ADHD-1xfffghjhgcccccfffffcffggggggg.pptx

Psychiatry

1. ADHD DR AKUL GUPTA

2. INTRODUCTION Attention-deficit/hyperactivity disorder is a common disorder characterized by inattention or hyperactivity–impulsivity, or both. The evidence base for the diagnosis and treatment of ADHD has been growing exponentially since the syndrome was first described by a German physician in 1775. In 1937, the efficacy of amphetamine use to reduce symptom severity was discovered. In the 1940s, the brain was implicated as the source of ADHD-like symptoms, which were described as minimal brain damage in the wake of an encephalitis epidemic.

3. In 1980, the third edition of the DSM created the first reliable operational diagnostic criteria for the disorder. These criteria initiated many programmes of research that ultimately led the scientific community to view ADHD as a seriously impairing, often persistent neurobiological disorder of high prevalence that is caused by a complex interplay between genetic and environmental risk factors. These risk factors affect the structural and functional capacity of brain networks and lead to ADHD symptoms, neurocognitive deficits and a wide range of functional impairments.

4. We now have many large and well-designed epidemiological, clinical and longitudinal studies that have clarified the features, co-morbidities and impairments associated with ADHD. These studies have created reliable and valid measurement tools for screening, diagnosis and monitoring of treatment. Likewise, rigorous clinical trials have documented the safety and efficacy of ADHD treatment, and it is now clear which ADHD treatments work, which do not and which require further study.

5. HISTORY OF ADHD Attention-deficit/hyperactivity disorder (ADHD) ‘syndromes’ have been described in the medical literature since the eighteenth century, but the growth of systematic research required the development of operational diagnostic criteria in the late twentieth century.

6. EPIDEMIOLOGY Age-dependent prevalence of ADHD ADHD is a common disorder among young people worldwide. In 2007, a meta-analysis of more than 100 studies estimated the worldwide prevalence of ADHD in children and adolescents to be 5.3% (5.01–5.56). Three methodological factors explained this variability among studies: the choice of diagnostic criteria The source of information used the inclusion of a requirement for functional impairment as well as symptoms for diagnosis.

7. After adjusting for these factors, a subsequent meta-analysis concluded that the prevalence of ADHD does not significantly differ between countries in Europe, Asia, Africa and the Americas, as well as in Australia. In addition, there is no evidence, worldwide, of an increase in the real prevalence of ADHD over the past three decades.

8. ADHD also affects adults. Although the majority of children with ADHD will not continue to meet the full set of criteria for ADHD as adults, the persistence of either functional impairment or subthreshold (three or fewer) impairing symptoms into adulthood is high. Simon and colleagues found the pooled prevalence of ADHD to be 2.5% (2.1–3.1) in adults. In addition, studies in older adults have found prevalence rates in the same range. Prospective longitudinal studies support the notion that approximately two-thirds of youths with ADHD retain impairing symptoms of the disorder in adulthood.

9. Recent alterations to diagnostic criteria have had an impact on ADHD prevalence measures in both young and adult populations. Overall, these new criteria have yielded an increase in ADHD prevalence, which is insubstantial for children but is likely to have had a more considerable effect on diagnosis rates in adults.

10. Sociodemographic factors Alongside age, other factors such as sex, ethnicity and socioeconomic status are also important when considering the prevalence of ADHD. In children and adolescents, ADHD predominantly affects males and exhibits a male-to-female sex ratio of 4:1 in clinical studies and 2.4:1 in population studies. In adulthood, this sex discrepancy almost disappears, possibly owing to referral biases among treatment-seeking patients or to sex‑specific effects of ADHD over the course of the disorder.

11. Larsson and colleagues found that low family income predicted an increased likelihood of ADHD in a Swedish population-based cohort study of 811,803 individuals. However, this finding does not necessarily support the conclusion that socioeconomic status increases the risk of ADHD because the disorder runs in families and leads to educational and occupational under attainment. Underemployment could in turn lead to the over-representation of socioeconomic disadvantage among families affected by ADHD.

12. PATHOPHYSIOLOGY Genetic Epidemiology ADHD runs in families, with parents and siblings of patients with ADHD showing between a fivefold and tenfold increased risk of developing the disorder compared with the general population. Twin studies show that ADHD has a heritability of 70–80% in both children and adults. Environmental risk factors play their greatest part in the non-shared familial environment and/or act through interactions with genes and DNA variants that regulate gene expression.

13. The disorder is influenced by both stable genetic factors and those that emerge at different developmental stages from childhood through to adulthood. Thus, genes contribute to the onset, persistence and remission of ADHD, presumably through stable neurobiological deficits as well as maturational or compensatory processes that influence development. Family and twin studies have also demonstrated that genetic influences are shared between ADHD and a wide range of other neurodevelopmental and psychopathological traits and disorders, including conduct disorder and problems, cognitive performance, autism spectrum disorders and mood disorders.

14. Molecular Genetics On the basis of data from genome wide association studies (GWAS), approximately 40% of the heritability of ADHD can be attributed to numerous common genetic variants. The polygenic risk for clinically diagnosed ADHD predicts ADHD symptoms in the population more broadly, confirming the conclusion from twin studies that the genes determining the diagnosis of ADHD also regulate the expression of subclinical levels of ADHD symptoms. In addition, these analyses have confirmed earlier evidence from family and twin studies that found significant co‑aggregation of ADHD with depression, conduct problems and schizophrenia.

15. In addition, rare genomic insertions and deletions known as copy number variants (CNVs) have a role in ADHD. One study found that 15.6% of patients with ADHD carry large CNVs compared with 7.5% of individuals without the disorder. The rate of large CNV carriage was even higher (42.4%) in those with both ADHD and an IQ below 70 ± 5.

16. These findings have been replicated, and together these studies implicate genes at 16p13.11 along with the 15q11–15q13 region in ADHD. The 15q11–15q13 region contains the gene that encodes the nicotinic α7 acetylcholine receptor subunit , which participates in neuronal and nicotinic signaling pathways. ADHD-associated CNVs also span several glutamate receptor genes , which are essential for neuronal glutamatergic transmission, and the gene encoding neuropeptide Y , which is involved in signaling in the brain and autonomic nervous system.

17. Candidate genes involved in the monoamine neurotransmitter systems had been implicated in the pathophysiology of ADHD by the mechanisms of action of drugs used in clinical management. Methylphenidate and amphetamine target the sodium-dependent dopamine transporter (encoded by SLC6A3 ). Atomoxetine targets the sodium-dependent noradrenaline transporter. Both extended-release guanfacine and extended-release clonidine target the α2A-adrenergic receptor.

18. Within the monoamine systems, the strongest evidence of ADHD association is for variants in the genes encoding the D4 and D1B dopamine receptors . Other genes that show possible associations with ADHD include: SLC6A4 (which encodes the sodium-dependent serotonin transporter) HTR1B (which encodes 5‑hydroxytryptamine receptor 1B (also known as serotonin receptor 1B)) SNAP25 (which encodes synaptosomal -associated protein 25).

19. Environmental Risk Factors Identifying environmental causes of ADHD is difficult because environmental associations might arise from other sources, such as from child or parental behaviours that shape the environment. For example, children with ADHD might evoke ‘hostile’ styles of parenting Genes linked to ADHD might explain the association of parental variables, such as maternal smoking during pregnancy, with offspring who have ADHD.

20. Similar to genetic risk factors, the effects of any one environmental risk factor are small and could reflect either small effects in many cases or larger effects in a few cases. One notable study found a role for genetically influenced early child behaviour on the hostility of biologically unrelated mothers, which in turn was a predictor of subsequent ADHD symptoms developed by the children. Another study showed a dose-dependent relationship between length of severe maternal deprivation and risk of developing ADHD-like symptoms.

21. Other environmental risk factors that have been associated with ADHD include prenatal and perinatal factors, such as: Maternal smoking and alcohol use, Use of non-prescribed drugs of abuse, prescribed drugs such as anticonvulsants and anxiolytics Maternal stress Maternal hypothyroidism. Low birth weight, Premature birth

22. In postnatal life Inadequate diet Iodine deficiency and major B vitamin deficiencies, Iron and lead poisoning, High exposure to industrially contaminated areas, old paint, and soft-water areas where lead water pipes are common Some artificial food colorings and preservatives Exposure to environmental toxins, such as organophosphate pesticides, polychlorinated biphenyls, zinc and lead.

23. The high heritability of ADHD suggests that gene–environment (G × E) interactions might be the main mechanism by which environmental risk factors increase the risk of ADHD. For example, a variant of 5‑HTTLPR — a polymorphic region located in the promoter of SLC6A4 — is involved in the hyperactivity and impulsivity dimensions of ADHD in interaction with stress. Epigenetics provides a mechanism by which environmental risk factors alter gene function, for example, Environmental toxins and stress can all induce epigenetic changes.

24. Clinical Implications Knowledge of risks has advanced to the point where it can inform advice to patients and their families. The understanding that there are genetic influences often comes as a liberation from personal guilt. Parents are vulnerable to societal views that their parenting failures have produced the features of ADHD. It is also important to avoid any impression that genetic influences imply an unalterable course. Parents and teachers can have a major influence for good on their children’s ability to cope with ADHD.

25. Clinical Implications Minor obstetric complications are seldom “the cause,” any more than minor infractions of health advice in pregnancy. A public view that broad social factors are responsible—for instance, rises in television viewing or internet use. It is therefore worth noting that shared environmental factors appear to play very little part.

26. BRAIN MECHANISMS Cognition: ADHD is characterized by deficits in multiple, relatively independent, cognitive domains. Executive functioning deficits are seen in visuospatial and verbal working memory, inhibitory control, vigilance and planning.

27. Studies of reward dysregulation show that patients with ADHD make suboptimal decisions, prefer immediate rather than delayed rewards overestimate the magnitude of proximal relative to distal rewards. Other domains impaired in ADHD include temporal information processing and timing; speech and language; memory span, processing speed and response time variability; arousal and activation; motor control. Although most patients with ADHD show deficits in one or two cognitive domains, some have no deficits and very few show deficits in all domains.

28. BRAIN MECHANISMS Structural and Functional Brain Imaging: Several brain regions and neural pathways have been implicated in ADHD.

29. DIAGNOSIS The key concept underlying the diagnoses of ADHD and hyperkinetic disorder (HKD) is that of maladaptively high levels of inattention , overactivity , and impulsiveness . These problems occur in different combinations in different individuals, and with different levels and types of associated problems.

30. A “ Classical ” presentation would be of the full picture without other problems. A child presents because of disorganized behavior in which: Inattention describes a lack of attention to detail, a short attention span in unmotivating situations, forgetfulness, distractibility in situations requiring focus on a task, and a slapdash attitude. Overactivity describes an excess of movement in situations requiring calm, such as the classroom, family meals, or visits to church or relatives. Impulsiveness refers to action without reflection, so affected people are accident-prone, impatient, intrusive on the activities of other people, and hasty (and therefore inept) in making decisions.

31. DIMENSIONS The separation of dimensions of inattentiveness and overactive impulsiveness has clinical and scientific value. There is “overwhelming” support for the distinction, not only from the internal, statistical correlations of symptoms, but also from stability over time, and the differential prediction of external associations. The dimensions are correlated with each other; but they deserve separate attention in clinical assessment. A dimensional way of thinking allows the balance of components to be assessed, and related problems brought in.

32. CATEGORIES AND SUBTYPES The categorical subtypes of DSM-IV— predominantly inattentive , predominantly hyperactive , and combined show only modest differences between themselves, and they are unstable over time. The DSM-5 and ICD-11 downgrades them from “subtypes” to “presentations”.

33. According to DSM-V (>=6 in each category): Inattention: Poor attention to detail/frequent mistakes Hard to maintain attention/focus When spoken to, appears not to listen Poor follow through on tasks Poor organizational skills Procrastinates from tasks requiring attention Loses things Distractible Forgetfulness Hyperactivity/impulsivity: Fidgety/restless Cannot stay seated Runs/climbs inappropriately Cannot do things quietly (e.g., play) Cannot keep still Inappropriately talkative Inappropriately blurts out answers Cannot wait his turn Interrupts others

34. According to ICD-11 (symptoms from the following clusters that are persistent, and sufficiently severe that they have a direct negative impact on academic, occupational, or social functioning) : Inattention: Difficulty sustaining attention to tasks that do not provide a high level of stimulation or reward or require sustained mental effort; lacking attention to detail; making careless mistakes in school or work assignments; not completing tasks. Easily distracted by extraneous stimuli or thoughts not related to the task at hand; often does not seem to listen when spoken to directly; frequently appears to be daydreaming or to have mind elsewhere. Loses things; is forgetful in daily activities; has difficulty remembering to complete upcoming daily tasks or activities; difficulty planning, managing and organizing schoolwork, tasks and other activities.

35. Hyperactivity/impulsivity: Excessive motor activity; leaves seat when expected to sit still; often runs about; has difficulty sitting still without fidgeting (younger children); feelings of physical restlessness, a sense of discomfort with being quiet or sitting still (adolescents and adults). Difficulty engaging in activities quietly; talks too much. Blurts out answers in school, comments at work; difficulty waiting turn in conversation, games, or activities; interrupts or intrudes on others conversations or games. A tendency to act in response to immediate stimuli without deliberation or consideration of risks and consequences (e.g., engaging in behaviours with potential for physical injury; impulsive decisions; reckless driving).

36. Clinical Implications: Categories of ADHD help clinicians who must make binary decisions such as whether or not to refer or to medicate, and it helps people who suffer from the condition, their families, and the public at large to understand the nature of the condition. Most clinicians find it useful to use a mixture of categorical and dimensional approaches. The first step in assessment will probably be to define the presence or absence of ADHD; A fuller analysis should quantify the levels of Severity of inattentiveness and hyperactivity/impulsivity separately Associated problems, functional impairment, impact on others, other strengths and weaknesses (e.g., athletic ability), peer acceptance, and risk.

37. CLINICAL ASSESSMENT A range of screening questionnaires are available. Some were developed to monitor response to therapy and subsequently refined statistically, e.g., Conner's’ Teacher and Parent Rating Scales Some other scales came from an epidemiological tradition, e.g., the Strengths and Difficulties Questionnaire (SDQ), and the longer Child Behavior Problems Checklist. Other scales were developed from DSM-III or DSM-IV criteria, such as the ADHD Rating Scale, the Vanderbilt Rating Scale, and the SNAP-IV scale.

38. PROBLEMS IN DIAGNOSIS Cut-offs The continuous distribution of ADHD symptoms in the population makes for uncertainty about where to place the division between normal variation and psychopathology. For research purposes, where replicability is key, it is sensible to follow the international conventions: at least six out of the nine inattentiveness criteria, and/or at least six out of nine hyperactive-impulsive. For clinical purposes, however, an unintelligent addition of criteria is not always best.

39. Developmental appropriateness Symptoms need to be considered in the light of what is appropriate to different ages and levels of development. “Hyperactivity,” for example, may be a whirlwind in the preschool period, fidgetiness in adolescence, and subjective restlessness in adulthood. Sufficient experience of attention and activity at different ages, both in typically developing children and in differing forms of psychopathology, is required so that it can be recognized when a child’s attention and activity are deviating from what is expected.

40. Misdiagnosis is particularly easy for children with intellectual disability. The diagnosis can be Missed by attributing all the problems to a low IQ, or Over recognized by treating the cognitive problems of intellectual disability as evidence for ADHD. There are two styles of coping with this problem: The first is to refer the child’s level of difficulty to that of others at similar levels of intellectual delay. A second approach is to refer the child’s level of difficulty to those of ordinary children whose chronological age corresponds to the developmental age of the child being assessed.

41. DIFFERENTIAL DIAGNOSIS The presence of ADHD or HKD should be recognized even in the presence of other psychiatric conditions. Some conditions, however, may masquerade as ADHD by reproducing some of its features. Other forms of overactivity Manic overactivity is goal-directed, rather than the disorganized pattern of ADHD. Autism may show a driven, stereotyped pattern of overactivity that can be extreme and worsened by anti-hyperactivity medication. Tics may appear to show impulsive overactivity (activity level is composed solely of a large number of sudden, repetitive movements).

42. Other forms of Inattentiveness Learning disorders may be accompanied by reluctance to engage in academic tasks, but it is often specific to tasks that are unduly difficult for the individual. Other forms of Disruptive Behavior Insomnia may produce an irritable child who is not engaging in classroom activity, but it is accompanied by daytime sleepiness. Oppositional behavior alone may be responsible for task refusal, so the absence of inattention is a helpful guide when the problem is oppositionality without ADHD.

43. Other forms of Emotional Dysregulation Emotional dysregulation is also a feature of bipolar disorder. The ADHD pattern is not episodic but a persisting trait, and by the absence of the euphoria and grandiosity that characterize the episodes of mania. Different Etiology Brain syndromes, such as fragile-X, tuberous sclerosis, Jacobsen syndrome (deletions of the end of 11q), Turner syndrome (X0), Klinefelter syndrome (XXY) may well be responsible for ADHD features. Severe neglect in early childhood is probably a cause of attention and activity abnormalities.

44. L ONGITUDINAL COURSE Referral for ADHD is most common in middle childhood negative impact on everyday function across a range of psychological domains and social and educational arenas 2007). Longitudinal studies, however, make clear that these patterns of impairment nearly always have their roots early on in the preschool period and very often persist across the life span in one form or another.