Impact of Comorbid Depressive Symptoms on Neuropsychological Performance in Obsessive–Compulsive Disorder

Impact of Comorbid Depressive Symptoms on Neuropsychological Performance in Obsessive–Compulsive Disorder
[Short Report]
Moritz, Steffen1,2; Birkner, Christiane1; Kloss, Martin1; Jacobsen, Dirk1; Fricke, Susanne1; Böthern, Aenne1; Hand, Iver1
1Hospital for Psychiatry and Psychotherapy, Neuropsychological and Behavioral Unit, University Hospital of Hamburg-Eppendorf, Hamburg, Germany.
2Correspondence concerning this article should be addressed to University Hospital Hamburg-Eppendorf, Hospital for Psychiatry and Psychotherapy, Neuropsychological and Behavioral Unit, Martinistra[beta]e 52, D-20246 Hamburg, Germany. E-mail: moritz@uke.uni-hamburg.de.
Received July 10, 2000; Revision received April 6, 2001; Accepted April 12, 2001
Abstract
There is indirect evidence from previous research that several executive disturbances in obsessive–compulsive disorder (OCD) are mediated by comorbid depressive symptoms. For the present study, the authors investigated whether OCD patients with elevated Hamilton Rating Scale for Depression (HRSD; M. Hamilton, 1967) scores would exhibit deficits in tasks sensitive to the medial and dorsolateral frontal cortex as well as other executive tasks. The 36 OCD patients were split along the median according to their HRSD scores and compared with matched control subjects. Patients with high HRSD scores performed significantly worse than control subjects and patients with low HRSD scores on the Wisconsin Card Sorting Test (J. Loong, 1990), the Trail-Making Test (TMT, Part B; R. M. Reitan, 1992), and the TMT difference score. Moreover, patients with high HRSD scores exhibited deficits on a (creative) verbal fluency task. It is suggested that comorbid depressive symptoms may have artificially inflated some executive deficit scores in previous studies.
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Neurocognitive studies using the Wisconsin Card Sorting Test (WCST; Loong, 1990) and other executive tasks have yielded mixed results regarding patients with obsessive–compulsive disorder (OCD; Moritz, Kloss, Katenkamp, Birkner, & Hand, 1999; Schmidtke, Schorb, Winkelmann, & Hohagen, 1998). Several researchers have speculated that WCST deficits (i.e., dysfunctions in set-shifting), which are inferred to be mediated by dysfunctions of the dorsolateral frontal cortex, may be confined to OCD patients exhibiting comorbid depressive or psychotic symptoms (e.g., Cox, 1997; Malloy, 1987). However, this hypothesis has not been directly tested but inferred post hoc: Whereas studies that excluded patients with high depression severity scores have mostly shown that set-shifting performance is unimpaired in OCD (e.g., Boone, Ananth, Philpott, Kaur, & Djenderedjian, 1991; Purcell, Maruff, Kyrios, & Pantelis, 1998a), investigations that did not control for depressive symptoms have revealed dysfunctions (e.g., Cox, Fedio, & Rapoport, 1989; Moritz et al., 1999). Moreover, dorsolateral prefrontal impairment, which is considered to be a major contributor to set-shifting deficits (e.g., Lombardi et al., 1999), has been implicated in the pathogenesis of depression (for reviews, see Rogers, Bradshaw, Pantelis, & Phillips, 1998) but not OCD. For OCD, on the other hand, there is increasing evidence for orbito-frontal impairment (for a review, see Saxena, Brody, Schwartz, & Baxter, 1998).
Following the suggestion of Purcell et al. (1998a) that “future research should explicitly measure comorbid depressive symptoms in patients with OCD to examine any relationship between depressive symptoms and set-shifting deficits” (p. 422), for the present study an OCD sample was split according to the severity of depressive symptoms and compared with matched healthy control subjects with regard to WCST performance. In addition, researchers investigated whether comorbid depressive symptoms can also account for divergent findings regarding other executive tasks—most important being fluency tests, which are considered correlates of the medial-frontal cortex (Crosson et al., 1999; Hugdahl et al., 1999).
Method
A total of 36 patients fulfilling criteria of the Diagnostic and Statistical Manual of Mental Disorders (4th edition; DSM–IV; German version: Sass, Wittchen, & Zaudig, 1996) for OCD entered the study. Diagnoses were determined through clinical interview (Neuropsychiatric Interview for DSM–IV, Sheehan et al., 1998) and confirmed by at least one other clinician. Moreover, medical records were carefully screened for symptoms incompatible with a diagnosis of OCD. Subjects did not reveal a history of comorbid drug abuse, substantial neurological disorder (e.g., stroke, multiple sclerosis, head trauma, or previous brain operations), or current or previous psychotic symptoms. Healthy subjects (n = 36) matched for gender, years of education (±1 year) and age (±5 years) served as controls. Subjects were recruited from various sources, including students and hospital staff. The main sociodemographic and psychopathological characteristics of the samples are displayed in Table 1. OCD symptoms were rated using the Yale-Brown Obsessive–Compulsive Scale (Y-BOCS; Goodman et al., 1989; German version: Hand & Büttner-Westphal, 1991). Depression was indexed with the Hamilton Rating Scale for Depression (HRSD, 17-item version; Hamilton, 1967) and the Beck Depression Inventory (BDI, self-report; Beck & Steer, 1987). Y-BOCS and HRSD were administered by a clinician after extensive rater training. The Y-BOCS and HRSD scores of the present study fall in the range of previous results, with HRSD scores being slightly higher because comorbid depressive symptoms were not exclusion criteria (10 patients were diagnosed with comorbid major depression). Another 4 patients were additionally diagnosed with another anxiety disorder. A total of 15 patients did not receive any medication at the time of testing. The OCD sample was tested before participating in multimodal cognitive–behavioral therapy. After the study was completely described to the subjects, written informed consent was obtained.

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Table 1 Sociodemographic Data of the Subjects
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Subjects were administered the following tasks, thought to represent distinct aspects of executive functioning:
(a) Wisconsin Card Sorting Test: A computerized version (Loong, 1990) was used that followed the original procedure (the subject has to sort cards according to color, shape, and number of objects; after 10 consecutive right responses, the target category is changed, which is not announced, however).
(b) Trail Making Test, Parts A and B (TMT-A, TMT-B; adult version): In Part A, the subject is required to quickly combine encircled numbers (1–25) and in Part B to alternately combine numbers (1–13) and characters (A–L) in ascending order (Reitan, 1992). Part B is considered to tap set-shifting. The TMT difference was calculated as follows: TMTdiff = TMT-B - TMT-A.
(c) Digit span: In the first subtest, the participant has to repeat strings of numbers in the order presented by the experimenter. In the second subtest, the subject is instructed to repeat the presented numbers in reverse order. Digit span tasks are administered to assess the phonological loop of working memory.
(d) Creative verbal fluency: The subject has 4 min to write down as many alternate uses he or she can think of for a can and a piece of string (e.g., using a can as a football; Schoppe 1975).
Results
The OCD sample was median split according to the severity of HRSD scores (Mdn = 13). Simple t tests showed that the OCD subsample with elevated depression scores had an increased length of illness (statistical trend) and exhibited significantly elevated Y-BOCS obsession scores compared with the OCD sample with low depression scores (see Table 1; the Y-BOCS total score, however, was comparable between groups). Medication status was not different between groups, [chi]2(1, N = 72) =. 00; ns. Each OCD subsample contained 2 subjects with another anxiety disorder.
An analysis of variance (ANOVA) showed that patients with high HRSD scores completed significantly fewer categories and committed more perseveration errors in the WCST than both healthy control subjects and patients with low HRSD scores (see Table 2). Length of illness and the extent of obsessions were controlled for in a subsequent analysis of covariance (ANCOVA), which confirmed the ANOVA results (p <= .05). The difference between high HRSD patients and healthy control subjects was highly significant for both WCST parameters (p <= .001). Direct correlational inspection revealed that length of illness and severity of obsessions did not correlate significantly with any of the neurocognitive parameters (|[rho]|s < .12; ps > .50, except for length of illness and TMT-A: [rho] = .26, p > .10).

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Table 2 Neuropsychological Data of the Subjects
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Similar results emerged for the TMT-B and TMT difference score, that is, patients with low HRSD scores performed comparably to healthy control subjects, whereas both samples performed significantly better than patients with high HRSD scores. Again, the difference between high HRSD patients and healthy control subjects was highly significant (p <= .001). Differences between the two OCD subsamples did not remain significant when length of illness and the Y-BOCS obsession score were controlled for (p < .20).
Creative verbal fluency was significantly disturbed for the high HRSD subsample compared with healthy control subjects (p <= .005). Irrespective of accompanying depressive symptoms, patients showed a greater slowness in the TMT-A. No group differences occurred for both digit span subtests.
When both subsamples were combined, the differences between the OCD total sample and healthy controls achieved significance for all parameters except the digit span (see Table 2).
Correlational analyses yielded no significant correlations between the two Y-BOCS scores (obsessions and compulsions) and the total score with any neuropsychological parameter (|[rho]| <= .20, p >=.20), whereas HRSD scores significantly correlated with WCST performance (categories: [rho] = -.34, p = .04; perseveration errors: [rho] = .36, p = .03). At trend level, HRSD scores correlated with creative verbal fluency and digit span backward ([rho] = -.35, p = .09; [rho] = -.30, p = .07). HRSD scores were highly correlated with BDI scores ([rho] = .63, p = .0001) and the Y-BOCS obsession score ([rho] = .61, p = .0001). Correlations between HRSD score and the Y-BOCS compulsion and total score did not achieve significance ([rho]s = -.03 and .26, respectively). When severity of obsessions was controlled for, correlations did not essentially change regarding creative verbal fluency and WCST performance with HRSD scores (creative verbal fluency: r = -.35, p = .09; categories: r = -.30, p = .08; perseveration errors: r = .42, p = .01).
Patients from the high depression group with an established diagnosis of major depression and those with no such diagnosis did not differ on any of the neurocognitive parameters (all ps >= .30).
Discussion
This is the first study to provide direct evidence that set-shifting performance as assessed with the WCST (a correlate of dorsolateral prefrontal functioning; see Lombardi et al., 1999; Weinberger, Berman, & Zec, 1986) is merely disturbed in OCD patients with elevated depression scores. Patients with low HRSD scores and healthy control subjects did not significantly differ regarding WCST performance. On measures putatively assessing set-shifting (TMT-B and TMT difference score), OCD patients with low HRSD scores and healthy control subjects also significantly exceeded OCD patients with elevated depression scores. However, differences in TMT-B and TMT difference scores between the two OCD samples did not withstand a subsequent ANCOVA controlling for length of illness and obsessions. For creative verbal fluency, only the OCD group with high depression scores was significantly impaired relative to healthy controls.
Results are in accordance with a growing literature revealing that depressive patients have substantial neuropsychological abnormalities subserved by the dorsolateral prefrontal cortex (Purcell, Maruff, Kyrios, & Pantelis, 1998b; Rogers et al., 1998). In line with this, a recent study conducted by Merriam, Thase, Haas, Keshavan, and Sweeney (1999) found that severity of depression was significantly correlated with dysfunctions in the WCST for patients with major depression.
Our findings give further evidence that dorsolateral frontal functioning is not primarily disturbed in OCD, confirming previous results from neuroimaging studies that infer orbito-frontal but not dorsolateral frontal impairment in the pathogenesis of OCD (Saxena et al., 1998). In line with this, recent neuropsychological studies have found deficits for patients with OCD in the Delayed Alternation Task (Freedman et al., 1998), which is sensitive to orbito-frontal damage (Cavedini et al., 1998; Moritz, Fricke, & Hand, in press).
In another study we have provided evidence that the mediating effect of depression on neuropsychological disturbances in OCD extends to mnestic dysfunctions. On the basis of extensive data that depressive patients show severe memory dysfunctions (e.g., Moritz, Heeren, Andresen, & Krausz, 2001), we split a sample of OCD patients not participating in the present study according to HRSD scores. High HRSD patients were significantly impaired regarding the recall of the Rey figure and Corsi Block Tapping. However, independent of comorbid depressive symptoms, visuospatial transformation was disturbed in OCD (Moritz, Fricke, Böthern, & Hand, 2001).
The present results indicate that more attention must be paid to comorbid depressive symptoms in OCD. We suggest that studies attempting to extract the cognitive profile of OCD patients as well as studies using brain-imaging techniques should carefully look for possible associations between target variables and depression. Moreover, because OCD is a heterogeneous disorder with various syndromatic patterns, other possible dichotomies of OCD (e.g., washers and checkers) need careful inspection regarding their impact on neuropsychological disturbances.
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