DEPRESSION AND ANXIETY 00:1–9 (2014)

Research Article NEUROPSYCHOLOGICAL PERFORMANCE ACROSS SYMPTOM DIMENSIONS IN PEDIATRIC OBSESSIVE COMPULSIVE DISORDER Joseph F. McGuire, M.A.,1,2 Erika A. Crawford, B.A.,2 Jennifer M. Park, M.A.,1,2 Eric A. Storch, Ph.D.,1,2,3 Tanya K. Murphy, M.D., M.S.,1 Michael J. Larson, Ph.D.,4 and Adam B. Lewin, Ph.D.1,2,3 ∗

Background: Few studies have examined neuropsychological functioning among youth with obsessive compulsive disorder (OCD), with inconclusive results. Although methodological differences may contribute to inconsistent findings, clinical factors may also account for differential performance. Symptom dimensions are associated with specific patterns of genetic transmission, comorbidity, and treatment outcome, and may also be uniquely associated with neuropsychological performance. This study examined differences in cognitive sequelae and neurocognitive impairment across symptom dimensions among youth with OCD. Method: Participants included 93 treatment-seeking youth diagnosed with OCD. A trained clinician administered the Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) to parents and children together. Afterward, youth completed a battery of neuropsychological tests that assessed nonverbal memory and fluency, verbal memory, verbal fluency, verbal learning, processing speed, and inhibition/switching. Results: Across five symptom dimensions, youth exhibiting Hoarding symptoms (χ 2 = 5.21, P = .02) and Symmetry/Ordering symptoms had a greater occurrence of cognitive sequelae (χ 2 = 4.86, P = .03). Additionally, youth with Symmetry/Ordering symptoms had a greater magnitude of cognitive impairment (Mann–Whitney U = 442.50, Z = –2.49, P < .02), with specific deficits identified on nonverbal fluency (P < .01), processing speed (P < .01), and inhibition and switching (P < .02). Conclusions: Neuropsychological deficits identified in youth with Hoarding and Symmetry/Ordering symptoms may suggest that these symptoms have characteristics specific to neurocognitive impairment. Alternatively, symptoms associated with these dimensions may impede youth’s performance during testing. Findings advise neuropsychological testing for youth with symptoms on either of these dimensions when concerns about neuropsychological and/or academic impairment are present. Depression  C 2014 Wiley Periodicals, Inc. and Anxiety 00:1–9, 2014.

Contract grant sponsors: International OCD Foundation. ∗ Correspondence

1 Department

of Psychology, University of South Florida, Tampa, Florida 2 Department of Pediatrics, University of South Florida, Saint Petersburg, Florida 3 Department of Psychiatry, University of South Florida, Saint Petersburg, Florida 4 Department of Psychology and Neuroscience Center, Brigham Young University, Utah

 C 2014 Wiley Periodicals, Inc.

to: Adam B. Lewin, Ph.D., ABPP, Department of Pediatrics, Rothman Center for Neuropsychiatry, University of South Florida, Child Development and Rehabilitation Building, 880 6th Street South, Suite 460 Box 7523, Saint Petersburg, FL 33701. E-mail: [email protected] Received for publication 31 October 2013; Revised 7 December 2013; Accepted 3 January 2014 DOI 10.1002/da.22241 Published online 00 xxxx 0000 in Wiley Online Library (wileyonlinelibrary.com).

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Key words: children; neuropsychological functioning; memory; executive functioning; symptom dimensions

O

INTRODUCTION

bsessive compulsive disorder (OCD) is a neuropsychiatric condition that affects between 1 and 2% of the population.[1] The disorder is characterized by obsessive thoughts and compulsive rituals that cause distress and impairment. Various imaging and research approaches have identified structural,[2] and functional abnormalities in multiple brain regions among youth with OCD.[3] Consistent with the cortico-striato-thalamic model of OCD,[4, 5] many of the identified impaired brain regions are located in the prefrontal cortex.[6, 7] As abnormal brain functioning should be consistently reflected by neuropsychological impairments,[8, 9] performance deficits on neuropsychological tasks that rely on prefrontal brain regions would be anticipated. Although there has been some evidence of impairment in neuropsychological performance, there have been few replicated findings among youth with OCD. In comparison to healthy controls, Andres et al.[10] found that youth with OCD had impaired sorting and set-shifting abilities (Wisconsin Card Sorting Task; WCST), concentration (Stroop Color Word Task), verbal memory (Wechsler Memory Scale-III Logical Memory Task), visual reproduction (WMS-III Visual Reproduction), perceptual organization (Rey Complex Figure Test; RCFT), and difficulty with processing speed and velocity tasks (Wechsler Intelligence Scale for Children Coding task; WISC-III Coding; RCFT). Similarly, other studies have identified impaired performance with set-shifting on the WCST, attention on the Stroop, cognitive flexibility (perseveration errors on the California Verbal Learning Test-Child Version, CVLT-C), planning ability (D-KEFS Tower Test), and difficulty with processing speed and velocity tasks (WISC-III Coding, D-KEFS trail making test, Tower tasks).[11–14] Despite these reported neuropsychological deficits, several other studies have failed to identify significant differences between youth with OCD and healthy control participants on the WCST, Object Alternation Test, Trail Making Task, RCFT, and CVLT-C.[9, 12, 15, 16] Although these discrepancies have been attributed to sample sizes, comorbidity within samples, methodology (e.g., tests administered, sample characterization), and developmental considerations,[6] an underlying factor that may account for these differing reports is obsessive-compulsive symptom dimensions across participants. Although OCD has a heterogeneous presentation, symptoms often cluster around specific characteristics (referred to as symptom dimensions). Between four and five symptom dimensions have been reported among individuals with OCD,[17–19] which include: Symmetry, Ordering, Counting, and Magical Thinking symptoms (called Symmetry/Ordering); Contamination and Cleaning symptoms (called ContaminaDepression and Anxiety

tion/Cleaning); Hoarding symptoms; Sexual, Religious, and Somatic symptoms (called Forbidden Thoughts); and Aggressive and Checking symptoms (called Aggressive/Checking). While Symmetry/Ordering, Contamination/Cleaning, and Hoarding symptom dimensions have been consistently replicated across factor analytic studies, some debate exists between the separation or integration of Forbidden Thoughts and Aggressive/Checking symptoms.[19–21] Irrespective of the exact number of OCD symptom dimensions, they have been associated with unique patterns of genetic transmission,[22] comorbidity,[23] and treatment response.[24] Although Hoarding Disorder is recognized as a separate condition with distinct neuropsychological characteristics,[25, 26] youth with OCD who exhibit hoarding symptoms have been shown to be associated with unique clinical characteristics (e.g., worse insight, greater internalizing, and externalizing symptoms),[27] and symptom persistence into adulthood.[28] Despite these distinctive associations, there has been minimal examination of the association between symptom dimensions and neuropsychological functioning among youth with OCD. Among the few studies that have examined neuropsychological impairment by symptom dimension, the most consistent finding has been impairment related to adults who endorse Symmetry/Ordering symptoms. Specifically, Symmetry/Ordering symptoms have been associated with poor performance on tasks of nonverbal memory and organization,[29, 30] verbal memory,[31] and inhibition.[31, 32] Differences in performance on these types of tasks have been supported by structural imaging studies that have suggested distinct neural circuits are involved in each symptom dimension.[33–35] For instance, Koch et al.[35] found decreased white matter activity in those with ordering symptoms, particularly in areas projecting to the visual cortex. Additionally, two other reports identified a relationship between the Symmetry/Ordering symptom dimension, and functional abnormalities in striatal areas,[36] and the dorsal prefrontal cortex.[34] Taken together, these findings suggest that Symmetry/Ordering symptoms are associated with dysfunctional neural pathways. Beyond Symmetry/Ordering symptoms, Contamination/Cleaning symptoms have been associated with increased performance on tasks of memory and inhibition.[31] Furthermore, Contamination/Cleaning symptoms have been linked to increased activity in the visual cortex, ventral prefrontal cortex, caudate nucleus, and anterior insula.[33] Although these patterns have emerged in adults with OCD, they have yet to be fully examined in youth. Presently, neural correlates of symptom dimensions in pediatric OCD have only been examined in a single functional imaging study. Using a symptom provocation paradigm during MRI, Gilbert et al.[37]

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found that youth with OCD had reduced activity in the right insula, putamen, thalamus, and dorsolateral prefrontal cortex. During provocation tasks, youth exhibited activation of the left orbito-frontal cortex during the Contamination/Cleaning condition, whereas the right thalamus and right insula were activated during the Symmetry/Ordering condition. Given symptom dimensions’ distinctive associations with brain functioning, clinical characteristics, and treatment outcome, differences may also exist for neuropsychological performance. Accordingly, the present study examined the neuropsychological performance of youth with OCD in relation to obsessive-compulsive symptom dimensions. Understanding these associations is important for several reasons. First, specific symptom dimensions may serve as a phenotypic marker for greater neuropsychological impairment. Second, mixed findings from previous reports may be a function of varied symptom presentation among samples. Based on previous reports and OCD-related pathology, a battery of neuropsychological tests was specifically selected to assess memory abilities and executive functioning. Given that Symmetry/Ordering has consistently been associated with increased impairment, we first hypothesized that differences would exist in the frequency of cognitive sequelae for youth with Symmetry/Ordering symptoms. Second, we hypothesized that the magnitude of neurocognitive impairment would be greater for youth with Symmetry/Ordering symptoms. Following up on anticipated differences for these youth, we hypothesized that there would be differences on specific neurocognitive domains (e.g., nonverbal memory, nonverbal fluency, verbal memory, verbal fluency, verbal learning, processing speed, and inhibition/switching).

METHODS PARTICIPANTS Participants included 93 treatment-seeking youth between 7 and 17 years of age, who presented for an evaluation at a southeastern OCD specialty clinic and received a principle diagnosis of OCD. Diagnoses were determined using evidence-based procedures via a clinical interview with a child and adolescent clinical psychologist or psychiatrist experienced with OCD and confirmed by the administration of either a structured diagnostic interview (the Anxiety Disorders Interview Schedule)[38] by a trained research assistant, or consensus review by two expert clinicians using all available information (e.g., clinical interview, chart review, participants’ completed measures as part of this study).[39] Youth were excluded from participation if they had a severe mental illness (e.g., mental retardation, autism spectrum disorders, psychosis, bipolar disorder) or physical condition (e.g., visual impairment, hearing impairment, seizure disorder, traumatic brain injury, or encephalitis) that could affect testing performance. Participant characteristics are detailed in Table 1.

MEASURES Anxiety Disorders Interview Schedule-Child and Parent Versions (ADIS-C/P). The ADIS-C/P is a structured clinical interview that assesses current episodes of Axis I disorders (including OCD) and

TABLE 1. Characteristics of pediatric OCD participants (N = 93) Mean (SD) [range] Age CYBOCS total score

11.85 (2.94) [7–18] 24.48 (5.76) [8–37] N (%)

Gender Male Female Ethnicity Caucasian Hispanic Asian American Other/nondisclosed ethnicity Cooccurring psychiatric Disordersa ,b Non-OCD anxiety disorders Tic disorders Depressive disorders Attention deficit hyperactivity disorders (ADHD) Disruptive behavior disorder Trichotillomania Medication status Taking any psychotropic medication Stimulants Antidepressants (SSRIs, SRIs, SNRIs) Atypical antipsychotics/neuroleptics Alpha-2-agnosists

41 (44%) 52 (56%) 87 (94%) 3 (3%) 1 (1%) 2 (2%) 34 (37%) 28 (30%) 18 (20%) 16 (17%) 8 (9%) 2 (2%) 49 (53%) 6 (7%) 43 (46%) 11 (12%) 8 (9%)

CYBOCS, Children’s Yale-Brown Obsessive Compulsive Scale; NonOCD anxiety disorders, separation anxiety, generalized anxiety, social phobia, specific phobia, selective mutism, panic disorder. Tic Disorders, Tourette disorder, chronic Tic disorder; Depressive Disorders, major depressive disorder, dysthymia, depression not otherwise specified and adjustment disorder; Disruptive Behavior Disorders, oppositional defiance disorder and disruptive behavior disorder not otherwise specified. a Total n = 92 for analysis of comorbidity. b Youth may have more than one cooccurring disorder. Please note—the above are subset of youth presented in Lewin et al.[52] provides differential diagnosis based on DSM-IV-TR criteria.[38] All ADIS-generated OCD diagnoses were in agreement with a clinical interview by a separate doctoral-level clinician. Delis-Kaplan Executive Function System (D-KEFS). The DKEFS is a comprehensive battery normed for participants between 7 and 89 years of age, which was used to assess a wide range of executive processes.[40] Executive processes assessed by the D-KEFS include: flexibility of thinking, inhibition, problem solving, planning, impulse control, concept formation, abstract thinking, and creativity in both verbal and spatial modalities. Youth completed the following subtests: Trail Making; Verbal Fluency; Design Fluency; Card Sorting; and Stroop Color-Word Interference. Rey-Osterreith Complex Figure Test (RCFT). The RCFT was used to assess youth’s planning, organizational skills, problem solving, motor functioning, perceptual, and memory abilities.[41] Youth were asked to copy the figure with the stimulus card present (copy trial), and later to reproduce the figure from memory at two separate time points (3 min delay and 30 min delay). Accuracy scores and organizational strategy scores for the three conditions (copy trial, 3 min delay, and 30 min delay) were scored according to the manual. Normative data for ages six and older were used to derive standard scores for the conditions.[42] Recognition of items was administered after the 30 min delay condition. Depression and Anxiety

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Wide Range Assessment of Memory and Learning, 2nd Edition (WRAML-II) Story Memory. The Story Memory test was used to evaluate verbal memory via ability to recall details of a story presented by the examiner.[43] The Story Memory subtest includes an immediate recall condition and a delayed recall condition that occurs after 30 min. Recognition of story memory items was administered after the delayed recall condition. California Verbal Learning Test, Child Version (CVLT-C). The CVLT-C was used to assess youth’s ability to learn and remember verbally presented information.[44, 45] The CVLT-C involves the administration of a shopping list (List A) that contains 15 items representing three semantic categories. After each of five initial List A repetitions, participants are asked to repeat as many items as they can remember, in any order, to assess immediate-free recall. Following this, a distracter word list (List B) is presented to the participant once and immediate-free recall of List B is completed. After this short delay, both free and cued recall of List A are evaluated. For the cued recall trial, participants are required to recall words based on a category cue. Free recall, cued recall, and recognition of List A are also assessed after a delay of 20 min; to assess recognition; the examiner reads a list of words and asks the child to indicate whether or not the item was part of List A. Children’s Yale-Brown Obsessive Compulsive Scale (CYBOCS). The CY-BOCS is a clinician-administered interview that was used to assess the presence and severity of obsessive-compulsive symptoms.[46] The CY-BOCS symptom checklist comprised of 71 commonly reported obsessions and compulsions. The clinician uses these checklist items to gauge the time occupied by symptoms, symptom interference, distress associated with symptoms, resistance, and degree of control over symptoms for youth’s obsessions and compulsions past week, which are summed to produce a total severity score. The CY-BOCS has demonstrated strong psychometric properties.[46–48]

PROCEDURES The local institutional review board approved all study procedures. Children and parents completed a clinical interview as part of regular clinical care. Afterward, eligible children and parents were invited to participate in the study. After written consent and assent was obtained, a trained clinician administered the CY-BOCS to parents and children together. While parents completed demographics questionnaires and rating scales, children completed neuropsychological tests. Prior to any testing administration, examiners underwent training on all neuropsychological tests. Training included educational readings, observation of administration by an experienced administrator, and several practice administrations with directive feedback. Administrations were completed by doctoral students in clinical psychology under the supervision of two clinical psychologists, one of whom was a neuropsychologist with experience in OCD.

DATA ANALYSIS Similar to previous studies,[49] an a priori definition of the presence of cognitive sequelae was assigned when two or more cognitive test scores were 1.5 standard deviations (SD) or two test score was two SD below the normative population mean values using demographically corrected T-scores, including age, gender, and education when available. A second, more conservative, estimate of cognitive sequelae was also investigated including cases when two or more cognitive test scores were two SD below the normative population mean. Cases were classified according to these two definitions. To derive the magnitude of cognitive sequelae, demographically corrected z-scores were assigned a value of one for each SD the zscores fell one SD below the mean based on normative values for each Depression and Anxiety

test obtained from the testing manuals. Using this convention, z-scores equal or more positive than –0.99 received a score of 0, scores one SD below the mean (e.g., z = –1.00 to –1.99) received a score of 1, scores two SD below the mean (z = –2.00 to –2.99) received a score of 2, and scores three SD below the mean (z = –3.00 to –3.99) received a score of 3. Afterward, these values were summed to identify the total the number of standard deviations participant’s scored below the mean on tests. To reduce Type I error, tests that have been theoretically and empirically shown to assess similar cognitive functions were grouped together to create separate domain scores.[50] Domains included nonverbal memory (RCFT three minute recall, RCFT 30 min recall), nonverbal fluency (DKEFS Design Fluency Combined Sum of Scaled Scores), verbal memory (WRAML-II delayed recall, CVLT-C long delay-free recall), verbal fluency (DKEFS Letter Fluency, DKEFS Category Fluency), verbal learning (CVLT-C total recall trials 1–5, WRAML-II immediate recall), inhibition/switching (DKEFS LetterNumber Switching Trails, DKEFS Color-Word Interference), and processing speed (DKEFS Number Sequencing Trails, DKEFS Letter Sequencing Trails, DKEFS Motor Speed Trails). The CY-BOCS Symptom Checklist was used to examine the difference in neuropsychological performance across symptom dimensions. Symptoms on the CY-BOCS Symptom Checklist were coded as either absent or present. Consistent with previous examinations in pediatric OCD patients,[24] a five-factor model was selected to facilitate comparisons between youth and adults. Miscellaneous symptoms that did not fall into these categories were excluded (n = 17 symptoms).[24] The five symptom dimensions included Hoarding (n = 3 symptoms), Contamination/Cleaning (n = 15 symptoms), Symmetry/Ordering (n = 8 symptoms), Forbidden Thoughts (n = 9 symptoms), and Aggressive/Checking (n = 19 symptoms). The use of dimensional subgroups with single participants in multiple groups renders omnibus betweengroup tests inappropriate. Therefore, comparisons were made based on the presence/absence of any symptom on the five symptom dimensions (e.g., comparison of performance of patients who endorsed Hoarding symptoms to participants who did not endorse any Hoarding symptoms). Chi-square analyses were used to examine the presence of cognitive sequelae by the endorsement of symptoms on each symptom dimension. Mann–Whitney U tests were used to compare the countlevel variable of magnitude of cognitive sequelae between participants with and without specific symptom dimensions, and across the seven domains assessed. Mann–Whitney U tests also examined the difference in the magnitude of cognitive sequelae for participants with either comorbid attention deficit hyperactivity disorder (ADHD) or non-OCD anxiety disorders for each symptom dimension. Nonparametric effect √ sizes (ES) were obtained using the formula: ES = (z/ N),[51] with small, medium, and large effects corresponding to values of 0.10, 0.30, and 0.50, respectively. Spearman rho correlations examined the association between obsessive-compulsive symptom severity (CY-BOCS total score) and the magnitude of cognitive sequelae for each symptom dimension, as well as the association between the number of symptom dimension symptoms endorsed, and the magnitude of cognitive sequelae. Given the exploratory nature of these comparisons, significance was set at P = .05.

RESULTS Although the original sample included 96 participants,[52] three participants were excluded from analyses due to incomplete CY-BOCS symptom checklists. Among the remaining 93 youth, 27 participants (29%) endorsed Hoarding symptoms, 62 participants (67%) endorsed Contamination/Cleaning

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TABLE 2. The presence of neurocognitive sequelae across symptom dimensions (N = 93)

Symptom dimension Hoarding (n = 27) Contamination/cleaning (n = 62) Forbidden thoughts (n = 48) Symmetry/ordering/counting/magical (n = 74) Checking/aggressive (n = 71)

Cognitive sequelae N (%)

χ2

18 (67%) 40 (65%) 33 (69%) 52 (70%) 47 (66%)

0.08 0.00 0.78 5.24 0.37

symptoms, 48 participants (52%) endorsed Forbidden Thought symptoms, 74 participants (80%) endorsed Symmetry/Ordering symptoms, and 71 participants (76%) endorsed Aggressive/Checking symptoms. Nine youth (10%) endorsed symptoms on only one dimension, whereas 82 youth (88%) endorsed symptoms on more than one dimension. Only two youth (2%) reported miscellaneous symptoms that did not fall into any symptom dimension. COGNITIVE SEQUELAE

Table 2 examines the frequency of cognitive sequelae across symptom dimensions using chi-square tests. Youth with Symmetry/Ordering symptoms had a significantly greater occurrence of both the standard definition of cognitive sequelae, and the more conservative definition. Although youth with Hoarding symptoms did not exhibit a difference using the standard definition of cognitive sequelae, a significant difference was identified using the more conservative definition of cognitive sequelae. MAGNITUDE OF COGNITIVE IMPAIRMENT

Mann–Whitney U tests identified that youth who reported Symmetry/Ordering symptoms had a significantly greater magnitude of cognitive impairment than youth who did not endorse these symptoms (U = 442.50, z = –2.49, P = .013, ES = 0.29). Mann–Whitney U tests found no other significant differences in the magnitude of cognitive impairment across symptom dimensions (Hoarding, P = .30; Contamination/Cleaning, P = .67; Forbidden Thoughts, P = .43; Checking/Aggressive, P = .99). Table 3 examines influence of cooccurring ADHD and non-OCD anxiety disorders on the magnitude of cognitive impairment for each symptom dimension. There were no significant differences across symptoms dimensions for either psychiatric condition. Spearman correlations found no significant association between obsessive-compulsive symptom severity and the magnitude of cognitive impairment for each symptom dimension (P = .23–.67). Furthermore, there was no significant association between the number of symptoms reported on each symptom dimension, and the overall magnitude of cognitive impairment (P = .17–.97).

P .78 1.00 .38 .02 .54

Conservative cognitive sequelae N (%)

χ2

P

15 (56%) 23 (37%) 20 (42%) 32 (43%) 27 (38%)

5.21 0.23 0.69 4.86 0.20

.02 .88 .41 .03 .88

IMPAIRMENT BY COGNITIVE DOMAIN

Table 4 presents impairment on specific cognitive domains by symptom dimension. Compared to youth who did not endorse Symmetry/Ordering symptoms, youth with Symmetry/Ordering symptoms performed significantly worse on Nonverbal Fluency Domain (P = .007, ES = 0.31), Processing Speed (P = .004, ES = 0.33), and Inhibition and Switching (P = .016, ES = 0.28). No other significant differences were observed.

DISCUSSION This study examined differences in neuropsychological performance across symptom dimensions among youth with OCD. Although many youth with OCD exhibit cognitive sequelae, youth with Hoarding symptoms had a higher incidence of sequelae relative to those without the same symptoms when a conservative definition of cognitive sequelae was used. This may represent the early emergence of executive functioning difficulties that adults with Hoarding symptoms have exhibited.[26, 53] Indeed, youth with Hoarding symptoms have been reported to experience greater academic impairment than youth who did not exhibit these symptoms.[27] Although youth with Hoarding symptoms exhibited elevated cognitive sequelae, unexamined factors may influence these results. For instance, children with Hoarding symptoms have been reported to exhibit more Symmetry/Ordering symptoms, pathological doubt, pervasive slowness, and indecisiveness than youth without Hoarding symptoms.[27] Additionally, preliminary research suggests an association exists between Hoarding and other disorders with executive functioning deficits (e.g., ADHD, learning disabilities).[54, 55] Thus, future research is needed to clarify whether this neuropsychological impairment is driven by underlying brain deficits associated with Hoarding symptoms or whether it can be attributed to its associated characteristics (e.g., Symmetry/Ordering symptoms, pervasive slowness, pathological doubt). Symmetry/Ordering symptoms were more commonly endorsed than Hoarding symptoms, and were associated with a greater incidence of both definitions of cognitive sequelae. Moreover, youth with these symptoms exhibited a greater magnitude of cognitive impairment and impaired performance on several specific cognitive domains (e.g., nonverbal fluency, processing speed, Depression and Anxiety

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TABLE 3. The impact of common comorbidity on the overall magnitude of cognitive impairment by symptom dimension (n = 92)

Hoarding symptoms (n = 27) Contamination/cleaning symptoms (n = 62) Forbidden thought symptoms (n = 48) Symmetry/ordering symptoms (n = 73) Checking/aggressive symptoms (n = 70)

N (%)

ADHD Mann–Whitney U

Z

5 (19%) 13 (21%) 7 (14%) 14 (19%) 14 (20%)

48.00 266.00 100.50 360.00 331.00

0.66 −0.91 −1.26 −0.75 −0.90

Non-OCD Anxiety Disordersa N (%) Mann–Whitney U 13 (48%) 23 (37%) 22 (46%) 31 (42%) 29 (41%)

60.00 343.00 245.00 567.50 543.50

Z −1.53 −1.54 −0.85 −0.93 −0.61

ADHD, attention deficit/hyperactivity disorder; Non-OCD anxiety disorders, separation anxiety, generalized anxiety disorder, social phobia, specific phobia, selective mutism, panic disorder, agoraphobia and/or anxiety disorder not otherwise specified. a Participants may have more than one non-OCD anxiety disorder. *P < 0.05; **P < 0.01.

inhibition, and switching). As structural imaging studies indicate there is an association between alterations in visual processing tracts and ordering symptoms,[35] it may be that youth with these symptoms have an attention bias toward observing symmetrical and/or ordered stimuli that draws their attention away from task performance. Indeed, visual attention bias has been reported to exist for individuals with OCD who have elevated contamination fears.[56] As such, youth with Symmetry/Ordering symptoms may have difficulty completing neuropsychological tasks and/or similar academic tasks when in the presence of any distracting stimuli that would divert their visual attention. Alternatively, symptoms associated with this dimension may have emerged during testing and taxed youth’s limited cognitive resources (e.g., counting numbers on paper, excessive attention to detail) and slowed task performance. Because many cognitive tests have time constraints, youth experiencing these symptoms during testing would likely perform worse than youth not experiencing these symptoms in a testing session. While Hoarding and Symmetry/Ordering symptoms were associated with neurocognitive impairment in this sample, no difference was identified between the other symptom dimensions and neuropsychological perfor-

mance. This may be explained by phenomenological differences between symptom dimensions. For instance, Contamination/Cleaning, Forbidden Thoughts, and Aggressive/Checking symptoms are more feardriven symptoms whereas Symmetry/Ordering symptoms may be more etiologically related to Tourette Syndrome (TS). Indeed, differences in symptom presentation have been found between tic and nontic-related OCD.[57–59] These phenotypic differences in symptom presentation may be reflective of dysfunctional neural pathways associated with OCD and TS. With regard to previous neuropsychological examinations, differential findings may be explained by differing symptom presentation among the samples (e.g., more or less Symmetry/Ordering symptoms). Although Hoarding and Symmetry/Ordering symptoms were associated with neuropsychological impairment, some evidence suggests that these symptom dimensions exhibit a differential response to CBT in adults,[60–62] with no differing response observed in youth.[24] While emerging evidence exists linking neuropsychological performance to treatment outcome in OCD,[63, 64] further research is needed to clarify this relationship by integrating neuropsychological tests and symptom dimension analysis within evidence-based treatment.

TABLE 4. Neuropsychological performance on cognitive domains by symptom dimension

Cognitive domain Nonverbal memory Nonverbal fluency Verbal memory Verbal fluency Verbal learning Processing speed Inhibition/switching *P < .02, **P < .01. Depression and Anxiety

Hoarding symptoms Mann– Whitney U Z 726.50 707.50 780.50 790.50 797.50 684.50 618.50

−0.67 −1.12 −0.35 −0.59 −0.31 −1.51 −1.90

Contamination/cleaning symptoms Mann– Whitney U Z 851.00 868.50 879.00 841.50 882.50 890.50 767.00

−0.30 −0.27 −0.05 −0.74 −0.15 −0.33 −1.14

Forbidden thought symptoms Mann– Whitney U Z 931.00 868.50 881.00 1014.50 896.00 854.00 907.50

−0.78 −1.17 −0.90 −0.34 −0.94 −1.59 −0.85

Symmetry/ordering symptoms Mann– Whitney U Z 482.50 403.50 454.50 637.50 463.50 397.50 431.50

− 1.60 − 2.70** − 1.89 − 0.54 − 1.86 − 2.86** − 2.41*

Checking/aggressive symptoms Mann– Whitney U Z 652.00 671.00 719.50 649.00 647.00 760.00 618.00

−0.60 −0.73 −0.17 −1.11 −0.95 −0.09 −1.22

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This study should be interpreted within the context of its limitations. First, the current sample included a wide age range of pediatric OCD patients. Although this aids the generalizability of findings, the wide age range may complicate interpretation due to maturation of cognitive processes and development. Performance scores were compared to well-normed standardization samples thereby partially mitigating this concern. Second, the testing battery used in this study focused on executive functioning and memory abilities. Although these tests and domains were specifically selected based on OCD-related pathology, there may have been additional differences on other areas of neuropsychological functioning that were not assessed. Third, the symptom dimensions were created based on symptoms that the patient currently endorsed. Although symptom dimensions have been reported to be temporally stable,[65] it may be that task performance could also be related to youth’s symptom history. Fourth, we did not correct for multiple comparison testing. Although multiple comparisons were made, we attempted to limit the number of comparisons by creating composite variables for each neuropsychological domain. Finally, we did not ask participants if they were ritualizing during test administration. This would have been particularly useful to clarify whether Symmetry/Ordering symptoms were impeding test performance, or whether these symptoms serve as a phenotypic indicator of increased neurocognitive impairment.

CONCLUSIONS Within these limitations, these findings offer three important implications. First, this examination identified varied impairment in neuropsychological performance across symptom dimensions. As symptom dimensions examined in previous neuropsychological studies of youth with OCD, varied symptoms present among sampled youth may account for the discrepant findings. Second, these findings provide converging evidence to support structural imaging studies that specific symptom dimensions may be associated with distinct alterations in brain functioning.[31, 35] An improved understanding on the pathogenesis of OCD will foster improved outcomes through targeted and individualized treatments. Third, given that youth with either Hoarding or Symmetry/Ordering symptoms exhibited worse neuropsychological performance than youth without these respective symptoms, these children in particular may benefit from neuropsychological testing to identify appropriate compensatory strategies to provide assistance in academic settings. The extent to which evidence-based treatment of obsessive-compulsive symptoms provides benefit for neuropsychological performance remains unclear and should be examined. Acknowledgments. The authors would like to express their appreciation to Mr. Alex De Nadai for his statistical expertise, and thank the children and fami-

lies who participated in this project. This work was supported by a grant to Dr. Lewin from the International OCD Foundation. Mr. McGuire, Ms. Crawford, Ms. Park, and Dr. Larson report no relevant disclosures. Dr. Storch has received grant funding in the last three years from the National Institutes of Health, Centers for Disease Control, Agency for Healthcare Research and Quality, National Alliance for Research on Schizophrenia and Affective Disorders, International OCD Foundation, Tourette Syndrome Association, and Janssen Pharmaceuticals. He receives textbook honorarium from Springer publishers, American Psychological Association, and Lawrence Erlbaum. Dr. Storch has been an educational consultant for Rogers Memorial Hospital. He is a consultant for Prophase, Inc. and CroNos, Inc., and is on the Speaker’s Bureau and Scientific Advisory Board for the International OCD Foundation. He receives research support from the All Children’s Hospital Guild Endowed Chair. Dr. Murphy has received research funding in the past three years from National Institutes of Health, Centers for Disease Control, Otsuka Pharmaceuticals, National Alliance for Research on Schizophrenia and Depression, International OCD Foundation, Roche Pharmaceuticals, Shire Pharmaceuticals, Pfizer, Inc. and Indevus Pharmaceuticals. She serves on the Medical Advisory Board for the Tourette Syndrome Association, and the Scientific Advisory Board for the International OCD Foundation. She receives textbook honorarium from Lawrence Erlbaum. Dr. Lewin has served as a consultant for Otsuka America Pharmaceutical and ProPhase, Inc. He has received grant support from International Obsessive Compulsive Disorder Foundation; National Alliance for Research on Schizophrenia and Depression; University of South Florida Research Foundation, Inc. He has received travel support from University of South Florida Research Foundation and the National Institute of Mental Health. He has received speaker’s honorarium from the Tourette Syndrome Association and a publication advance from Springer textbook publisher.

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Depression and Anxiety

Neuropsychological performance across symptom dimensions in pediatric obsessive compulsive disorder.

Few studies have examined neuropsychological functioning among youth with obsessive compulsive disorder (OCD), with inconclusive results. Although met...
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