Materiały źródłowe

• #1 Adult attention-deficit/hyperactivity disorder (ADHD) – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/adult-adhd/symptoms-causes/syc-20350878

  Adult attention-deficit/hyperactivity disorder (ADHD) is a mental health disorder that includes a combination of persistent problems, such as difficulty paying attention, hyperactivity and impulsive behavior. […] Though it’s called adult ADHD, symptoms start in early childhood and continue into adulthood. […] Diagnosis of ADHD in adults can be difficult because certain ADHD symptoms are similar to those caused by other conditions, such as anxiety or mood disorders. […] While the exact cause of ADHD is not clear, research efforts continue. Factors that may be involved in the development of ADHD include: Genetics. ADHD can run in families, and studies indicate that genes may play a role. […] ADHD can make life difficult for you. ADHD has been linked to: Poor school or work performance, Unemployment, Financial problems, Trouble with the law, Alcohol or other substance misuse, Frequent car accidents or other accidents, Unstable relationships, Poor physical and mental health, Poor self-image, Suicide attempts. […] Although ADHD doesn’t cause other psychological or developmental problems, other disorders often occur along with ADHD and make treatment more challenging.

• #2 Attention deficit hyperactivity disorder in adults: Epidemiology, clinical features, assessment, and diagnosis – UpToDate

  https://www.uptodate.com/contents/attention-deficit-hyperactivity-disorder-in-adults-epidemiology-clinical-features-assessment-and-diagnosis/print

  Attention deficit hyperactivity disorder (ADHD), one of the most common neuropsychiatric disorders of childhood and adolescence, often persists into adulthood. Studies have found that a majority of people diagnosed with ADHD in childhood continue to meet criteria for the disorder as adults. More recent studies have found that a substantial proportion of those with adult ADHD did not have the condition in childhood. ADHD in adulthood is associated with significant impairment in occupational, academic, and social functioning. […] ADHD in adults is characterized by symptoms of inattention, impulsivity, and restlessness, resulting in functional impairment. Impairment in executive function is common. Emotional dysregulation is often seen in these patients. […] This topic discusses the epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis of ADHD in adults.

• #3 Adult Attention-deficit/Hyperactivity Disorder (aADHD)

  https://www.psychiatrictimes.com/view/adult-attention-deficit-hyperactivity-disorder

  Although normally associated with children, attention-deficit/hyperactivity disorder can also persist in adulthood, presenting challenges to both patients and clinicians. […] There is growing evidence that symptoms of ADHD can persist into adulthood and can cause significant impairments in social, academic, and occupational functioning. […] Additionally, there is new evidence to suggest that adult ADHD (aADHD) is not just a continuation of childhood onset ADHD (cADHD), as many individuals do not have a history of this disorder in childhood. […] It is postulated that there may be 2 distinct subtypes of aADHD: the first with childhood onset and the other with onset exclusively in adulthood. […] Adult ADHD results in significant impairments in the individuals personal, social, and professional life.

• #4 Attention deficit hyperactivity disorder in adults: Epidemiology, clinical features, assessment, and diagnosis – UpToDate

  https://www.uptodate.com/contents/attention-deficit-hyperactivity-disorder-in-adults-epidemiology-clinical-features-assessment-and-diagnosis/print

  Attention deficit hyperactivity disorder (ADHD), one of the most common neuropsychiatric disorders of childhood and adolescence, often persists into adulthood. Studies have found that a majority of people diagnosed with ADHD in childhood continue to meet criteria for the disorder as adults. More recent studies have found that a substantial proportion of those with adult ADHD did not have the condition in childhood. ADHD in adulthood is associated with significant impairment in occupational, academic, and social functioning. […] ADHD in adults is characterized by symptoms of inattention, impulsivity, and restlessness, resulting in functional impairment. Impairment in executive function is common. Emotional dysregulation is often seen in these patients. […] This topic discusses the epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis of ADHD in adults.

• #5

  https://link.springer.com/article/10.1007/s44192-022-00030-1

  ADHD has a multifactorial etiology, in which genetic and environmental factors are involved in its development. […] The understanding of the genetic architecture of ADHD has significantly evolved with the technological advances in the molecular genetics field, especially with the availability of large-scale genome-wide association studies (GWAS). […] The physiological changes induced by the binding of dopamine and norepinephrine to their respective receptors involve the modulation of several cognitive and executive processes usually impaired in ADHD, corroborating the monoaminergic hypothesis for ADHD pathophysiology. […] Pathophysiological insights can also be inferred from neuroimaging studies, which has reported differences in structural and functional brain architecture between patients with ADHD and neurotypical individuals, especially in children.

• #6 Attention deficit hyperactivity disorder – Wikipedia

  https://en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder

  ADHD arises from maldevelopment in brain regions such as the prefrontal cortex, basal ganglia and anterior cingulate cortex, which regulate the executive functions necessary for human self-regulation. […] ADHD symptoms arise from executive dysfunction. […] The precise causes of ADHD are unknown in most individual cases. […] Meta-analyses have shown that the disorder is primarily genetic with a heritability rate of 70-80%, where risk factors are highly accumulative. […] ADHD presents with reduced size, functional connectivity and activation as well as low noradrenergic and dopaminergic functioning in brain regions and networks crucial for executive functioning and self-regulation. […] Current models of ADHD suggest that it is associated with functional impairments in some of the brain’s neurotransmitter systems, particularly those involving dopamine and norepinephrine.

• #7 ADHD – Pathophysiology – Management – TeachMePaediatrics

  https://teachmepaediatrics.com/community/neurodevelopmental-disorders/adhd/

  The pathophysiology of ADHD is not well understood. Evidence has been found of structural and functional changes in the brains of children with ADHD, as well as changes in the levels of certain neurotransmitters, such as dopamine. […] It also has a genetic component, often running through families; twin studies have shown the heritability to be 88%. There is also some evidence of interplay between genetic and environmental factors. […] For many children with ADHD, symptoms improve over time as they learn strategies to deal with the problems they have. Around two-thirds will show no evidence of emotional or behavioural problems in adulthood. […] However, ADHD is associated with many adverse outcomes compared with peers without ADHD, such as increased substance abuse, more criminal convictions and lower educational attainment and unemployment.

• #8 Attention Deficit Hyperactivity Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441838/

  ADHD is associated with cognitive and functional deficits that relate to diffuse abnormalities in the brain. The anterior cingulate gyrus and dorsolateral prefrontal cortex (DLFPC) are found to be small in individuals who are suffering from ADHD. It is thought that these changes account for the deficits in goal-directed behavior. Moreover, activity in the frontostriatal region is also reduced in these individuals as measured by fMRI. It is important to understand these pathophysiological mechanisms so that pharmacotherapy is directed toward them. […] The etiology of ADHD is related to a variety of factors that include both a genetic and an environmental component. It is one of the most heritable conditions in terms of psychiatric disorders. There is a much greater concordance in monozygotic twins than dizygotic. Siblings have twice the risk of having ADHD than the general population. Similarly, viral infections, smoking during pregnancy, nutritional deficiency, and alcohol exposure in the fetus have also been explored as possible causes of the disorder. There are no consistent findings on brain imaging of patients with ADHD. The number of dopaminergic receptors has also been implicated in the development of the disorder, whereby research has shown that the receptors are decreased in the frontal lobes in individuals with ADHD. There is also evidence for the role of noradrenergic receptor involvement in ADHD.

• #9

  https://link.springer.com/article/10.1007/s44192-022-00030-1

  ADHD has a multifactorial etiology, in which genetic and environmental factors are involved in its development. […] The understanding of the genetic architecture of ADHD has significantly evolved with the technological advances in the molecular genetics field, especially with the availability of large-scale genome-wide association studies (GWAS). […] The physiological changes induced by the binding of dopamine and norepinephrine to their respective receptors involve the modulation of several cognitive and executive processes usually impaired in ADHD, corroborating the monoaminergic hypothesis for ADHD pathophysiology. […] Pathophysiological insights can also be inferred from neuroimaging studies, which has reported differences in structural and functional brain architecture between patients with ADHD and neurotypical individuals, especially in children.

• #10 Attention Deficit Hyperactivity Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441838/

  ADHD is associated with cognitive and functional deficits that relate to diffuse abnormalities in the brain. The anterior cingulate gyrus and dorsolateral prefrontal cortex (DLFPC) are found to be small in individuals who are suffering from ADHD. It is thought that these changes account for the deficits in goal-directed behavior. Moreover, activity in the frontostriatal region is also reduced in these individuals as measured by fMRI. It is important to understand these pathophysiological mechanisms so that pharmacotherapy is directed toward them. […] The etiology of ADHD is related to a variety of factors that include both a genetic and an environmental component. It is one of the most heritable conditions in terms of psychiatric disorders. There is a much greater concordance in monozygotic twins than dizygotic. Siblings have twice the risk of having ADHD than the general population. Similarly, viral infections, smoking during pregnancy, nutritional deficiency, and alcohol exposure in the fetus have also been explored as possible causes of the disorder. There are no consistent findings on brain imaging of patients with ADHD. The number of dopaminergic receptors has also been implicated in the development of the disorder, whereby research has shown that the receptors are decreased in the frontal lobes in individuals with ADHD. There is also evidence for the role of noradrenergic receptor involvement in ADHD.

• #11

  https://journals.lww.com/annals-of-medicine-and-surgery/fulltext/2023/05000/adult_attention_deficit_hyperactivity_disorder__a.74.aspx

  Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder, with only 23% prevalence into adulthood. The epidemiology and proposed causes of ADHD are multifactorial, including genetic, prenatal and environmental influences. The diagnosis of ADHD is often complicated by masking coping mechanisms, an overlap of symptoms with other, more commonly diagnosed disorders. Traditionally, it has been treated with stimulant medications. Non-stimulant options often target norepinephrine and dopamine regulation and are preferred in cases of comorbid substance use disorder, anxiety and other complicating factors, due to an improved side-effect profile and patient preference. They include atomoxetine and viloxazine. The latter, Viloxazine, in the form of extended-release capsules, is the first novel, non-stimulant option approved for adults with ADHD, in the past two decades. Its therapeutic effects are predominantly produced by its action as a norepinephrine reuptake inhibitor and may also modulate the serotonergic system. Viloxazine is relatively safe and effective in treating other disorders such as depression, anxiety, epilepsy and substance use disorder. A thorough review of the history, mechanism of action, pharmacokinetics and drug-drug interactions has been presented here, with special attention on treatment in adults with comorbid conditions. Several factors contribute to ADHD symptoms, including genetics, neurodevelopmental disorders, abnormal neuronal maturation, brain injury, environmental exposure and consanguinity. A recent study by Posner and colleagues reported that environmental risk factors contribute to ADHD symptoms at prenatal, perinatal, and postnatal stages. Prenatal and perinatal risk factors such as prematurity, low birth weight, maternal smoking history, stress, trauma and obesity are substantially associated with ADHD. Postnatal risk factors such as trauma, parenting style, artificial colours and fragrances, pollutants, and pesticides can exacerbate ADHD symptoms. Medication-based treatment strategies have proven effective and inexpensive in the short term, and many compounds are available, recommended and widely used. The long-term efficacy of these treatments on clinical, occupational and social outcomes remains unknown. It is clear that better long-term treatments for ADHD are urgently needed. The American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders (DSM) is a widely used approach for diagnosing ADHD in adults and requires childhood onset. The purpose of this review is to describe the characteristics and the associated comorbidities of Adult ADHD and to depict the scope of available treatment. Two-thirds of ADHD adults present with one comorbid psychiatric disorder. Studies also show that ADHD is found in 15% of psychiatric patients. These comorbidities are responsible for masking ADHD which reduces the frequency of correct diagnosis. Comorbidity rates of 57-92% have been shown in various studies. ADHD is associated with poor academic and professional performance because it presents with reading disabilities which lead to repeating grades and attending special educational facilities hindering higher educational opportunities. ADHD adults often feel different from others due to their inability to comprehend social cues and because they lack propriety. Diagnosis is essential as it helps them to come to term with their shortcomings. The patients are creative and thus usually prosper in the art industry. Accomplishing tasks is rewarding when it is in their interest. Viloxazine is a non-stimulant drug that may be helpful for patients whose anxiety is worsened with first-line medications. Viloxazine is another drug in the toolbox of practitioners co-treating ADHD and substance use disorder. It is hypothesized that because Viloxazine does not antagonize dopamine reuptake in the reward centre of the brain, it lacks the addictive effects of methylphenidate and dexamphetamine.

• #12

  https://journals.lww.com/annals-of-medicine-and-surgery/fulltext/2023/05000/adult_attention_deficit_hyperactivity_disorder__a.74.aspx

  Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder, with only 23% prevalence into adulthood. The epidemiology and proposed causes of ADHD are multifactorial, including genetic, prenatal and environmental influences. The diagnosis of ADHD is often complicated by masking coping mechanisms, an overlap of symptoms with other, more commonly diagnosed disorders. Traditionally, it has been treated with stimulant medications. Non-stimulant options often target norepinephrine and dopamine regulation and are preferred in cases of comorbid substance use disorder, anxiety and other complicating factors, due to an improved side-effect profile and patient preference. They include atomoxetine and viloxazine. The latter, Viloxazine, in the form of extended-release capsules, is the first novel, non-stimulant option approved for adults with ADHD, in the past two decades. Its therapeutic effects are predominantly produced by its action as a norepinephrine reuptake inhibitor and may also modulate the serotonergic system. Viloxazine is relatively safe and effective in treating other disorders such as depression, anxiety, epilepsy and substance use disorder. A thorough review of the history, mechanism of action, pharmacokinetics and drug-drug interactions has been presented here, with special attention on treatment in adults with comorbid conditions. Several factors contribute to ADHD symptoms, including genetics, neurodevelopmental disorders, abnormal neuronal maturation, brain injury, environmental exposure and consanguinity. A recent study by Posner and colleagues reported that environmental risk factors contribute to ADHD symptoms at prenatal, perinatal, and postnatal stages. Prenatal and perinatal risk factors such as prematurity, low birth weight, maternal smoking history, stress, trauma and obesity are substantially associated with ADHD. Postnatal risk factors such as trauma, parenting style, artificial colours and fragrances, pollutants, and pesticides can exacerbate ADHD symptoms. Medication-based treatment strategies have proven effective and inexpensive in the short term, and many compounds are available, recommended and widely used. The long-term efficacy of these treatments on clinical, occupational and social outcomes remains unknown. It is clear that better long-term treatments for ADHD are urgently needed. The American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders (DSM) is a widely used approach for diagnosing ADHD in adults and requires childhood onset. The purpose of this review is to describe the characteristics and the associated comorbidities of Adult ADHD and to depict the scope of available treatment. Two-thirds of ADHD adults present with one comorbid psychiatric disorder. Studies also show that ADHD is found in 15% of psychiatric patients. These comorbidities are responsible for masking ADHD which reduces the frequency of correct diagnosis. Comorbidity rates of 57-92% have been shown in various studies. ADHD is associated with poor academic and professional performance because it presents with reading disabilities which lead to repeating grades and attending special educational facilities hindering higher educational opportunities. ADHD adults often feel different from others due to their inability to comprehend social cues and because they lack propriety. Diagnosis is essential as it helps them to come to term with their shortcomings. The patients are creative and thus usually prosper in the art industry. Accomplishing tasks is rewarding when it is in their interest. Viloxazine is a non-stimulant drug that may be helpful for patients whose anxiety is worsened with first-line medications. Viloxazine is another drug in the toolbox of practitioners co-treating ADHD and substance use disorder. It is hypothesized that because Viloxazine does not antagonize dopamine reuptake in the reward centre of the brain, it lacks the addictive effects of methylphenidate and dexamphetamine.

• #13 Attention Deficit Hyperactivity Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441838/

  ADHD is associated with cognitive and functional deficits that relate to diffuse abnormalities in the brain. The anterior cingulate gyrus and dorsolateral prefrontal cortex (DLFPC) are found to be small in individuals who are suffering from ADHD. It is thought that these changes account for the deficits in goal-directed behavior. Moreover, activity in the frontostriatal region is also reduced in these individuals as measured by fMRI. It is important to understand these pathophysiological mechanisms so that pharmacotherapy is directed toward them. […] The etiology of ADHD is related to a variety of factors that include both a genetic and an environmental component. It is one of the most heritable conditions in terms of psychiatric disorders. There is a much greater concordance in monozygotic twins than dizygotic. Siblings have twice the risk of having ADHD than the general population. Similarly, viral infections, smoking during pregnancy, nutritional deficiency, and alcohol exposure in the fetus have also been explored as possible causes of the disorder. There are no consistent findings on brain imaging of patients with ADHD. The number of dopaminergic receptors has also been implicated in the development of the disorder, whereby research has shown that the receptors are decreased in the frontal lobes in individuals with ADHD. There is also evidence for the role of noradrenergic receptor involvement in ADHD.

• #14 Attention Deficit-Hyperactivity Disorder (ADHD): From Abnormal Behavior to Impairment in Synaptic Plasticity

  https://www.mdpi.com/2079-7737/12/9/1241

  A significantly lower cortical thickness (most prominent in the prefrontal cortex, PFC) in children with ADHD as evaluated by brain MRI has been reported. The fitting of curves of thickness values obtained from sequential brain scanning in children diagnosed with ADHD and healthy controls show a delay of ≈3 years to attain the peak of cortical thickness during childhood, supporting a delay in cortical maturation in ADHD. […] Meta-analysis of neuroimaging data obtained in children, adolescents and adults with ADHD show a statistically significant reduction (compared to control groups) in cortical thickness, cortical surface area and volume of subcortical areas such as the accumbens, amygdala, caudate, putamen and hippocampus, in children with ADHD. […] Extensive evidence supporting a polygenic origin of ADHD with additional environmental risk factors has been reported. A recent genome-wide analysis has uncovered 12 significant risk loci in ADHD. The biological activities in these loci include neuronal differentiation (FOXP2), glutamate receptor trafficking and anchorage to postsynaptic density (SORCS3), regulation of dopamine transporter trafficking (DUSP6) and axon guidance (SEMA6D).

• #15 Attention Deficit Hyperactivity Disorder (ADHD): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/289350-overview

  Although ADHD has been associated with structural and functional alterations in the frontostriatal circuitry, recent studies have further demonstrated changes just outside that region and more specifically in the cerebellum and the parietal lobes. […] Another study using proton magnetic spectroscopy demonstrated right prefrontal neurochemical changes in adolescents with ADHD. […] Work by Sobel et al has demonstrated deformations in the basal ganglia nuclei (caudate, putamen, globus pallidus) in children with ADHD. The more prominent the deformations, the greater the severity of symptoms. Furthermore, Sobel et al have shown that stimulants may normalize the deformations. […] Adults with ADHD also have been reported to have deficits in anterior cingulate activation while performing similar tasks.

• #16 Attention Deficit Hyperactivity Disorder (ADHD): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/289350-overview

  Although ADHD has been associated with structural and functional alterations in the frontostriatal circuitry, recent studies have further demonstrated changes just outside that region and more specifically in the cerebellum and the parietal lobes. […] Another study using proton magnetic spectroscopy demonstrated right prefrontal neurochemical changes in adolescents with ADHD. […] Work by Sobel et al has demonstrated deformations in the basal ganglia nuclei (caudate, putamen, globus pallidus) in children with ADHD. The more prominent the deformations, the greater the severity of symptoms. Furthermore, Sobel et al have shown that stimulants may normalize the deformations. […] Adults with ADHD also have been reported to have deficits in anterior cingulate activation while performing similar tasks.

• #17 Neuronal Mechanisms Underlying Attention Deficit Hyperactivity Disorder

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2863119/

  Neuropsychological and imaging studies indicate that attention deficit hyperactivity disorder (ADHD) is associated with alterations in prefrontal cortex (PFC) and its connections to striatum and cerebellum. […] The PFC is very sensitive to its neurochemical environment, and either too little (drowsiness) or too much (stress) catecholamine release in PFC weakens cognitive control of behavior and attention. […] Genetic alterations in catecholamine pathways may contribute to dysregulation of PFC circuits in this disorder. […] The PFC has particular relevance to ADHD, as imaging studies indicate that ADHD patients often have smaller PFC volume, particularly on the right side. […] Lesions of the PFC produce symptoms similar to ADHD, for example, impairment in tasks of behavioral inhibition, working memory, and reward reversal.

• #18 Attention Deficit Hyperactivity Disorder (ADHD): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/289350-overview

  A PET scan study by Volkow et al revealed that in adults with ADHD, depressed dopamine activity in caudate and preliminary evidence in limbic regions was associated with inattention and enhanced reinforcing responses to intravenous methylphenidate. This concludes that dopamine dysfunction may be involved with symptoms of inattention but may also contribute to substance abuse comorbidity. […] Individuals with ADHD have inhibition impairment, which is difficulty stopping their responses. […] According to a study of young children, there is evidence of early brain structural changes in pre-schoolers with ADHD. Researchers used high resolution anatomical (MPRAGE) images and cognitive and behavioral measures in a cohort of 90 medication-naive preschoolers, aged 4-5 years (52 with ADHD, 38 controls; 64.4% boys). Results show reductions in bilateral frontal, parietal, and temporal lobe gray matter volumes in children with ADHD relative to typically developing children. The largest effect sizes were noted for right frontal and left temporal lobe volumes. Examination of frontal lobe sub-regions revealed that the largest between group effect sizes were evident in the left orbitofrontal cortex, left primary motor cortex (M1), and left supplementary motor complex (SMC). ADHD-related reductions in specific sub-regions (left prefrontal, left premotor, left frontal eye field, left M1, and right SMC) were significantly correlated with symptom severity, such that higher ratings of hyperactive/impulsive symptoms were associated with reduced cortical volumes. […] Evidence of a neurobiologic contribution to the cause of ADHD continues to grow.

• #19 Azthena logo with the word Azthena

  https://www.news-medical.net/health/ADHD-Pathophysiology.aspx

  The exact pathophysiology of Attention Deficit Hyperactivity Disorder (ADHD) is not clear. […] Several mechanisms have been proposed as factors associated with the condition. These include abnormalities in the functioning of neurotransmitters, brain structure and cognitive function. […] Although it remains unknown if these mechanisms cause or are consequences of the condition, they appear to be linked to the pathophysiology of ADHD and are evident in affected individuals. […] Due to the efficacy of medications such as psychostimulants and noradrenergic tricyclics in the treatment of ADHD, neurotransmitters such as dopamine and noradrenaline have been suggested as key players in the pathophysiology of ADHD. […] A deficiency in neural transmission may be linked to the pathophysiology and symptoms of ADHD.

• #20 Attention Deficit Hyperactivity Disorder (ADHD): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/289350-overview

  A PET scan study by Volkow et al revealed that in adults with ADHD, depressed dopamine activity in caudate and preliminary evidence in limbic regions was associated with inattention and enhanced reinforcing responses to intravenous methylphenidate. This concludes that dopamine dysfunction may be involved with symptoms of inattention but may also contribute to substance abuse comorbidity. […] Individuals with ADHD have inhibition impairment, which is difficulty stopping their responses. […] According to a study of young children, there is evidence of early brain structural changes in pre-schoolers with ADHD. Researchers used high resolution anatomical (MPRAGE) images and cognitive and behavioral measures in a cohort of 90 medication-naive preschoolers, aged 4-5 years (52 with ADHD, 38 controls; 64.4% boys). Results show reductions in bilateral frontal, parietal, and temporal lobe gray matter volumes in children with ADHD relative to typically developing children. The largest effect sizes were noted for right frontal and left temporal lobe volumes. Examination of frontal lobe sub-regions revealed that the largest between group effect sizes were evident in the left orbitofrontal cortex, left primary motor cortex (M1), and left supplementary motor complex (SMC). ADHD-related reductions in specific sub-regions (left prefrontal, left premotor, left frontal eye field, left M1, and right SMC) were significantly correlated with symptom severity, such that higher ratings of hyperactive/impulsive symptoms were associated with reduced cortical volumes. […] Evidence of a neurobiologic contribution to the cause of ADHD continues to grow.

• #21 Attention Deficit Hyperactivity Disorder (ADHD): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/289350-overview

  A PET scan study by Volkow et al revealed that in adults with ADHD, depressed dopamine activity in caudate and preliminary evidence in limbic regions was associated with inattention and enhanced reinforcing responses to intravenous methylphenidate. This concludes that dopamine dysfunction may be involved with symptoms of inattention but may also contribute to substance abuse comorbidity. […] Individuals with ADHD have inhibition impairment, which is difficulty stopping their responses. […] According to a study of young children, there is evidence of early brain structural changes in pre-schoolers with ADHD. Researchers used high resolution anatomical (MPRAGE) images and cognitive and behavioral measures in a cohort of 90 medication-naive preschoolers, aged 4-5 years (52 with ADHD, 38 controls; 64.4% boys). Results show reductions in bilateral frontal, parietal, and temporal lobe gray matter volumes in children with ADHD relative to typically developing children. The largest effect sizes were noted for right frontal and left temporal lobe volumes. Examination of frontal lobe sub-regions revealed that the largest between group effect sizes were evident in the left orbitofrontal cortex, left primary motor cortex (M1), and left supplementary motor complex (SMC). ADHD-related reductions in specific sub-regions (left prefrontal, left premotor, left frontal eye field, left M1, and right SMC) were significantly correlated with symptom severity, such that higher ratings of hyperactive/impulsive symptoms were associated with reduced cortical volumes. […] Evidence of a neurobiologic contribution to the cause of ADHD continues to grow.

• #22 Azthena logo with the word Azthena

  https://www.news-medical.net/health/ADHD-Pathophysiology.aspx

  Depressed dopamine activity has been associated with the condition, and has been identified in affected individuals with the use of positive electron transmission (PET) scans. […] The frontal and prefrontal regions of the brain, as well as possibly the parietal lobe and cerebellum, are thought to be associated with ADHD. […] Deformations of the basal ganglia nuclei in children with ADHD may also be involved. […] This theory may be supported by the efficacy of stimulant drugs in treating ADHD, which may help to reduce the deformations. […] ADHD is also linked to some neurophysiological deficits and abnormalities in cognitive function. […] Abnormalities in the function of this system may be seen in patients with ADHD and lead to the symptoms characteristic of the condition.

• #23 Attention Deficit Hyperactivity Disorder – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441838/

  ADHD is associated with cognitive and functional deficits that relate to diffuse abnormalities in the brain. The anterior cingulate gyrus and dorsolateral prefrontal cortex (DLFPC) are found to be small in individuals who are suffering from ADHD. It is thought that these changes account for the deficits in goal-directed behavior. Moreover, activity in the frontostriatal region is also reduced in these individuals as measured by fMRI. It is important to understand these pathophysiological mechanisms so that pharmacotherapy is directed toward them. […] The etiology of ADHD is related to a variety of factors that include both a genetic and an environmental component. It is one of the most heritable conditions in terms of psychiatric disorders. There is a much greater concordance in monozygotic twins than dizygotic. Siblings have twice the risk of having ADHD than the general population. Similarly, viral infections, smoking during pregnancy, nutritional deficiency, and alcohol exposure in the fetus have also been explored as possible causes of the disorder. There are no consistent findings on brain imaging of patients with ADHD. The number of dopaminergic receptors has also been implicated in the development of the disorder, whereby research has shown that the receptors are decreased in the frontal lobes in individuals with ADHD. There is also evidence for the role of noradrenergic receptor involvement in ADHD.

• #24

  https://link.springer.com/article/10.1007/s44192-022-00030-1

  ADHD has a multifactorial etiology, in which genetic and environmental factors are involved in its development. […] The understanding of the genetic architecture of ADHD has significantly evolved with the technological advances in the molecular genetics field, especially with the availability of large-scale genome-wide association studies (GWAS). […] The physiological changes induced by the binding of dopamine and norepinephrine to their respective receptors involve the modulation of several cognitive and executive processes usually impaired in ADHD, corroborating the monoaminergic hypothesis for ADHD pathophysiology. […] Pathophysiological insights can also be inferred from neuroimaging studies, which has reported differences in structural and functional brain architecture between patients with ADHD and neurotypical individuals, especially in children.

• #25 Inside the ADHD Brain: Structure, Function, and Chemistry – ADDA – Attention Deficit Disorder Association

  https://add.org/adhd-brain/

  Research has found deficits in the neural networks linked to attention and executive function in children and adults with ADHD. This may affect your ability to organize, prioritize, plan, focus, remember instructions, and work toward your goals. […] In addition, ADHD may alter the network connections between your prefrontal cortex and other areas of the brain. Scientists believe this is associated with poor planning, distractibility, impulsivity, and forgetfulness in ADHD. […] Neurotransmitters are chemical messengers that transmit signals from nerve cells to other target cells in your body. […] As noted earlier, dopamine and norepinephrine are two neurotransmitters that might be associated with ADHD. […] In ADHD, there might be lower levels of dopamine in the brain. This makes it harder to maintain motivation, especially when the rewards seem small or not immediate. ADHD brains tend to favor short-term, smaller rewards over long-term, more significant ones.

• #26 Attention deficit hyperactivity disorder – Wikipedia

  https://en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder

  The dopamine pathways and norepinephrine pathways which project to the prefrontal cortex and striatum are directly responsible for modulating executive function (cognitive control of behaviour), motivation, reward perception, and motor function; these pathways are known to play a central role in the pathophysiology of ADHD. […] ADHD arises from a core deficit in executive functions (e.g., attentional control, inhibitory control, and working memory), which are a set of cognitive processes that are required to successfully select and monitor behaviours that facilitate the attainment of one’s chosen goals. […] ADHD has also been associated with motivational deficits in children.

• #27 Neuronal Mechanisms Underlying Attention Deficit Hyperactivity Disorder

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2863119/

  Neuropsychological and imaging studies indicate that attention deficit hyperactivity disorder (ADHD) is associated with alterations in prefrontal cortex (PFC) and its connections to striatum and cerebellum. […] The PFC is very sensitive to its neurochemical environment, and either too little (drowsiness) or too much (stress) catecholamine release in PFC weakens cognitive control of behavior and attention. […] Genetic alterations in catecholamine pathways may contribute to dysregulation of PFC circuits in this disorder. […] The PFC has particular relevance to ADHD, as imaging studies indicate that ADHD patients often have smaller PFC volume, particularly on the right side. […] Lesions of the PFC produce symptoms similar to ADHD, for example, impairment in tasks of behavioral inhibition, working memory, and reward reversal.

• #28 Neuronal Mechanisms Underlying Attention Deficit Hyperactivity Disorder

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2863119/

  Neuropsychological and imaging studies indicate that attention deficit hyperactivity disorder (ADHD) is associated with alterations in prefrontal cortex (PFC) and its connections to striatum and cerebellum. […] The PFC is very sensitive to its neurochemical environment, and either too little (drowsiness) or too much (stress) catecholamine release in PFC weakens cognitive control of behavior and attention. […] Genetic alterations in catecholamine pathways may contribute to dysregulation of PFC circuits in this disorder. […] The PFC has particular relevance to ADHD, as imaging studies indicate that ADHD patients often have smaller PFC volume, particularly on the right side. […] Lesions of the PFC produce symptoms similar to ADHD, for example, impairment in tasks of behavioral inhibition, working memory, and reward reversal.

• #29 Neuronal Mechanisms Underlying Attention Deficit Hyperactivity Disorder

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2863119/

  Deficits in divided and focused attention have been associated with lesions in the left, superior PFC. […] Imaging studies have reported reduced volume of the caudate nucleus, and particularly parts of the cerebellum in ADHD. […] The PFC appears to thrive under conditions of moderate catecholamine release, when NE 2A-receptor stimulation increases signals, and optimal DA D1-receptor stimulation decreases noise. […] In contrast, PFC working-memory functions are impaired under conditions of high catecholamine release that engage 1 and receptors, and excessive D1-receptor stimulation. […] A large number of studies have found that ADHD symptoms are often associated with alterations in genes involved with catecholamine transmission. […] Thus, suboptimal catecholamine regulation of PFC may contribute to impaired regulation of attention and behavior in patients with ADHD.

• #30 Attention Deficit Hyperactivity Disorder (ADHD): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/289350-overview

  A PET scan study by Volkow et al revealed that in adults with ADHD, depressed dopamine activity in caudate and preliminary evidence in limbic regions was associated with inattention and enhanced reinforcing responses to intravenous methylphenidate. This concludes that dopamine dysfunction may be involved with symptoms of inattention but may also contribute to substance abuse comorbidity. […] Individuals with ADHD have inhibition impairment, which is difficulty stopping their responses. […] According to a study of young children, there is evidence of early brain structural changes in pre-schoolers with ADHD. Researchers used high resolution anatomical (MPRAGE) images and cognitive and behavioral measures in a cohort of 90 medication-naive preschoolers, aged 4-5 years (52 with ADHD, 38 controls; 64.4% boys). Results show reductions in bilateral frontal, parietal, and temporal lobe gray matter volumes in children with ADHD relative to typically developing children. The largest effect sizes were noted for right frontal and left temporal lobe volumes. Examination of frontal lobe sub-regions revealed that the largest between group effect sizes were evident in the left orbitofrontal cortex, left primary motor cortex (M1), and left supplementary motor complex (SMC). ADHD-related reductions in specific sub-regions (left prefrontal, left premotor, left frontal eye field, left M1, and right SMC) were significantly correlated with symptom severity, such that higher ratings of hyperactive/impulsive symptoms were associated with reduced cortical volumes. […] Evidence of a neurobiologic contribution to the cause of ADHD continues to grow.

• #31 Attention Deficit Hyperactivity Disorder (ADHD): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/289350-overview

  The pathology of ADHD is not clear. Psychostimulants (which facilitate dopamine release) and noradrenergic tricyclics used to treat this condition have led to speculation that certain brain areas related to attention are deficient in neural transmission. PET scan imaging indicates that methylphenidate acts to increase dopamine. […] The neurotransmitters dopamine and norepinephrine have been associated with ADHD. […] The underlying brain regions predominantly thought to be involved are frontal and prefrontal; the parietal lobe and cerebellum may also be involved. In one functional MRI study, children with ADHD who performed response-inhibition tasks were reported to have differing activation in frontostriatal areas compared with healthy controls. A 2010 study again indicated the presence of frontostriatal malfunctioning in the etiology of ADHD.

• #32 Inside the ADHD Brain: Structure, Function, and Chemistry – ADDA – Attention Deficit Disorder Association

  https://add.org/adhd-brain/

  Research has found deficits in the neural networks linked to attention and executive function in children and adults with ADHD. This may affect your ability to organize, prioritize, plan, focus, remember instructions, and work toward your goals. […] In addition, ADHD may alter the network connections between your prefrontal cortex and other areas of the brain. Scientists believe this is associated with poor planning, distractibility, impulsivity, and forgetfulness in ADHD. […] Neurotransmitters are chemical messengers that transmit signals from nerve cells to other target cells in your body. […] As noted earlier, dopamine and norepinephrine are two neurotransmitters that might be associated with ADHD. […] In ADHD, there might be lower levels of dopamine in the brain. This makes it harder to maintain motivation, especially when the rewards seem small or not immediate. ADHD brains tend to favor short-term, smaller rewards over long-term, more significant ones.

• #33 Inside the ADHD Brain: Structure, Function, and Chemistry – ADDA – Attention Deficit Disorder Association

  https://add.org/adhd-brain/

  Research has found deficits in the neural networks linked to attention and executive function in children and adults with ADHD. This may affect your ability to organize, prioritize, plan, focus, remember instructions, and work toward your goals. […] In addition, ADHD may alter the network connections between your prefrontal cortex and other areas of the brain. Scientists believe this is associated with poor planning, distractibility, impulsivity, and forgetfulness in ADHD. […] Neurotransmitters are chemical messengers that transmit signals from nerve cells to other target cells in your body. […] As noted earlier, dopamine and norepinephrine are two neurotransmitters that might be associated with ADHD. […] In ADHD, there might be lower levels of dopamine in the brain. This makes it harder to maintain motivation, especially when the rewards seem small or not immediate. ADHD brains tend to favor short-term, smaller rewards over long-term, more significant ones.

• #34 The brain anatomy of attention-deficit/hyperactivity disorder in young adults – a magnetic resonance imaging study | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175433

  Our findings revealed reduced gray matter concentrations in the right middle frontal gyrus, right inferior frontal gyrus, right superior temporal gyrus, right middle temporal gyrus, left caudate head, and left parahippocampal gyrus with corresponding white matter increases associated with an ADHD diagnosis in young adults. […] The present findings also corroborated the hypothesis that brain microstructural abnormalities were more associated with child symptoms of ADHD compared to adult symptoms of ADHD. […] At the brain circuitry level, the present findings may suggest that the superior longitudinal fasciculus (SLF) and the cortico-limbic associated circuitry are dysfunctional in individuals with ADHD. […] An adult ADHD diagnosis and in particular child symptoms were associated with widespread micro- and macrostructural changes in the frontal, basal ganglia, anterior cingulate, temporal, and occipito-parietal regions in young adults with ADHD. The associations between brain structure and ADHD symptoms in childhood were more widespread and prominent than ADHD symptoms in adulthood. […] This highlights the importance of the microstructural architecture in the pathophysiology of ADHD.

• #35 Attention deficit hyperactivity disorder – Wikipedia

  https://en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder

  ADHD arises from maldevelopment in brain regions such as the prefrontal cortex, basal ganglia and anterior cingulate cortex, which regulate the executive functions necessary for human self-regulation. […] ADHD symptoms arise from executive dysfunction. […] The precise causes of ADHD are unknown in most individual cases. […] Meta-analyses have shown that the disorder is primarily genetic with a heritability rate of 70-80%, where risk factors are highly accumulative. […] ADHD presents with reduced size, functional connectivity and activation as well as low noradrenergic and dopaminergic functioning in brain regions and networks crucial for executive functioning and self-regulation. […] Current models of ADHD suggest that it is associated with functional impairments in some of the brain’s neurotransmitter systems, particularly those involving dopamine and norepinephrine.

• #36 Cerebellar network alterations in adult attention-deficit/hyperactivity disorder | JPN

  https://www.jpn.ca/content/49/4/E233

  Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition that often persists into adulthood. Underlying alterations in brain connectivity have been identified but some relevant connections, such as the middle, superior, and inferior cerebellar peduncles (MCP, SCP, and ICP, respectively), have remained largely unexplored; thus, we sought to investigate whether the cerebellar peduncles contribute to ADHD pathophysiology among adults. […] The cerebellar networks likely contribute to ADHD pathophysiology because the cerebellum supports motor, cognitive, and emotion regulation skills that are impaired in ADHD. […] The suggestion that the MCP plays a role in ADHD pathophysiology is further supported by the significant correlation between MCP microstructural organization and neuropsychological profiles. […] The present study provided evidence that the cerebellar peduncles play a role in adult ADHD pathophysiology.

• #37 Cerebellar network alterations in adult attention-deficit/hyperactivity disorder | JPN

  https://www.jpn.ca/content/49/4/E233

  Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition that often persists into adulthood. Underlying alterations in brain connectivity have been identified but some relevant connections, such as the middle, superior, and inferior cerebellar peduncles (MCP, SCP, and ICP, respectively), have remained largely unexplored; thus, we sought to investigate whether the cerebellar peduncles contribute to ADHD pathophysiology among adults. […] The cerebellar networks likely contribute to ADHD pathophysiology because the cerebellum supports motor, cognitive, and emotion regulation skills that are impaired in ADHD. […] The suggestion that the MCP plays a role in ADHD pathophysiology is further supported by the significant correlation between MCP microstructural organization and neuropsychological profiles. […] The present study provided evidence that the cerebellar peduncles play a role in adult ADHD pathophysiology.

• #38 Attention deficit hyperactivity disorder in adults: Epidemiology, clinical features, assessment, and diagnosis – UpToDate

  https://www.uptodate.com/contents/attention-deficit-hyperactivity-disorder-in-adults-epidemiology-clinical-features-assessment-and-diagnosis/print

  Attention deficit hyperactivity disorder (ADHD), one of the most common neuropsychiatric disorders of childhood and adolescence, often persists into adulthood. Studies have found that a majority of people diagnosed with ADHD in childhood continue to meet criteria for the disorder as adults. More recent studies have found that a substantial proportion of those with adult ADHD did not have the condition in childhood. ADHD in adulthood is associated with significant impairment in occupational, academic, and social functioning. […] ADHD in adults is characterized by symptoms of inattention, impulsivity, and restlessness, resulting in functional impairment. Impairment in executive function is common. Emotional dysregulation is often seen in these patients. […] This topic discusses the epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis of ADHD in adults.

• #39 The brain anatomy of attention-deficit/hyperactivity disorder in young adults – a magnetic resonance imaging study | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175433

  Our findings revealed reduced gray matter concentrations in the right middle frontal gyrus, right inferior frontal gyrus, right superior temporal gyrus, right middle temporal gyrus, left caudate head, and left parahippocampal gyrus with corresponding white matter increases associated with an ADHD diagnosis in young adults. […] The present findings also corroborated the hypothesis that brain microstructural abnormalities were more associated with child symptoms of ADHD compared to adult symptoms of ADHD. […] At the brain circuitry level, the present findings may suggest that the superior longitudinal fasciculus (SLF) and the cortico-limbic associated circuitry are dysfunctional in individuals with ADHD. […] An adult ADHD diagnosis and in particular child symptoms were associated with widespread micro- and macrostructural changes in the frontal, basal ganglia, anterior cingulate, temporal, and occipito-parietal regions in young adults with ADHD. The associations between brain structure and ADHD symptoms in childhood were more widespread and prominent than ADHD symptoms in adulthood. […] This highlights the importance of the microstructural architecture in the pathophysiology of ADHD.

• #40 Attention deficit hyperactivity disorder in adults: Epidemiology, clinical features, assessment, and diagnosis – UpToDate

  https://www.uptodate.com/contents/attention-deficit-hyperactivity-disorder-in-adults-epidemiology-clinical-features-assessment-and-diagnosis/print

  Attention deficit hyperactivity disorder (ADHD), one of the most common neuropsychiatric disorders of childhood and adolescence, often persists into adulthood. Studies have found that a majority of people diagnosed with ADHD in childhood continue to meet criteria for the disorder as adults. More recent studies have found that a substantial proportion of those with adult ADHD did not have the condition in childhood. ADHD in adulthood is associated with significant impairment in occupational, academic, and social functioning. […] ADHD in adults is characterized by symptoms of inattention, impulsivity, and restlessness, resulting in functional impairment. Impairment in executive function is common. Emotional dysregulation is often seen in these patients. […] This topic discusses the epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis of ADHD in adults.

• #41 Adult Attention-deficit/Hyperactivity Disorder (aADHD)

  https://www.psychiatrictimes.com/view/adult-attention-deficit-hyperactivity-disorder

  Individuals with aADHD tend to have poor self-esteem and reduced quality of interpersonal and professional relationships. […] Approximately 80% of aADHD cases present with at least 1 lifetime psychiatric comorbidity. […] Available evidence from family, twin, and adoption studies indicates that ADHD tends to run in families, with a high heritability rate of 74%. […] Current evidence indicates that some of the same genes that may be involved in cADHD may also be involved in aADHD. […] There is evidence from neuroimaging studies that among individuals with ADHD there is a dysfunction of dopamine pathways that are involved in attention, executive function, and motivation and reward. […] A simultaneous electroencephalography and functional magnetic resonance imaging (fMRI) study found that aADHD individuals had increased medial/lateral frontal and parietal activity during the voluntary selection task on fMRI.

• #42 Molecular Mechanisms Underlying NMDARs Dysfunction and Their Role in ADHD Pathogenesis

  https://www.mdpi.com/1422-0067/24/16/12983

  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. […] 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. […] While dopamine deficit is the best-known factor associated with ADHD, an increasing amount of evidence indicates that disrupted glutamatergic transmission also plays a significant role in the disorder pathogenesis.

• #43 Molecular Mechanisms Underlying NMDARs Dysfunction and Their Role in ADHD Pathogenesis

  https://www.mdpi.com/1422-0067/24/16/12983

  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. […] 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. […] While dopamine deficit is the best-known factor associated with ADHD, an increasing amount of evidence indicates that disrupted glutamatergic transmission also plays a significant role in the disorder pathogenesis.

• #44 Molecular Mechanisms Underlying NMDARs Dysfunction and Their Role in ADHD Pathogenesis

  https://www.mdpi.com/1422-0067/24/16/12983

  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. […] 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. […] While dopamine deficit is the best-known factor associated with ADHD, an increasing amount of evidence indicates that disrupted glutamatergic transmission also plays a significant role in the disorder pathogenesis.

• #45 Molecular Mechanisms Underlying NMDARs Dysfunction and Their Role in ADHD Pathogenesis

  https://www.mdpi.com/1422-0067/24/16/12983

  The potential causal role of NMDAR dysfunction in the pathogenesis of ADHD has become a new area of research interest. For this reason, this review paper is aimed to focus on the role of NMDAR dysregulation in ADHD pathophysiology, which to date has not been studied extensively and is not well-understood. NMDAR dysfunction is one of the suggested mechanisms underlying ADHD pathogenesis in humans, as the role of NMDAR dysregulation has been well-established in a rat model of ADHD. […] Research regarding NMDAR role in ADHD might be useful in the development of novel treatment strategies, as currently most effective drugs, atomoxetine and methylphenidate, beside inhibiting monoamine reuptake, also influence NMDAR function. […] NMDAR dysregulation might be an important mechanism underlying the development of the disorder, and may at least by part explain the heterogeneity of patient’s symptoms. A better understanding of the role of NMDAR in the disease pathogenesis may lead to the development of novel, targeted therapies that could bring relief to ADHD patients.

• #46 Molecular Mechanisms Underlying NMDARs Dysfunction and Their Role in ADHD Pathogenesis

  https://www.mdpi.com/1422-0067/24/16/12983

  The potential causal role of NMDAR dysfunction in the pathogenesis of ADHD has become a new area of research interest. For this reason, this review paper is aimed to focus on the role of NMDAR dysregulation in ADHD pathophysiology, which to date has not been studied extensively and is not well-understood. NMDAR dysfunction is one of the suggested mechanisms underlying ADHD pathogenesis in humans, as the role of NMDAR dysregulation has been well-established in a rat model of ADHD. […] Research regarding NMDAR role in ADHD might be useful in the development of novel treatment strategies, as currently most effective drugs, atomoxetine and methylphenidate, beside inhibiting monoamine reuptake, also influence NMDAR function. […] NMDAR dysregulation might be an important mechanism underlying the development of the disorder, and may at least by part explain the heterogeneity of patient’s symptoms. A better understanding of the role of NMDAR in the disease pathogenesis may lead to the development of novel, targeted therapies that could bring relief to ADHD patients.

• #47 Attention Deficit-Hyperactivity Disorder (ADHD): From Abnormal Behavior to Impairment in Synaptic Plasticity

  https://www.mdpi.com/2079-7737/12/9/1241

  Attention deficit-hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high incidence in children and adolescents characterized by hyperactivity, impulsivity, and inattention. Neuroanatomical anomalies such as the volume reduction in the neocortex and hippocampus and the abnormal dendritic spine pruning during postnatal development are shared by several neuropsychiatric diseases such as schizophrenia, autism spectrum disorder and ADHD. This review presents recent evidence focused on the molecular mechanisms involved in dendritic spine remodeling in the context of synaptic plasticity and learning. The impairment in synaptic plasticity, working memory and spine phenotype in a murine model of ADHD are also discussed. […] ADHD is a neurodevelopmental disorder with high prevalence (around 5%) among children worldwide characterized by hyperactivity, inattention and/or impulsivity affecting learning and sociability at school. Several studies support a polygenic cause for ADHD and non-genetic factors involved in the etiology of this disorder. Environmental factors such as smoking and alcohol consumption during pregnancy, exposure to contaminants such as lead, diet deficiencies and low educational attainment have been correlated with ADHD.

• #48 Attention Deficit-Hyperactivity Disorder (ADHD): From Abnormal Behavior to Impairment in Synaptic Plasticity

  https://www.mdpi.com/2079-7737/12/9/1241

  Attention deficit-hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high incidence in children and adolescents characterized by hyperactivity, impulsivity, and inattention. Neuroanatomical anomalies such as the volume reduction in the neocortex and hippocampus and the abnormal dendritic spine pruning during postnatal development are shared by several neuropsychiatric diseases such as schizophrenia, autism spectrum disorder and ADHD. This review presents recent evidence focused on the molecular mechanisms involved in dendritic spine remodeling in the context of synaptic plasticity and learning. The impairment in synaptic plasticity, working memory and spine phenotype in a murine model of ADHD are also discussed. […] ADHD is a neurodevelopmental disorder with high prevalence (around 5%) among children worldwide characterized by hyperactivity, inattention and/or impulsivity affecting learning and sociability at school. Several studies support a polygenic cause for ADHD and non-genetic factors involved in the etiology of this disorder. Environmental factors such as smoking and alcohol consumption during pregnancy, exposure to contaminants such as lead, diet deficiencies and low educational attainment have been correlated with ADHD.

• #49 Attention Deficit-Hyperactivity Disorder (ADHD): From Abnormal Behavior to Impairment in Synaptic Plasticity

  https://www.mdpi.com/2079-7737/12/9/1241

  Several human neurodevelopmental and neuropsychiatric disorders such as ASD, SCZ and ADHD are correlated with abnormal development and maturation of dendritic spines in the neocortex including changes in the pruning phase occurring during late childhood and early adolescence. […] The intracellular cascade involved in the structural and functional remodeling of dendritic spines during processes of synaptic plasticity has been studied mainly by investigating the effect of knock-out or block of specific proteins during the induction of LTP or long-term depression (LTD). […] Morphological analysis of dendritic spines in hippocampal CA1 neurons in the PNE murine model of ADHD suggests an impairment in postnatal spine maturation. Further studies using in vivo spine imaging in CA1 pyramidal neurons of PNE mice are required to confirm the correlations between spine remodeling, impairment in hippocampal LTP and defective working memory.

• #50 Attention Deficit-Hyperactivity Disorder (ADHD): From Abnormal Behavior to Impairment in Synaptic Plasticity

  https://www.mdpi.com/2079-7737/12/9/1241

  ADHD is associated with a dysfunction of dopamine and noradrenergic systems involving cortical areas such as the PFC (dorsolateral and ventromedial), cingulate cortex and basal ganglia (nucleus accumbens, caudate nucleus and putamen) affecting neural networks driving executive control, motor function, reward processing and decision-making. […] The analysis of the dopamine levels in different brain areas by positron emission tomography (PET) imaging based on the competition between endogenous dopamine and a synthetic radioligand of the D2/D3 dopamine receptor, show that MPH administration in ADHD patients decreases the radioactivity-associated signal in hippocampus to a lower magnitude compared to healthy controls. […] Among symptoms associated with ADHD are the working memory impairments in children. However, little is known about the neurophysiological basis of this memory deficit. Recently, using the PNE murine model of ADHD it has been found that the defect in working memory is associated with a significant reduction in LTP at the CA3-CA1 hippocampal synapse.

• #51 Attention Deficit-Hyperactivity Disorder (ADHD): From Abnormal Behavior to Impairment in Synaptic Plasticity

  https://www.mdpi.com/2079-7737/12/9/1241

  Several human neurodevelopmental and neuropsychiatric disorders such as ASD, SCZ and ADHD are correlated with abnormal development and maturation of dendritic spines in the neocortex including changes in the pruning phase occurring during late childhood and early adolescence. […] The intracellular cascade involved in the structural and functional remodeling of dendritic spines during processes of synaptic plasticity has been studied mainly by investigating the effect of knock-out or block of specific proteins during the induction of LTP or long-term depression (LTD). […] Morphological analysis of dendritic spines in hippocampal CA1 neurons in the PNE murine model of ADHD suggests an impairment in postnatal spine maturation. Further studies using in vivo spine imaging in CA1 pyramidal neurons of PNE mice are required to confirm the correlations between spine remodeling, impairment in hippocampal LTP and defective working memory.

• #52 Psychopathology of attention deficit/hyperactivity disorder: from an inflammatory perspective | The Egyptian Journal of Neurology, Psychiatry and Neurosurgery | Full Text

  https://ejnpn.springeropen.com/articles/10.1186/s41983-022-00561-y

  Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattentiveness, hyperactivity and impulsivity, which may affect ones cognitive and psychosocial functioning. […] The exact cause of ADHD remains unknown, and the aetiology of the disorder is believed to be multifactorial. Numerous genetic and environmental factors have been linked to the development of ADHD. […] Like many psychiatric disorders, ADHD has been associated with inflammation that occurs locally and peripherally. A growing body of evidence shows that maternal inflammatory status during pregnancy is associated with diagnosis of ADHD in the offspring, whereas oxidative stress, inflammatory biochemical markers and immune-mediated diseases have been observed in individuals with ADHD.

• #53 Psychopathology of attention deficit/hyperactivity disorder: from an inflammatory perspective | The Egyptian Journal of Neurology, Psychiatry and Neurosurgery | Full Text

  https://ejnpn.springeropen.com/articles/10.1186/s41983-022-00561-y

  The underlying inflammatory processes and mechanisms in ADHD are not clearly understood. Therefore, further exploration is warranted in future research. This has clinical implications as inflammation may be a potential target in the treatment of ADHD. […] Current literature cannot pinpoint the exact cause of ADHD but suggests that an interplay of genetic and environmental factors plays a role in the pathogenesis and psychopathology of ADHD. […] It is also increasingly evident that factors such as oxidative stress, neuroinflammation, autoimmune diseases, maternal immune activation, allergic diseases and other immune-mediated conditions are linked to ADHD. […] However, the underlying mechanisms are not clearly understood, which warrant further exploration. This has clinical significance in terms of treatment of ADHD. Current treatment approach focusses on behavioural therapy, stimulant drugs and/or non-stimulant drugs. If the underlying mechanisms of the immune responses are known in patients whose ADHD is associated with inflammation, then inflammation may be a potential therapeutic target and treatment strategies may include immune modulation, antioxidants or anti-inflammatory agents. […] The neuroinflammatory process has important implications on the treatment of ADHD. Being a common feature in many CNS pathologies, neuroinflammation has become an emerging therapeutic target.

• #54 Psychopathology of attention deficit/hyperactivity disorder: from an inflammatory perspective | The Egyptian Journal of Neurology, Psychiatry and Neurosurgery | Full Text

  https://ejnpn.springeropen.com/articles/10.1186/s41983-022-00561-y

  The underlying inflammatory processes and mechanisms in ADHD are not clearly understood. Therefore, further exploration is warranted in future research. This has clinical implications as inflammation may be a potential target in the treatment of ADHD. […] Current literature cannot pinpoint the exact cause of ADHD but suggests that an interplay of genetic and environmental factors plays a role in the pathogenesis and psychopathology of ADHD. […] It is also increasingly evident that factors such as oxidative stress, neuroinflammation, autoimmune diseases, maternal immune activation, allergic diseases and other immune-mediated conditions are linked to ADHD. […] However, the underlying mechanisms are not clearly understood, which warrant further exploration. This has clinical significance in terms of treatment of ADHD. Current treatment approach focusses on behavioural therapy, stimulant drugs and/or non-stimulant drugs. If the underlying mechanisms of the immune responses are known in patients whose ADHD is associated with inflammation, then inflammation may be a potential therapeutic target and treatment strategies may include immune modulation, antioxidants or anti-inflammatory agents. […] The neuroinflammatory process has important implications on the treatment of ADHD. Being a common feature in many CNS pathologies, neuroinflammation has become an emerging therapeutic target.

• #55 Mechanism of Action of Stimulants in Attention-Deficit/Hyperactivity Disorder

  https://www.psychiatrist.com/jcp/mechanism-action-stimulants-attention-deficit-hyperactivity/

  Mechanism of Action of Stimulants in Attention-Deficit/Hyperactivity Disorder […] Stimulants hypothetically increase the availability of both dopamine and norepinephrine in prefrontal cortex, which enhances the efficiency of information processing at pyramidal neurons, resulting in the improvement of symptoms in attention-deficit/hyperactivity disorder (ADHD). […] Symptoms of ADHD are theoretically linked to inefficient information processing by pyramidal neurons in PFC, perhaps due in part to imbalances in the neurotransmitters DA and NE. […] Stimulants such as methylphenidate and amphetamine hypothetically act at these pyramidal neurons to enhance signal strength by increasing NE and to reduce noise by increasing DA, thereby reducing symptoms of inattention, hyperactivity, and impulsivity in ADHD.

• #56 Mechanism of Action of Stimulants in Attention-Deficit/Hyperactivity Disorder

  https://www.psychiatrist.com/jcp/mechanism-action-stimulants-attention-deficit-hyperactivity/

  Mechanism of Action of Stimulants in Attention-Deficit/Hyperactivity Disorder […] Stimulants hypothetically increase the availability of both dopamine and norepinephrine in prefrontal cortex, which enhances the efficiency of information processing at pyramidal neurons, resulting in the improvement of symptoms in attention-deficit/hyperactivity disorder (ADHD). […] Symptoms of ADHD are theoretically linked to inefficient information processing by pyramidal neurons in PFC, perhaps due in part to imbalances in the neurotransmitters DA and NE. […] Stimulants such as methylphenidate and amphetamine hypothetically act at these pyramidal neurons to enhance signal strength by increasing NE and to reduce noise by increasing DA, thereby reducing symptoms of inattention, hyperactivity, and impulsivity in ADHD.

• #57 Mechanism of Action of Stimulants in Attention-Deficit/Hyperactivity Disorder

  https://www.psychiatrist.com/jcp/mechanism-action-stimulants-attention-deficit-hyperactivity/

  Mechanism of Action of Stimulants in Attention-Deficit/Hyperactivity Disorder […] Stimulants hypothetically increase the availability of both dopamine and norepinephrine in prefrontal cortex, which enhances the efficiency of information processing at pyramidal neurons, resulting in the improvement of symptoms in attention-deficit/hyperactivity disorder (ADHD). […] Symptoms of ADHD are theoretically linked to inefficient information processing by pyramidal neurons in PFC, perhaps due in part to imbalances in the neurotransmitters DA and NE. […] Stimulants such as methylphenidate and amphetamine hypothetically act at these pyramidal neurons to enhance signal strength by increasing NE and to reduce noise by increasing DA, thereby reducing symptoms of inattention, hyperactivity, and impulsivity in ADHD.

• #58 Neuronal Mechanisms Underlying Attention Deficit Hyperactivity Disorder

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2863119/

  Deficits in divided and focused attention have been associated with lesions in the left, superior PFC. […] Imaging studies have reported reduced volume of the caudate nucleus, and particularly parts of the cerebellum in ADHD. […] The PFC appears to thrive under conditions of moderate catecholamine release, when NE 2A-receptor stimulation increases signals, and optimal DA D1-receptor stimulation decreases noise. […] In contrast, PFC working-memory functions are impaired under conditions of high catecholamine release that engage 1 and receptors, and excessive D1-receptor stimulation. […] A large number of studies have found that ADHD symptoms are often associated with alterations in genes involved with catecholamine transmission. […] Thus, suboptimal catecholamine regulation of PFC may contribute to impaired regulation of attention and behavior in patients with ADHD.

• #59 Neuronal Mechanisms Underlying Attention Deficit Hyperactivity Disorder

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2863119/

  Medications for the treatment of ADHD all enhance catecholamine transmission. […] It is likely that both DA and NE actions contribute to the therapeutic effects of stimulants in patients with ADHD. […] In summary, catecholamines have powerful influences on the brain circuits, and genetic studies have often linked alterations in catecholamine genes with ADHD.

• #60 Neuronal Mechanisms Underlying Attention Deficit Hyperactivity Disorder

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2863119/

  Medications for the treatment of ADHD all enhance catecholamine transmission. […] It is likely that both DA and NE actions contribute to the therapeutic effects of stimulants in patients with ADHD. […] In summary, catecholamines have powerful influences on the brain circuits, and genetic studies have often linked alterations in catecholamine genes with ADHD.

• #61 Attention-Deficit/Hyperactivity Disorder (ADHD) – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/learning-and-developmental-disorders/attention-deficit-hyperactivity-disorder-adhd

  Although correction of the underlying neurophysiologic differences of patients with ADHD does not occur with medication therapy, medications are effective in alleviating ADHD symptoms and they permit participation in activities previously inaccessible because of poor attention and impulsivity. […] Stimulant preparations that include methylphenidate or amphetamine salts are most widely used. […] Atomoxetine, a selective norepinephrine reuptake inhibitor, is also used. […] Adverse drug interactions are a concern with ADHD treatment.

• #62 Diagnosis and Management of Attention-Deficit/Hyperactivity Disorder in Adults | AAFP

  https://www.aafp.org/pubs/afp/issues/2012/0501/p890.html

  Attention-deficit/hyperactivity disorder in childhood can persist into adulthood in at least 30 percent of patients, with 3 to 4 percent of adults meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., diagnostic criteria. […] Current estimates indicate that approximately 3 to 4 percent of adults meet the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV), diagnostic criteria for ADHD, whereas approximately 16 percent of adults meet some of these criteria, but not enough for diagnosis. […] The mainstay of ADHD treatment is pharmacotherapy. Most studies focus on medications in children, yet these medications have been shown to be safe and effective in adults as well. […] Stimulants and antidepressants (e.g., bupropion [Wellbutrin], desipramine [Norpramin]) have similar effectiveness, although no direct comparison trials have been conducted.

• #63 Mechanism of Action of Stimulants in Attention-Deficit/Hyperactivity Disorder

  https://www.psychiatrist.com/jcp/mechanism-action-stimulants-attention-deficit-hyperactivity/

  Mechanism of Action of Stimulants in Attention-Deficit/Hyperactivity Disorder […] Stimulants hypothetically increase the availability of both dopamine and norepinephrine in prefrontal cortex, which enhances the efficiency of information processing at pyramidal neurons, resulting in the improvement of symptoms in attention-deficit/hyperactivity disorder (ADHD). […] Symptoms of ADHD are theoretically linked to inefficient information processing by pyramidal neurons in PFC, perhaps due in part to imbalances in the neurotransmitters DA and NE. […] Stimulants such as methylphenidate and amphetamine hypothetically act at these pyramidal neurons to enhance signal strength by increasing NE and to reduce noise by increasing DA, thereby reducing symptoms of inattention, hyperactivity, and impulsivity in ADHD.

• #64 Attention Deficit Hyperactivity Disorder (ADHD): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/289350-overview

  The pathology of ADHD is not clear. Psychostimulants (which facilitate dopamine release) and noradrenergic tricyclics used to treat this condition have led to speculation that certain brain areas related to attention are deficient in neural transmission. PET scan imaging indicates that methylphenidate acts to increase dopamine. […] The neurotransmitters dopamine and norepinephrine have been associated with ADHD. […] The underlying brain regions predominantly thought to be involved are frontal and prefrontal; the parietal lobe and cerebellum may also be involved. In one functional MRI study, children with ADHD who performed response-inhibition tasks were reported to have differing activation in frontostriatal areas compared with healthy controls. A 2010 study again indicated the presence of frontostriatal malfunctioning in the etiology of ADHD.

• #65 Attention-Deficit/Hyperactivity Disorder (ADHD) – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/learning-and-developmental-disorders/attention-deficit-hyperactivity-disorder-adhd

  Although correction of the underlying neurophysiologic differences of patients with ADHD does not occur with medication therapy, medications are effective in alleviating ADHD symptoms and they permit participation in activities previously inaccessible because of poor attention and impulsivity. […] Stimulant preparations that include methylphenidate or amphetamine salts are most widely used. […] Atomoxetine, a selective norepinephrine reuptake inhibitor, is also used. […] Adverse drug interactions are a concern with ADHD treatment.

• #66 Diagnosis and Management of Attention-Deficit/Hyperactivity Disorder in Adults | AAFP

  https://www.aafp.org/pubs/afp/issues/2012/0501/p890.html

  In a recent meta-analysis, stimulant and nonstimulant medications showed clinically significant improvements compared with placebo. […] Clinical guidelines recommend stimulants and atomoxetine (Strattera) as first-line treatments, followed by antidepressants. […] Small studies have found that cognitive behavior therapy is helpful as an adjunct to medication in the treatment of ADHD in adults. […] The mechanism of how cognitive behavior therapy helps treat ADHD is uncertain, but it may help improve daily life skills affected by ADHD.

• #67 Diagnosis and Management of Attention-Deficit/Hyperactivity Disorder in Adults | AAFP

  https://www.aafp.org/pubs/afp/issues/2012/0501/p890.html

  In a recent meta-analysis, stimulant and nonstimulant medications showed clinically significant improvements compared with placebo. […] Clinical guidelines recommend stimulants and atomoxetine (Strattera) as first-line treatments, followed by antidepressants. […] Small studies have found that cognitive behavior therapy is helpful as an adjunct to medication in the treatment of ADHD in adults. […] The mechanism of how cognitive behavior therapy helps treat ADHD is uncertain, but it may help improve daily life skills affected by ADHD.

• #68 Diagnosis and Management of Attention-Deficit/Hyperactivity Disorder in Adults | AAFP

  https://www.aafp.org/pubs/afp/issues/2012/0501/p890.html

  Attention-deficit/hyperactivity disorder in childhood can persist into adulthood in at least 30 percent of patients, with 3 to 4 percent of adults meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., diagnostic criteria. […] Current estimates indicate that approximately 3 to 4 percent of adults meet the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV), diagnostic criteria for ADHD, whereas approximately 16 percent of adults meet some of these criteria, but not enough for diagnosis. […] The mainstay of ADHD treatment is pharmacotherapy. Most studies focus on medications in children, yet these medications have been shown to be safe and effective in adults as well. […] Stimulants and antidepressants (e.g., bupropion [Wellbutrin], desipramine [Norpramin]) have similar effectiveness, although no direct comparison trials have been conducted.

• #69

  https://journals.lww.com/annals-of-medicine-and-surgery/fulltext/2023/05000/adult_attention_deficit_hyperactivity_disorder__a.74.aspx

  Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder, with only 23% prevalence into adulthood. The epidemiology and proposed causes of ADHD are multifactorial, including genetic, prenatal and environmental influences. The diagnosis of ADHD is often complicated by masking coping mechanisms, an overlap of symptoms with other, more commonly diagnosed disorders. Traditionally, it has been treated with stimulant medications. Non-stimulant options often target norepinephrine and dopamine regulation and are preferred in cases of comorbid substance use disorder, anxiety and other complicating factors, due to an improved side-effect profile and patient preference. They include atomoxetine and viloxazine. The latter, Viloxazine, in the form of extended-release capsules, is the first novel, non-stimulant option approved for adults with ADHD, in the past two decades. Its therapeutic effects are predominantly produced by its action as a norepinephrine reuptake inhibitor and may also modulate the serotonergic system. Viloxazine is relatively safe and effective in treating other disorders such as depression, anxiety, epilepsy and substance use disorder. A thorough review of the history, mechanism of action, pharmacokinetics and drug-drug interactions has been presented here, with special attention on treatment in adults with comorbid conditions. Several factors contribute to ADHD symptoms, including genetics, neurodevelopmental disorders, abnormal neuronal maturation, brain injury, environmental exposure and consanguinity. A recent study by Posner and colleagues reported that environmental risk factors contribute to ADHD symptoms at prenatal, perinatal, and postnatal stages. Prenatal and perinatal risk factors such as prematurity, low birth weight, maternal smoking history, stress, trauma and obesity are substantially associated with ADHD. Postnatal risk factors such as trauma, parenting style, artificial colours and fragrances, pollutants, and pesticides can exacerbate ADHD symptoms. Medication-based treatment strategies have proven effective and inexpensive in the short term, and many compounds are available, recommended and widely used. The long-term efficacy of these treatments on clinical, occupational and social outcomes remains unknown. It is clear that better long-term treatments for ADHD are urgently needed. The American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders (DSM) is a widely used approach for diagnosing ADHD in adults and requires childhood onset. The purpose of this review is to describe the characteristics and the associated comorbidities of Adult ADHD and to depict the scope of available treatment. Two-thirds of ADHD adults present with one comorbid psychiatric disorder. Studies also show that ADHD is found in 15% of psychiatric patients. These comorbidities are responsible for masking ADHD which reduces the frequency of correct diagnosis. Comorbidity rates of 57-92% have been shown in various studies. ADHD is associated with poor academic and professional performance because it presents with reading disabilities which lead to repeating grades and attending special educational facilities hindering higher educational opportunities. ADHD adults often feel different from others due to their inability to comprehend social cues and because they lack propriety. Diagnosis is essential as it helps them to come to term with their shortcomings. The patients are creative and thus usually prosper in the art industry. Accomplishing tasks is rewarding when it is in their interest. Viloxazine is a non-stimulant drug that may be helpful for patients whose anxiety is worsened with first-line medications. Viloxazine is another drug in the toolbox of practitioners co-treating ADHD and substance use disorder. It is hypothesized that because Viloxazine does not antagonize dopamine reuptake in the reward centre of the brain, it lacks the addictive effects of methylphenidate and dexamphetamine.

• #70 Molecular Mechanisms Underlying NMDARs Dysfunction and Their Role in ADHD Pathogenesis

  https://www.mdpi.com/1422-0067/24/16/12983

  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. […] 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. […] While dopamine deficit is the best-known factor associated with ADHD, an increasing amount of evidence indicates that disrupted glutamatergic transmission also plays a significant role in the disorder pathogenesis.

• #71 Molecular Mechanisms Underlying NMDARs Dysfunction and Their Role in ADHD Pathogenesis

  https://www.mdpi.com/1422-0067/24/16/12983

  The potential causal role of NMDAR dysfunction in the pathogenesis of ADHD has become a new area of research interest. For this reason, this review paper is aimed to focus on the role of NMDAR dysregulation in ADHD pathophysiology, which to date has not been studied extensively and is not well-understood. NMDAR dysfunction is one of the suggested mechanisms underlying ADHD pathogenesis in humans, as the role of NMDAR dysregulation has been well-established in a rat model of ADHD. […] Research regarding NMDAR role in ADHD might be useful in the development of novel treatment strategies, as currently most effective drugs, atomoxetine and methylphenidate, beside inhibiting monoamine reuptake, also influence NMDAR function. […] NMDAR dysregulation might be an important mechanism underlying the development of the disorder, and may at least by part explain the heterogeneity of patient’s symptoms. A better understanding of the role of NMDAR in the disease pathogenesis may lead to the development of novel, targeted therapies that could bring relief to ADHD patients.

• #72 Psychopathology of attention deficit/hyperactivity disorder: from an inflammatory perspective | The Egyptian Journal of Neurology, Psychiatry and Neurosurgery | Full Text

  https://ejnpn.springeropen.com/articles/10.1186/s41983-022-00561-y

  The underlying inflammatory processes and mechanisms in ADHD are not clearly understood. Therefore, further exploration is warranted in future research. This has clinical implications as inflammation may be a potential target in the treatment of ADHD. […] Current literature cannot pinpoint the exact cause of ADHD but suggests that an interplay of genetic and environmental factors plays a role in the pathogenesis and psychopathology of ADHD. […] It is also increasingly evident that factors such as oxidative stress, neuroinflammation, autoimmune diseases, maternal immune activation, allergic diseases and other immune-mediated conditions are linked to ADHD. […] However, the underlying mechanisms are not clearly understood, which warrant further exploration. This has clinical significance in terms of treatment of ADHD. Current treatment approach focusses on behavioural therapy, stimulant drugs and/or non-stimulant drugs. If the underlying mechanisms of the immune responses are known in patients whose ADHD is associated with inflammation, then inflammation may be a potential therapeutic target and treatment strategies may include immune modulation, antioxidants or anti-inflammatory agents. […] The neuroinflammatory process has important implications on the treatment of ADHD. Being a common feature in many CNS pathologies, neuroinflammation has become an emerging therapeutic target.

• #73 Psychopathology of attention deficit/hyperactivity disorder: from an inflammatory perspective | The Egyptian Journal of Neurology, Psychiatry and Neurosurgery | Full Text

  https://ejnpn.springeropen.com/articles/10.1186/s41983-022-00561-y

  The underlying inflammatory processes and mechanisms in ADHD are not clearly understood. Therefore, further exploration is warranted in future research. This has clinical implications as inflammation may be a potential target in the treatment of ADHD. […] Current literature cannot pinpoint the exact cause of ADHD but suggests that an interplay of genetic and environmental factors plays a role in the pathogenesis and psychopathology of ADHD. […] It is also increasingly evident that factors such as oxidative stress, neuroinflammation, autoimmune diseases, maternal immune activation, allergic diseases and other immune-mediated conditions are linked to ADHD. […] However, the underlying mechanisms are not clearly understood, which warrant further exploration. This has clinical significance in terms of treatment of ADHD. Current treatment approach focusses on behavioural therapy, stimulant drugs and/or non-stimulant drugs. If the underlying mechanisms of the immune responses are known in patients whose ADHD is associated with inflammation, then inflammation may be a potential therapeutic target and treatment strategies may include immune modulation, antioxidants or anti-inflammatory agents. […] The neuroinflammatory process has important implications on the treatment of ADHD. Being a common feature in many CNS pathologies, neuroinflammation has become an emerging therapeutic target.

• #74 Attention-deficit/hyperactivity disorder | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-024-00495-0

  Attention-deficit/hyperactivity disorder (ADHD; also known as hyperkinetic disorder) is a common neurodevelopmental condition that affects children and adults worldwide. ADHD has a predominantly genetic aetiology that involves common and rare genetic variants. Some environmental correlates of the disorder have been discovered but causation has been difficult to establish. The heterogeneity of the condition is evident in the diverse presentation of symptoms and levels of impairment, the numerous co-occurring mental and physical conditions, the various domains of neurocognitive impairment, and extensive minor structural and functional brain differences. […] Clinical and neurobiological research is ongoing and could lead to the creation of personalized diagnostic and therapeutic approaches for this disorder.

• #75

  https://journals.lww.com/annals-of-medicine-and-surgery/fulltext/2023/05000/adult_attention_deficit_hyperactivity_disorder__a.74.aspx

  Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder, with only 23% prevalence into adulthood. The epidemiology and proposed causes of ADHD are multifactorial, including genetic, prenatal and environmental influences. The diagnosis of ADHD is often complicated by masking coping mechanisms, an overlap of symptoms with other, more commonly diagnosed disorders. Traditionally, it has been treated with stimulant medications. Non-stimulant options often target norepinephrine and dopamine regulation and are preferred in cases of comorbid substance use disorder, anxiety and other complicating factors, due to an improved side-effect profile and patient preference. They include atomoxetine and viloxazine. The latter, Viloxazine, in the form of extended-release capsules, is the first novel, non-stimulant option approved for adults with ADHD, in the past two decades. Its therapeutic effects are predominantly produced by its action as a norepinephrine reuptake inhibitor and may also modulate the serotonergic system. Viloxazine is relatively safe and effective in treating other disorders such as depression, anxiety, epilepsy and substance use disorder. A thorough review of the history, mechanism of action, pharmacokinetics and drug-drug interactions has been presented here, with special attention on treatment in adults with comorbid conditions. Several factors contribute to ADHD symptoms, including genetics, neurodevelopmental disorders, abnormal neuronal maturation, brain injury, environmental exposure and consanguinity. A recent study by Posner and colleagues reported that environmental risk factors contribute to ADHD symptoms at prenatal, perinatal, and postnatal stages. Prenatal and perinatal risk factors such as prematurity, low birth weight, maternal smoking history, stress, trauma and obesity are substantially associated with ADHD. Postnatal risk factors such as trauma, parenting style, artificial colours and fragrances, pollutants, and pesticides can exacerbate ADHD symptoms. Medication-based treatment strategies have proven effective and inexpensive in the short term, and many compounds are available, recommended and widely used. The long-term efficacy of these treatments on clinical, occupational and social outcomes remains unknown. It is clear that better long-term treatments for ADHD are urgently needed. The American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders (DSM) is a widely used approach for diagnosing ADHD in adults and requires childhood onset. The purpose of this review is to describe the characteristics and the associated comorbidities of Adult ADHD and to depict the scope of available treatment. Two-thirds of ADHD adults present with one comorbid psychiatric disorder. Studies also show that ADHD is found in 15% of psychiatric patients. These comorbidities are responsible for masking ADHD which reduces the frequency of correct diagnosis. Comorbidity rates of 57-92% have been shown in various studies. ADHD is associated with poor academic and professional performance because it presents with reading disabilities which lead to repeating grades and attending special educational facilities hindering higher educational opportunities. ADHD adults often feel different from others due to their inability to comprehend social cues and because they lack propriety. Diagnosis is essential as it helps them to come to term with their shortcomings. The patients are creative and thus usually prosper in the art industry. Accomplishing tasks is rewarding when it is in their interest. Viloxazine is a non-stimulant drug that may be helpful for patients whose anxiety is worsened with first-line medications. Viloxazine is another drug in the toolbox of practitioners co-treating ADHD and substance use disorder. It is hypothesized that because Viloxazine does not antagonize dopamine reuptake in the reward centre of the brain, it lacks the addictive effects of methylphenidate and dexamphetamine.

• #76 Adult Attention-deficit/Hyperactivity Disorder (aADHD)

  https://www.psychiatrictimes.com/view/adult-attention-deficit-hyperactivity-disorder

  Adult ADHD is often underdiagnosed. […] Given this overlap in symptomatology, it is recommended that aADHD should be evaluated using a dimensional rather than a categorical approach. […] Early diagnosis and treatment of comorbid disorders appear to improve the outcomes among individuals with aADHD. […] Pharmacological agents are considered first line interventions for the treatment of aADHD. […] Stimulant medications are the treatment of choice among individuals with aADHD with similar efficacy noted for the amphetamine and methylphenidate group of drugs. […] CBT has the best evidence among non-pharmacological treatments and is beneficial for those individuals who decline pharmacotherapy, are intolerant to medications, or have residual symptoms despite adequate pharmacotherapeutic trials.

• #77 Diagnosis and Management of Attention-Deficit/Hyperactivity Disorder in Adults | AAFP

  https://www.aafp.org/pubs/afp/issues/2012/0501/p890.html

  In a recent meta-analysis, stimulant and nonstimulant medications showed clinically significant improvements compared with placebo. […] Clinical guidelines recommend stimulants and atomoxetine (Strattera) as first-line treatments, followed by antidepressants. […] Small studies have found that cognitive behavior therapy is helpful as an adjunct to medication in the treatment of ADHD in adults. […] The mechanism of how cognitive behavior therapy helps treat ADHD is uncertain, but it may help improve daily life skills affected by ADHD.

• #78 Diagnosis and Management of Attention-Deficit/Hyperactivity Disorder in Adults | AAFP

  https://www.aafp.org/pubs/afp/issues/2012/0501/p890.html

  In a recent meta-analysis, stimulant and nonstimulant medications showed clinically significant improvements compared with placebo. […] Clinical guidelines recommend stimulants and atomoxetine (Strattera) as first-line treatments, followed by antidepressants. […] Small studies have found that cognitive behavior therapy is helpful as an adjunct to medication in the treatment of ADHD in adults. […] The mechanism of how cognitive behavior therapy helps treat ADHD is uncertain, but it may help improve daily life skills affected by ADHD.

• #79 Adult Attention-deficit/Hyperactivity Disorder (aADHD)

  https://www.psychiatrictimes.com/view/adult-attention-deficit-hyperactivity-disorder

  Adult ADHD is often underdiagnosed. […] Given this overlap in symptomatology, it is recommended that aADHD should be evaluated using a dimensional rather than a categorical approach. […] Early diagnosis and treatment of comorbid disorders appear to improve the outcomes among individuals with aADHD. […] Pharmacological agents are considered first line interventions for the treatment of aADHD. […] Stimulant medications are the treatment of choice among individuals with aADHD with similar efficacy noted for the amphetamine and methylphenidate group of drugs. […] CBT has the best evidence among non-pharmacological treatments and is beneficial for those individuals who decline pharmacotherapy, are intolerant to medications, or have residual symptoms despite adequate pharmacotherapeutic trials.

• #80 Attention-Deficit/Hyperactivity Disorder (ADHD) – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/learning-and-developmental-disorders/attention-deficit-hyperactivity-disorder-adhd

  Although correction of the underlying neurophysiologic differences of patients with ADHD does not occur with medication therapy, medications are effective in alleviating ADHD symptoms and they permit participation in activities previously inaccessible because of poor attention and impulsivity. […] Stimulant preparations that include methylphenidate or amphetamine salts are most widely used. […] Atomoxetine, a selective norepinephrine reuptake inhibitor, is also used. […] Adverse drug interactions are a concern with ADHD treatment.

• #81

  https://link.springer.com/article/10.1007/s44192-022-00030-1

  Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition characterized by developmentally inappropriate symptoms of inattention and/or hyperactivity/impulsivity, which leads to impairments in the social, academic, and professional contexts. […] Despite the difficulties imposed by the high complexity of ADHD etiology, the growing body of research and technological advances provide good perspectives for understanding the neurobiology of the disorder. […] ADHD diagnosis is sometimes challenging due to the substantial heterogeneity of the disorder in terms of clinical and pathophysiological aspects, a fact that impacts research on the etiological and neurobiological specificities of ADHD. […] More than 60% of individuals with ADHD present at least one comorbid psychiatric disorder, frequently including depressive, anxiety, and disruptive behavioral disorders.

• #82 The impact of psychological theory on the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults: A scoping review | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261247

  Psychological theory and interpretation of research are key elements influencing clinical treatment development and design in Attention Deficit Hyperactivity Disorder (ADHD). […] A wide variety of approaches have developed to improve ADHD outcomes in adults, and this review aimed to map the theoretical foundations of treatment design to understand their impact. […] Results showed that despite variation in the application, current treatments characterise ADHD from a single paradigm of cognitive behavioural theory. […] A single theoretical perspective is limiting research for effective treatments for ADHD to address ongoing issues such as accommodating context variability and heterogeneity. […] Research into alternative theoretical characterisations of ADHD is recommended to provide treatment design opportunities to better understand and address symptoms.

• #83 The impact of psychological theory on the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults: A scoping review | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261247

  It is hypothesised that much of current research for the characterisation of ADHD is based on a cognitive behavioural theoretical paradigm that does not account comprehensively for the broad spectrum of ADHD presentation. […] This paradigm is deficit-focused with primary treatment outcomes of symptom reduction and control of maladaptive behaviours. […] This scoping review aims to map the evidence and understand the influence of current psychological theories on design and treatment recommendations in adult ADHD. […] This review reflects current research understanding that ADHD is complex and multidimensional in its presentation and impact. […] Critically, it highlights that a single theoretical perspective limits research into effective treatments for ADHD. […] Hence, the findings in this scoping review identify a gap in research and practice for alternative theoretical perspectives of ADHD. […] This review concludes that further research into additional theoretical models of self-regulation would provide opportunities to develop alternative treatment approaches and benefit research and understanding of the symptomology of ADHD.

• #84 The impact of psychological theory on the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults: A scoping review | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261247

  Psychological theory and interpretation of research are key elements influencing clinical treatment development and design in Attention Deficit Hyperactivity Disorder (ADHD). […] A wide variety of approaches have developed to improve ADHD outcomes in adults, and this review aimed to map the theoretical foundations of treatment design to understand their impact. […] Results showed that despite variation in the application, current treatments characterise ADHD from a single paradigm of cognitive behavioural theory. […] A single theoretical perspective is limiting research for effective treatments for ADHD to address ongoing issues such as accommodating context variability and heterogeneity. […] Research into alternative theoretical characterisations of ADHD is recommended to provide treatment design opportunities to better understand and address symptoms.

• #85 Management of Attention-Deficit/Hyperactivity Disorder in Adults: A Systematic Review | Effective Health Care (EHC) Program

  https://effectivehealthcare.ahrq.gov/products/management-adhd-adults/protocol

  Treatment decisions will be influenced by whether the interventions are likely to help the core symptoms of ADHD or other domains of functional impairment, the costs of treatment, and the likelihood of side effects. Other treatment decisions must also be made — for example, which class and which medication within each class should be tried, whether a short- or long-acting form of medication should be prescribed, what dose of medication should be targeted, whether medication should be taken on a daily basis or only as needed, which alternative treatments should be considered when side effects limit the dose or tolerability of a medication, whether to combine treatments, and whether to employ smart phone apps, pharmacogenetic testing, or clinical and biological predictors of treatment response to aid the management of ADHD. Even when these decisions are made and ADHD treatments prove helpful, management is often complicated by poor long-term adherence.

• #86 Management of Attention-Deficit/Hyperactivity Disorder in Adults: A Systematic Review | Effective Health Care (EHC) Program

  https://effectivehealthcare.ahrq.gov/products/management-adhd-adults/protocol

  Treatment decisions for adults with ADHD are most often made by primary care practitioners who have limited training in mental health care, rather than by mental health specialists. Both specialists and non-specialists would benefit from guidelines for the treatment of ADHD. Despite the publication of several international treatment guidelines, however, none have been specific for the treatment of adults with ADHD, and their evidence base has been limited. No guidelines for the treatment of adults with ADHD have thus far been developed in the United States, though one is in development. […] Adults with ADHD are treated with U.S. Food and Drug Administration (FDA)-approved stimulants (e.g., methylphenidates, amphetamines), FDA-approved non-stimulant medications (selective norepinephrine reuptake inhibitors, alpha agonists, bupropion), FDA-approved digital therapeutics and nerve stimulators, non-FDA-approved interventions (e.g., modafinil, nutritional supplements, cognitive training, neurofeedback, and neuromodulation) and psychological therapies, including psychosocial interventions, behavioral interventions, and various psychotherapies.

• #87

  https://link.springer.com/article/10.1007/s44192-022-00030-1

  The role of microbiota in the pathogenesis of ADHD has been suggested by studies showing differences in microbiota composition and/or abundance between patients with ADHD and controls. […] The treatment options can be non-pharmacological, pharmacological, or a combination of both. […] The safety and efficacy of commonly used ADHD medications are supported by metanalyses, which provide the basis for the guidelines recommendations mentioned above. […] ADHD is an important impairing condition of public health due to its prevalence and persistence across the lifespan, and because it leads to a higher risk of adverse outcomes, such as academic underachievement, substance use and abuse, other psychiatric disorders, somatic diseases, risky behaviors, and premature death. […] The growing body of research and technological advances provide good perspectives for understanding the neurobiology of ADHD, refining diagnosis, and identifying new therapeutic options to optimize treatment outcomes and associated impairments, leading to improvements in all domains of patient care.

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