Journal of Clinical and Experimental Neuropsychology, 28:1273–1287, 2006Copyright Taylor & Francis Group, LLCISSN: 1380-3395DOI: 10.1080/13803390500507246
Neuropsychological Impairment in Obsessive- Compulsive Disorder—Improvement Over the Course of Cognitive Behavioral Treatment
. cal Impairment Before and After Therapy
ANNE KATRIN KUELZ,1 DIETER RIEMANN,1 ULRIKE HALSBAND,2 KIRSTIN VIELHABER,1 JOSEF UNTERRAINER,2 ANDREAS KORDON,3 AND ULRICH VODERHOLZER1
1Department of Psychiatry and Psychotherapy, University Hospital of Freiburg,Germany2Department of Psychology, Neuropsychology, University of Freiburg, Germany3Department of Psychiatry and Psychotherapy, University Hospital of Luebeck,Germany
A large body of studies demonstrates mild cognitive dysfunction in patients withObsessive Compulsive Disorder (OCD). Few trials have investigated whether this dys-function can be improved by treatment. Thirty unmedicated inpatients with OCD wereadministered a comprehensive neuropsychological test battery before and after 12weeks of cognitive behavioral therapy (CBT). Thirty-nine carefully matched healthycontrols were tested twice within the same interval. At baseline, patients exhibited sig-nificant impairments on several tests which normalized at follow-up. A significantgroup × time interaction was found for tests of nonverbal memory, set shifting and flex-ible, self guided behavior. Major responders improved significantly more than minorresponders on the Rey-Osterrieth Figure immediate and delayed recall. Results sug-gest that cognitive dysfunction in OCD can improve in the course of treatment. Wehypothesize that particularly cognitive behavioral treatment enables OCD patients tothink and act in a more flexible way that helps them to develop more effective cognitivestrategies.Introduction
Obsessive-compulsive (OCD) disorder is among the most common psychiatric disorders,with a 12 month prevalence of 0.6% and lifetime prevalence rates estimated at 2%–3%(Crino, Slade & Andrews, 2005; Karno, Golding, Sorenson & Burnam, 1988). OCD ischaracterized by recurrent intrusive thoughts, images or impulses and ritualized stereo-typed behaviors or mental acts. Symptoms cause significant personal distress and interferewith daily activities. Both cognitive-behavior therapy (CBT) and pharmacological treat-ment with serotonin reuptake inhibitors (SRI) have been proven to be effective (Hohagenet al., 1998; McDonough & Kennedy, 2002). However, CBT seems to be most effective(Foa et al., 2005).
Received 27 July 2005; accepted 28 October 2005. Address correspondence to Ulrich Voderholzer, MD, Department of Psychiatry and Psycho-
therapy, Klinikum of the Albert-Ludwig-University, Hauptstrasse 5, 79104 Freiburg, Germany. E-mail: [email protected]
There is a growing body of evidence indicating that OCD is associated with distinct
patterns of dysfunction involving the orbitofrontal-subcortical circuitry (Baxter et al.,1988; Saxena, Brody, Schwartz & Baxter, 1998; Saxena, Bota & Brody, 2001). In most ofthe studies a hypermetabolism in the fronto-striatal loop was observed that was found tobe decreased after both successful pharmacological and behavioural treatment (Baxteret al., 1992; Nakatani et al., 2003; Saxena et al., 1999; Schwarz, Stoessel, Baxter, Martin& Phelps, 1996).
Results of investigations into neuropsychological functioning have been inconsistent
so far. Several studies in subjects with OCD suggest impairment on tests of set shiftingability (Abbruzzese, Bellodi, Ferri & Scarone, 1995; Abbruzzese, Ferri & Scarone, 1997;Purcell, Maruff, Kyrios & Pantelis, 1998), fluency (Harris & Dinn, 2003; Schmidtke,Schorb, Winkelman & Hohagen, 1998), planning and problem solving (van den Heuvenet al., 2005) and visuospatial memory (Deckersbach, Otto, Savage, Baer & Jenike, 2000;Kim et al., 2003; Savage et al., 1999). In contrast, in some studies, results of OCD patientsdid not differ from those of healthy controls, or cognitive impairment was partially shownto be secondary to concomitant depression (Aycicegi, Dinn, Harris & Erkman, 2003;Basso, Bornstein, Carona & Morton, 2001; Moritz et al., 2001; Bohne et al., 2005). How-ever, the majority of studies suggests that OCD is commonly associated with mild cogni-tive dysfunction on tasks involving executive functioning and nonverbal memory (forreviews see Greisberg and McKay, 2003; Kuelz, Hohagen & Voderholzer, 2004a).
Based on recent results of an underlying metabolic dysfunction that can be amelio-
rated by successful behavioral or pharmacological therapy, one can assume that neuropsy-chological deficits associated with OCD are reversible during the course of treatment aswell. However, though postulated some years ago (Head, Bolton & Hymas, 1989), only afew studies have systematically examined the effects of behavioural or pharmacologicaltreatment on cognitive functioning in OCD.
In several studies using a within-subject-design across time, no comparison group
was included (Bolton, Raven, Madronal-Luque & Marks, 2000; Kang et al., 2003;Thienemann Koran, 1995). Thus, the interpretation of these results has therefore beensomewhat limited due to possible practice effects as a confound.
In a study by Kim and colleagues (2002), OCD patients were significantly impaired
on speed of information processing, visuospatial memory and verbal fluency at baseline. After 4 months of SSRI treatment, performance had significantly improved compared tothat of healthy controls, but patients still displayed deficits on verbal fluency and visu-ospatial memory. However, almost half of the patients had already been medicated atbaseline and patients were still symptomatic at follow up.
Nielen and Den Boer (2003) examined cognitive performance of 19 OCD patients
before and after 12 weeks of treatment with fluoxetine. Compared with healthy controls,patients were impaired on planning ability, spatial memory and motor speed before andafter treatment. The authors conclude that neuropsychological deficits in OCD are trait-related features that persist after pharmacological treatment. However, they also point outthat their test battery may have not been sensitive enough for evaluation of cognitive func-tions involving the orbitofrontal loop.
To our knowledge, there are only two studies so far examining changes of cognitive
functioning before and after behavioral treatment compared with healthy controls (Moritz,Kloss, Katenkamp, Birkner & Hand, 1999; Sieg, Leplow & Hand, 1999).
Moritz and colleagues (1999) compared neuropsychological performance of OCD
responders (n = 14) and nonresponders (n = 7) before and after behavioral treatment. Theyfound that the whole sample of OCD patients performed worse than healthy controls on
Neuropsychological Impairment Before and After Therapy
tasks of set shifting and selective attention at baseline, but that after therapy only nonre-sponders were still impaired on these tasks, whereas responders reached normal scores.
Sieg and colleagues (1999) compared neurocognitive performance of 24 initially
unmedicated OCD patients before and after 9 weeks of behavioral therapy with perfor-mance of 13 healthy controls tested within the same time interval. Minor responders, whoshowed less improvement of OC symptoms, obtained significantly lower scores on verbalfluency tasks as well as on a visual learning test compared to controls. These cognitiveimpairments were found before and after therapy. However, the potential effects of addi-tional medication during behavioural treatment were not considered.
The aim of the following study was to systematically evaluate the impact of cognitive
behavioral therapy on neuropsychological functioning of initially unmedicated OCDpatients. Thirty patients with OCD were tested before and after three months of cognitivebehavioral therapy with stimulus exposure and response management in comparison witha group of healthy controls. To consider possible confounding factors, the potential impactof depressive symptoms, severity and duration of illness as well as additional medicationduring behavioral therapy were taken into account. Subjects
Thirty-five inpatients diagnosed with OCD by an experienced clinician according to theDSM-IV criteria were recruited from the Department of Psychiatry and Psychotherapy,University Hospital of Freiburg. Four patients were lost to follow-up and one patient wasprescribed neuroleptic medication during the course of treatment, giving a final number of30 patients that were included. All patients were unmedicated for at least two weeks priorto baseline testing. Exclusion criteria included the presence of substantial neurologicalimpairment, head injury, substance abuse, current or previous psychotic episodes, MajorDepression and age above 65 years. Comorbid Axis-I disorders were systematicallyassessed via clinical interview. One patient was additionally diagnosed with a panic disor-der and one patient had a history of alcohol abuse but was abstinent at the time of testing.
Forty healthy volunteers were recruited through newspaper advertisements that did not
specify the disorder under investigation. A total of 39 healthy control subjects completedboth sessions. Additional exclusion criteria for the normal subjects were evidence for per-sonal or family lifetime history of Axis I disorder as assessed by a clinical interview.
The study protocols were approved by the Ethical Commitee of the Albert Ludwig Uni-
versity Freiburg. Informed written consent was obtained from each subject before testing. Study Design and Experimental Procedure
Neuropsychological and questionnaire data were collected before and after 12 weeks ofmanualized inpatient CBT with stimulus exposure and response management, a procedurethat has been proven to be strongly effective (Hohagen et al., 1998). There were two indi-vidual therapeutic sessions per week, each lasting about 50–60 min. In the initial phase,the treating clinician, experienced in therapy of OCD, explored OCD symptomatology,pre-disposing, precipitating and maintaining factors. Based on this information, a workingmodel was introduced to guide the treatment procedure. In the following, an exposurehierarchy was developed and the patient exposed himself to the individually triggeringstimuli. Furthermore, cognitive appraisals of feared situations or intrusive thoughts were
challenged and alternate, more adequate appraisals were developed. Individual treatmentwas supplemented by physiotherapeutic and ergotherapeutic groups.
Healthy controls were tested within the same interval without undergoing any behav-
ioral treatment. At baseline, all patients were unmedicated. After baseline testing, sevenpatients were given citalopram with a mean daily dose of 40 mg additionally to CBT. Allother patients were drug-free during CBT. Groups were matched for age, sex and educa-tion as well as for intelligence as assessed by a verbal IQ test (Mehrfachwahl-Wortschatz-test B, MWT-B; Lehrl 1992) and the Standard Progressive Matrices (Raven 1991).
For quantitative assessment of obsessive-compulsive and depressive symptoms the fol-
lowing scales were used: Yale-Brown Obsessive-Compulsive Scale (Y-BOCS; Goodman et al. 1989), Beck Depression Inventory (BDI, Beck, Ward, Mendelson, Mock & Erbaugh, 1961)and the Hamilton Rating Scale for Depression (HDRS; Hamilton, 1960). Item 21 of theHDRS, assessing obsessive-compulsive symptoms, was not included in the overall score.
Tasks were administered at the beginning of treatment (max. 14 days after assign-
ment) and immediately before discharge. Baseline results of a part of the sample and a partof the test battery have been published elsewhere (Kuelz, Riemann, Zahn & Voderholzer,2004b). The rationale for the selection of measures is based on previous neuropsychologi-cal studies in OCD. Since the aim was to evaluate the impact of CBT on cognitive func-tioning, predominantly those tests were chosen, which have been shown to discriminatebetween OCD patients and healthy controls.
All subjects were tested at the University Clinic Freiburg by an experienced clinical
psychologist. Neuropsychological tests were administered in one session that lasted abouttwo and a half hours. To avoid positional effects, tests were presented in a randomizedorder that was alternated between subjects. Neuropsychological Assessment Trail Making Test A. Trail Making Test A (TMT A; Reitan, 1958) requires connect-
ing digits from 1–25, which are arranged on a sheet, with a continuous line. The measureof performance is the time needed to complete the trial. Verbal Fluency. The verbal fluency task is derived from the performance-test-system
(“Leistungsprüfsystem”, Horn, 1962), subtest 6. The subject has to write down as manywords as possible, beginning with a certain letter, within one minute. The test consists ofthree trials, covering the letters F, P and K. Nonverbal Fluency. The Five-Points Test (Regard, Strauss & Knapp, 1985), a task
similar to the design fluency test, was applied to assess nonverbal fluency. The testinvolves a sheet with 35 squares, each containing five black dots. The subject’s task is toconnect any number of dots with any number of straight lines. In each square a differentpattern of connection has to be produced. The number of correct solutions produced by thesubject within 3 minutes is taken as the measure of performance. Verbal Creativity. The subject’s task is to write down as many different and unusual
uses for a can and for a piece of string as possible (e.g., use a can as a flower-pot). Themeasure of performance is the number of ideas produced within 4 minutes (Schoppe,1975). At second testing, a parallel version covering different items was used. Neuropsychological Impairment Before and After TherapyTest of Planning and Problem SolvingTower of London—planning version. A computerized version of the Tower of London
(ToL; Shallice 1982) similar to the Tower of London paradigm of the CANTAB (Robbinset al., 1994) was performed. On the problem solving condition, the subject’s task is torearrange a set of balls presented on the lower half of the screen to reach a goal state pre-sented on the upper half of the screen. The minimum number of moves needed to solve theproblem is specified before each trial on the screen. The number of moves needed to com-plete the trial varied between two and six moves. Planning accuracy was measured by thenumber of trials solved in the minimum number of moves. Initial thinking times (timebetween presentation of the problem and the first move) and subsequent movement times(time needed to complete the move) were also recorded. Test of Visuoconstructive Functioning and Nonverbal MemoryRey-Osterrieth Complex Figure Test (RCFT). The subject is instructed to draw a
complex figure and to subsequently draw what he or she remembers immediately as wellas after a delay of 30 minutes. Construction accuracy was quantified using the system ofMeyers and Meyers (1995). In this approach, 18 segments of the complex figure are iden-tified and evaluated according to accuracy and correct placement irrespective of the orderof drawing. Organizational strategy was evaluated according to Savage et al. (2000). Thefigure is divided in five configural elements defined by Binder (1982). To underline theimportance of the large rectangle for organization, it is assigned two points. The measureof performance is the number of configural elements drawn as unfragmented units. Tower of London—memory version. On the memory condition of the Tower of Lon-
don, the subject has to repeat a combination of moves of the balls that was presented on thescreen immediately before. The number of moves needed to complete the trial varies betweentwo and six moves. Thinking times and subsequent movement times were also considered. Object Alternation Test (OAT). The OAT (Freedman & Oscar-Berman 1986) was
administered in a computerized version. The investigator instructs the participant to detect avirtual coin that is hidden under one of two objects presented on the computer screen (a bluetriangle and a red square). Every time the objects appear on the screen, the participant hasfour seconds to choose one of the objects by pressing one of two corresponding keys, respec-tively. A detailed description of the procedure can be found elsewhere (Kuelz et al., 2004b). TAP—Change of Reaction. This test is a computerized task of the Test Battery for
the Assessment of Attentional Dysfunction (TAP; Zimmermann and Fimm, 1994). Thetests consists of 70 trials; on each trial a letter and a digit appear on the left and on the rightside of the monitor. The subject’s task is to alternatively press the left or the right buttoncorresponding to the position of the letter or to the position of the digit, respectively. Theprogram records the average reaction time as well as the number of errors. Trail Making Test B. Trail Making Test B (TMT B; Reitan, 1958) involves alter-
nately connecting digits (1–13) and letters (A–L) that are arranged on a sheet. The timeneeded to complete the trial and the number of errors are registered. Test of Self-guided, Flexible Behaviour. The Weight-Sorting Test (WST) involves 28identical looking plastic cylinders that should be arranged according to their varying
weights on a double-S shaped chain of circles within a time limit of 9 minutes. The sum ofthe deviations in grams between the chosen and the correct serial positions was the mea-sure of performance. This test requires coordinated, goal directed and flexible behaviorand persistency and is described to be sensitive to cerebral dysfunction (Bäumler, 1995). Statistical Analysis
Data were analyzed using the SPSS-PC package, version 11.5. To evaluate an overallgroup-difference, the neuropsychological measures were entered into a multivariate analy-sis of variance (MANOVA). Subsequently, repeated measures of the analysis of variance(ANOVA) with the time of testing as the within-subject factor and the group as between-subject factor were calculated. To minimize type I errors, only for those domains subse-quent univariate comparisons at baseline and follow-up were conducted, where a signifi-cant group x time interaction was observed. The relationship between neuropsychologicaltest scores and the results of the questionnaires in OC patients was explored by use ofPearson’s product moment correlations
The strict criterion of p < 0.01 was chosen for all separate group comparisons and cor-
relational analyses to indicate statistical significance. To get a clear grasp of the magni-tude of differences between groups at both baseline and at follow-up, effect sizes wereadditionally calculated for all neurocognitive parameters. Demographic Measures and Clinical Results
Table 1 summarizes the demographic and clinical characteristics of both groups at base-line and at follow-up. There were no significant differences between groups regardingage, sex, educational level and general intelligence (for intelligence, see Table 2).
Demographic and clinical characteristics of the samples
Demographic characteristics Age Clinical data Y-BOCS total score
Demographic characteristics of major responders and minor responders
number of recalled elements after 30 minutes
Figure 1. Delayed recall on the Rey-Osterrieth Complex Figure Test in major responders, minor responders and healthy controls. Effect of interaction between time and patient group (major responders vs. minor responders): p = .009.
At follow-up, OC symptoms as measured by the Y-BOCS were significantly reduced
(−42.1% ± 26.3%, t(29) = 8.01, p < .001) compared with baseline. Neuropsychological Test Results at Baseline and Follow-up
MANOVA including all of the baseline measures with exception of general intelligenceyielded a highly significant difference between groups (F = 3.75, p < .001).
As can be derived from Table 2, there was a significant effect of group in 10 out of 14
measures with patients performing worse than healthy controls. As expected, there wasalso an effect of time on 11 parameters. With regard to effect sizes, there was a very largeeffect (>1.0) on 7 measures when comparing performance of patients and controls at base-line, but not at follow-up.
A significant effect of interaction (p < .05) was found for delayed recall on the Rey
Figure. Univariate follow-up tests revealed that patients performed significantly worse
Neuropsychological Impairment Before and After Therapy
than controls at baseline (t(67) = −3.39, p = .001), but reached results comparable tothose of controls at follow-up (t(67) = −1.37, p = .176). A highly significant interactioneffect (p < .001) was also observed for the strategy score of the Rey Figure withpatients drawing much fewer configural elements as unfragmented units comparedwith healthy controls at baseline (t(67) = −3.0, p = .002) but not at follow-up (t(67) =.197, p = .845). Furthermore, there was a tendency towards a significant interaction forRCFT immediate recall, which, however, became not significant at .05-level (F(1,67) =3.75, p = .057).
Furthermore, the repeated measures ANOVA performed on the test “change of reac-
tion” of the TAP showed a significant group × time interaction (p < .01) for time requiredto complete the task with patients performing more slowly than controls only at baseline(t(67) = 2.67, p = .01 and t(67) = 1.67, p = .10, resp.). There was also a significant (p <.01) group × time interaction with regard to the Weight Sorting Test, assessing flexible,self-guided behavior. OCD patients showed significantly more deviations than healthycontrols at baseline (t(67) = 3.38, p < .001), but did no longer differ significantly fromcontrols at follow-up (t(67) = 1.82, p = .073). Secondary Analyses
Secondary analyses regarding total number of errors and response time on the OAT didnot reveal any difference between groups. Even no effects of group or interaction for num-ber of errors were found with respect to the TAP and the TMT B. Regarding the RCFT,there was no significant effect when testing for response time of drawing the figure. How-ever, a significant effect of interaction was found for thinking times and movement timeson the ToL problem solving condition (F(1,67) = 5.24, p = .03 and F(1,67) = 4.93, p = .04,resp.) and for thinking times on the ToL memory condition (F(1,67) = 4.41, p = .04). There were no significant differences between groups at baseline or follow up. OCDpatients, however, tended to be more slowly than controls regarding all parameters of theToL. Impact of Depressive Symptoms on Neuropsychological Measurements
At baseline, depression as measured by the HDRS and by the BDI was not significantlycorrelated with any cognitive parameter. At follow-up, both the HDRS score and the BDIscore were significantly correlated with delayed recall on the RCFT (r = −.533, p = .002and r = −.498, p = .005, resp.). Impact of Therapy Response on Neuropsychological Improvement
To evaluate the impact of therapy response, the OCD sample was divided into two groupsaccording to the Median of symptom improvement (43.4%). Demographic characteristicsof the groups can be derived from Table 3.
At baseline, both major responders (n = 15) and minor responders (n = 15) showed
significant impairment on seven measures assessing nonverbal fluency and memory andflexible, self-guided behavior at .01 level (immediate and delayed recall as well asstrategy score of the Rey Figure, Weight-Sorting Test, Change of Reaction of the TAP,Five-Points-Test and Trail Making B). Additionally, minor responders differed signifi-cantly from controls on Trail Making A (t(42) = 4.03, p < .001) indicating impaired speedof information processing. After cognitive behavioural treatment, major responders
performed comparable to controls on all tests, whereas minor responders still showeddeficits on nonverbal fluency (t(42) = −3.34, p = .002).
An effect of group × time interaction regarding response to treatment was found for
both immediate and delayed recall on the Rey Figure (F(1,28) = 7.75, p = .010 and F(1,28) =8.04, p = .009, resp.) (see Figure 1) with major responders improving to a significantlylarger extent. There were no significant differences with respect to depressive symptomsbetween major responders and minor responders at any time of testing.
Besides, there was a correlation at .05-level between symptom change, as measured
by the Y-BOCS, and cognitive improvement on both immediate (r = .410, p = .027) anddelayed (r = .449, p = .015) recall condition of the RCFT. Impact of Severity and Duration of Illness and Effects of Medication
There was no significant correlation between severity or length of illness and any of theneuropsychological parameters at baseline. At follow-up, length of illness was signifi-cantly correlated with the number of correct solutions on the ToL memory condition (r =.494, p = .006).
Medicated (n = 7) and unmedicated patients (n = 23) did not differ with regard to
cognitive improvement on any parameter. In addition, at baseline as well as at follow-up,there were no differences between treatment groups on any clinical or cognitiveparameter. Discussion
The major finding of our study is that some of the cognitive functions improve in thecourse of cognitive behavioral treatment of OCD. There was a significant group x timeinteraction for measures of delayed nonverbal memory, organizational strategies, flexible,self-guided behavior and speed related set shifting with patients performing significantly(p < .01) worse than controls at baseline but not at follow-up. These improvements cannotbe explained by practice effects alone, which were controlled by a large sample of healthysubjects tested twice within the same time interval. With respect to therapy response, afterCBT, performance of major responders was comparable to that of controls on all cognitivemeasures. Minor responders improved to a significantly smaller extent on immediate anddelayed recall of the Rey Figure compared with major responders and were still impairedon nonverbal fluency at follow-up.
Our results are in contrast to the findings of Nielen and den Boer (2003) suggesting
persistent cognitive deficits in OCD patients after treatment. Patients in the latter study,however, were solely treated with pharmacological therapy. In the study of Kim et al. (2002), patients showed significant improvements on nonverbal memory and verbal flu-ency, but were still impaired at follow up. However, only 8 out of 39 patients receivedcognitive behavioral therapy. We propose that particularly systematic cognitive behav-ioral treatment enables OCD patients to think and to act in a more flexible way that helpsthem to develop more effective cognitive strategies. Hence, patients might benefit from amore adaptive way of thinking at follow-up testing although they were not directlyinstructed how to act on the neuropsychological tasks, of course. This hypothesis is sup-ported by the fact that our patients mainly improved on tasks requiring flexible, productivethinking (organizational strategies, flexible, self-guided behavior). Interestingly, improve-ment in cognitive performance of patients being additionally treated with SSRI did notdiffer significantly from the one in patients treated with CBT alone. These results suggest
Neuropsychological Impairment Before and After Therapy
that CBT might be similarly effective as combination therapy regarding cognitive func-tioning. Sub-samples, however, were too small to draw further conclusions.
In view of the low association between neuropsychological and psychometric scores
it is unlikely that neuropsychological dysfunction at baseline resulted from a loweredmood. In addition, unlike severity of OC symptoms and neuropsychological performance,symptoms of depression, which were only mild, were not markedly reduced at follow-up(see Table 1).
Regarding the predictive value of neuropsychological functioning, only speed of
information processing (Trail Making A) discriminated between major responders andminor responders at baseline. We have to bear in mind that response to treatment wassolely assessed by the Y-BOCS-score. Thus, it can not be excluded that a more compre-hensive assessment of OC symptoms would yield some association between cognitivedysfunction at baseline and clinical improvement. However, the lack of a consistent pat-tern of cognitive dysfunction as a predictor for nonresponse contradicts the findings ofSieg et al. (1999), but is in line with the results of several other studies (Bolton et al.,2000, Moritz et al., 2005; Thienemann and Koran, 1995).
No marked impairment was found in patients regarding the number of correct solu-
tions on the ToL. Previous results on planning ability in OCD have been contradictory(Nielen and Den Boer, 2003; Purcell et al., 1998; Schmidtke et al., 1998; van den Heuvelet al., 2005). As suggested by neuroimagung studies (Rowe, Owen, Johnstrude & Passingham,2001, Unterrainer et al., 2004) performance on the ToL is mainly associated with dorsolat-eral-prefrontal activation, which seems to go along with decreased responsiveness ofdorsal prefrontal-striatal circuits during planning in OCD patients (van den Heuvel et al.,2005).
Previous studies on effects of treatment, however, suggest that neural activity in OCD
changes predominantly within the orbitofrontal-striatal circuit (Baxter et al., 1992;Schwartz et al., 1996). Based on the assumption that the observed state-dependency ofneuropsychological performance in OCD is secondary to the metabolic changes describedin the literature (Baxter et al., 1992; Nakatani et al., 2003; Schwartz et al., 1996; Saxena etal., 1999), one might hypothesize that cognitive functions corresponding to the orbitofron-tal feedback-loop are particularly susceptible to CBT. In a study by Kang et al. (2003), forexample, there were metabolic decreases in the orbitofrontal cortex, the hippocampus, thecerebellum and the right putamen after treatment. Interestingly, the metabolic changeswere significantly correlated with improvement on the immediate- and delayed recall ofthe Rey Figure, a task where improvement was significant in our OCD sample, too. Poorperformance on this test is suggested to be based on ineffective encoding strategies thatare hypothesized to result from dysfunction of the frontal-subcortical circuits (Deckers-bach 2000; Savage, 1999, 2000). Our patients indeed showed poor organizational strate-gies when copying the Figure. These were related to accuracy of recall and improvedsignificantly after behavioural therapy. In particular, major responders showed signifi-cantly larger improvement on immediate and delayed recall of the Rey Figure comparedto minor responders. In addition, recent studies using positron emission tomography(PET) suggest that the orbitofrontal cortex, together with its bi-directional connections tothe medial temporal cortex, is a critical frontal region underlying memory formation (Freyand Petrides, 2002). Interestingly, in a PET study of Savage and colleagues (2001) bloodflow in the orbitofrontal cortex during the first spontaneously encoding of 24 words wascorrelated with semantic clustering scores during immediate free recall. The authors sug-gest that the orbitofrontal cortex is an important region to support the mobilization ofstrategies during novel and ambiguous tasks.
Taken together, these data confirm our hypothesis that neuropsychological impair-
ment before therapy is based on metabolic dysfunction of the orbitofrontal feedback-loopthat may return to normal during the course of treatment.
The OAT, however, a task that is also considered to be sensitive for orbitofrontal dys-
function, did not show any significant differences between patients and controls in ourstudy. In face of recent results, it seems questionable whether the OAT is a valid instru-ment for measuring cognitive impairment in OCD (Kuelz et al., 2004b). This issue, how-ever, requires further investigation.
In conclusion, results of our study hint at cognitive improvement in OCD patients
after CBT on tasks of nonverbal memory, organizational strategies, flexible, self guidedbehavior and set-shifting. Especially, our results suggest that successful CBT may mainlyinfluence performance on cognitive tasks involving the orbitofrontal-striatal feedbackloop and/or involving skills that are improved by cognitive treatment in OCD in general(e.g., cognitive flexibility).
However, there are also some limitations of our study. First, we cannot rule out that
unspecific effects of hospitalization may have contributed to improvement of cognitivesymptoms in our patients. An additional comparison group consisting of inpatients suffer-ing from a different disorder could help in identifying characteristic patterns of cognitiveimprovement in OCD by CBT.
Secondly, from a statistical point of view, cognitive improvement in OCD patients
can only be attributed to treatment in those measures, where a significant interaction effectwas found. This was the case for some measures of nonverbal memory (delayed recall)and organizational strategies, flexible, self guided behavior and set-shifting, but not fortasks assessing speed of information processing, fluency and planning ability. Improve-ment of other test results may be confounded by practice effects. With regard to healthycontrols, we cannot exclude that ceiling effects may have contributed to lack of change inthat group. Thus, for future studies a careful selection of sensitive tasks seems to be neces-sary to focus on those cognitive functions that are particularly susceptible to treatment-induced changes.
An interesting avenue to explore would be the inclusion of an additional sample of
untreated OCD patients tested twice within the same time span without undergoing behav-ioral treatment. Finally, neuroimaging studies should be of value in revealing neuronalcorrelates of the described cognitive dysfunctions before and after CBT. References
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00(1). Alphabetical index remedies 27/8/11 12:00 Page xxiii A L P H A B E T I C A L I N D E X R E M E D I E S Numbers in bold refer to grouping number (see Page li) Abelmoschus moschatus 79 Actaea spicata 116.2 Abies alba 103 Actinidia deliciosa 3 Abies balsamea 103 Adansonia digitata 79 Abies canadensis 103 Adenandra uniflora 121 Abies nigra 103 Adhatoda vasica 1
Efficacy of anthElminthic control programs against natural Muellerius capillaris infEction in shEEp in thE north-wEst of spain. EffEct on blood gasEs and ph in vEnous blood samplEs LóPez C.M., Cienfuegos s., DaCaL V., Vázquez L., PanaDeRo R., feRnánDez g., Díaz P., Lago n., Díez-baÑos P. & MoRRonDo M.P.* Summary: Résumé : Efficacité dE différEnts anthElminthi