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ADHD: Mimicry, Comorbidity And Correlates When assessing children referred for suspected ADHD it is essential to obtain objective information regarding the presence of ADHD symptoms across situations. It is also important to obtain information regarding the age at which these symptoms developed, how long these symptoms have been present, and to make a determination of the degree of impairment in functioning, across situations, the child experiences as a result of these symptoms. All of these issues must be addressed in attempting to make a formal diagnosis of this extremely common childhood disorder. While obtaining all of this information is necessary, it is not enough. It is not enough for two reasons. First, it is possible for other conditions to mimic symptoms of ADHD such that, while the topography of the child’s behavior may be highly suggestive of ADHD, “symptoms” may arise from causes other than ADHD. Prior to making a diagnosis it is important to rule out these causes so that the focus of treatment is directed toward appropriate targets for intervention. Secondly, we now know that children with ADHD often display diagnosable conditions in addition to this primary diagnosis. In such cases it is important to appropriately assess for possible comorbid conditions so that intervention efforts can be directed toward the full range of problems displayed by the child. The focus here will be on providing a brief overview of some of the factors and conditions that can mimic symptoms of ADHD and discuss, in somewhat more detail, the issue of comorbidity as it relates to assessing problems displayed by children with ADHD ADHD: THE ISSUE OF MIMICRY In conducting an assessment of a child suspected of having ADHD it is essential that the clinician to be aware of and be attentive to the fact that problems of activity level, impulsivity and inattention can be caused by a variety of factors other than ADHD. Some of these conditions are of a psychological nature while others result from physical conditions. Psychological Issues Both child anxiety and depressive disorders can result in problems in concentration and symptoms of inattention as well as increased levels of activity, in some instances. Children with histories of physical or sexual abuse or who have been repeatedly exposed to parental violence may display post traumatic stress symptoms, that may be reflected in clinically significant problems of inattention. And, the degree of behavioral disorganization that can occur in such cases may result in increased levels of activity, which can be confused with ADHD, in the absence of an adequate assessment. With the preschool child, it can sometimes be difficult to distinguish between the noncompliant (and seemingly inattentive) and oppositional and defiant behaviors 1 displayed by the child with early Oppositional Defiant Disorder and the child with ADHD. It is also the case that assessing for ADHD in the presence of conditions such as mental retardation and certain pervasive developmental disorders can sometimes pose a challenge due to the problems of inattention and disorganization of behavior that may be seen in each of these conditions. Appropriate diagnosis in such instances is best accomplished by considering the total clinical picture rather than simply those behaviors commonly seen as core symptoms of ADHD. Physical Factors Sensory deficits such as visual or auditory impairments can result in problems of both inattention and behavioral disorganization, that can be confused with ADHD core symptoms if these impairments are not sufficiently assessed and taken into account. Medication side effects from drugs such as Phenobarbital and Dilantin can contribute to problems of inattention and activity level. While the findings are less clear, there is clinical evidence that certain asthma medications such as Theophylline can also cause side effects such as inattention and increased activity level. Significant problems of inattention, mimicking the symptoms of ADHD Inattentive Type, can also occur in the child with absence seizures. Likewise, children with RTH (Resistance to Thyroid Hormone) frequently display a full complement of ADHD symptomatology. One might also include developmental and genetic disorders (Fragile X syndrome), and endocrine and autoimmune disorders (PANDAS) among those conditions that may be manifested in such a way as to mimic ADHD symptoms. Although it is unlikely that any of these conditions perfectly mimic the developmental history or constellation of symptoms of ADHD, children with these disorders are often referred for evaluation of ADHD. Given that psychological and physical factors, such as the ones cited here, can result in problems of inattention and/or activity level that can mimic the symptoms of ADHD, it is clear that such factors must be ruled out prior to rendering a diagnosis of ADHD. In attempting to make a differential diagnosis, it is important to evaluate possible causal factors, neuroanatomical and physiological data, and the pattern and severity of symptoms developmentally and across settings. ADHD: THE ISSUE OF COMORBIDITY WHAT IS COMORBIDITY? The term comorbidity first appeared in the psychological and psychiatric literature in the 2 mid 1980's. Since that time there has been a dramatic increase in interest in this topic as reflected in the number of journal articles containing the term comorbidity in the title. In 1986 there were only two such articles; by 1993 the number had increased to 243. Since that time, work in this area has continued unabated. Indeed, it has been suggested that, comorbidity has emerged as perhaps the single most important concept for psychiatric research and practice and that its potential implications for theory and treatment are just beginning to be realized. A variety of definitions of comorbidity have been offered. From a medical epidemiology perspective, Feinstein has defined comorbidity as “any distinct additional entity that has existed or that may occur during the clinical course of a patient who has the index disease under study” (p. 467). Blashfield has referred to comorbidity as “the co-occurrence of different diseases in the same individual (p.61)". Caron and Rutter have defined comorbidity as “the simultaneous occurrence of two or more unrelated [italics added] conditions (p. 1063)”. As can be seen from these definitions, the term comorbidity refers to a situation in which an individual, who has been diagnosed with one specific disorder, is also found to meet diagnostic criteria for one or more additional disorders. Although the use of the concept of comorbidity seems relatively straightforward, there has been considerable controversy regarding the use of this term with reference to most psychiatric disorders. The primary reason for this concern is highlighted in the definition of comorbidity provided by Caron and Rutter, presented above. Here, comorbidity was defined in terms of the co-occurrence of two or more unrelated conditions. The word unrelated is most relevant. It has been argued that, unlike in the medical arena, where the etiology and pathological processes of specific disease entities are often reasonably well understood (and where the existence of specific disease processes can be assumed) there is seldom a detailed understanding of underlying causal factors in the case of psychiatric disorders. Without knowledge regarding the etiology of coexisting disorders, one cannot be certain that individuals who meet diagnostic criteria for more than one psychiatric disorder actually have unrelated conditions. It has been suggested that, what appear to be separate disorders may actually be the result of overlapping diagnostic criteria or the result of arbitrary diagnostic distinctions between different syndromes which may be variations on the same underlying disorder. Increased estimates of comorbidity may also result from the fact that, especially with younger children, what looks like comorbidity may reflect relatively nonspecific expressions of psychopathology, associated with lowered levels of cognitive development, as opposed to more clearly articulated examples of psychopathology that are more likely to be seen in older children and adolescents. As a result of these issues it has been suggested that, while the term comorbidity may be appropriate for use in referring to the presence of multiple medical “disease” entities, it’s use is less appropriate in the psychological/psychiatric arena where we are dealing with 3 putative “syndromes”, defined largely in terms of signs and symptoms, without detailed knowledge of underlying etiological factors. Those who have criticized the use of the term comorbidity in referring to examples of child and adult psychopathology have advocated substitute terms such as “diagnostic cooccurrence” or “diagnostic covariation” as these terms do not imply an association among disease entities, and refer to overlap at the descriptive, rather than pathological/etiological level. While acknowledging that use of the term comorbidity with reference to psychopathology must be done cautiously for the reasons just outlined, the term comorbidity will be used here for purposes of the present discussion. This term, rather than suggested alternatives, is preferred for the following reasons; The term comorbidity has come to be widely used in the psychopathology literature to refer to instances where individuals with one disorder are also found to meet criteria for another disorder. There are comorbidity studies of child psychopathology, specifically studies of ADHD, which provide data suggesting that (despite some exceptions) evidence of comorbidity is often found even when one controls for overlapping diagnostic criteria. There are recent research findings which provide support for the view that there are distinct subgroups of children, defined in terms of the presence of ADHD and different comorbid features, which suggest specific family-genetic risk factors, varying clinical course and, in some cases, differential responses to pharmacological treatment. COMORBID CONDITIONS ASSOCIATED WITH ADHD A number of studies have provided information regarding the type and degree of comorbidity found with children and adolescents diagnosed with ADHD. These findings are considered in the sections to follow. LEARNING DISABILITIES Children with ADHD often show problems functioning in the academic environment. These problems include behaviors which impede learning and cause disruptions in the classroom, poor academic performance, lowered levels of school achievement, and specific learning disabilities. With regard to more general school-related difficulties, research findings clearly suggest that children with attention deficit hyperactivity disorder perform more poorly in school relative to control subjects. They typically show evidence of more grade repetitions and more frequent placement in special classes. Follow-up studies of children with ADHD have also found that the academic and learning problems of such children often persist into adolescence and are associated with chronic underachievement and school failure. While academic and school related difficulties seem ubiquitous in children diagnosed with ADHD, specific learning disabilities are somewhat less frequent, although still commonly 4 found. In reviewing comorbidity findings prior to 1991, Biederman, et al found that the degree of overlap between ADHD and learning disabilities defined in various ways ranged from a low of 10 % to a high of 92%. Barkley , reviewing this and the more recent literature, has suggested that the best estimate of comorbidity is likely to be in the range of 19 to 26 per cent when learning disability is “conservatively” defined (i.e., significant delay in reading, math, or spelling relative to IQ, with achievement in one of these areas at or below the 7th percentile). He notes that, if learning disability is defined simply in terms of a significant discrepancy between IQ and achievement, comorbidity estimates are as high as 53%. When a more lax criterion, such as having achievement levels at least two grades below current grade placement are used, then comorbidity estimates as high as 80% are found. Apart from more general problems of school performance, school achievement and learning disabilities, children with ADHD also frequently show other types of developmentally related difficulties that can impair their functioning in the school environment. Most prominent in this regard are speech and language disorders which have been found to occur in as many as 30 to 64 % of children diagnosed with ADHD. OPPOSITIONAL DEFIANT AND CONDUCT DISORDER The finding of high levels of comorbidity with oppositional defiant disorder and with conduct disorder is very common, although relatively few studies have focused specifically on oppositional defiant disorder. In reviewing research findings up to 1990, Biederman, et al found that the few studies which had looked at oppositional defiant disorder consistently reported comorbidity rates around 35 %. Studies focusing on conduct disorder suggested comorbidity estimates in the 30 to 50 per cent range. More recent reviews of this literature have yielded somewhat similar findings. Barkley, for example, has suggested that, by the age of seven, 35 to 60 % of clinic-referred children with ADHD meet diagnostic criteria for ODD and that, at some point, 30 to 50% of children/adolescents with ADHD will meet criteria for CD. Findings in this area suggest that, not only is comorbidity common, but that when oppositional defiant or conduct disorder occur in conjunction with ADHD the clinical picture is one of increased severity compared to that found in children and adolescents with ADHD alone. Children with combined ADHD and ODD seem to represent an intermediate group with regard to severity of symptoms when compared to ADHD only children, who show less severe problems, and children with ADHD and CD, who show more severe problems. Commenting on cases where ADHD exists with a comorbid conduct disorder, Biederman et al have noted that “...there is increasing evidence that children with attention deficit hyperactivity disorder plus conduct disorder appear to have a particularly severe form of attention deficit hyperactivity disorder.” These investigators go on to indicate that “...subgrouping based on comorbidity with conduct disorder may be of potential value in determining which children with attention deficit hyperactivity disorder have a more 5 serious prognosis and different family-genetic risk factors and [who may] require specialized comprehensive therapeutic interventions1 (p.568).” ANXIETY DISORDERS ADHD has not only been found to be related to disruptive behavior disorders such as oppositional defiant and conduct disorder but also to internalizing problems such as anxiety disorders and depression. Biederman, et al, reviewing studies prior to 1991, on the association between ADHD and anxiety disorders found a comorbidity rate of approximately 25 per-cent. More recently, comorbidity rates between 25 and 40% have been found in clinically referred samples, and rates between 23 and 58.8% have been found in general population studies. These findings, which suggest relatively high rates of comorbidity, must be tempered by the fact that they relate primarily to younger children; this link between ADHD and anxiety disorders has been found to be markedly reduced in adolescents. In further qualifying the nature of the relationship between ADHD and comorbid anxiety disorders, it should be noted that there is other research which suggests that there are significant differences in comorbidity estimates between children displaying attention deficit disorder with and without hyperactivity. Here, children with DSM III diagnosed attention deficit disorder without hyperactivity (analogous to DSM IV - predominately inattentive type) have been found to show the highest degree of comorbidity with regard to anxiety disorders. Regarding the effects of anxiety disorder on the clinical picture of children with ADHD, it has been suggested that comorbid anxiety reduces the impulsiveness often associated with ADHD. MOOD DISORDERS While not all investigators have found an association between ADHD and mood disorders, early epidemiologic and clinical studies have typically suggested comorbidity estimates between 15 and 75%. Reviewing more recent findings, Barkley has suggested that the overall comorbidity rate for some type of mood disorder is most likely in the 40 to 50% range. The presence of major depressive disorder in combination with ADHD seems to complicate the usual clinical picture seen in children with ADHD. Follow up studies of children with ADHD and major depressive disorder have suggested that, while both disorders are independently associated with significant psychiatric morbidity, the combination of the two disorders appears to suggest a subgroup of children who show an especially poor long term outcome. While research findings typically support the notion that children with ADHD often display comorbid depressive disorders, findings concerning comorbidity with bipolar disorders is somewhat more controversial, despite the fact that a small number of studies suggest that the degree of overlap between ADHD and bipolar disorder is in the range of 11 to 22 per-cent. Despite these findings, it has been suggested that this degree of apparent comorbidity may be, in part, an artifact due to the fact that similar symptoms (e.g., attentional 6 problems, poor judgment, high activity level) are taken as diagnostic indicators of both disorders. It also seems to be the case that the relationship between ADHD and bipolar disorder is largely unidirectional. That is, the presence of bipolar disorder seems to suggest an increased risk for ADHD, while the presence of ADHD does not seem to suggest an increased risk of developing bipolar disorder. Additional research is needed to further investigate the precise relationship between ADHD and bipolar disorder. This seems to be especially important since there is at least one study which has suggested that adolescents who commit suicide show higher rates of both bipolarity and ADHD than do adolescents who attempt suicide without success. TOURETTE’S DISORDER There is data to suggest that Tourette’s Disorder may also be a comorbid feature of ADHD. Clinical studies suggest that, of those individuals with Tourette’s Disorder, somewhere between 40 and 50 % show features of ADHD, with symptoms of ADHD typically preceding the onset of Tourette’s symptoms. While such findings are of interest in suggesting overlap between the two disorders, it is possible that the magnitude of overlap is in part related to referral practices. That is, children displaying both disorders may be more likely to be referred for assessment and/or treatment than children who show either of the disorders alone. It is noteworthy that the only published population-based study suggests a much lower rate of ADHD diagnoses (12%) in children with Tourette’s disorder. While these findings support the existence of some degree of comorbidity, they suggest that the actual degree of comorbidity is likely to be lower than that suggested by clinical studies. Additional studies in this area are necessary to more carefully ascertain the degree of comorbidity and the nature of the underlying relationships between ADHD and Tourette’s Disorder. THE RELEVANCE OF COMORBIDITY FOR CHILDREN WITH ADHD While it is clear that many questions regarding comorbid features of ADHD remain to be answered, it is also clear that the issue of comorbidity is one with important implications for the understanding, assessment, and treatment of children with ADHD. First, the available findings suggest that children with ADHD, especially younger children, frequently show evidence of significant comorbidity. Indeed, there seems to be strong evidence that many children with ADHD also display Learning Disabilities, Oppositional Defiant Disorder or Conduct Disorder, Anxiety Disorders, and Depressive Disorders, while still others may show evidence of co-occurring tic disorders and perhaps bi-polar disorder. Some show more than one comorbid disorder. These patterns of comorbidity have been interpreted by Biederman, et al as suggesting that “...attention deficit hyperactivity disorder is most likely a group of conditions with potentially different and modifying risk factors and different outcomes rather than a single homogeneous clinical entity (p. 564)”. Not only does research support the ubiquitous nature of comorbidity in children with ADHD, there are also findings to suggest that the presence of comorbid conditions likely 7 have significant implications for long term outcome. That is, children with comorbid features often show more serious levels of impairment, are more likely to have continuing problems, and show a greater utilization of mental health services than do those without evidence of comorbidity. Considering the frequency and range of comorbid conditions found in children and adolescents with ADHD, and the fact that comorbidity adds to the seriousness and complexity of the problem, assessing for the presence of comorbid features that may complicate the clinical picture seems essential in working with children with ADHD. Given that proper assessment should lead to optimal treatment, it follows that treatment programs for children with ADHD and comorbid conditions should address the full range of problems highlighted by assessment findings. For example, in instances where a child, not only shows features of ADHD but also meets diagnostic criteria for Oppositional Defiant Disorder and Learning Disability, treatment should focus on problems associated with each of these areas. This might involve pharmacological treatment for dealing with the child’s hyperactive/impulsive and inattentive behavior, parent oriented behavior management approaches to modify oppositional behavior, and specially designed educational approaches to assist the child academically. Likewise, in the case of a child with ADHD and comorbid depression, it will be necessary to treat the child’s depression as well as the symptoms of ADHD. With children displaying other patterns of comorbidity, other combinations and/or approaches to treatment may be called for. Simply treating symptoms of ADHD is not enough! Appropriate case management involves addressing the full range of clinical problems displayed. Indeed, effective treatments for children with ADHD and comorbid conditions are likely to be multimodal and multidisciplinary in nature and necessarily more extensive and complex that treatments for children with “uncomplicated” ADHD. Clearly, more research is needed to guide the treatment of children with ADHD who display specific patterns of comorbidity. This is especially important given findings that children with certain comorbid features may respond differently to specific therapeutic approaches. To give but one example, it is clear that stimulant drugs work quite well with most children with ADHD. They also seem to be effective in managing ADHD symptoms of children who have both ADHD and comorbid conduct disorder. It has been shown, however, that stimulant drug effectiveness is often attenuated in children with ADHD who have comorbid anxiety and/or depressive disorders. In such cases it may be important to not only treat the symptoms of ADHD and the anxiety or depression, but it may be necessary to treat the symptoms of ADHD differently than they might be treated in the absence of comorbidity. Examples such as this clearly suggest that, in working with children with ADHD, it is important to assess for comorbid conditions and, to the extent possible, take these findings into account in treatment planning. ADDITIONAL PROBLEMS AND CORRELATES OF ADHD Apart from specific disorders that may coexist with ADHD, there are other associated 8 problems that may not rise to the status of a diagnosable disorder but which may nevertheless need to be considered when addressing the problems displayed by the child with ADHD. While the range of difficulties displayed by such children are numerous I want to briefly highlight just a few of them. PROBLEMS OF INTELLECTUAL DEVELOPMENT Children with ADHD are more likely to be behind in their intellectual development than either normal children or the siblings of the ADHD children. They tend to score on the average 7 to 15 points below control children on standardized measure of intelligence. Lowered scores are especially apparent in verbal intelligence. It is not totally clear whether these differences represent real differences in ability or just differences in test taking behavior. To the extent that IQ tests in older children are in part influenced by achievement rather than serving as pure measures of ability, the lower scores may also be due to the fact that the child has simply missed out on information other children have attained due to his problems of inattention and disorganized behavior. In any event levels of intellectual functioning may be lowered compared to age related peers . PROBLEMS OF ADAPTIVE BEHAVIOR Adaptive functioning refers to the child's development of age-appropriate motor skills, self-help skills, and personal responsibility and the ability to function independently at an age-appropriate level. A number of studies suggest that, compared to normal controls, children with ADHD show significantly lower levels of adaptive behavior. Here they often are found to function in the low average or borderline range. While children with other psychiatric disorders often show low levels of adaptive functioning, the discrepancy between overall IQ and level of adaptive functioning in children with ADHD is often found to be greater than in most other conditions. ADHD may take a special toll on adaptive functioning. There are also some findings to suggest that the greater the degree of social or adaptive impairment the greater the risk, at follow-up, for the child with ADHD to show comorbid substance abuse and psychiatric disorders. SPEECH DIFFICULTIES There is a tendency for children with ADHD to be somewhat more delayed in talking than non AHDH children. Studies generally suggest that ADHD children are likely to have problems with expressive language but not receptive language. Here, anywhere from 10 to 54% of ADHD children have speech problems compared from 2 to 25 percent of normal children. Such children often have special problems on tasks of 9 verbal fluency. ACCIDENTAL INJURIES Children with ADHD are considerably more likely to experience injuries due to accidents than normal children with up to 57% being described as “accident prone” and 15% having had at least four or more serious accidental injuries. Studies have been conducted to determine whether overactivity or aggressiveness were the main contributors to accidents. Findings suggest that both features contribute independently to accidental injury. Research on children who experience accidents suggest they are more likely to be overactive, impulsive and defiant. Children who are injured as pedestrians or bicycle riders in traffic accidents have been shown to perform more poorly on tests of vigilance and impulse control and receive higher ratings from parents and teachers on measures of hypearactive and aggressive behavior. This suggests that children having serious accidents are likely to be the children who have a greater than average number of ADHD symptoms. SLEEP PROBLEMS Studies suggest that children with ADHD have a higher likelihood of sleep problems than normal children. As many as 56% of ADHD children have problems falling asleep as compared to 23% of normal children. Up to 39% of ADHD children show problems of frequent nite time awakening. Resistance to going to bed and fewer total hours of sleep seem to be a major problem with many children with ADHD. Studies of sleep patterns do not, however, suggest any specific difficult with the nature of sleep itself in these children. Many ADHD children are put on medications (e.g., clonidine) to help with these sorts of sleep problems. VARIABILITY IN TASK PERFORMANCE Another characteristics of ADHD children is their excessive variability in task performance over time. This is not only found on research tasks, such as the CPT, but teachers often report much greater variability in homework and test grades as well as in class performance than in seen in normal children. [Cite Case of Ben R. Marked variability despite carefully controlled behavioral program.] MOTIVATIONAL DIFFICULTIES This problems was discussed briefly in the first class. Children with ADHD are often characterized by their apparent low level of sustained motivation. This is especially true on tasks that require repetitive responding that involves little or no reinforcement. 10 Multiple studies have documented an impairment in persistence of effort in laboratory tasks in children with ADHD. It is not clear whether this is due to the lack of sensitivity of the ADHD child to reinforcement, unless it is continuous, or due to some other type of deficit. Barkley has suggested that the problem here may relate to the fact that, while normal children develop the capacity to bridge temporal delays across times when rewards are not forthcoming (as in thin partial reinforcement schedules) children with ADHD are delayed in this ability and remain more contingency bound and more specifically under the control of immediate external rewards. He suggests the problem is not that ADHD children are insensitive to rewards or dominated by the tendency to seek immediate rewards, but instead they have a diminished capacity to bridge delays in reinforcement and permit the persistence of goal directed acts. THESE TYPES OF DIFFICULTIES, LIKE COMORBID CONDITIONS ALSO NEED TO BE TAKEN INTO ACCOUNT IN THE EDUCATIONAL AND TREATMENT PLANNING FOR CHILDREN WITH ADHD. 1. 11