Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Cognition in anxious children with attention deficit hyperactivity disorder: a comparison with clinical and normal children

Cognition in anxious children with attention deficit hyperactivity disorder: a comparison with... Background: Cognition in children with anxiety disorders (ANX) and comorbid Attention Deficit Disorder (ADHD) has received little attention, potentially impacting clinical and academic interventions in this highly disabled group. This study examined several cognitive features relative to children with either pure condition and to normal controls. Methods: One hundred and eight children ages 8–12 and parents were diagnosed by semi- structured parent interview and teacher report as having: ANX (any anxiety disorder except OCD or PTSD; n = 52), ADHD (n = 21), or ANX + ADHD (n = 35). All completed measures of academic ability, emotional perception, and working memory. Clinical subjects were compared to 35 normal controls from local schools. Results: Groups did not differ significantly on age, gender, or estimated IQ. On analyses of variance, groups differed on academic functioning (Wide Range Achievement Test, p < .001), perception of emotion (auditory perception of anger, p < .05), and working memory (backwards digits, p < .01; backwards finger windows, p < .05; Chipasat task, p < .001). ANX + ADHD and children with ADHD did poorly relative to controls on all differentiating measures except auditory perception of anger, where ANX + ADHD showed less sensitivity than children with ANX or with ADHD. Conclusion: Though requiring replication, findings suggest that ANX + ADHD relates to greater cognitive and academic vulnerability than ANX, but may relate to reduced perception of anger. Background Rates of ANX in the presence of ADHD range from 13 to Anxiety Disorders (ANX) and Attention Deficit Hyperac- 50% in various studies [2] and these comorbid children tivity Disorder (ADHD) both constitute major mental are less responsive to certain treatments [3] and are at even health problems of childhood, with affected children fac- greater risk of long-term impairment and development of ing impairment at home, at school, and with peers [1]. further psychopathology [4] than children with either Page 1 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 "pure" condition. Although family studies suggest that the in comparison to children with ANX only, children with comorbid condition (ANX + ADHD) is more closely ADHD only, and normal controls. Executive dysfunction, linked to anxiety disorders than ADHD [2], the best treat- particularly impairments in inhibitory control and work- ment for it is unknown. ing memory, have been demonstrated repeatedly in ADHD (reviewed in [4]). Given that the foremost evi- To develop effective treatments and academic interven- dence-based treatment for anxiety disorders is cognitively tions for these children, an understanding of the cognitive based (cognitive-behavioral therapy; [5]), however, a processes that underlie ANX + ADHD is crucial. Effective 'pure' ANX comparison group was considered particularly treatments for anxiety, for example, place high demands relevant. on certain language-based cognitive processes [5]. Cogni- tive measures also provide a useful approach to investigat- Cognition in anxious children has been characterized as ing whether or not ADHD + ANX constitutes a unique biased by selective perception and selective memory for subtype (ie. differs from either ADHD or ANX), since they threatening stimuli or emotions (reviewed in [7]). Anxi- constitute direct and objective measures and are inde- ety-related deficits in executive function, particularly pendent of diagnostic criteria. For example, cognitive working memory, have also been proposed [9]. There is resemblance to either pure condition would suggest ANX some evidence to suggest that these may play a role in + ADHD may have a similar etiology to that condition. combined ANX and ADHD [10-12]. Therefore, we were Thus, cognitive studies have important therapeutic and particularly interested in examining emotional perception etiological implications. and working memory in children with ANX + ADHD rel- ative to children with either 'pure' condition and to nor- Studies of information processing are challenging to con- mal controls. This study represents a first step to further duct for both theoretical and methodological reasons our etiological and therapeutic understanding of (reviewed in [6]). Small sample sizes and lack of measure- ANX+ADHD. The cognitive domains of interest are ment reliability, construct validity, or ecological validity described briefly before detailing our hypotheses and are common methodological challenges. Use of stimulus methods. sets inappropriate to age or developmental level and lack Emotional perception of attention to task-related fatigue are further challenges in child studies. Common theoretical challenges include The cognitive vulnerability to anxiety is thought to relate insufficient construct specificity, examining cognitive to an automatic tendency for anxious individuals to selec- processes in isolation (without reference to other aspects tively encode emotionally threatening information of information processing), and interpreting cognitive (reviewed in [13]). This encoding bias is demonstrated processes as contributing to psychopathology when they when subjects show selective attention to threatening may be mere epiphenomena of clinical problems. Of stimuli [13], selective interpretation of ambiguous stimuli course, it is also erroneous to assume that information as threatening [14], selective memory for threatening processing factors in children always operate as they do in words [14] or interference with task performance due to adults. exposure to threatening stimuli [15]. The bias is most evi- dent on tasks involving implicit rather than explicit atten- With these considerations in mind, we undertook an ini- tion to threat [13], suggesting that a conscious decision- tial cognitive study and demonstrated that children with making process is not involved. ANX + ADHD are cognitively distinct from either pure condition [7]. We examined several aspects of informa- In children with clinical anxiety disorders, Vasey and oth- tion processing, utilizing state-of-the-art measures of each ers [16] demonstrated an attentional bias towards emo- construct, with age-appropriate stimuli, and a protocol tionally threatening words on a probe detection task. On that minimized order effects and subject fatigue. Consist- a dichotic listening task, clinically anxious children ent with high rates of comorbidity among certain anxiety showed enhanced perception of emotions relative to nor- disorders in this age group [8], ANX was defined as any mal controls, possibly reflecting hypervigilance to emo- anxiety disorder other than OCD or PTSD. We found that tional cues [17]. High trait anxious children have been ANX + ADHD was associated with neither the inhibitory found to show a bias toward negative relative to neutral control deficits of 'pure' ADHD, nor the heightened sensi- information for conceptual memory tasks [18], a process- tivity to negative emotions of 'pure' ANX. It is the only ing bias for generally threatening information on an emo- study to date to examine emotional perception in this tional Stroop task [19], and a tendency to interpret population. homophones as threatening rather than neutral [20]. In the only study to date of emotional perception in anxious The present study sought to build on this work by further children comorbid for ADHD, these children showed elucidating the cognitive characteristics of these children, reduced perception of emotions relative to normal con- Page 2 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 trols [7], rather than the heightened perception of threat- those with ADHD alone [10-12]. Tannock et al. [12], ening or negative emotion characteristic of anxious using a serial addition task, showed that ANX + ADHD children. On the other hand, the few available studies of was associated with significantly worse performance on emotional perception in ADHD yield inconsistent find- the slower trials of the task, but no difference at higher ings [21,22]. The findings also suggest that comorbid con- speeds where performance declined for children with duct problems may influence response to emotional ADHD. Compared to children in the ADHD-only group, stimuli [22,23]. those with ANX + ADHD also failed to show improve- ments on auditory-verbal working memory tasks when Working memory treated with stimulant medication [10]. Pliszka [10] Working memory is an aspect of executive function. It has administered a memory scanning task that placed been described as a limited capacity system for the tempo- demands on nonverbal working memory to children with rary storage and processing of information [24]. It is ADHD with or without comorbid ANX. ANX + ADHD was thought to underlie a wide range of cognitive processes, associated with longer, sluggish reaction times on this including planning, learning, problem solving, reasoning task. and comprehension [25], and predicts academic achieve- ment [26]. Tasks requiring working memory test the abil- Hypotheses ity to simultaneously store and manipulate retained Based on the above, we hypothesized (1) that children information in order to complete complex tasks [27]. For with ANX would show heightened perception of negative example, asking a subject to remember a particular emotions relative to the other children studied, a bias that number (storage) while adding a different set of numbers might not be evident in the comorbid group [7]; (2) that (manipulation) would constitute a test of working mem- children with ANX + ADHD would be particularly ory. Deficits in this ability are seen in a variety of clinical impaired on working memory relative to the other chil- conditions. dren studied, given that both anxiety and ADHD have been linked to working memory problems through differ- In children with ANX, deficits may occur due to the inter- ent mechanisms. ference of worry with normal processing of information [9]. Eysenck postulates that anxious individuals have clus- We were also interested in overall academic ability, and ters of anxiety-related information in long term memory hypothesized difficulty in all clinical groups relative to which are easily accessible, rapidly activated, and retrieved normal controls, but perhaps more so in the comorbid quickly thus interfering with information-processing. group. Studies support an inability of anxious individuals to inhibit anxiety-provoking stimuli [28-30]. Anxiety Methods enhances motivation, however, potentially compensating Subjects for the effect of worry on some tasks. Francis-John and Children were recruited from two outpatient clinics (one colleagues (submitted) recently found impairment in specializing in anxiety disorders; the other in learning dif- complex verbal working memory in anxious children rel- ficulties) in two university-based clinical research centers ative to normal controls, but not in visual-spatial working serving a large urban and suburban population. Investiga- memory. However, the sample included a substantial tors met regularly to ensure standardized procedures at number of children with comorbid ADHD. Working the two clinics. A consecutive sample of children ages 8 to memory has not been examined in other studies of anx- 12 years meeting study criteria were recruited. All racial ious children. and socioeconomic groups were represented, but with some over-representation of Caucasian versus non-Cauca- In ADHD, working memory impairments have been sian families and more affluent versus less affluent fami- linked theoretically [31] to the disorder, and recent meta- lies, relative to the local census population. analyses have empirically shown that working memory tasks discriminate between ADHD and controls [32]. Fur- Control subjects were recruited from local schools in the thermore, these meta-analyses demonstrate impairments same geographic area, based on principals' nomination of in visual-spatial as well as auditory-verbal working mem- students with no evidence of emotional or behavioral ory abilities in ADHD which remain robust even after problems. Each student was also asked to nominate a controlling for comorbidity with other psychiatric disor- friend (snowball technique). Controls were only included ders and general intellectual function [32]. if they were within one standard deviation of the popula- tion mean for total scores on standardized measures of Studies using complex tasks that place a high demand on anxiety and ADHD symptoms (see below). While two working memory have shown greater impairment for chil- potential controls were excluded for this reason, neither dren with internalizing disorders and ADHD than for showed evidence of clinical disorder on interview. Page 3 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 All children were in an unmedicated state at the time of bid Oppositional Defiant Disorder alters the cognitive the study. Children receiving psychoactive medication (all features of ANX or ADHD. The other three comorbidities had been diagnosed with ADHD and were on psychostim- listed were assessed for each participating child. LD was ulants: 9 comorbid children and 6 ADD children) discon- defined as a standardized score on the Wide Range tinued it for a period of seven medication half-lives prior Achievement Test (WRAT-R; [36]) that was at least 1.5 SD to study participation, to ensure adequate washout. Chil- below mean for age and below full-scale IQ score on the dren who had received a course of cognitive behavioral WISC-III [37]. Depression was defined by a score > 16 on therapy (8 sessions or more) for their anxieties were the Children's Depression Inventory [38,39], or by the excluded, as this form of therapy may alter cognitive proc- diagnostic interview. CD was assessed by the diagnostic esses. There were no differences among clinical groups for interview. In practice, there were no children meeting the number of mental health services received in the pre- diagnostic criteria for either depression or CD. There were vious 4 years, nor for the proportion of children receiving several children in each clinical group meeting criteria for ongoing mental health follow-up in the previous year LD by the above definition (39 total). However, chi- (about 60% in each clinical group). square analyses showed significant group differences for reading disability only (6 anxious, 3 comorbid, and 6 Prior to participation, potential subjects and their parents ADHD children; chi-square = 12.10, p = .007). Post hoc completed the Anxiety Disorders Interview Schedule analyses used continuous measures of comorbidity as cov- (ADIS; [33]), a well-validated, semi-structured diagnostic ariates in interpreting data, to detect any comorbidity- interview using DSM – IV criteria. Diagnosis was based related effects (analysis described in [40]). primarily on this instrument, but teacher reports (by structured telephone interview and Conners' Question- We excluded children who had a full-scale IQ < 80, lacked naire[34]) were required to confirm ADHD in the school fluency in English, or were suffering from psychosis or environment. Anxiety disorders were diagnosed when serious visual, auditory, or speech deficits. present either by parent or child report. All interviewers were child psychiatrists or child psychologists, trained to Procedure reliability on the instrument, and with at least 3 years The project was approved by our hospital Research Ethics Board, and children and parents provided informed experience using it in other research studies. With parental consent, 10% of these diagnostic interviews (randomly assent and consent respectively. Research was carried out selected) were videotaped and scored by an independent in compliance with the Helsinki Declaration. Administra- rater to ensure reliability among interviewers. No discrep- tion of measures was done by a research technician blind ancies between interviewers and raters were found for to child diagnosis, and counterbalanced to control for any group assignment. Children also completed the Multidi- order effects. Children completed the Wide Range mensional Anxiety Scale for Children (MASC; [35]) and Achievement Test-Revised (WRAT-R, [36]; tests academic parents the Parent Conners' Questionnaire [34], to obtain achievement) and the Vocabulary and Block Design sub- well-validated, continuous measures of anxiety and tests of the Wechsler Intelligence Scale for Children ADHD symptoms respectively. (WISC-III [41]). This two-subtest short form has been shown to reliably estimate verbal and non-verbal intelli- All ADHD subtypes were included, and all childhood anx- gence respectively [42]. Parents were asked to complete a iety disorders were included apart from post-traumatic set of questionnaires and to provide basic demographic stress disorder and obsessive compulsive disorder (as the information (Ontario Child Health Study, [43]). Normal latter are likely to be cognitively distinct). Childhood anx- hearing was confirmed by audiological screening and iety disorders are highly comorbid: 40% of anxious chil- handedness was verified by a preference inventory (Water- dren have more than one disorder [8], so mixed anxious loo Handedness Questionnaire, [44]). If the child had samples are commonly studied in this type of research. completed either a WRAT-R or WISC-III within the past Generalized Anxiety Disoder (GAD) was the primary diag- year, scores were obtained with parental consent and the nosis in about 50% of both the ANX and ANX + ADHD test was not re-administered. groups. Cognitive measures Because this was a clinical sample, other comorbid condi- Measures targeted the cognitive domains of interest, with tions (Learning Disabilities, Oppositional Defiant Disor- verbal and nonverbal working memory examined sepa- der, Conduct Disorder, Depression) were expected. rately. A timed verbal working memory task was also Although these could potentially confound interpretation included, as the stress of a timed task may affect anxious of data, they are so frequent in this population that children differently than non-anxious children. All meas- excluding subjects with them would likely have rendered ures are widely used research tools, and have acceptable the study non-feasible. There is no evidence that comor- reliability and validity data. Page 4 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 Emotional perception ity. Standard scores were used for the forward administra- Diagnostic analysis of nonverbal accuracy 2 tion, and raw scores for the backward version. (DANVA2)[45]: The DANVA2 consists of four receptive and three expressive subtests designed to measure the Statistical analysis accuracy of nonverbal social information processing in The Statistical Package for the Social Sciences – PC version children. Two receptive subtests (Adult Faces 2 and Adult (SPSSPC) was used for all analyses. Groups were com- Voices 2) were selected for use in the current study. Chil- pared on demographic characteristics and cognitive char- dren had to identify the emotional valence of the facial acteristics using analyses of variance (ANOVA). Chi- expression or tone of voice respectively. Adult stimuli square was used for categorical measures. To test our were chosen because child stimuli on the measure are less hypotheses about specific group differences, post-hoc subtle, sometimes resulting in ceiling effects. tests were done for all variables that showed significant group differences on ANOVA, with Bonferroni correction Working memory: verbal for multiple comparisons. CHIPASAT (Children's paced auditory serial addition test; [46]): The CHIPASAT is a precisely timed task in which To further corroborate relationships between ADHD, tape-recorded, single-digit numbers are presented in trials ANX, and various cognitive measures, bivariate correla- of differing speeds. Children are required to add each new tions between these measures and maternal Conners' number to the immediately preceding number and give ADHD Symptom Index and child MASC scores, respec- the answer aloud. The numerical knowledge required is tively, were examined in secondary analyses. Further post usually acquired by grade 1. The traditional dependent hoc analyses were done to include estimated IQ (based on variable is the total number of correct responses for each Vocabulary and Block Design scores) and each of the three speed. Some strategies for doing the task (e.g., adding comorbidities likely to affect cognition (LD, Depression, stimuli discontinuously; [12]) allow for many correct CD) measured as continuous variables. These variables responses without a high demand on working memory, were entered as covariates, one at a time, in analyses of so variables pertaining to strategy were also compared covariance (ANCOVAs) to determine if between-group across groups. These were found not to differ by group, differences remained, as described by Nigg et al. [40]. however, so correct responses only are reported in this Thus, we determined the effect (if any) of these comorbid paper. More detailed analyses of this task for a subset of conditions on our results. this sample can be found in Francis-John et al., (submit- ted). Results Sample characteristics by group are described in Table 1. Backward digit span (WISC-III;[41]): Standard procedure There were no significant group differences in age, gender, for the WISC-III was used, and the highest number of dig- socioeconomic status, or handedness. As expected, ANX its recalled under the Backward condition was recorded and ANX + ADHD groups reported significantly more (whether or not the child was able to recall the same anxiety than normal controls, although their mean scores number of digits once or twice), then converted to a scaled still appeared to be in the normal range. This is not unu- score. Only scaled scores were reported and used in anal- sual in clinics where the anxiety prompting referral is yses. identified by parents or clinicians (rather than the chil- dren themselves), given that correspondence between Working memory: nonverbal informants is only fair in childhood internalizing disor- Finger windows backwards: The Finger Windows subtest ders [48]. On the Conners', mothers reported significant from the Wide Range Assessment of Memory and Learn- differences between children with ADHD, ANX, and nor- ing (WRAML) [47] was administered. In the forward mal controls, while teachers only distinguished clinical administration, the examiner indicates a series of spatial versus nonclinical groups. locations by inserting a pencil through a series of ran- domly spaced holes ("windows") on an 8 × 11 inch card Data was screened for outliers and conformity with the at a rate of one hole per second. The child must then statistical assumptions of analysis of variance. Also, the reproduce the same visual-spatial sequence by putting his effect of specific anxiety diagnosis was examined by com- or her finger through each window in the same order as paring children with a primary diagnosis of GAD (about the presentation. Items gradually increase in length from 50% of both ANX and ANX + ADHD groups) with those sets of 2 to sets of 6 windows, demonstrating spatial mem- with other primary anxiety diagnoses on all measures of ory span. With backward administration, that is the child interest. No significant differences were found, so all anx- reproducing the sequences in backward order, this iety diagnoses were examined together in subsequent becomes a measure of spatial working memory. Lower analyses. scores are associated with greater impairment in this abil- Page 5 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 Table 1: Description of Sample: Means and Standard Deviations Anxiety Only (n = 52) Comorbid for ADHD* (n = 35) ADHD Only (n = 21)** Normal Controls (n = 35) Total (n = 143) Age in Years 9.42 (1.23) 9.82 (1.27) 9.60 (1.43) 9.71 (1.32) 9.61 (1.28) Socioeconomic Status (Hollingshead 48.45 (12.21) 46.56 (15.46) 44.22 (18.36) 53.92 (8.85) 48.19 (13.61) Index [54]) Gender (% Males) 66% 74% 81% 63% 69% Handedness (% Right vs. Left/Mixed) 67% 53% 70% 74% 64% DSM-IV Conners' ADHD Symptom 57.08 (11.09) 69.00 (12.63) 69.80 (7.00) 49.50 (7.67) 58.86 (12.81) Index (t-score) Mother Report Teacher Report (n = 69) 55.15 (12.35) 61.11 (18.81) 74.33 (11.68) 50.08 (5.87) 56.01 (14.60) Multidimensional Anxiety Scale for 53.12 (1.08) 54.97 (13.24) 50.10 (11.00) 46.23(10.09) 51.52 (11.82) Children (t-score) a 1 2 3 standard deviations are shown in brackets; p < .05, p < .01, p < .001 * 19 Inattentive Type; 16 Combined Type ** 11 Inattentive Type; 10 Combined Type To test our main hypotheses regarding emotional percep- DSM-IV ADHD Symptom Index and the cognitive meas- tion in ANX and working memory in ANX + ADHD, ures of interest. Significant correlations (p < .05) were evi- groups were compared on measures relevant to these dent for: Chipasat 2.0, Chipasat 2.8, Digit Span domains. Table 2 shows group means on these cognitive Backwards (ie. verbal working memory measures), WRAT measures of interest. Group differences were found on all Spelling, and WRAT Arithmetic subtests. All correlations academic achievement tests, the Chipasat (verbal working were in the expected direction (ie. worsening test perform- memory), Digit span backwards (verbal working mem- ance with increasing Mother Conners' symptoms). Corre- ory), finger windows backwards (nonverbal working lations were also examined between the child-report memory), and DANVA – adult angry voice (emotional MASC (our continuous measure of anxiety) and the cog- perception). Group differences are reported uncorrected nitive measures of interest. A significant correlation (p < in the table. However, we also applied the Bonferroni cor- .05) was evident for DANVA: angry adult voice, detected rection within each domain, consistent with our initial more by children with higher MASC scores. hypotheses. Doing so, the following comparisons remained significant: all academic achievement differ- When covarying for estimated IQ, all previously signifi- ences, the Chipasat 2.0 and 2.8, and the Digit Span Back- cant comparisons remained significant. When covarying wards. for depressive symptoms and for conduct disorder symp- toms, all previously significant comparisons remained For all significant ANOVAs, post-hoc analyses were done significant. To assess the effect of learning problems, we to test our hypotheses regarding specific group differences ran group comparisons covarying for the discrepancy (see Table 3). As hypothesized for emotional perception, between estimated IQ and specific WRAT scores for each ANX were indeed more sensitive to adult anger (the most subject, consistent with our operational definition of LD threatening emotion) than ANX + ADHD. Interestingly, above. Using this approach, all previously significant children with ADHD also showed this sensitivity relative working memory and emotional perception comparisons to ANX + ADHD. For working memory (second hypothe- remained significant (obviously not applicable to WRAT sis), both ADHD groups appeared impaired relative to comparisons). Interestingly, covarying for the actual normal controls, but ANX did not. The effect appeared WRAT scores (without relating them to IQ) showed that somewhat stronger for verbal working memory, with ANX reading ability on WRAT eliminated all group differences + ADHD showing only a trend level difference from nor- apart from that for the DANVA: auditory anger. mal controls on nonverbal working memory. Significant academic impairments were evident in all clinical groups Although we did not hypothesize any gender differences, relative to normal controls, but appeared more pro- we re-ran all group comparisons covarying for gender. All nounced in the ADHD groups. significant group differences remained, and a significant effect for gender was found only on one measure, the Chi- Secondary analyses pasat, where females tended to score lower than males at To determine whether anxiety and ADHD measured as the slower speed (F = 10.66, p < .01). continuous variables related to cognitive measures regard- less of diagnostic group, bivariate correlations were exam- ined for the whole sample between Mother Conners' Page 6 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 Table 2: Cognitive Tasks by Group TASK ANX ANX + ADHD ADHD NORMAL Signif. ANOVA Effect Size (Partial Eta Squared) WISC-III: IQ 107.1 (12.4) 103.53 (10.95) 103.37 (12.63) 110.41(8.42) - - Perception of Emotion: DANVA Happy (raw) 3.79 (1.54) 4.21 (1.43) 3.37 (1.38) 4.09 (1.36) - - Sad (raw) 4.17 (1.12) 3.85 (1.16) 3.84 (1.34) 3.83 (1.15) - - Angry (raw) 4.58 (1.01) 4.03 (1.27) 4.79 (0.98) 4.26 (0.89) * .063 Fearful (raw) 4.08 (2.34) 3.71 (1.71) 3.95 (1.68) 3.83 (1.64) - - Working Memory: Nonverbal: Finger – Windows Forward (scaled) 8.91 (3.46) 7.91 (2.94) 9.19 (2.82) 9.39 (2.91) - - Backward (raw) 10.13 (4.78) 9.32 (4.23) 7.74 (5.20) 11.33 (3.79) * .059 Working Memory Verbal: Digit Span Forward (scaled) 10.81 (2.81) 10.90 (3.30) 9.00 (3.04) 10.63 (3.23) - - Backward (scaled) 10.67 (2.74) 8.84 (3.50) 7.94 (3.17) 10.40 (3.25) ** .099 Chipasat Task Speed: 2.8 (raw) 31.49 (12.21) 25.60 (8.43) 23.41 (11.02) 34.88 (9.76) *** .101 Speed: 2.0 (raw) 25.51 (10.65) 22.00 (7.62) 18.82 (7.68) 29.36 (7.55) *** .084 Academics WRAT: Reading 110.4 (14.6) 105.41 (17.59) 99.71 (19.20) 118.63 (11.04) *** .144 Spelling 106.7 (51.1) 96.94 (15.51) 93.52 (17.17) 113.09 (11.85) *** .193 Arithmetic 99.3 (15.5) 92.27 (15.99) 93.05 (16.48) 109.89 (10.59) *** .176 Word attack 108.4 (13.8) 100.12 (16.03) 94.05 (20.93) 109.12 (8.13) *** .131 *p < .05 **p < .01 ***p < .001; t-scores unless otherwise indicated; WRAT, Chipasat, and Digit Span Backward significant after Bonferroni correction; WISC-III = Wechsler Intelligence Scale for Children-III; WRAT = Wide Range Achievement Test; DANVA = Diagnostic Assessment of Nonverbal Accuracy Specific findings Discussion Although effect sizes were modest, group differences We hypothesized that 'pure' anxious children would show between anxious children, anxious children comorbid for enhanced perception of negative emotions. Consistent ADHD, and normal controls were found on several cogni- with this hypothesis, 'pure' anxious children were found tive measures. The lack of group differences in demo- to have an enhanced perception of auditory anger relative graphic characteristics (age, gender, socioeconomic to comorbid children, with normal control scores inter- status) suggests that these factors are unlikely to account mediate between these two groups. This finding partially for these findings. The degree of anxiety reported for the replicates our previous work showing reduced perception two ANX groups was also very similar, as was the degree of negative emotion in ANX + ADHD [7]. Our continuous of severity of ADHD symptoms in the two ADHD groups, measure of anxiety (MASC) was also correlated with per- suggesting that cognitive differences are unlikely to be due ception of auditory anger. Anger is considered the most to symptom severity in one or the other group. Clinical threatening of negative emotions (from the listener's per- groups were also comparable in prior mental health serv- spective) so it was not surprising that sensitivity to it was ice utilization, suggesting that length of illness is unlikely heightened in ANX, where threat sensitivity has been con- to account for cognitive differences. firmed in other studies [7,16]. Notably, the ANX + ADHD Table 3: Post-hoc Group Comparisons for Differentiating Measures (p values; in bold if significant) Measure ANX vs. ANX + ADHD ANX vs. ADHD ANX vs. Normal ANX + ADHD vs. ADHD ANX + ADHD vs. Normal ADHD vs. Normal DANVA angry .026 .447 .121 .028 .389 .047 Chipasat (2.8) .037 .021 .233 .470 .001 .001 Chipasat (2.0) .162 .023 .119 .198 .001 .000 Digits Backward .009 .001 .674 .384 .064 .013 Finger Windows .423 .071 .225 .234 .045 .006 Backward WRAT reading .158 .012 .006 .265 .000 .000 WRAT spelling .005 .002 .037 .453 .000 .000 WRAT arith. .046 .128 .001 .864 .000 .000 WRAT w. attack .012 .001 .778 .236 .005 .000 Page 7 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 group was least sensitive to this emotion, suggesting that One possible model for ANX + ADHD their anxiety may be of a different nature to that of the Although needing replication, these findings have poten- ANX group and that anxiety may not relate to threat sen- tially interesting implications for understanding the sitivity. If replicated, this finding suggests that other etio- comorbidity between ANX and ADHD. Vance and Luk logical mechanisms for anxiety should be examined in [50] hypothesized that a neurodevelopmental deficit this population (see below). Interestingly, 'pure' ADHD underlies both anxious and ADHD symptoms in these children also showed the perceptual bias towards anger children. Our findings suggest one candidate for such a relative to ANX + ADHD. deficit: impaired working memory, especially verbal working memory. Working memory has been linked to In relation to working memory, we hypothesized the the frontal lobes, with verbal ability predominantly on greatest impairment in ANX + ADHD. Instead, we found the left side in most individuals. Studies linking approach that both ADHD groups were impaired relative to normal behavior in anxious individuals to left anterior activation controls and ANX. This difference was more robust for on EEG [51], reduced left anterior activation in behavio- verbal than nonverbal working memory, and occurred rally inhibited children [52], successful treatment of anxi- whether or not the task was timed. Maternal (continuous) ety using verbally mediated cognitive behavioral strategies report of ADHD symptoms also correlated with verbal [5], and deficits in frontal lobe functions in ADHD [53] working memory. These findings are consistent with pre- are all consistent with this idea. The lack of sensitivity to vious reports suggesting that lack of vigilance or distrac- threat (angry voice) we found in ANX + ADHD (in con- tion by external stimuli can interfere with working trast to 'pure' ANX) is also consistent with this model. memory in ADHD [49]. We did not replicate earlier find- Thus, children with ADHD + ANX may have frontal lobe ings of greater impairment in ANX + ADHD than in 'pure' deficits that affect their ability to inhibit both negative ADHD [10-12]. The findings appear contrary to Eysenck affect (resulting in anxiety symptoms, even in the absence and Calvo's [9] hypothesis regarding the adverse effects of of threat sensitivity) and responses to stimuli (resulting in worry on working memory. It is possible, however, that ADHD symptoms). Understanding the nature of these findings in ANX might be different in a less reassuring test impairments more precisely may suggest fruitful avenues situation than that in our laboratory. Studies of such chil- of clinical and academic intervention for them. dren in anxious states (for example, during examinations at school) might show greater effects of worry on working Limitations memory. Further studies that include larger, more diverse samples are needed to replicate and extend these findings. The col- Academic differences were greatest between children with lection of the sample from two university-based clinics ADHD and normal controls, though some academic may also have resulted in some sample bias. This bias may impairment was evident in ANX as well. ANX + ADHD did limit generalizability to other populations (for example, not appear to have worse academic performance than children with ANX + ADHD in the community). Vasey children with 'pure' ADHD, highlighting the need for and colleagues [6] have also advocated the use of multiple school supports for all children meeting ADHD criteria. measures of each construct to allow the generation of composite scores, and longitudinal studies that clarify the We examined other reasons for the group differences relationship between deficit and disorder (eg. determin- (apart from diagnosis per se) by covarying for IQ, gender, ing if deficits are present prior to the onset of disorder or academic deficits relative to IQ, comorbid depressive can be modified such that symptomatology changes). symptoms, and comorbid conduct symptoms. All group differences remained significant, and only one measure Clinical implications (Chipasat at slower speed) showed a significant gender The nature of the cognitive deficits in ANX + ADHD may effect (males performed better). Controlling for academic be relevant to these children's ability to benefit from cog- ability, however, eliminated all but one group difference: nitive behavioral therapy for anxiety, particularly since the difference in auditory perception of anger. Thus, emo- these deficits are less likely to be ameliorated by stimulant tional perception may be relatively independent of aca- treatment than in 'pure' ADHD children. Thus, even a demic ability, but working memory appears to show some medicated child with comorbid ANX + ADHD may find association. This association disappears, however, when the verbal reasoning required in cognitive behavioral ther- academic ability is measured relative to IQ. This finding apy confusing, due to limited verbal working memory. suggests that group differences in working memory can- ADHD may also make the child appear disruptive or dif- not be accounted for entirely by differential academic def- ficult to manage if CBT is offered in a group format icits. (increasingly favored to contain costs). CBT may require modification and/or administration in an individual for- mat in order for these children to benefit. Page 8 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 ders and ADHD. J Am Acad Child Adolesc Psychiatry 2000, Given the above deficits, children with ANX + ADHD are 39:1152-1159. also likely to be disadvantaged academically. They may 8. Bernstein GA, Borchartdt CM, Perwien AR: Anxiety disorders in require different teaching strategies geared to their unique children and adolescents: A review of the past 10 years. J Am Acad Child Adolesc Psychiatry 1996, 35:1110-1119. cognitive profile. If they encounter school failure, this 9. Eysenck MW, Calvo MG: Anxiety and performance: The may exacerbate anxiety leading to further problems. processing efficiency theory. Cogn Emot 1992, 6:409-434. 10. Pliszka SR: Effect of anxiety on cognition, behavior, and stim- Enhancing teachers' and clinicians' awareness of the par- ulant response in ADHD. J Am Acad Child Adolesc Psychiatry 1989, ticular vulnerabilities of these children may improve their 28:882-887. therapeutic and academic outcomes. 11. Pliszka SR: Comorbidity of attention-deficit hyperactivity dis- order and overanxious disorder. J Am Acad Child Adolesc Psychia- try 1992, 31:197-203. Conclusion 12. Tannock R, Ickowicz A, Schachar R: Differential effects of meth- Findings suggest that ANX + ADHD relates to greater cog- ylphenidate on working memory in ADHD children with and without anxiety. J Am Acad Child Adolesc Psychiatry 1995, nitive and academic vulnerability than ANX, especially 34:886-896. with respect to working memory, but may relate to 13. MacLeod C: Clinical anxiety and the selective encoding of threatening information. Int Rev Psychiatry 1991, 3:279-292. reduced perception of anger. Awareness of this vulnerabil- 14. Mathews A, Mogg K, May J, Eysenck M: Implicit and explicit mem- ity may allow tailoring of psychological and academic ory bias in anxiety. J Abnorm Psychol 1989, 98:236-240. intervention to better meet the needs of affected children. 15. Stroop JR: Studies of interference in serial verbal reactions. J Exp Psychol 1935, 18:643-662. Further studies of larger, more diverse samples are indi- 16. Vasey MW, Daleiden EL, Williams LL, Brown LM: Biased attention cated to replicate these findings and further elucidate the in childhood anxiety disorders: A preliminary study. J Abnorm Child Psychol 1995, 23:267-279. cognitive and neurological substrates of ANX + ADHD. 17. Manassis K, Tannock R, Masellis M: Cognitive differences between anxious, normal, and ADHD children on a dichotic Competing interests listening task. Anxiety 1996, 2:279-285. 18. Daleiden EL: Childhood anxiety and memory functioning: a The author(s) declare that they have no competing inter- comparison of systemic and processing accounts. J Exp Child ests. Psychol 1998, 68:216-235. 19. Kindt M, Broschot JF, Everaerd W: Cognitive processing bias of children in a real life stress situation and a neutral situation. Authors' contributions J Exp Child Psychol 1997, 64:79-97. KM was the principal investigator of this study, principal 20. Hadwin J, Frost S, French CC, Richards A: Cognitive processing author of this paper, and leads one of the participating and trait anxiety in typically developing children: evidence for an interpretation bias. J Abnorm Psychol 1997, 106:486-490. outpatient clinics. RT was a co-investigator of this study, 21. Corbett B, Glidden H: Processing affective stimuli in children and developed the initial study design jointly with KM. AY with Attention Deficit Hyperactivity Disorder. Child Neuropsy- chol 2000, 6:144-155. contributed valuable ideas to the final design and proce- 22. Cadesky EB, Mota VL, Schachar RJ: Beyond words: how do chil- dures of the study, and leads the second participating out- dren with ADHD and/or conduct problems process nonver- patient clinic. All authors read and approved the final bal information about affect? J Am Acad Child Adolesc Psychiatry 2000, 39:1160-1167. manuscript. 23. Du J, Li J, Wang Y, Jiang Q: Event-related potentials in adoles- cents with comorbid ADHD and CD disorder: a single stim- ulus paradigm. Brain Cogn 2006, 60:70-75. Acknowledgements 24. Baddeley A: Modularity, mass-action and memory. Q J Exp Psy- We wish to acknowledge the financial support of the Ontario Mental chol A 1986, 38:527-533. Health Foundation for this work. 25. Swanson HL: Short-term memory and working memory: do both contribute to our understanding of academic achieve- ment in children and adults with learning disabilities? J Learn References Disabil 1994, 27:34-50. 1. Bird HR, Canino G, Rubio-Stipec M: Estimates of the prevalence 26. Aronen ET, Vuontela V, Steenari MR: Working memory, psychi- of childhood maladjustment in a community survey in atric symptoms, and academic performance at school. Neu- Puerto Rico. Arch Gen Psychiatry 1988, 45:1120-1126. robiol Learn Mem 2005, 83:33-42. 2. Jensen PS, Martin D, Cantwell DP: Comorbidity in ADHD: impli- 27. Eslinger PJ: Conceptualizing, describing, and measuring com- cations for research, practice, and DSM-V. J Am Acad Child Ado- ponents of executive function: a summary. In Attention, Mem- lesc Psychiatry 1997, 36:1065-1079. ory, and Executive Function Edited by: Lyon GR, Krasnegor NA. 3. MTA Cooperative Group: Moderators and mediators of treat- Baltimore, MD: Paul H. Brookes Publishing; 1996. ment response for children with ADHD. Arch Gen Psychiatry 28. Calvo MG, Eysenck MW: Phonological working memory and 1999, 56:1088-1096. reading in test anxiety. Memory 1996, 4:289-305. 4. Tannock R: Attention deficit disorders with anxiety disorders. 29. Pratt P, Tallis F, Eysenck M: Information processing, storage In Subtypes of Attention Disorders in Children, Adolescents, and Adults characteristics and worry. Behav Res Ther 1997, 35:1015-1023. Edited by: Brown TE. Washington DC: American Psychiatric Press; 30. Hopko DR, Ashcraft MH, Gute J, Ruggiero KJ, Lewis C: Mathemat- ics anxiety and working memory: support for the existence 5. Kendall PC, Flannery-Schroeder E, Panichelli-Mindel SM, Southam- of a deficient inhibition mechanism. J Anxiety Disord 1998, Gerow M, Heni M: Therapy for youths with anxiety disorders: 4:343-355. a second randomized clinical trial. J Consult Clin Psychol 1997, 31. Barkley RA: Behavioral inhibition, sustained attention, and 65:366-380. executive functions: constructing a unifying theory of 6. Vasey MW, Dagleish T, Silverman WK: Research on information- ADHD. Psychol Bull 1997, 121:65-94. processing factors in child and adolescent psychopathology: 32. Martinussen R, Hayden J, Hogg-Johnson S, Tannock R: A meta-anal- A critical commentary. J Clin Child Adolesc Psychol 2003, 32:81-93. ysis of working memory impairments in children with Atten- 7. Manassis K, Tannock R, Barbosa J: Dichotic listening and tion-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc response inhibition in children with comorbid anxiety disor- Psychiatry 2005, 44:377-384. Page 9 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 33. Silverman WK, Albano AM: Anxiety Disorders Interview Schedule for DSM-IV San Antonio: The Psychological Corporation; 1996. 34. Conners CK: Manual for Conners' Rating Scales Toronto, Canada: Multi-Health Systems Inc; 1989. 35. March J: Multidimensional Anxiety Scale for Children (MASC) Toronto, Canada: Multi-Health Systems, Inc; 1998. 36. Wilkinson GS: Wide Range Achievement Test 3rd Edition (WRAT-3) Wilmington, Delaware: Wide Range, Inc; 1993. 37. Semrud-Clikeman M, Biederman J, Sprich-Buckminster S, Krifcher Lehman B, Faraone SV, Norman D: Comorbidity between ADHD and learning disability: A review and report in a clinically referred sample. J Am Acad Child Adolesc Psychiatry 1992, 31:439-448. 38. Kovacs M: The Children's Depression Inventory: A self-rated depression scale for school-aged youngsters University of Pittsburgh; 1983. 39. Saylor CF, Finch AJ, Spirito A: The Children's Depression Inven- tory: A systematic evaluation of psychometric properties. J Consult Clin Psychol 1984, 52:955-967. 40. Nigg JT, Hinshaw SP, Carte ET, Treuting JJ: Neuropsychological correlates of childhood Attention Deficit/Hyperactivity Dis- order: Explainable by comorbid disruptive behavior or read- ing problems? J Abnorm Psychol 1998, 107:468-480. 41. Wechsler D: Wechsler Intelligence Scale for Children-Third Edition San Antonio: The Psychological Corporation; 1991. 42. Sattler JM: Assessment of Children Cognitive Applications Fourth edition. San Diego: Jerome M. Sattler, Publisher, Inc; 2001. 43. Boyle MH, Offord DR, Racine Y: Evaluation of the Revised Ontario Child Health Study Scales. J Child Psychol Psychiatry 1993, 43:189-213. 44. Steenhuis RE, Bryden MP: Different dimensions of hand prefer- ence that relate to skilled and unskilled activities. Cortex 1989, 25:289-304. 45. Nowicki S Jr, Duke MP: Individual differences in the nonverbal communication of affect: The Diagnostic Analysis of Non- verbal Accuracy Scale. J Nonverb Behav 1994, 18:9-35. 46. Johnson DA, Roethig-Johnston K, Middleton J: Development and evaluation of an attentional test for head injured children: Information processing capacity in a normal sample. J Child Psychol Psychiatry 1988, 29:199-208. 47. Sheslow D, Adams W: Wide Range Assessment of Memory and Learning Administration Manual DE: Jastak; 1990. 48. Klein RG: Parent-child agreement in clinical assessment of anxiety and other psychopathology: A review. J Anxiety Disord 1991, 5:187-198. 49. Pennington BF, Ozonoff S: Executive functions and developmen- tal psychopathology. J Child Psychol Psychiatry 1996, 37:51-87. 50. Vance AL, Luk ES: Attention deficit hyperactivity disorder and anxiety: is there an association with neurodevelopmental deficits? Aust NZ J Psychiatry 1998, 32:650-657. 51. Davidson RJ: Anterior cerebral asymmetry and the nature of emotion. Brain Cogn 1992, 20:125-151. 52. Kagan J, Reznick JS, Snidman N: The physiology and psychology of behavioral inhibition in children. Child Dev 1987, 58:1459-1473. 53. Barkley RA: Impaired delayed responding: A unified theory of Attention Deficit Hyperactivity Disorder. In Disruptive Behavior Disorders in Childhood: Essays Honoring Herbert C. Quay Edited by: Routh DK. New York: Plenum Press; 1994:2-72. 54. Hollingshead AB, Redlich FC: Social Class and Mental Illness New York: Wiley; 1958. Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 10 of 10 (page number not for citation purposes) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Behavioral and Brain Functions Springer Journals

Cognition in anxious children with attention deficit hyperactivity disorder: a comparison with clinical and normal children

Loading next page...
 
/lp/springer-journals/cognition-in-anxious-children-with-attention-deficit-hyperactivity-T0GawDixCo

References (67)

Publisher
Springer Journals
Copyright
Copyright © 2007 by Manassis et al; licensee BioMed Central Ltd.
Subject
Biomedicine; Neurosciences; Neurology; Behavioral Therapy; Psychiatry
eISSN
1744-9081
DOI
10.1186/1744-9081-3-4
pmid
17224054
Publisher site
See Article on Publisher Site

Abstract

Background: Cognition in children with anxiety disorders (ANX) and comorbid Attention Deficit Disorder (ADHD) has received little attention, potentially impacting clinical and academic interventions in this highly disabled group. This study examined several cognitive features relative to children with either pure condition and to normal controls. Methods: One hundred and eight children ages 8–12 and parents were diagnosed by semi- structured parent interview and teacher report as having: ANX (any anxiety disorder except OCD or PTSD; n = 52), ADHD (n = 21), or ANX + ADHD (n = 35). All completed measures of academic ability, emotional perception, and working memory. Clinical subjects were compared to 35 normal controls from local schools. Results: Groups did not differ significantly on age, gender, or estimated IQ. On analyses of variance, groups differed on academic functioning (Wide Range Achievement Test, p < .001), perception of emotion (auditory perception of anger, p < .05), and working memory (backwards digits, p < .01; backwards finger windows, p < .05; Chipasat task, p < .001). ANX + ADHD and children with ADHD did poorly relative to controls on all differentiating measures except auditory perception of anger, where ANX + ADHD showed less sensitivity than children with ANX or with ADHD. Conclusion: Though requiring replication, findings suggest that ANX + ADHD relates to greater cognitive and academic vulnerability than ANX, but may relate to reduced perception of anger. Background Rates of ANX in the presence of ADHD range from 13 to Anxiety Disorders (ANX) and Attention Deficit Hyperac- 50% in various studies [2] and these comorbid children tivity Disorder (ADHD) both constitute major mental are less responsive to certain treatments [3] and are at even health problems of childhood, with affected children fac- greater risk of long-term impairment and development of ing impairment at home, at school, and with peers [1]. further psychopathology [4] than children with either Page 1 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 "pure" condition. Although family studies suggest that the in comparison to children with ANX only, children with comorbid condition (ANX + ADHD) is more closely ADHD only, and normal controls. Executive dysfunction, linked to anxiety disorders than ADHD [2], the best treat- particularly impairments in inhibitory control and work- ment for it is unknown. ing memory, have been demonstrated repeatedly in ADHD (reviewed in [4]). Given that the foremost evi- To develop effective treatments and academic interven- dence-based treatment for anxiety disorders is cognitively tions for these children, an understanding of the cognitive based (cognitive-behavioral therapy; [5]), however, a processes that underlie ANX + ADHD is crucial. Effective 'pure' ANX comparison group was considered particularly treatments for anxiety, for example, place high demands relevant. on certain language-based cognitive processes [5]. Cogni- tive measures also provide a useful approach to investigat- Cognition in anxious children has been characterized as ing whether or not ADHD + ANX constitutes a unique biased by selective perception and selective memory for subtype (ie. differs from either ADHD or ANX), since they threatening stimuli or emotions (reviewed in [7]). Anxi- constitute direct and objective measures and are inde- ety-related deficits in executive function, particularly pendent of diagnostic criteria. For example, cognitive working memory, have also been proposed [9]. There is resemblance to either pure condition would suggest ANX some evidence to suggest that these may play a role in + ADHD may have a similar etiology to that condition. combined ANX and ADHD [10-12]. Therefore, we were Thus, cognitive studies have important therapeutic and particularly interested in examining emotional perception etiological implications. and working memory in children with ANX + ADHD rel- ative to children with either 'pure' condition and to nor- Studies of information processing are challenging to con- mal controls. This study represents a first step to further duct for both theoretical and methodological reasons our etiological and therapeutic understanding of (reviewed in [6]). Small sample sizes and lack of measure- ANX+ADHD. The cognitive domains of interest are ment reliability, construct validity, or ecological validity described briefly before detailing our hypotheses and are common methodological challenges. Use of stimulus methods. sets inappropriate to age or developmental level and lack Emotional perception of attention to task-related fatigue are further challenges in child studies. Common theoretical challenges include The cognitive vulnerability to anxiety is thought to relate insufficient construct specificity, examining cognitive to an automatic tendency for anxious individuals to selec- processes in isolation (without reference to other aspects tively encode emotionally threatening information of information processing), and interpreting cognitive (reviewed in [13]). This encoding bias is demonstrated processes as contributing to psychopathology when they when subjects show selective attention to threatening may be mere epiphenomena of clinical problems. Of stimuli [13], selective interpretation of ambiguous stimuli course, it is also erroneous to assume that information as threatening [14], selective memory for threatening processing factors in children always operate as they do in words [14] or interference with task performance due to adults. exposure to threatening stimuli [15]. The bias is most evi- dent on tasks involving implicit rather than explicit atten- With these considerations in mind, we undertook an ini- tion to threat [13], suggesting that a conscious decision- tial cognitive study and demonstrated that children with making process is not involved. ANX + ADHD are cognitively distinct from either pure condition [7]. We examined several aspects of informa- In children with clinical anxiety disorders, Vasey and oth- tion processing, utilizing state-of-the-art measures of each ers [16] demonstrated an attentional bias towards emo- construct, with age-appropriate stimuli, and a protocol tionally threatening words on a probe detection task. On that minimized order effects and subject fatigue. Consist- a dichotic listening task, clinically anxious children ent with high rates of comorbidity among certain anxiety showed enhanced perception of emotions relative to nor- disorders in this age group [8], ANX was defined as any mal controls, possibly reflecting hypervigilance to emo- anxiety disorder other than OCD or PTSD. We found that tional cues [17]. High trait anxious children have been ANX + ADHD was associated with neither the inhibitory found to show a bias toward negative relative to neutral control deficits of 'pure' ADHD, nor the heightened sensi- information for conceptual memory tasks [18], a process- tivity to negative emotions of 'pure' ANX. It is the only ing bias for generally threatening information on an emo- study to date to examine emotional perception in this tional Stroop task [19], and a tendency to interpret population. homophones as threatening rather than neutral [20]. In the only study to date of emotional perception in anxious The present study sought to build on this work by further children comorbid for ADHD, these children showed elucidating the cognitive characteristics of these children, reduced perception of emotions relative to normal con- Page 2 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 trols [7], rather than the heightened perception of threat- those with ADHD alone [10-12]. Tannock et al. [12], ening or negative emotion characteristic of anxious using a serial addition task, showed that ANX + ADHD children. On the other hand, the few available studies of was associated with significantly worse performance on emotional perception in ADHD yield inconsistent find- the slower trials of the task, but no difference at higher ings [21,22]. The findings also suggest that comorbid con- speeds where performance declined for children with duct problems may influence response to emotional ADHD. Compared to children in the ADHD-only group, stimuli [22,23]. those with ANX + ADHD also failed to show improve- ments on auditory-verbal working memory tasks when Working memory treated with stimulant medication [10]. Pliszka [10] Working memory is an aspect of executive function. It has administered a memory scanning task that placed been described as a limited capacity system for the tempo- demands on nonverbal working memory to children with rary storage and processing of information [24]. It is ADHD with or without comorbid ANX. ANX + ADHD was thought to underlie a wide range of cognitive processes, associated with longer, sluggish reaction times on this including planning, learning, problem solving, reasoning task. and comprehension [25], and predicts academic achieve- ment [26]. Tasks requiring working memory test the abil- Hypotheses ity to simultaneously store and manipulate retained Based on the above, we hypothesized (1) that children information in order to complete complex tasks [27]. For with ANX would show heightened perception of negative example, asking a subject to remember a particular emotions relative to the other children studied, a bias that number (storage) while adding a different set of numbers might not be evident in the comorbid group [7]; (2) that (manipulation) would constitute a test of working mem- children with ANX + ADHD would be particularly ory. Deficits in this ability are seen in a variety of clinical impaired on working memory relative to the other chil- conditions. dren studied, given that both anxiety and ADHD have been linked to working memory problems through differ- In children with ANX, deficits may occur due to the inter- ent mechanisms. ference of worry with normal processing of information [9]. Eysenck postulates that anxious individuals have clus- We were also interested in overall academic ability, and ters of anxiety-related information in long term memory hypothesized difficulty in all clinical groups relative to which are easily accessible, rapidly activated, and retrieved normal controls, but perhaps more so in the comorbid quickly thus interfering with information-processing. group. Studies support an inability of anxious individuals to inhibit anxiety-provoking stimuli [28-30]. Anxiety Methods enhances motivation, however, potentially compensating Subjects for the effect of worry on some tasks. Francis-John and Children were recruited from two outpatient clinics (one colleagues (submitted) recently found impairment in specializing in anxiety disorders; the other in learning dif- complex verbal working memory in anxious children rel- ficulties) in two university-based clinical research centers ative to normal controls, but not in visual-spatial working serving a large urban and suburban population. Investiga- memory. However, the sample included a substantial tors met regularly to ensure standardized procedures at number of children with comorbid ADHD. Working the two clinics. A consecutive sample of children ages 8 to memory has not been examined in other studies of anx- 12 years meeting study criteria were recruited. All racial ious children. and socioeconomic groups were represented, but with some over-representation of Caucasian versus non-Cauca- In ADHD, working memory impairments have been sian families and more affluent versus less affluent fami- linked theoretically [31] to the disorder, and recent meta- lies, relative to the local census population. analyses have empirically shown that working memory tasks discriminate between ADHD and controls [32]. Fur- Control subjects were recruited from local schools in the thermore, these meta-analyses demonstrate impairments same geographic area, based on principals' nomination of in visual-spatial as well as auditory-verbal working mem- students with no evidence of emotional or behavioral ory abilities in ADHD which remain robust even after problems. Each student was also asked to nominate a controlling for comorbidity with other psychiatric disor- friend (snowball technique). Controls were only included ders and general intellectual function [32]. if they were within one standard deviation of the popula- tion mean for total scores on standardized measures of Studies using complex tasks that place a high demand on anxiety and ADHD symptoms (see below). While two working memory have shown greater impairment for chil- potential controls were excluded for this reason, neither dren with internalizing disorders and ADHD than for showed evidence of clinical disorder on interview. Page 3 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 All children were in an unmedicated state at the time of bid Oppositional Defiant Disorder alters the cognitive the study. Children receiving psychoactive medication (all features of ANX or ADHD. The other three comorbidities had been diagnosed with ADHD and were on psychostim- listed were assessed for each participating child. LD was ulants: 9 comorbid children and 6 ADD children) discon- defined as a standardized score on the Wide Range tinued it for a period of seven medication half-lives prior Achievement Test (WRAT-R; [36]) that was at least 1.5 SD to study participation, to ensure adequate washout. Chil- below mean for age and below full-scale IQ score on the dren who had received a course of cognitive behavioral WISC-III [37]. Depression was defined by a score > 16 on therapy (8 sessions or more) for their anxieties were the Children's Depression Inventory [38,39], or by the excluded, as this form of therapy may alter cognitive proc- diagnostic interview. CD was assessed by the diagnostic esses. There were no differences among clinical groups for interview. In practice, there were no children meeting the number of mental health services received in the pre- diagnostic criteria for either depression or CD. There were vious 4 years, nor for the proportion of children receiving several children in each clinical group meeting criteria for ongoing mental health follow-up in the previous year LD by the above definition (39 total). However, chi- (about 60% in each clinical group). square analyses showed significant group differences for reading disability only (6 anxious, 3 comorbid, and 6 Prior to participation, potential subjects and their parents ADHD children; chi-square = 12.10, p = .007). Post hoc completed the Anxiety Disorders Interview Schedule analyses used continuous measures of comorbidity as cov- (ADIS; [33]), a well-validated, semi-structured diagnostic ariates in interpreting data, to detect any comorbidity- interview using DSM – IV criteria. Diagnosis was based related effects (analysis described in [40]). primarily on this instrument, but teacher reports (by structured telephone interview and Conners' Question- We excluded children who had a full-scale IQ < 80, lacked naire[34]) were required to confirm ADHD in the school fluency in English, or were suffering from psychosis or environment. Anxiety disorders were diagnosed when serious visual, auditory, or speech deficits. present either by parent or child report. All interviewers were child psychiatrists or child psychologists, trained to Procedure reliability on the instrument, and with at least 3 years The project was approved by our hospital Research Ethics Board, and children and parents provided informed experience using it in other research studies. With parental consent, 10% of these diagnostic interviews (randomly assent and consent respectively. Research was carried out selected) were videotaped and scored by an independent in compliance with the Helsinki Declaration. Administra- rater to ensure reliability among interviewers. No discrep- tion of measures was done by a research technician blind ancies between interviewers and raters were found for to child diagnosis, and counterbalanced to control for any group assignment. Children also completed the Multidi- order effects. Children completed the Wide Range mensional Anxiety Scale for Children (MASC; [35]) and Achievement Test-Revised (WRAT-R, [36]; tests academic parents the Parent Conners' Questionnaire [34], to obtain achievement) and the Vocabulary and Block Design sub- well-validated, continuous measures of anxiety and tests of the Wechsler Intelligence Scale for Children ADHD symptoms respectively. (WISC-III [41]). This two-subtest short form has been shown to reliably estimate verbal and non-verbal intelli- All ADHD subtypes were included, and all childhood anx- gence respectively [42]. Parents were asked to complete a iety disorders were included apart from post-traumatic set of questionnaires and to provide basic demographic stress disorder and obsessive compulsive disorder (as the information (Ontario Child Health Study, [43]). Normal latter are likely to be cognitively distinct). Childhood anx- hearing was confirmed by audiological screening and iety disorders are highly comorbid: 40% of anxious chil- handedness was verified by a preference inventory (Water- dren have more than one disorder [8], so mixed anxious loo Handedness Questionnaire, [44]). If the child had samples are commonly studied in this type of research. completed either a WRAT-R or WISC-III within the past Generalized Anxiety Disoder (GAD) was the primary diag- year, scores were obtained with parental consent and the nosis in about 50% of both the ANX and ANX + ADHD test was not re-administered. groups. Cognitive measures Because this was a clinical sample, other comorbid condi- Measures targeted the cognitive domains of interest, with tions (Learning Disabilities, Oppositional Defiant Disor- verbal and nonverbal working memory examined sepa- der, Conduct Disorder, Depression) were expected. rately. A timed verbal working memory task was also Although these could potentially confound interpretation included, as the stress of a timed task may affect anxious of data, they are so frequent in this population that children differently than non-anxious children. All meas- excluding subjects with them would likely have rendered ures are widely used research tools, and have acceptable the study non-feasible. There is no evidence that comor- reliability and validity data. Page 4 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 Emotional perception ity. Standard scores were used for the forward administra- Diagnostic analysis of nonverbal accuracy 2 tion, and raw scores for the backward version. (DANVA2)[45]: The DANVA2 consists of four receptive and three expressive subtests designed to measure the Statistical analysis accuracy of nonverbal social information processing in The Statistical Package for the Social Sciences – PC version children. Two receptive subtests (Adult Faces 2 and Adult (SPSSPC) was used for all analyses. Groups were com- Voices 2) were selected for use in the current study. Chil- pared on demographic characteristics and cognitive char- dren had to identify the emotional valence of the facial acteristics using analyses of variance (ANOVA). Chi- expression or tone of voice respectively. Adult stimuli square was used for categorical measures. To test our were chosen because child stimuli on the measure are less hypotheses about specific group differences, post-hoc subtle, sometimes resulting in ceiling effects. tests were done for all variables that showed significant group differences on ANOVA, with Bonferroni correction Working memory: verbal for multiple comparisons. CHIPASAT (Children's paced auditory serial addition test; [46]): The CHIPASAT is a precisely timed task in which To further corroborate relationships between ADHD, tape-recorded, single-digit numbers are presented in trials ANX, and various cognitive measures, bivariate correla- of differing speeds. Children are required to add each new tions between these measures and maternal Conners' number to the immediately preceding number and give ADHD Symptom Index and child MASC scores, respec- the answer aloud. The numerical knowledge required is tively, were examined in secondary analyses. Further post usually acquired by grade 1. The traditional dependent hoc analyses were done to include estimated IQ (based on variable is the total number of correct responses for each Vocabulary and Block Design scores) and each of the three speed. Some strategies for doing the task (e.g., adding comorbidities likely to affect cognition (LD, Depression, stimuli discontinuously; [12]) allow for many correct CD) measured as continuous variables. These variables responses without a high demand on working memory, were entered as covariates, one at a time, in analyses of so variables pertaining to strategy were also compared covariance (ANCOVAs) to determine if between-group across groups. These were found not to differ by group, differences remained, as described by Nigg et al. [40]. however, so correct responses only are reported in this Thus, we determined the effect (if any) of these comorbid paper. More detailed analyses of this task for a subset of conditions on our results. this sample can be found in Francis-John et al., (submit- ted). Results Sample characteristics by group are described in Table 1. Backward digit span (WISC-III;[41]): Standard procedure There were no significant group differences in age, gender, for the WISC-III was used, and the highest number of dig- socioeconomic status, or handedness. As expected, ANX its recalled under the Backward condition was recorded and ANX + ADHD groups reported significantly more (whether or not the child was able to recall the same anxiety than normal controls, although their mean scores number of digits once or twice), then converted to a scaled still appeared to be in the normal range. This is not unu- score. Only scaled scores were reported and used in anal- sual in clinics where the anxiety prompting referral is yses. identified by parents or clinicians (rather than the chil- dren themselves), given that correspondence between Working memory: nonverbal informants is only fair in childhood internalizing disor- Finger windows backwards: The Finger Windows subtest ders [48]. On the Conners', mothers reported significant from the Wide Range Assessment of Memory and Learn- differences between children with ADHD, ANX, and nor- ing (WRAML) [47] was administered. In the forward mal controls, while teachers only distinguished clinical administration, the examiner indicates a series of spatial versus nonclinical groups. locations by inserting a pencil through a series of ran- domly spaced holes ("windows") on an 8 × 11 inch card Data was screened for outliers and conformity with the at a rate of one hole per second. The child must then statistical assumptions of analysis of variance. Also, the reproduce the same visual-spatial sequence by putting his effect of specific anxiety diagnosis was examined by com- or her finger through each window in the same order as paring children with a primary diagnosis of GAD (about the presentation. Items gradually increase in length from 50% of both ANX and ANX + ADHD groups) with those sets of 2 to sets of 6 windows, demonstrating spatial mem- with other primary anxiety diagnoses on all measures of ory span. With backward administration, that is the child interest. No significant differences were found, so all anx- reproducing the sequences in backward order, this iety diagnoses were examined together in subsequent becomes a measure of spatial working memory. Lower analyses. scores are associated with greater impairment in this abil- Page 5 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 Table 1: Description of Sample: Means and Standard Deviations Anxiety Only (n = 52) Comorbid for ADHD* (n = 35) ADHD Only (n = 21)** Normal Controls (n = 35) Total (n = 143) Age in Years 9.42 (1.23) 9.82 (1.27) 9.60 (1.43) 9.71 (1.32) 9.61 (1.28) Socioeconomic Status (Hollingshead 48.45 (12.21) 46.56 (15.46) 44.22 (18.36) 53.92 (8.85) 48.19 (13.61) Index [54]) Gender (% Males) 66% 74% 81% 63% 69% Handedness (% Right vs. Left/Mixed) 67% 53% 70% 74% 64% DSM-IV Conners' ADHD Symptom 57.08 (11.09) 69.00 (12.63) 69.80 (7.00) 49.50 (7.67) 58.86 (12.81) Index (t-score) Mother Report Teacher Report (n = 69) 55.15 (12.35) 61.11 (18.81) 74.33 (11.68) 50.08 (5.87) 56.01 (14.60) Multidimensional Anxiety Scale for 53.12 (1.08) 54.97 (13.24) 50.10 (11.00) 46.23(10.09) 51.52 (11.82) Children (t-score) a 1 2 3 standard deviations are shown in brackets; p < .05, p < .01, p < .001 * 19 Inattentive Type; 16 Combined Type ** 11 Inattentive Type; 10 Combined Type To test our main hypotheses regarding emotional percep- DSM-IV ADHD Symptom Index and the cognitive meas- tion in ANX and working memory in ANX + ADHD, ures of interest. Significant correlations (p < .05) were evi- groups were compared on measures relevant to these dent for: Chipasat 2.0, Chipasat 2.8, Digit Span domains. Table 2 shows group means on these cognitive Backwards (ie. verbal working memory measures), WRAT measures of interest. Group differences were found on all Spelling, and WRAT Arithmetic subtests. All correlations academic achievement tests, the Chipasat (verbal working were in the expected direction (ie. worsening test perform- memory), Digit span backwards (verbal working mem- ance with increasing Mother Conners' symptoms). Corre- ory), finger windows backwards (nonverbal working lations were also examined between the child-report memory), and DANVA – adult angry voice (emotional MASC (our continuous measure of anxiety) and the cog- perception). Group differences are reported uncorrected nitive measures of interest. A significant correlation (p < in the table. However, we also applied the Bonferroni cor- .05) was evident for DANVA: angry adult voice, detected rection within each domain, consistent with our initial more by children with higher MASC scores. hypotheses. Doing so, the following comparisons remained significant: all academic achievement differ- When covarying for estimated IQ, all previously signifi- ences, the Chipasat 2.0 and 2.8, and the Digit Span Back- cant comparisons remained significant. When covarying wards. for depressive symptoms and for conduct disorder symp- toms, all previously significant comparisons remained For all significant ANOVAs, post-hoc analyses were done significant. To assess the effect of learning problems, we to test our hypotheses regarding specific group differences ran group comparisons covarying for the discrepancy (see Table 3). As hypothesized for emotional perception, between estimated IQ and specific WRAT scores for each ANX were indeed more sensitive to adult anger (the most subject, consistent with our operational definition of LD threatening emotion) than ANX + ADHD. Interestingly, above. Using this approach, all previously significant children with ADHD also showed this sensitivity relative working memory and emotional perception comparisons to ANX + ADHD. For working memory (second hypothe- remained significant (obviously not applicable to WRAT sis), both ADHD groups appeared impaired relative to comparisons). Interestingly, covarying for the actual normal controls, but ANX did not. The effect appeared WRAT scores (without relating them to IQ) showed that somewhat stronger for verbal working memory, with ANX reading ability on WRAT eliminated all group differences + ADHD showing only a trend level difference from nor- apart from that for the DANVA: auditory anger. mal controls on nonverbal working memory. Significant academic impairments were evident in all clinical groups Although we did not hypothesize any gender differences, relative to normal controls, but appeared more pro- we re-ran all group comparisons covarying for gender. All nounced in the ADHD groups. significant group differences remained, and a significant effect for gender was found only on one measure, the Chi- Secondary analyses pasat, where females tended to score lower than males at To determine whether anxiety and ADHD measured as the slower speed (F = 10.66, p < .01). continuous variables related to cognitive measures regard- less of diagnostic group, bivariate correlations were exam- ined for the whole sample between Mother Conners' Page 6 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 Table 2: Cognitive Tasks by Group TASK ANX ANX + ADHD ADHD NORMAL Signif. ANOVA Effect Size (Partial Eta Squared) WISC-III: IQ 107.1 (12.4) 103.53 (10.95) 103.37 (12.63) 110.41(8.42) - - Perception of Emotion: DANVA Happy (raw) 3.79 (1.54) 4.21 (1.43) 3.37 (1.38) 4.09 (1.36) - - Sad (raw) 4.17 (1.12) 3.85 (1.16) 3.84 (1.34) 3.83 (1.15) - - Angry (raw) 4.58 (1.01) 4.03 (1.27) 4.79 (0.98) 4.26 (0.89) * .063 Fearful (raw) 4.08 (2.34) 3.71 (1.71) 3.95 (1.68) 3.83 (1.64) - - Working Memory: Nonverbal: Finger – Windows Forward (scaled) 8.91 (3.46) 7.91 (2.94) 9.19 (2.82) 9.39 (2.91) - - Backward (raw) 10.13 (4.78) 9.32 (4.23) 7.74 (5.20) 11.33 (3.79) * .059 Working Memory Verbal: Digit Span Forward (scaled) 10.81 (2.81) 10.90 (3.30) 9.00 (3.04) 10.63 (3.23) - - Backward (scaled) 10.67 (2.74) 8.84 (3.50) 7.94 (3.17) 10.40 (3.25) ** .099 Chipasat Task Speed: 2.8 (raw) 31.49 (12.21) 25.60 (8.43) 23.41 (11.02) 34.88 (9.76) *** .101 Speed: 2.0 (raw) 25.51 (10.65) 22.00 (7.62) 18.82 (7.68) 29.36 (7.55) *** .084 Academics WRAT: Reading 110.4 (14.6) 105.41 (17.59) 99.71 (19.20) 118.63 (11.04) *** .144 Spelling 106.7 (51.1) 96.94 (15.51) 93.52 (17.17) 113.09 (11.85) *** .193 Arithmetic 99.3 (15.5) 92.27 (15.99) 93.05 (16.48) 109.89 (10.59) *** .176 Word attack 108.4 (13.8) 100.12 (16.03) 94.05 (20.93) 109.12 (8.13) *** .131 *p < .05 **p < .01 ***p < .001; t-scores unless otherwise indicated; WRAT, Chipasat, and Digit Span Backward significant after Bonferroni correction; WISC-III = Wechsler Intelligence Scale for Children-III; WRAT = Wide Range Achievement Test; DANVA = Diagnostic Assessment of Nonverbal Accuracy Specific findings Discussion Although effect sizes were modest, group differences We hypothesized that 'pure' anxious children would show between anxious children, anxious children comorbid for enhanced perception of negative emotions. Consistent ADHD, and normal controls were found on several cogni- with this hypothesis, 'pure' anxious children were found tive measures. The lack of group differences in demo- to have an enhanced perception of auditory anger relative graphic characteristics (age, gender, socioeconomic to comorbid children, with normal control scores inter- status) suggests that these factors are unlikely to account mediate between these two groups. This finding partially for these findings. The degree of anxiety reported for the replicates our previous work showing reduced perception two ANX groups was also very similar, as was the degree of negative emotion in ANX + ADHD [7]. Our continuous of severity of ADHD symptoms in the two ADHD groups, measure of anxiety (MASC) was also correlated with per- suggesting that cognitive differences are unlikely to be due ception of auditory anger. Anger is considered the most to symptom severity in one or the other group. Clinical threatening of negative emotions (from the listener's per- groups were also comparable in prior mental health serv- spective) so it was not surprising that sensitivity to it was ice utilization, suggesting that length of illness is unlikely heightened in ANX, where threat sensitivity has been con- to account for cognitive differences. firmed in other studies [7,16]. Notably, the ANX + ADHD Table 3: Post-hoc Group Comparisons for Differentiating Measures (p values; in bold if significant) Measure ANX vs. ANX + ADHD ANX vs. ADHD ANX vs. Normal ANX + ADHD vs. ADHD ANX + ADHD vs. Normal ADHD vs. Normal DANVA angry .026 .447 .121 .028 .389 .047 Chipasat (2.8) .037 .021 .233 .470 .001 .001 Chipasat (2.0) .162 .023 .119 .198 .001 .000 Digits Backward .009 .001 .674 .384 .064 .013 Finger Windows .423 .071 .225 .234 .045 .006 Backward WRAT reading .158 .012 .006 .265 .000 .000 WRAT spelling .005 .002 .037 .453 .000 .000 WRAT arith. .046 .128 .001 .864 .000 .000 WRAT w. attack .012 .001 .778 .236 .005 .000 Page 7 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 group was least sensitive to this emotion, suggesting that One possible model for ANX + ADHD their anxiety may be of a different nature to that of the Although needing replication, these findings have poten- ANX group and that anxiety may not relate to threat sen- tially interesting implications for understanding the sitivity. If replicated, this finding suggests that other etio- comorbidity between ANX and ADHD. Vance and Luk logical mechanisms for anxiety should be examined in [50] hypothesized that a neurodevelopmental deficit this population (see below). Interestingly, 'pure' ADHD underlies both anxious and ADHD symptoms in these children also showed the perceptual bias towards anger children. Our findings suggest one candidate for such a relative to ANX + ADHD. deficit: impaired working memory, especially verbal working memory. Working memory has been linked to In relation to working memory, we hypothesized the the frontal lobes, with verbal ability predominantly on greatest impairment in ANX + ADHD. Instead, we found the left side in most individuals. Studies linking approach that both ADHD groups were impaired relative to normal behavior in anxious individuals to left anterior activation controls and ANX. This difference was more robust for on EEG [51], reduced left anterior activation in behavio- verbal than nonverbal working memory, and occurred rally inhibited children [52], successful treatment of anxi- whether or not the task was timed. Maternal (continuous) ety using verbally mediated cognitive behavioral strategies report of ADHD symptoms also correlated with verbal [5], and deficits in frontal lobe functions in ADHD [53] working memory. These findings are consistent with pre- are all consistent with this idea. The lack of sensitivity to vious reports suggesting that lack of vigilance or distrac- threat (angry voice) we found in ANX + ADHD (in con- tion by external stimuli can interfere with working trast to 'pure' ANX) is also consistent with this model. memory in ADHD [49]. We did not replicate earlier find- Thus, children with ADHD + ANX may have frontal lobe ings of greater impairment in ANX + ADHD than in 'pure' deficits that affect their ability to inhibit both negative ADHD [10-12]. The findings appear contrary to Eysenck affect (resulting in anxiety symptoms, even in the absence and Calvo's [9] hypothesis regarding the adverse effects of of threat sensitivity) and responses to stimuli (resulting in worry on working memory. It is possible, however, that ADHD symptoms). Understanding the nature of these findings in ANX might be different in a less reassuring test impairments more precisely may suggest fruitful avenues situation than that in our laboratory. Studies of such chil- of clinical and academic intervention for them. dren in anxious states (for example, during examinations at school) might show greater effects of worry on working Limitations memory. Further studies that include larger, more diverse samples are needed to replicate and extend these findings. The col- Academic differences were greatest between children with lection of the sample from two university-based clinics ADHD and normal controls, though some academic may also have resulted in some sample bias. This bias may impairment was evident in ANX as well. ANX + ADHD did limit generalizability to other populations (for example, not appear to have worse academic performance than children with ANX + ADHD in the community). Vasey children with 'pure' ADHD, highlighting the need for and colleagues [6] have also advocated the use of multiple school supports for all children meeting ADHD criteria. measures of each construct to allow the generation of composite scores, and longitudinal studies that clarify the We examined other reasons for the group differences relationship between deficit and disorder (eg. determin- (apart from diagnosis per se) by covarying for IQ, gender, ing if deficits are present prior to the onset of disorder or academic deficits relative to IQ, comorbid depressive can be modified such that symptomatology changes). symptoms, and comorbid conduct symptoms. All group differences remained significant, and only one measure Clinical implications (Chipasat at slower speed) showed a significant gender The nature of the cognitive deficits in ANX + ADHD may effect (males performed better). Controlling for academic be relevant to these children's ability to benefit from cog- ability, however, eliminated all but one group difference: nitive behavioral therapy for anxiety, particularly since the difference in auditory perception of anger. Thus, emo- these deficits are less likely to be ameliorated by stimulant tional perception may be relatively independent of aca- treatment than in 'pure' ADHD children. Thus, even a demic ability, but working memory appears to show some medicated child with comorbid ANX + ADHD may find association. This association disappears, however, when the verbal reasoning required in cognitive behavioral ther- academic ability is measured relative to IQ. This finding apy confusing, due to limited verbal working memory. suggests that group differences in working memory can- ADHD may also make the child appear disruptive or dif- not be accounted for entirely by differential academic def- ficult to manage if CBT is offered in a group format icits. (increasingly favored to contain costs). CBT may require modification and/or administration in an individual for- mat in order for these children to benefit. Page 8 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 ders and ADHD. J Am Acad Child Adolesc Psychiatry 2000, Given the above deficits, children with ANX + ADHD are 39:1152-1159. also likely to be disadvantaged academically. They may 8. Bernstein GA, Borchartdt CM, Perwien AR: Anxiety disorders in require different teaching strategies geared to their unique children and adolescents: A review of the past 10 years. J Am Acad Child Adolesc Psychiatry 1996, 35:1110-1119. cognitive profile. If they encounter school failure, this 9. Eysenck MW, Calvo MG: Anxiety and performance: The may exacerbate anxiety leading to further problems. processing efficiency theory. Cogn Emot 1992, 6:409-434. 10. Pliszka SR: Effect of anxiety on cognition, behavior, and stim- Enhancing teachers' and clinicians' awareness of the par- ulant response in ADHD. J Am Acad Child Adolesc Psychiatry 1989, ticular vulnerabilities of these children may improve their 28:882-887. therapeutic and academic outcomes. 11. Pliszka SR: Comorbidity of attention-deficit hyperactivity dis- order and overanxious disorder. J Am Acad Child Adolesc Psychia- try 1992, 31:197-203. Conclusion 12. Tannock R, Ickowicz A, Schachar R: Differential effects of meth- Findings suggest that ANX + ADHD relates to greater cog- ylphenidate on working memory in ADHD children with and without anxiety. J Am Acad Child Adolesc Psychiatry 1995, nitive and academic vulnerability than ANX, especially 34:886-896. with respect to working memory, but may relate to 13. MacLeod C: Clinical anxiety and the selective encoding of threatening information. Int Rev Psychiatry 1991, 3:279-292. reduced perception of anger. Awareness of this vulnerabil- 14. Mathews A, Mogg K, May J, Eysenck M: Implicit and explicit mem- ity may allow tailoring of psychological and academic ory bias in anxiety. J Abnorm Psychol 1989, 98:236-240. intervention to better meet the needs of affected children. 15. Stroop JR: Studies of interference in serial verbal reactions. J Exp Psychol 1935, 18:643-662. Further studies of larger, more diverse samples are indi- 16. Vasey MW, Daleiden EL, Williams LL, Brown LM: Biased attention cated to replicate these findings and further elucidate the in childhood anxiety disorders: A preliminary study. J Abnorm Child Psychol 1995, 23:267-279. cognitive and neurological substrates of ANX + ADHD. 17. Manassis K, Tannock R, Masellis M: Cognitive differences between anxious, normal, and ADHD children on a dichotic Competing interests listening task. Anxiety 1996, 2:279-285. 18. Daleiden EL: Childhood anxiety and memory functioning: a The author(s) declare that they have no competing inter- comparison of systemic and processing accounts. J Exp Child ests. Psychol 1998, 68:216-235. 19. Kindt M, Broschot JF, Everaerd W: Cognitive processing bias of children in a real life stress situation and a neutral situation. Authors' contributions J Exp Child Psychol 1997, 64:79-97. KM was the principal investigator of this study, principal 20. Hadwin J, Frost S, French CC, Richards A: Cognitive processing author of this paper, and leads one of the participating and trait anxiety in typically developing children: evidence for an interpretation bias. J Abnorm Psychol 1997, 106:486-490. outpatient clinics. RT was a co-investigator of this study, 21. Corbett B, Glidden H: Processing affective stimuli in children and developed the initial study design jointly with KM. AY with Attention Deficit Hyperactivity Disorder. Child Neuropsy- chol 2000, 6:144-155. contributed valuable ideas to the final design and proce- 22. Cadesky EB, Mota VL, Schachar RJ: Beyond words: how do chil- dures of the study, and leads the second participating out- dren with ADHD and/or conduct problems process nonver- patient clinic. All authors read and approved the final bal information about affect? J Am Acad Child Adolesc Psychiatry 2000, 39:1160-1167. manuscript. 23. Du J, Li J, Wang Y, Jiang Q: Event-related potentials in adoles- cents with comorbid ADHD and CD disorder: a single stim- ulus paradigm. Brain Cogn 2006, 60:70-75. Acknowledgements 24. Baddeley A: Modularity, mass-action and memory. Q J Exp Psy- We wish to acknowledge the financial support of the Ontario Mental chol A 1986, 38:527-533. Health Foundation for this work. 25. Swanson HL: Short-term memory and working memory: do both contribute to our understanding of academic achieve- ment in children and adults with learning disabilities? J Learn References Disabil 1994, 27:34-50. 1. Bird HR, Canino G, Rubio-Stipec M: Estimates of the prevalence 26. Aronen ET, Vuontela V, Steenari MR: Working memory, psychi- of childhood maladjustment in a community survey in atric symptoms, and academic performance at school. Neu- Puerto Rico. Arch Gen Psychiatry 1988, 45:1120-1126. robiol Learn Mem 2005, 83:33-42. 2. Jensen PS, Martin D, Cantwell DP: Comorbidity in ADHD: impli- 27. Eslinger PJ: Conceptualizing, describing, and measuring com- cations for research, practice, and DSM-V. J Am Acad Child Ado- ponents of executive function: a summary. In Attention, Mem- lesc Psychiatry 1997, 36:1065-1079. ory, and Executive Function Edited by: Lyon GR, Krasnegor NA. 3. MTA Cooperative Group: Moderators and mediators of treat- Baltimore, MD: Paul H. Brookes Publishing; 1996. ment response for children with ADHD. Arch Gen Psychiatry 28. Calvo MG, Eysenck MW: Phonological working memory and 1999, 56:1088-1096. reading in test anxiety. Memory 1996, 4:289-305. 4. Tannock R: Attention deficit disorders with anxiety disorders. 29. Pratt P, Tallis F, Eysenck M: Information processing, storage In Subtypes of Attention Disorders in Children, Adolescents, and Adults characteristics and worry. Behav Res Ther 1997, 35:1015-1023. Edited by: Brown TE. Washington DC: American Psychiatric Press; 30. Hopko DR, Ashcraft MH, Gute J, Ruggiero KJ, Lewis C: Mathemat- ics anxiety and working memory: support for the existence 5. Kendall PC, Flannery-Schroeder E, Panichelli-Mindel SM, Southam- of a deficient inhibition mechanism. J Anxiety Disord 1998, Gerow M, Heni M: Therapy for youths with anxiety disorders: 4:343-355. a second randomized clinical trial. J Consult Clin Psychol 1997, 31. Barkley RA: Behavioral inhibition, sustained attention, and 65:366-380. executive functions: constructing a unifying theory of 6. Vasey MW, Dagleish T, Silverman WK: Research on information- ADHD. Psychol Bull 1997, 121:65-94. processing factors in child and adolescent psychopathology: 32. Martinussen R, Hayden J, Hogg-Johnson S, Tannock R: A meta-anal- A critical commentary. J Clin Child Adolesc Psychol 2003, 32:81-93. ysis of working memory impairments in children with Atten- 7. Manassis K, Tannock R, Barbosa J: Dichotic listening and tion-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc response inhibition in children with comorbid anxiety disor- Psychiatry 2005, 44:377-384. Page 9 of 10 (page number not for citation purposes) Behavioral and Brain Functions 2007, 3:4 http://www.behavioralandbrainfunctions.com/content/3/1/4 33. Silverman WK, Albano AM: Anxiety Disorders Interview Schedule for DSM-IV San Antonio: The Psychological Corporation; 1996. 34. Conners CK: Manual for Conners' Rating Scales Toronto, Canada: Multi-Health Systems Inc; 1989. 35. March J: Multidimensional Anxiety Scale for Children (MASC) Toronto, Canada: Multi-Health Systems, Inc; 1998. 36. Wilkinson GS: Wide Range Achievement Test 3rd Edition (WRAT-3) Wilmington, Delaware: Wide Range, Inc; 1993. 37. Semrud-Clikeman M, Biederman J, Sprich-Buckminster S, Krifcher Lehman B, Faraone SV, Norman D: Comorbidity between ADHD and learning disability: A review and report in a clinically referred sample. J Am Acad Child Adolesc Psychiatry 1992, 31:439-448. 38. Kovacs M: The Children's Depression Inventory: A self-rated depression scale for school-aged youngsters University of Pittsburgh; 1983. 39. Saylor CF, Finch AJ, Spirito A: The Children's Depression Inven- tory: A systematic evaluation of psychometric properties. J Consult Clin Psychol 1984, 52:955-967. 40. Nigg JT, Hinshaw SP, Carte ET, Treuting JJ: Neuropsychological correlates of childhood Attention Deficit/Hyperactivity Dis- order: Explainable by comorbid disruptive behavior or read- ing problems? J Abnorm Psychol 1998, 107:468-480. 41. Wechsler D: Wechsler Intelligence Scale for Children-Third Edition San Antonio: The Psychological Corporation; 1991. 42. Sattler JM: Assessment of Children Cognitive Applications Fourth edition. San Diego: Jerome M. Sattler, Publisher, Inc; 2001. 43. Boyle MH, Offord DR, Racine Y: Evaluation of the Revised Ontario Child Health Study Scales. J Child Psychol Psychiatry 1993, 43:189-213. 44. Steenhuis RE, Bryden MP: Different dimensions of hand prefer- ence that relate to skilled and unskilled activities. Cortex 1989, 25:289-304. 45. Nowicki S Jr, Duke MP: Individual differences in the nonverbal communication of affect: The Diagnostic Analysis of Non- verbal Accuracy Scale. J Nonverb Behav 1994, 18:9-35. 46. Johnson DA, Roethig-Johnston K, Middleton J: Development and evaluation of an attentional test for head injured children: Information processing capacity in a normal sample. J Child Psychol Psychiatry 1988, 29:199-208. 47. Sheslow D, Adams W: Wide Range Assessment of Memory and Learning Administration Manual DE: Jastak; 1990. 48. Klein RG: Parent-child agreement in clinical assessment of anxiety and other psychopathology: A review. J Anxiety Disord 1991, 5:187-198. 49. Pennington BF, Ozonoff S: Executive functions and developmen- tal psychopathology. J Child Psychol Psychiatry 1996, 37:51-87. 50. Vance AL, Luk ES: Attention deficit hyperactivity disorder and anxiety: is there an association with neurodevelopmental deficits? Aust NZ J Psychiatry 1998, 32:650-657. 51. Davidson RJ: Anterior cerebral asymmetry and the nature of emotion. Brain Cogn 1992, 20:125-151. 52. Kagan J, Reznick JS, Snidman N: The physiology and psychology of behavioral inhibition in children. Child Dev 1987, 58:1459-1473. 53. Barkley RA: Impaired delayed responding: A unified theory of Attention Deficit Hyperactivity Disorder. In Disruptive Behavior Disorders in Childhood: Essays Honoring Herbert C. Quay Edited by: Routh DK. New York: Plenum Press; 1994:2-72. 54. Hollingshead AB, Redlich FC: Social Class and Mental Illness New York: Wiley; 1958. Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 10 of 10 (page number not for citation purposes)

Journal

Behavioral and Brain FunctionsSpringer Journals

Published: Jan 15, 2007

There are no references for this article.