophrenia for school-aged children, lifetime version." The Child Behavior Checklist (CBCL) was also administered to all participants. Serum BPA levels were significantly higher in the ADHD group than in the healthy control group. In addition, significant, weak positive correlation was found between BPA levels and CBCL attention and CBCL total problem scores. Our results show that BPA may be an environmental toxic agent with a potential role in the etiology of ADHD and particularly attention deficiency. Preventive interventions can be developed if this can be confirmed with longitudinal studies and repeated measurements.

Moderating effects of impulsivity and morning cortisol on the genotype-phenotype relationship of attention deficit hyperactivity disorder in young adults.

Dysregulation of the morning cortisol response in young adults with attention deficit hyperactivity disorder (ADHD) has been shown to underlie several of the alterations present in their lives. Thus, the interaction of this mechanism with genetic and behavioural characteristics could explain a large proportion of the aetiology of ADHD in this population. For these reasons, the present study explores the associations of 30 single nucleotide polymorphisms (SNPs) previously identified as significant (after correction for multiple comparisons) in the aetiology of ADHD with an assessment of morning cortisol and impulsivity traits in a group of 120 adults aged 18-24years. Participants were recruited through private centres of neuropsychology and psychiatry, as well as through events in local universities. Morning cortisol within 30min of awakening and motor impulsivity traits were shown to moderate the effect of SNP rs10129500 on the severity of the symptoms of ADHD measured by the Adult Self-Report Scale. This variant associated with cortisol-binding globulin would explain the low concentrations of this hormone found in young adults with high symptoms of ADHD, which is accentuated when there are high levels of impulsivity. The proposed model allows for transferring the theoretical relationships between the dimensions that explain the aetiology of ADHD to an applied exploratory model with good performance.

Molecular Mechanisms Underlying NMDARs Dysfunction and Their Role in ADHD Pathogenesis.

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, although the aetiology of ADHD is not yet understood. One proposed theory for developing ADHD is N-methyl-D-aspartate receptors (NMDARs) dysfunction. NMDARs are involved in regulating synaptic plasticity and memory function in the brain. Abnormal expression or polymorphism of some genes associated with ADHD results in NMDAR dysfunction. Correspondingly, NMDAR malfunction in animal models results in ADHD-like symptoms, such as impulsivity and hyperactivity. Currently, there are no drugs for ADHD that specifically target NMDARs. However, NMDAR-stabilizing drugs have shown promise in improving ADHD symptoms with fewer side effects than the currently most widely used psychostimulant in ADHD treatment, methylphenidate. In this review, we outline the molecular and genetic basis of NMDAR malfunction and how it affects the course of ADHD. We also present new therapeutic options related to treating ADHD by targeting NMDAR.

Asian Indian American Parental Help-Seeking Intentions for ADHD.

Minoritized ethnic groups experience both delay to treatment and low rate of treatment contact for attention deficit/hyperactivity disorder (ADHD). To date, Asian Indian Americans have been excluded completely from ADHD help-seeking research. To fill this void, the Theory of Planned Behavior (TPB) was used to investigate the influence of race/ethnicity on parents' help-seeking intentions for their child's elevated ADHD symptoms. Parents (n = 191, 53% Asian Indian American, 47% European American; 63.9% fathers) of treatment naïve children at high risk for ADHD completed an online survey to assess their recognition of ADHD, knowledge of ADHD etiology, attitudes towards ADHD treatment, subjective norms regarding ADHD treatment, perceived control over their ADHD help-seeking behavior, and intention to seek help for their child's elevated ADHD symptoms. Hierarchical linear regressions demonstrated that perceived behavioral control independently predicted intention to seek help in the total sample and may be more impactful for European American parents than Asian Indian American parents. In contrast, subjective norms were more influential for help-seeking intentions among Asian Indian American parents. However, attitudes towards ADHD were not significantly associated with the intention to seek help among both ethnicities. Asian Indian American parents endorsed lower levels of biopsychosocial etiology beliefs. Together, the results inform possible methods of increasing treatment engagement for both groups of parents who have children at high risk for ADHD.

A twin study of genetic and environmental contributions to attention-deficit/hyperactivity disorder over time.

Attention-deficit/hyperactivity disorder (ADHD) is an increasingly commonly diagnosed neurodevelopmental condition. One possibility is that this reflects a genuine increase in the prevalence of ADHD due to secular environmental changes, yet this hypothesis remains untested. We therefore investigated whether the genetic and environmental variance underlying ADHD, and traits of ADHD, has changed over time. We identified twins born from 1982 to 2008 from the Swedish Twin Registry (STR). We linked the STR with the Swedish National Patient Register and Prescribed Drug Register to identify diagnoses of ADHD and prescriptions of ADHD medication for these twins. We also utilized data collected from participants in the Child and Adolescent Twin Study in Sweden (CATSS), born from 1992 to 2008. Their parents completed a structured ADHD screening tool, which was used to measure traits of ADHD and assign broad screening diagnoses of ADHD. We used the classical twin design to test whether the degree to which variation in these measures was influenced by genetic and environmental variation changed over time. We included 22,678 twin pairs from the STR and 15,036 pairs from CATSS. The heritability of ADHD in the STR ranged from 66% to 86% over time, although these fluctuations were not statistically significant. We observed a modest increase in variance in ADHD traits, from 0.98 to 1.09. This was driven by small increases in the underlying genetic and environmental variance, with heritability estimated as 64%-65%. No statistically significant changes in variance in screening diagnoses were observed. The relative contribution of genetic and environmental factors to ADHD has remained stable over time, despite its increasing prevalence. Thus, changes in the underlying etiology of ADHD over time are unlikely to explain the increase in ADHD diagnoses.

Shared genetic etiology between ADHD, task-related behavioral measures and brain activation during response inhibition in a youth ADHD case–control study

Impaired response inhibition is commonly present in individuals with attention-deficit/hyperactivity disorder (ADHD) and their unaffected relatives, suggesting impaired response inhibition as a candidate endophenotype in ADHD. Therefore, we explored whether behavioral and neural correlates of response inhibition are related to polygenic risk scores for ADHD (PRS-ADHD). We obtained functional magnetic resonance imaging of neural activity and behavioral measures during a stop-signal task in the NeuroIMAGE cohort, where inattention and hyperactivity-impulsivity symptoms were assessed with the Conners Parent Rating Scales. Our sample consisted of 178 ADHD cases, 103 unaffected siblings, and 173 controls (total N = 454; 8–29 years), for whom genome-wide genotyping was available. PRS-ADHD was constructed using the PRSice-2 software. We found PRS-ADHD to be associated with ADHD symptom severity, a slower and more variable response to Go-stimuli, and altered brain activation during response inhibition in several regions of the bilateral fronto-striatal network. Mean reaction time and intra-individual reaction time variability mediated the association of PRS-ADHD with ADHD symptoms (total, inattention, hyperactivity-impulsivity), and activity in the left temporal pole and anterior parahippocampal gyrus during failed inhibition mediated the relationship of PRS-ADHD with hyperactivity-impulsivity. Our findings indicate that PRS-ADHD are related to ADHD severity on a spectrum of clinical, sub-threshold, and normal levels; more importantly, we show a shared genetic etiology of ADHD and behavioral and neural correlates of response inhibition. Given the modest sample size of our study, future studies with higher power are warranted to explore mediation effects, suggesting that genetic liability to ADHD may adversely affect attention regulation on the behavioral level and point to a possible response inhibition-related mechanistic pathway from PRS-ADHD to hyperactivity-impulsivity.

Role of Glutamate Receptor-related Biomarkers in the Etiopathogenesis of ADHD.

: Pathways associated with glutamate receptors are known to play a role in the pathophysiology of attention-deficit hyperactivity disorder (ADHD). However, cyclin-dependent kinase 5 (CDK5), microtubule-associated protein-2 (MAP2), guanylate kinase-associated protein (GKAP), and postsynaptic density 95 (PSD95), all of which are biomarkers involved in neurodevelopmental processes closely related to glutamatergic pathways, have not previously been studied in patients with ADHD. The main purpose of this study was to evaluate the plasma levels of CDK5, MAP2, GKAP, and PSD95 in children with ADHD and investigate whether these markers have a role in the etiology of ADHD. : Ninety-six children with ADHD between 6 and 15 years of age and 72 healthy controls were included in the study. Five milliliters of blood samples were taken from all participants. The samples were stored at -80°C until analyzed by the enzyme-linked immunosorbent assay method. : Statistically significantly lower CDK5 levels were observed in children with ADHD than in healthy controls (p = 0.037). The MAP2, GKAP, and PSD95 levels were found to be statistically significantly higher in the ADHD group than in healthy controls (p = 0.012, p = 0.009, and p = 0.024, respectively). According to binary regression analysis, CDK5 and MAP2 levels were found to be predictors of ADHD. : In conclusion, we found that a close relationship existed between ADHD and glutamatergic pathways, and low levels of CDK5 and high levels of MAP2 and GKAP played a role in the etiopathogenesis of ADHD.

Expression alteration of Neuroligin family gene in attention deficit and hyperactivity disorder and autism spectrum disorder

BackgroundAutism spectrum disorder (ASD) is a complex neurodevelopment disorder with social and communicational deficiency, language impairment, and ritualistic behaviors. Attention deficit hyperactivity disorder (ADHD) is a pediatric psychiatric disorder with symptoms, including attention deficit, hyperactivity, and impulsiveness. ADHD is a childhood-onset disorder that can persist into adult life. Neuroligins are post-synaptic cell-adhesion molecules that connect neurons and have an essential role in the mediation of trans-synaptic signaling and shaping the synapse and circuits and neural network functioning. AimsPresent study aimed to shed light on the role of the Neuroligin gene family in ASD and ADHD. Methods and proceduresmRNA levels of the Neuroligin gene family (NLGN1, NLGN2, NLGN3, and NLGN4X) were studied in the peripheral blood of 450 unrelated ASD patients, 450 unrelated ADHD patients, and the normal group included 490 unrelated non-psychiatric children by quantitative PCR. Also, clinical situations were considered. Outcomes and resultsResults showed that mRNA levels of NLGN1, NLGN2, and NLGN3 were significantly down-regulated in the ASD group vs. control subjects. In ADHD, a significant reduction of NLGN2 and NLGN3 was detected in comparison with normal children. A comparison of ASD and ADHD subjects revealed that NLGN2 was significantly down-regulated in ASD subjects. ConclusionsThe Neuroligin family gene may play an essential role in the etiology of ASD and ADHD and thus be a source for a better understanding of neurodevelopment disorders. ImplicationsSimilar patterns of deficiency of Neuroligin family genes in ASDs and ADHDs may indicate the role of these genes in functions that have been affected in both disorders.

Association between genetic polymorphisms of synaptophysin (SYP) gene and attention deficit hyperactivity disorder in Korean subjects.

Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder, and the prevalence of ADHD among Korean children has attained about 8.5%. Various genetic factors can contribute to the etiology of the disease. Synaptophysin (SYP) regulates neurotransmitter release and synaptic plasticity. According to previous studies, several genetic polymorphisms on SYP were risk factors for ADHD. We investigated the effect of the SYP gene polymorphisms (rs2293945 and rs3817678) on ADHD in Korean children. In this study, we examined the case-control study in 150 ADHD cases and 322 controls. The genotyping of SYP gene polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Significant associations in the genotype and genetic models of SYP rs2293945 polymorphism between girls with ADHD and control girls were found. The girls with ADHD having the C/T genotype were significantly associated with ADHD. In the dominant model of rs3817678, C/T + T/T genotypes were significantly associated with ADHD. The haplotype analyses showed significant associations from haplotypes of rs2293945 T-rs3817678 G and rs2293945 C-rs3817678 A. Our results imply that the SYP rs2293945 C/T polymorphism in female participants may provide a possible effect on the genetic etiology of ADHD.

How does traditional chinese medicine treat attention deficit hyperactivity disorder-A different understanding and treatment strategy

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder, and the incidence in children is increasing year by year. The modern medical field lacks long-acting drugs for the treatment of ADHD and there is an urgent need to investigate new therapeutic drugs or complementary and alternative therapies. Recent studies have found that Traditional Chinese Medicine (TCM) has the advantages of individualization, precise efficacy and minimal side effects in improving attention deficit hyperactivity disorder. This paper reviews the progress of Chinese medicine in the treatment of ADHD in terms of its understanding of the etiology and pathogenesis of ADHD, treatment according to pattern identification and Chinese medicinal preparations.

Seeking connection, autonomy, and emotional feedback: A self-determination theory of self-regulation in attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is one of the most prevalent and highly debated diagnosis for mental disorder in practice today. Two decades of research have substantially contributed to evolving conceptualizations and understanding of the condition. However, this evolution has not been extended to theoretical research. Current cognitive behavioral-based theories aim to identify the etiology of ADHD and experience challenges in accommodating the full spectrum of both neurobiological and behavioral research evidence. Characterizations historically associated with mental illness have generated public stigma, influencing low self-esteem, negative self-concept, and identity development in ADHD individuals. Neurodiversity research and activism recognize a diversity of nonnormative development and highlight the need for alternatives to deficit models of functioning. Recent research in psychology recommends developing approaches beyond symptom control and seeking to develop positive psychological factors and well-being. We propose that the perspective presented by self-determination theory (SDT) on human motivation, self-regulation, and self-determination offers a new understanding of ADHD research evidence and symptomology. According to this theory, humans have a natural tendency toward growth and self-actualization. We propose a framework grounded in SDT that provides an alternative understanding of ADHD neural processing, motivation and engagement, self-regulation, and a potential foundation for treatment approaches with self-determination and positive identity outcomes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Pre-conception folic acid intake and attention deficit and hyperactivity disorder in children

Objectives: Attention Deficit Hyperactivity Disorder (ADHD) is a common disorder in children. It is thought to occur due to the interaction of many genetic and environmental factors during early development. Many studies have been conducted to investigate the etiology of ADHD. Some have investigated neurobiology, and others have investigated malnutrition and trace element deficiency. To investigate the effect of folic acid intake during the pre-conception period in terms of ADHD development. Methods: Five hundred and ninety-eight participants, 246 children with ADHD, and 352 healthy controls were enrolled. A questionnaire was completed, including socio-demographic information and the use of folic acid and other supplements such as a multivitamin, iron, and omega 3 during pregnancy. Data were examined to determine associations with ADHD. Mann-Whitney U tests for continuous variables, Pearson’s chi-square, and Fisher’s exact tests for categorical variables were used to compare groups. Results: The use of folic acid during pre-pregnancy among mothers who had a child with ADHD was 13% and this was 31% in the control group (p < 0.001). There was no statistically significant difference between the groups’ use of folic acid in pregnancy (p = 0.617). Other situations related to ADHD were advanced maternal age (p < 0.001 for both groups), abnormal double screening test results in pregnancy (27% vs. 5%, p < 0.001) and omega 3 use in pregnancy (p < 0.001). Conclusions: The use of folic acid before and during pregnancy is important for neurological development. However, there is little data on use before pregnancy in the literature. This study shows that folic acid taken before pregnancy may prevent ADHD in childhood. The present study recommends folic acid usage in planned pregnancy to prevent ADHD in the child.

Growth rates of human induced pluripotent stem cells and neural stem cells from attention-deficit hyperactivity disorder patients: a preliminary study

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental polygenic disorder that affects more than 5% of children and adolescents around the world. Genetic and environmental factors play important roles in ADHD etiology, which leads to a wide range of clinical outcomes and biological phenotypes across the population. Brain maturation delays of a 4-year lag are commonly found in patients, when compared to controls of the same age. Possible differences in cellular growth rates might reflect the clinical observations in ADHD patients. However, the cellular mechanisms are still not elucidated. To test this hypothesis, we analysed the proliferation of induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) derived from male children and adolescents diagnosed with ADHD and with genetic predisposition to it (assessed using polygenic risk scores), as well as their respective matched controls. In the current pilot study, it was noticeable that NSCs from the ADHD group proliferate less than controls, while no differences were seen at the iPSC developmental stage. Our results from two distinct proliferation methods indicate that the functional and structural delays found in patients might be associated with these in vitro phenotypic differences, but start at a distinct neurodevelopmental stage. These findings are the first ones in the field of disease modelling of ADHD and might be crucial to better understand the pathophysiology of this disorder.

Sex-specific responses to juvenile stress on the dopaminergic system in an animal model of attention-deficit hyperactivity disorder

The etiology of attention-deficit hyperactivity disorder (ADHD) strongly suggests a genetic component as the main cause; however, environmental factors such as early adverse experiences in childhood may play an interactive role with the genetic susceptibility. Spontaneously hypertensive rats (SHRs), a genetic ADHD model, and control Wistar Kyoto rats (WKYs) were subjected to chronic unpredictable mild stress during the juvenile period. The behavioral characteristics were monitored, and dopamine-related factors in the core regions of dopaminergic pathways were measured. Higher ADHD symptom-related behaviors were observed in response to juvenile stress in male SHRs than control WKYs. For the SHRs subjected to juvenile stress, hyperactivity in males, recognition in females, and depressant potential in both sexes were markedly observed. In the expression of 17 dopamine-related genes and proteins, greater changes were detected in male SHRs subjected to juvenile stress, especially in dopamine metabolic factors. Dopamine clearance factors involved in dopamine degradation and transport, especially catechol-O-methyltransferase (COMT) and dopamine transporter (DAT), showed sex-specific differences induced by juvenile stress in dopamine metabolite assays. Moreover, stressed male SHRs treated with methylphenidate showed better improvement in behavior than the females, resulting in different levels of COMT and DAT amelioration. These results suggest that juvenile stress potentially increased the incidence of ADHD in a genetic rat model, which showed sex-specific differences based on the expression of COMT and DAT. Therefore, our results could help develop gender-specific diagnostics and healthcare options for juvenile stress in patients with ADHD.

The distinct role of orbitofrontal and medial prefrontal cortex in encoding impulsive choices in an animal model of attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder affecting up to 5% of children worldwide. The lack of understanding of ADHD etiology prevented the development of effective treatment for the disease. Here, using in vivo electrophysiology recordings, we have recorded and analyzed the neuronal encoding of delay discounting behavior in prefrontal and orbitofrontal cortex of spontaneously hypertensive rat (SHR). We found that in the presence of rewards, neurons in the orbitofrontal cortex (OFC) were activated regardless to the value of the rewards and OFC neurons in SHR exhibited significantly higher rates of neuronal discharging towards the presence of rewards. While in the medial prefrontal cortex (mPFC), neurons of SHR responded similarly in the presence of large rewards compared with control rats whereas they displayed higher firing rates towards smaller rewards. In addition, the reward-predicting neurons in the OFC encodes for value of rewards in control animals and they were strongly activated upon receiving a small immediate reinforcer in the SHR whereas the reward-predicting neurons in the mPFC neurons generally did not respond to the value of the rewards. Our study characterized the neuronal discharging patterns of OFC and mPFC neurons in the SHR and the control animals and provided novel insights for further understanding the neuronal basis of ADHD pathology.