Attention Deficit Hyperactivity Disorder Research Articles

Contribution of childhood lead exposure to psychopathology in the US population over the past 75 years.

More than half of the current US population was exposed to adverse lead levels in childhood as a result of lead's past use in gasoline. The total contribution of childhood lead exposures to US-population mental health and personality has yet to be evaluated. We combined serial, cross-sectional blood-lead level (BLL) data from National Health and Nutrition Examination Surveys (NHANES) with historic leaded-gasoline data to estimate US childhood BLLs from 1940 to 2015 and calculate population mental-health symptom elevations from known lead-psychopathology associations. We utilized five outcomes: (1) General Psychopathology "points",reflecting an individual's liability to overall mental disorder, scaled to match IQ scores (M = 100, SD = 15); (2) Symptoms of Internalizing disorders (anxiety and depression) and Attention-deficit/Hyperactivity Disorder (AD/HD), both z-scored (M = 0, SD = 1); and (3) Differences in the personality traits of Neuroticism and Conscientiousness (M = 0, SD = 1). Assuming that published lead-psychopathology associations are causal and not purely correlational: We estimate that by 2015, the US population had gained 602-million General Psychopathology factor points because of exposure arising from leaded gasoline, reflecting a 0.13-standard-deviation increase in overall liability to mental illness in the population and an estimated 151 million excess mental disorders attributable to lead exposure. Investigation of specific disorder-domain symptoms identified a 0.64-standard-deviation increase in population-level Internalizing symptoms and a 0.42-standard-deviation increase in AD/HD symptoms. Population-level Neuroticism increased by 0.14 standard deviations and Conscientiousness decreased by 0.20 standard deviations. Lead-associated mental health and personality differences were most pronounced for cohorts born from 1966 through 1986 (Generation X). A significant burden of mental illness symptomatology and disadvantageous personality differences can be attributed to US children's exposure to lead over the past 75 years. Lead's potential contribution to psychiatry, medicine, and children's health may be larger than previously assumed.

Childhood risk factors and clinical and service outcomes in adulthood in people with intellectual disabilities.

Adults with intellectual disability experience increased rates of mental health disorders and adverse mental health outcomes. Explore childhood risk factors associated with adverse mental health outcomes during adulthood as defined by high cost of care, use of psychotropic medication without a severe mental illness and psychiatric hospital admissions. Data on 137 adults with intellectual disability were collected through an intellectual disability community service in an inner London borough. Childhood modifiable and non-modifiable risk factors were extracted from records to map onto variables identified as potential risk factors. Logistic and linear regression models were employed to analyse their associations with adverse outcomes. We showed that the co-occurrence of intellectual disability with autism spectrum disorder and/or attention-deficit hyperactivity disorder (ADHD) were associated with psychotropic medication use and high-cost care packages. However, when challenging behaviour during childhood was added, ADHD and autism spectrum disorder were no longer significant and challenging behaviour better explained medication prescribing and higher cost care. In addition, the severity of intellectual disability was associated with higher cost care packages. Ethnicity (Black and mixed) also predicted higher cost of care. Challenging behaviour during childhood emerged as a critical variable affecting outcomes in young adulthood and mediated the association between adult adverse mental health outcomes and co-occurring neurodevelopmental conditions, that is, ADHD and autism. These findings emphasise the need for effective early intervention strategies to address challenging behaviour during childhood. Such interventions for challenging behaviour will need to take into consideration autism and ADHD.

Stimulation of locus coeruleus inputs to the prelimbic cortex in mice induces cell type-specific expression of the Apoe gene.

The medial frontal cortex (mFC) and locus coeruleus (LC) are two brain areas that have been implicated in a range of cognitive phenomena, such as attention, memory, and decision making. Regulators of these brain regions at the molecular level are not well understood, but might help to elucidate underlying mechanisms of disorders that present with deficits in these cognitive domains. To probe this, we used chemogenetic stimulation of neurons in the LC with axonal projections to the prelimbic subregion (PrL) of the mFC, and subsequent bulk RNA-sequencing from the mouse PrL. We found that stimulation of this circuit caused an increase in transcription of a host of genes, including the Apoe gene. To investigate cell type-specific expression of Apoe in the PrL, we used a dual-virus approach to express either the excitatory DREADD receptor hM3Dq in LC neurons with projections to the PrL, or a control virus, and found that increases in Apoe expression in the PrL following depolarization of LC inputs is enriched in GABAergic neurons in a sex-dependent manner. The results of these experiments yield insights into how Apoe expression affects function in a cortical microcircuit that is important for attention, memory, and decision making, and point to interneuron-specific expression of Apoe as a potential biomarker for circuit function in disorders such as attention-deficit hyperactivity disorder (ADHD), schizophrenia, and Alzheimer's disease (AD).Significance Statement Identifying patterns of gene expression in specific brain circuits is an important first step toward developing treatments for cognitive and behavioral symptoms that rely on those circuits. In this paper, we describe a transcriptome-scale motif in one such circuit - neurons in the LC that project to the PrL. This circuit has been implicated in attention, memory, and decision making, and deficits in these cognitive domains are common across many neuropsychiatric disorders. We further explored one of the top differentially expressed genes, Apoe, to identify how it is expressed in distinct cell types following stimulation of this circuit, paving the way for spatially- and genetically-specific targeting of this gene in disorders that feature dysfunction in this circuit.

The changing doctor-patient relationship in psychiatry: observations on recent trends in autism, attention-deficit hyperactivity disorder, gender dysphoria and mental distress.

This editorial highlights increasing prevalence and treatment rates of apparently disparate disorders. We ask whether cross-disorder factors including greater mental health literacy, social media and a shift to psychiatric explanations for distress contribute to these trends. We highlight a consequence: the changing doctor-patient relationship and its impacts.

Differences in impulsivity between adolescents with ADHD and those with comorbidity of ADHD and IGD

BackgroundNumerous studies have demonstrated that patients with attention deficit hyperactivity disorder (ADHD) have high impulsivity. However, few studies have been published on the differences in impulsivity between patients presenting with comorbidity of ADHD and Internet gaming disorder (IGD) and ADHD alone. AimThe present study designed an experiment to address this significant question, to explore the differences in impulsivity between individuals with ADHD and those with comorbid ADHD and IGD, specifically focusing on various dimensions of impulsivity. MethodsA total of 81 adolescents with ADHD alone and 59 patients with comorbidity of ADHD and IGD were included in this study, and all of them were assessed using the Stop-signal Task (SST), Delay Discount Task (DDT), and Balloon Analogue Risk Task (BART). ResultsPatients with comorbid ADHD and IGD had higher impulsivity than those with only ADHD, and it was expressed in different dimensions. Additionally, response inhibition, delayed discount rate, risky decision-making behavior, inattention, and hyperactivity were identified as risk factors for comorbid ADHD and IGD. ConclusionThese findings can help distinguish whether ADHD is comorbid with IGD in clinical settings. They will also be helpful in the implementation of more precise treatments.

Exploring the Neurodiversity of Lithuanian College Students and Its link to Learning Difficulties and Supporting Measures

<p dir="ltr"><span>Enhancing the inclusion of neurodiverse students in higher education institutions represents a significant and evolving challenge for educators. Recognizing learning difficulties and equipping teachers with the knowledge and skills to effectively work with and communicate with neuro-diverse students are crucial steps toward achieving social inclusion. Aim – to explore the neurodiversity of Lithuanian college students and its link to learning difficulties and supporting measures. Two developmental adult disorders were presented to illustrate the expression of neurodiversity including attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). A cross-sectional survey included 512 students from Kauno Kolegija Higher Education Institution. The survey assessed 39 attributes related to students’ learning difficulties and supporting measures. The nine scales, consisting of 39 items, demonstrated good internal consistency, with a Cronbach's alpha coefficient of 0.76. Due to the unequal and smaller sample sizes of attention deficit hyperactivity and autism spectrum disorders having students, non-parametric statistics (Kruskal-Wallis) were used. Spearman's correlation coefficient (R²) was used for correlation analysis. Results. Nearly a quarter of the students associate their neurodiversity with ADHD, with 22.3 % suspecting they have the condition and 2 % noted that this is confirmed. 4.7% of students consider themselves to be on the autism spectrum disorder (ASD), with 0.6% having a confirmed diagnosis. Statistically significant differences were identified in the relationship between ADHD and attention difficulties at home, college, sensory sensitivity and specific learning difficulties (p ≤ 0.05). ADHD and ASS suspected of having students tend to have lower grade point average (GPAs). Students who suspect or confirm having ADHD express a higher preference for organizational tools compared to those without ADHD, with a significant difference (p ≤ 0.05). Preferences for explanations and illustrations are higher among those suspecting ADHD (p ≤ 0.05). The analysis of expectations from lecturers and organization concerning ASD shows minimal variation among groups (p≥0.05). Conclusions. Neurodiversity among students is a relevant phenomenon that is associated with learning difficulties that interfere with achieving good learning outcomes. However, the role of the teacher and organization is exclusively relevant for the ADHD student group. For ASD students and neurotypical students, universal approaches are appropriate.</span></p><div><span><br /></span></div>

The interaction of ADHD traits and trait anxiety on inhibitory control.

Attention-deficit/hyperactivity disorder (ADHD) and anxiety frequently occur together; however, the cognitive outcomes of comorbid anxiety and ADHD are not straightforward. A potential explanation for conflicting results in the literature may be that different core ADHD symptoms show different interactions with anxiety depending on the task-processing demands. To address this question, we investigated whether different ADHD traits are related to different inhibitory outcomes, contingent upon the level of trait anxiety. The sample consists of 60 non-clinical university students ( age = 20.5, 53% male). Conners' Adult ADHD Rating Scale and State Trait Anxiety Inventory were used to measure ADHD traits and anxiety, respectively. The participants completed a visual Go/NoGo task with and without distractor conditions while continuous EEG was recorded. Inhibitory control was operationalized as the frontocentral N2 maximum peak amplitude elicited in response inhibition (NoGo/No Distractor), cognitive inhibition (Go/Distractor), dual inhibition (NoGo/Distractor), and control (Go/No Distractor) conditions. We analyzed the moderating effect of trait anxiety on the prediction of inhibitory control by ADHD scores for each Go/NoGo condition with the varying inhibition demands. Results showed that trait anxiety moderated the effects of total ADHD and hyperactivity-impulsivity scores, but only in the response inhibition condition (NoGo/No Distractor). These findings suggest that depending on the inhibitory demands of the task, unique cognitive outcomes may occur when different ADHD traits coexist with anxiety.

Effectiveness of Community Based Group Therapy for Chronic Low Back Pain in Older Women in Bangladesh: A Randomised Controlled Trial

Objective: Group therapy involves multiple people being treated by one or more health professionals. It can cure physical and psychological conditions; such as attention-deficit/hyperactivity disorder (ADHD), emotional trauma, anxiety, despair, and post-traumatic stress disorder (PTSD). This study investigates whether community-based group therapy helps older women with chronic low back pain. Material and Methods: The study was a randomized controlled trial, with 40 patients divided into control and intervention groups. The control group received conventional treatment in an institute-based rehabilitation (IBR) facility, while the intervention group received the same exercise program in a community-based rehabilitation (CBR) setting. Both groups received supervised 30-minute sessions five days a week for eight weeks. The numeric pain rating scale (NPRS) was used to measure the severity of pain and the Roland-Morris Disability Questionnaire (RMDQ) measured physical disability due to low back pain in older women. Results: The average age of the participants was 56 (53 to 58.50). The BMI findings were 7.5% (n=3) of participants being underweight and 45% (n=18) of participants being overweight. In terms of pain and physical disability due to low back pain, the CBR group showed significant improvement (p-value<0.05) in cases of both inter- and intra-group comparison using the IBR treatment facility.Conclusion: Group therapy treatment reduces low back pain and prevents the severity of back pain in older women, thereby improving their quality of life. This study shows that group-based physical therapy helps relieve chronic low back pain. Strengthening, stretching, and flexion exercises in groups improve quality of life and minimise discomfort.

Loneliness in Adolescents with Attention Deficit Hyperactivity Disorder (ADHD)

Introduction: Attention deficit hyperactivity disorder is a disorder of children’s growth and development with neurodevelopmental disorders characterized by symptoms of inattention, hyperactivity, and impulsivity. ADHD in children can persist into adolescence in about 2.6% of the general population. About more than half of people with ADHD experience loneliness, a condition that is often not reported by patients but is evident in the negative emotions and behaviors they display. To explain the risk factors and impact of loneliness in adolescents with ADHD. Methods: Literature review. Results: The use of gadgets in today’s digital era increases the risk of increasing internet usage so that more contact is made online, which causes obstacles for adolescents in fostering social relationships and an increased risk of loneliness. Adolescents with ADHD have a negative assessment of themselves; they feel useless, lack confidence, and lack intelligence when compared to their peers. Economically, low-income family conditions and inappropriate parenting increase the risk of loneliness in ADHD adolescents. Adequate treatment will cause it to develop into other mental disorders such as anxiety, depression, defiant attitude disorder, and adolescent behavior disorder. Conclusions: Adolescents with ADHD are prone to experiencing loneliness. Parenting problems, family socioeconomics, past trauma, bullying, and several internal factors such as low self-confidence, insecurity, low adaptability, and lack of emotional control can cause loneliness. Keywords: ADHD, Adolescents, Loneliness, Mental Health, Psychological Well-Being

A Risk Factor for Attention Deficit Hyperactivity Disorder Induces Marked Long-Term Anatomical Changes at GABAergic-Dopaminergic Synapses in the Rat Ventral Tegmental Area

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. However, the core biology of the disorder that leads to the hypofunctioning of the cerebral dopaminergic network requires further elucidation. We investigated midbrain synaptic changes in male rats exposed to repeated hypoxia during the equivalent of extreme prematurity, which is a new animal model of the hyperactive/impulsive presentation of ADHD. We used a novel combination of a lentiviral vector, peroxidase-immunonanogold double-labelling, three-dimensional serial section transmission electron microscopy and stereological techniques to investigate the synapses formed between GABAergic axons of the rostromedial tegmental nucleus (RMTg) and dopaminergic neurons of the posterior ventral tegmental area (pVTA). This is a key site that sends extensive dopaminergic projections to the forebrain. We also compared the results to our previous study on a schizophrenia risk factor that produces cerebral hyperdopaminergia. In total, 117 reconstructed synapses were compared. Repeated hypoxic rats had a significantly thicker (22%) and longer (18%) postsynaptic density at RMTg GABAergic-pVTA dopaminergic synapses compared to their controls. These results were opposite to those previously observed in rats exposed to a schizophrenia risk factor. These findings for repeated hypoxic rats suggest that the enhanced inhibition of pVTA dopaminergic neurons may contribute to hypodopaminergia in ADHD motor hyperactivity. Synaptic triads, a key component of pVTA circuitry, were not detected in repeated hypoxic rats, indicating a marked deficit. The current knowledge may guide development in males of novel, site-specific ADHD drugs, which is necessary due to the rising prevalence of ADHD, the chronic nature of ADHD symptoms and the limitations of the currently available medications.

Drug Holidays May Attenuate Beneficial Effects of Treatment on Emotion Regulation and Recognition Among Children with ADHD: A Single-Center, Prospective Study.

In this study, we aimed to evaluate the effects of drug holidays during summer vacations on children with attention deficit/hyperactivity disorder (ADHD) treated with methylphenidate in terms of ADHD symptoms and emotion regulation (ER). This single-center, naturalistic, prospective cohort study included pre-, post-, and post-drug holiday evaluations. All patients diagnosed with ADHD and included in our study were administered the Clinical Global Impression Scale, Affective Reactivity Index-parent and child, reading the mind in the eyes test (RMET), Faces test and Cognitive Emotion Regulation Questionnaire for Children 3 times. Fifty-six patients met the inclusion criteria and ten were lost to follow-up. Thirty-nine participants had complete evaluations at all time points. Both parent and self-report ratings of child irritability were significantly reduced after methylphenidate (MPH) treatment (P=.003 and .002, respectively), although they returned to baseline after drug holidays (P=.618 and .974, respectively). The use of self-blame as a cognitive emotion regulation strategy increased significantly after treatment and remained significantly elevated even after drug holidays (P=.024 and .022, respectively). Children used planning as a cognitive strategy significantly more frequently during MPH treatment (P=.034), although this elevation was temporary and returned to baseline levels after the drug holidays (P=.890). Reading the mind in the eyes test performance was significantly improved after MPH treatment and did not change after drug holidays (P=.009 and .006, respectively), while there was a tendency for facial emotion recognition abilities to improve at the last visit (P=.051). Our results suggest that MPH treatment improves child- and parent-reported irritability, clinician-rated disorder severity, RMET performance, and the use of planning as a cognitive ER strategy, although only improvement in RMET performance continued after drug holidays. Our results may support the importance of continuing treatment over the holidays for most children with ADHD unless necessitated by adverse events, growth problems, or development of tolerance.

Phenome-wide diagnostic comparison among suicide deaths and living individuals with chronic pain diagnoses

BackgroundChronic pain, regardless of its type, is a significant risk factor for suicide. However, not all individuals with chronic pain also experience suicidal thoughts and behaviors. Better characterization of clinical risk profiles and comorbidities across the medical spectrum among people with chronic pain who die by suicide is urgently needed to aid treatment and prevention strategies.MethodsThis case–control study leverages population-based data from the Utah Suicide Mortality Risk Study. Specifically, we identify clinical phenotypes from diagnostic data that differentiate between individuals that died by suicide with chronic pain diagnoses (N = 1,410) and living control individuals who also had chronic pain diagnoses (N = 4,664). Medical diagnostic codes were aggregated via phecodes to perform a phenotype-based phenome-wide association study. Using multivariable logistic regression analysis adjusting for covariates and multiple testing, differences in 1,727 common clinical phenotypes (phecodes) were assessed between suicide deaths and controls with chronic pain diagnoses. Models were also stratified by sex.ResultsChronic pain diagnoses were nearly three times more prevalent in individuals who died by suicide compared with those who did not. Sixty-five phecodes were significantly overrepresented among suicide deaths with chronic pain diagnoses compared with controls with chronic pain diagnoses. Utah suicide deaths with chronic pain had significantly more psychiatric diagnoses (mood disorders, anxiety disorders, attention deficit hyperactivity disorder, posttraumatic stress disorder, personality disorders, schizophrenia/psychosis, substance use related traits and prior overdoses, and diagnoses related to previous suicidal thoughts and behaviors) in addition to insomnia and specific pain related diagnoses compared to Utah controls with chronic pain (odds ratios ranged from 1.40–7.10). Twenty-five phecodes were overrepresented in controls with chronic pain compared to suicides. These were related to preventative care, cancer, obesity and other conditions (odds ratios ranged from 0.16–0.73). Sex-specific analyses largely replicated the combined analyses, yet the strength of the association was stronger for women with phecodes related to prior self-harm.ConclusionsResults identified multiple clinical comorbidities with chronic pain that differentiate suicide deaths from living control individuals with a history of diagnosed chronic pain. Our findings may help discern individuals with chronic pain who may be at greater risk for suicide death.

Default at fault? Exploring neural correlates of default mode network in children with ADHD, their unaffected siblings versus neurotypical controls: A quantitative EEG study

BackgroundSustained activation of default mode network has been implicated for momentary lapses of attention and higher errors during performance of cognitive tasks in attention deficit hyperactive disorder (ADHD) children. Despite emerging evidence indicating the genetic basis of ADHD, there is paucity of literature investigating the alteration of DMN in children with ADHD and their unaffected siblings. AimTo study the cortical sources of DMN in children with ADHD compared to their siblings and neurotypical controls. MethodsEighty-six participants (35 ADHD (12.4(±2.7) years), 16 unaffected siblings (11.8(±4.3) years) and 35 matched neurotypical controls (12.6 (±3.6) years) participated in the study. 128 channel EEG data was acquired during rest and Stroop cognitive task and analyzed for cortical source estimation using LORETA software. ResultsHigher activation of DMN and DMN associated areas were observed during encoding of the color-word stimuli in children with ADHD. Sustained activation of core DMN areas namely medial frontal gyrus, posterior cingulate gyrus, parahippocampal gyrus and inferior parietal lobule was observed across all groups. Among the three groups, distinct cortical source activation differences were identified solely in the DMN and its associated areas among children with ADHD during the task encoding phase compared to baseline. In contrast, both siblings and neurotypical controls displayed activation in fronto-parieto-temporal areas subserving executive function were also observed. ConclusionSustained activity of DMN areas with minimal activity in executive network in ADHD children and unaffected siblings during encoding of stimulus implies potential endophenotypic marker in children with ADHD compared to neurotypical controls.

The use of augmented reality in assessing and training children with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a serious issue that must be addressed in the modern world. Treatment for ADHD is challenging because it is costly, has adverse effects, might not be successful, and is not considered an emergency. The reason that ADHD is hard to manage is because it causes people-especially children-to make impulsive decisions that hinder their ability to succeed in school, the workplace, and other areas of life. As an alternative approach, neurofeedback therapy or play therapy, which relies on real-time feedback of an individual's brainwave activity typically collected through electroencephalogram (EEG), has demonstrated promising outcomes in the treatment of mental disorders and enhancing cognitive capabilities. On the other hand, prolonged exposure to repetitive feedback might result in lower engagement since people may become disinterested in the process and find it difficult to continue participating. An extensive assessment on the use of augmented reality (AR) in the context of pediatric ADHD has been carried out, with an emphasis on the benefits of creating games specifically for kids with ADHD. By using AR technology in a group of children, the goal of this study was to investigate the basic characteristics of AR systems that aid in the identification and treatment of ADHD in children.

The Relationship Between Prenatal, Perinatal, and Postnatal Factors and ADHD: The Role of Nutrition, Diet, and Stress.

Attention-Deficit Hyperactive Disorder (ADHD) is a neurobehavioral syndrome affecting children aged 6-17 with symptoms manifesting before age 12. ADHD presents heterogeneously and is associated with various psychiatric disorders. The cause remains elusive, but genetic and environmental factors, brain region maturation delays, and neurotransmitter dysregulation are implicated. Effective treatment requires a multi-disciplinary approach, primarily involving pharmacological and behavioral intervention. Stimulants like methylphenidate and amphetamines are first-line medications, but non-stimulants may be considered for some patients. However, stimulants face challenges related to misuse, dependence, and long-term tolerability issues. The etiology of ADHD involved genetic predisposition, environmental influences, and prenatal, perinatal, and postnatal factors. Prenatal causes encompass maternal diet, alcohol consumption, viral infections, and stress. Postnatal factors include head trauma, meningitis, toxin, nutritional deficiencies, as well as iodine deficiency and hypothyroidism. The gut microbiome's role in ADHD is emerging, influencing neurodevelopment through microbiota-gut-brain axis. Understanding these diverse etiological factors is essential for comprehensive ADHD management.

Resting-State Functional Connectivity Predicts Attention Problems in Children: Evidence from the ABCD Study.

Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, and numerous functional and structural differences have been identified in the brains of individuals with ADHD compared to controls. This study uses data from the baseline sample of the large, epidemiologically informed Adolescent Brain Cognitive Development Study of children aged 9-10 years old (N = 7979). Cross-validated Poisson elastic net regression models were used to predict a dimensional measure of ADHD symptomatology from within- and between-network resting-state correlations and several known risk factors, such as biological sex, socioeconomic status, and parental history of problematic alcohol and drug use. We found parental history of drug use and biological sex to be the most important predictors of attention problems. The connection between the default mode network and the dorsal attention network was the only brain network identified as important for predicting attention problems. Specifically, we found that reduced magnitudes of the anticorrelation between the default mode and dorsal attention networks relate to increased attention problems in children. Our findings complement and extend recent studies that have connected individual differences in structural and task-based fMRI to ADHD symptomatology and individual differences in resting-state fMRI to ADHD diagnoses.

Advances in the Pathophysiology and Drug Discovery of Novel Therapeutics for Attention-Deficit/hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity and impulsivity. Psychostimulants such as methylphenidate are first-line treatments, but carry risks of severe side effects and addiction. Therefore, further research and the discovery of non-psychostimulant medications with novel mechanisms are urgently needed. We previously reported that juvenile stroke-prone spontaneously hypertensive rats (SHRSP/Ezo) are a suitable animal model of ADHD, and we identified N-methyl-D-aspartate (NMDA) receptor dysfunction in the prefrontal cortex of SHRSP/Ezo. D-Serine, a co-agonist for the glycine binding site of NMDA receptors, is synthesized from L-serine by serine racemase (SR) and degraded by D-amino acid oxidase (DAAO). Although D-serine dysregulation is implicated in psychiatric disorders, its pathophysiological role in ADHD is unclear. We measured D-serine in the medial prefrontal cortex (mPFC) of SHRSP/Ezo and addressed SR and DAAO expression. Additionally, we assessed cognitive function following DAAO inhibitor microinjection into the mPFC. SHRSP/Ezo showed a reduced D-serine/total serine (DL) ratio in the mPFC compared with the genetic control, Wistar Kyoto rat/Ezo (WKY/Ezo). DAAO expression in the mPFC was higher in SHRSP/Ezo rats compared with WKY/Ezo, however there was no difference in SR expression. The microinjection of a DAAO inhibitor into the mPFC of SHRSP/Ezo rats increased the DL ratio and ameliorated ADHD-like behaviors in the Y-maze test. These results suggest an association between abnormal D-serine metabolism and ADHD-like behaviors based on NMDA receptor dysfunction in the mPFC. Our findings provide insight into ADHD pathogenesis and should advance the development of new therapeutic approaches for the disorder.

A multicenter, single-group, open feasibility study of a new individual cognitive behavioral therapy program for adult Japanese patients with attention-deficit/hyperactivity disorder: Study protocol.

Attention-deficit/hyperactivity disorder (ADHD) symptoms, including executive function, emotional regulation, and motivation, can persist into adulthood and are often associated with mental illnesses. Cognitive behavioral therapy (CBT) may help ADHD adults in Japan, but the lack of studies and the variability in group CBT approaches make its effects unclear. Japan lacks unified CBT programs and adult ADHD guidelines, making it difficult to implement international individual CBT recommendations due to cultural differences. This study will assess the feasibility of a novel CBT program for Japanese adult ADHD patients. This feasibility study will be open, nonrandomized, single-arm, multicenter study. Twelve ADHD patients aged 20-65 years who are currently receiving treatment will be included based on Conners' Adult ADHD Rating Scale (CAARS) clinical severity threshold. An intervention phase of 12-16 weeks and a 12-week follow-up will total 24-28 weeks for all participants. The intervention will use a new CBT program tailored to individual assessments. The primary objective is to determine feasibility using dropout rates, adverse events, and CAARS score changes between Weeks 1 and 16. The secondary outcomes will assess long-term effects of treatment beyond the intervention period and provide descriptive statistics on sex, depression, quality of life, and autistic scores in relation to the intervention outcomes. The full analysis set and per protocol set will be used for statistical analysis. This study is essential for the development of CBT interventions in accordance with Japan's healthcare system that are tailored to the unique needs of its population.

High-dose Vitamin-B6 reduces sensory over-responsivity.

Sensory reactivity differences are experienced by between 5% and 15% of the population, often taking the form of sensory over-responsivity (SOR), in which sensory stimuli are experienced as unusually intense and everyday function is affected. A potential mechanism underlying over-responsivity is an imbalance between neural excitation and inhibition in which inhibitory influences are relatively weakened. Therefore, interventions that boost neural inhibition or reduce neural excitation may reduce SOR; Vitamin-B6 is the coenzyme for the conversion of excitatory glutamate to inhibitory gamma-aminobutyric acid (GABA), and in animal models, it both increases the concentration of GABA and reduces glutamate. To discover whether taking a high dose of Vitamin-B6 reduces SOR and other aspects of sensory reactivity. We recruited 300 adults (249 females) from the general population who completed the Sensory Processing 3-Dimensions Scale (SP-3D) first at baseline, and again following randomisation to either 1 month's supplementation with 100 mg Vitamin-B6, or one of two control conditions (1000 µg Vitamin-B12 or placebo). To focus on individuals who experience SOR, we analysed the effects of supplementation only on individuals with high baseline SOR scores (above the 87th percentile). In individuals with SOR at baseline, Vitamin-B6 selectively reduced SOR compared to both placebo and Vitamin-B12. We also found that Vitamin-B6 selectively reduced postural disorder in individuals with high scores on this subscale at baseline, but there were no effects on the four remaining SP-3D subscales. Clinical trials and mechanistic studies should now be conducted in autism, attention deficit hyperactivity disorder and other groups with SOR.

Impaired brainstem auditory evoked potentials after in utero exposure to high dose paracetamol exposure

Paracetamol is an analgesic and antipyretic medication regarded as the safest over-the-counter pain and fever relief option during pregnancy. Paracetamol and its metabolites are known to reach the developing fetus through direct placental transfer and can cross the blood brain barrier. Several recent, large-scale epidemiologic studies suggest that in utero paracetamol exposure can increase the risk of neurodevelopmental conditions, including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and developmental delay (DD). Since auditory processing deficits are a common feature of ASD, we hypothesized that animals exposed to paracetamol in utero will have impaired auditory brainstem function. We investigated this hypothesis by recording and analyzing click-evoked auditory brainstem responses (ABR) at postnatal day 21 and 29 in Sprague-Dawley rats. In utero exposure to high dose paracetamol exposure had no impact on body or brain weight. However, high dose paracetamol exposure did significantly delay ear opening and resulted in elevated ABR thresholds, and longer wave and interwave latencies. These changes in wave latency extended to the highest click intensity tested but were most severe near threshold. This data suggests that development and function of the auditory brainstem may be impacted by high dose paracetamol exposure and that simple, non-invasive tests of auditory function have utility as an early screening tool for neurodevelopmental disorders.