Supervisor: Professor Roger E. Graves
ABSTRACT
Converging neurobiological evidence strongly suggests that the neural substrate of obsessive-compulsive disorder
(OCD) involves components of cortical-basal ganglia- thalamocortical circuitry. Evidence is strongest for involvement of the basal ganglia and the orbital frontal cortex. Although much of the existing neuropsychological research supports an interpretation of some frontal system dysfunction in OCD, few of the psychological processes dependent upon frontal system integrity have been examined. There has been almost no attempt to differentially assess the integrity of psychological processes mediated by various
frontal lobe areas or the basal ganglia.
The current study examined the integrity of psychological processes presumed to be sensitive to dysfunction of the basal ganglia, the orbital frontal cortex, and the dorsolateral
prefrontal cortex. The performance of a sample of OCD (n = 27) and normal control (n = 25) subjects was compared on a battery of neuropsychological tests, A priori and post hoc analyses provided support primarily for dysfunction of the basal
ganglia in OCD. There was also some support for dysfunction of the orbital frontal cortex.
Post hoc analyses including cluster analyses revealed a number of differences in the basic ability structures of OCD and normal control subjects. In contrast to the normal
controls, OCD subjects did not show the basic distinction
between verbal and nonverbal abilities, and declarative memory seemed dissociated from measures of intelligence and
attention. Analyses of covariance indicated that impaired
performance on declarative memory tasks in the OCD group could be partly accounted for by performance on tests of frontal system function. However, the opposite effect was not
observed.
As predicted, there was evidence for some independence of affect, neuropsychological status, and symptom severity in the OCD group. There was an absence of any relationships between measures of affect, anxiety, or depression with the measures of cognitive performance in the OCD group whereas, as would be expected, there were several such relationships observed in the normal control group. Post hoc analyses revealed several relationships between neuropsychological variables and
measures of symptom severity in the OCD group. However,
observed relationships were generally with neuropsychological variables that did not differentiate between OCD and normal conrol groups. The meaning of these relationships remains unclear.
TITLE PAGE ... i
ABSTRACT ... Ü TABLE OF CONTENTS ... v
LIST OF TABLES ... viii
LIST OF FIGURES ... xi
ACKNOWLEDGEMENTS ... xii
DEDICATION ... xlii Page INTRODUCTION ... 1
A Clinical Overview of Obsessive-Compulsive Disorder ... 1
The Biological Basis and Neural Substrate of Obsessive-Compulsive Disorder ... 8
Overview of Suspected Anatomy ... 8
Genetics, associated disease states, lesion studies, and neurological soft signs ... 10
Neuropsychophramacological studies ... 18
Imaging studies ... 20
Electrophysiological studies ... 2 6 Psychosurgery ... 27
Summary of the evidence for the neural substrate in OCD ... 30
Neuropsychological Investigations of Obsessive-Compulsive Disorder ... 31
Dominant Hemisphere Dysfunction ... 31
Nondominant Hemisphere Dysfunction ... 3 3 Frontal Lobe Dysfunction ... 40
Dysfunction of the Basal Ganglia ... 42
Neuropsychological Studies of Obsessive-Compulsive Disorder and Related Disorders ... 4 6 Other F i n d i n g s ... 50
Models of Obsessive-Compulsive Disorder ... 58
Rationale for Study and Description of Measures Used in the Study ... 71
The Basal Ganglia ... 73
Tower of Toronto ... 79
Motor Procedural Learning ... 82
Conditional Associative Learning ... 83
Simple Go-NoGo Test ... 85
Orbital Frontal Cortex ... 86
Go-NoGo Tests ... 87
Object Alternation ... 39
Dorsolateral Prefrontal Cortex ... 90
Delayed Alternation and Delayed Paired Comparison ... 91
Self-Ordered Pointing ... 94
Symptoms, Affect, and Neuropsychological Status ... 95
Other Measures ... 98 Summary of Hypotheses to be T e s t e d ... 99 METHODS ... 102 Subjects ... 102 Procedures ... 105 Statistical Analyses ... 107 RESULTS ... 113 A priori hypotheses ... 114 Post-hoc analyses ... 122 Cluster Analyses ... 167 Normal Controls ... 169 OCD Subjects ... 175 DISCUSSION ... 183 Tests ... 185 Tower of Toronto ... 186
Conditional associative and motor procedural learning ... 199
Go-NoGo tests ... 206
Delayed alternation and object alternation ... 209
Delayed paired comparison and self-ordered pointing ... 211
Attention, declarative memory, psychomotor speed, visuospatial function, and drug status ... 214
Symptom severity, affect, and neuropsychological status ... 222
Cluster analysis ... 228
General summary and a proposed model ... 229
REFERENCES ... 234
APPENDIX A. Psychological Tests Cited in Text ... 274
B. Tests Used in the Study: Description, Administration Instructions, and Measures Derived... 276
C. Consent Form ... 289
D. History Questionnaire ... 291
E. Conditional Associative Learning Test Scoring Sheet ... 293
F. Self-Ordered Pointing Example Stimulus Sheets ... 296
G. Variable Labe].s With Explanation ... 299
H. Raw Data ... 301
Variables with Summary Explanation ... 301
Raw Data for OCD Subjects ... 3 05 Raw Data for Normal Control Subjects ... 314
LIST OF TABLES
Table Page
1. Summary Demographic Statistics ... 114 2. Summary Statistics for
Basal Ganglia Hypotheses ... 116 3. Summary Statistics for
Orbitofrontal Hypotheses ... 117 4. Summary Statistics for
Dorsolateral Hypotheses ... 118
5. Summary Statistics for MANOVA of
Basal Ganglia Variables ... 119 6. Summary Statistics for MANOVAs of
Orbitofrontal and Dorsolateral Variables ... 120 7. Relationship Between Affect
and Symptom Severity ... 121 8. Summary Statistics for MANOVA of Effect
of Group on all A Priori Variables ... 12 3 9. Summary Statistics for MANOVA of Effect
of Group on All A Priori Variables With
Replacement of Missing Values ... 125 10. Summary Statistics for Measures of
Attention Span and Declarative Memory ... 127 11. Summary Statistics for Reaction
Time Measures ... 128 12. Summary Statistics for New Variables
From Measures Previously Described ... 130 13. Summary Statistics for Tower of Toronto
Variables Not Previously Reported ... 134 14. Pearson Correlation and Probability
Matrices for Errors and Reaction Time:
OCD Subjects ... 135 15. Pearson Correlation and Probability
Matrices for Errors and Reaction Time:
16. Summary Statistics for Regression of Log-latency on Log-Trial for the
Tower of Toronto Test ... 138 17. Relationship Between Total Y-BOCS
Symptom Severity Score and
Neuropsychological Variables ... 141 18. Relationship of Neuropsychological Status
with Compulsions and Obsessions ... 14 5 19. Difference in Performance Related
to Drug Status ... 148
20. Summary Statistics for Differences Between Males and Females on
Neuropsychological Tests ... 151 21. Significant Correlations of Age
with Other Variables ... 153 22. Significant Correlations of Education
with Other Variables ... 153 23. Significant Correlations of NART-R I.Q.
with Other Variables ... 154 24. Significant Correlations of WAIS-R Picture
Completion with Other Variables ... 155
25. Relationship of Attention and Declarative
Memory Measures in the Normal Control Group ... 156
26. Relationship of Attention and Declarative
Memory Measures in the Obsessive-Compulsive
Disorder Group ... 157 27. Relationship of Attention and Declarative
Memory with Other Variables in the Study
for Normal Control Subjects ... 158 28. Relationship of Attention and Declarative
Memory with Other Variables in the Study
for OCD Subjects ... 159
29. ANCOVA for Selected Dependent Variables with Attention and Declarative Memory Measures as
Covariates ... 161 30. ANCOVA for Tower of Toronto Variables with
Attention and Declarative Memory Measures as
31. ANCOVA for Declarative Memory Dependent
LIST OF FIGURES
FIGURE PAGE
1. Dendogram of Average Linkage Cluster
Analysis for Normal Control Subjects ... 170
2. Dendogram of Single Linkage Cluster
Analysis for Normal Control Subjects ... 171
3. Dendogram of Complete Linkage Cluster
Analysis for Normal Control Subjects ... 172
4. Dendogram of Average Linkage Cluster
Analysis for Obsesssive-Compulsive
Disorder Subjects ... 176
5. Dendogram of Single Linkage Cluster
Analysis for Obsesssive-Compulsive
Disorder Subjects ... 17 7
6. Dendogram of Complete Linkage Cluster
Analysis for Obsesssive-Compulsive
Disorder Subjects ... 178
7. Schematic Summary of Average Cluster
ACKNOWLEDGMENTS
I would initially like to acknowledge Dr. Josef
Schubert who served as my supervisor during my M.A. program and has very much been my mentor in psychology. I would like to thank Dr. Robert A. Payne who agreed to act as my
supervisor when I initially entered the program at the University of Victoria. Dr. Payne's support and friendship was most appreciated. I would next like to thank Dr. Roger Graves who agreed to act as my supervisor following Dr. Payne's retirement. Dr. Graves was very helpful with all stages of the dissertation. The cooperation of Dr. Jean Saint-Cyr allowed the project to be carried out at the
Toronto Hospital, Toronto Western Division. Dr. Saint-Cyr's encouragement and advice has been helpful all along. I would also like to express my gratitude and appreciation to Dr. Ann Taylor at The Toronto Hospital, Toronto Western Division
for her support. Thanks is extended to the other members of my committee, Dr. Michael Joschko, Dr. Marsha Runtz, Dr. Roy Ferguson, and Dr. John MacDonald. I would also like to thank all the participants in the study and all those who referred subjects to the study.
My greatest appreciation is extended to my wife and children without which this project would not likely have been completed.
DEDICATION
This work is gratefully dedicated to the memory of ray parents, Keith and Eileen Nicholson.
A Clinical Overview of Obsessive-Compulsive Disorder
Salzman and Thaler (1981), in a review of the
literature on obsessive-compulsive disorder (OCD) from 1953 to 1978, concluded that there was a "paucity of information in all areas, physiological as well as psychological" (p. 295). The lack of systematized study of OCD may have been due to its perceived rarity. Prior to the early 1980s, the prevalence of OCD in the general population had widely been thought to be in the range of 5 in 1,000 (Rasmussen & Eisen,
1990a). However, several large community epidemiological studies conducted in the past decade suggest that the lifetime prevalence of OCD in the general population is likely between 1 and 2% (Bland, Newman, & Orn, 1988a, 1988b; Flament et al., 1988; Henderson & Pollard, 1988; Karno,
Golding, Sorenson, & Burnam, 1988; Rasmussen & Eisen, 1991; Robins et al., 1984), making OCD one of the more common mental disorders.
The Diagnostic and Statistical Manual of Mental Disorders, Third Edition - Revised (DSM-III-R) (American Psychiatric Association, 1987) classifies OCD as an Axis I anxiety disorder in which either obsessions or compulsions
cause marked distress, are time-consuming, or significantly interfere with aspects of the individual’s life. Obsessions are defined as "recurrent and persistent ideas, thoughts, impulses, or images that are experienced, at least
initially, as intrusive and senseless" (p. 247) . These
obsessions are recognized as the product of the individual's own mind and attempts are made to suppress or neutralize them with some other thought or action.
Compulsions are defined as "repetitive, purposeful, and intentional behaviors that are performed in response to an obsession, or according to certain rules or in a stereotyped fashion" (American Psychiatric Association, 1987, p. 247). Although the compulsive behavior is designed to neutralize some dreaded event or prevent discomfort, the behavior and the fear are not realistically connected, or the behavior is clearly excessive. Resistance to a compulsion is associated with increasing discomfort or tension which is alleviated by performing the compulsive behavior. Resistance may
eventually be abandoned when there is repeated failure to inhibit the compulsive behavior.
Insel (1990a) suggested that a syndrome identical to current clinical descriptions of OCD has been recognized for over 300 years. Insel was critical of DSM-III-R criteria which were described as "at best, a working model for
classifying the disorder" and that these criteria "fail to do justice to either the scope or the enigmatic nature of
this syndrome" (p. 5). Liebowitz and Hollander (1991) noted that current criteria for OCD are based only on clinical consensus and are not yet validated by biological markers, treatment outcome, family studies, or otherwise.
Several systematic studies in the past decade have begun to explicate the clinical features of OCD. Rasmussen and Eisen (1991) have reported on what may be the most comprehensive systematic study of a large sample of OCD patients. Their consecutive series of 250 patients meeting DSM-III-R criteria for OCD had a mean age of onset of 19.8 +/- 9.6 years. The men in this sample had a mean age of
onset of 17.5 +/- 8.7 years compared with 21.2 +/- 9.8 years for women. There is a preponderance of male subjects
presenting with childhood-onset OCD and early onset is associated with more checking whereas later onset is associated with more washing rituals (Swedo, Leonard, & Rapoport, 1990). Rituals are more frequently the presenting complaint than obsessions in childhood onset OCD (Swedo, Leonard, & Rapoport). The course is usually a chronic waxing and waning of symptoms with incomplete remissions that
permit episodic normal levels of functioning (Rasmussen & Eisen, 1990b, 1991; Swedo & Rapoport, 1989). The symptom pattern is consistent across cultures (Khanna &
Channabasavanna, 1987; Rachman & Hodgson, 1980).
Rasmussen and Eisen (1991) found that most patients presented with multiple obsessions and compulsions and that
there were few patients with only obsessions or compulsions. The frequency of obsessions was as follows: contamination
(45%), pathologic doubt (42%), somatic (36%), need for
symmetry (31%), aggressive (28%), sexual (26%), other (13%). The frequency of compulsions was as follows: checking (63%) , washing (50%), counting (36%), need to ask or confess (31%), symmetry and precision (28%), and hoarding (18%).
Rasmussen and Eisen (1991) found that obsessive fear of contamination with compulsive handwashing was the most
common phénoménologie presentation. Pathological doubt was evident across phénoménologie subtypes but was especially marked in checkers. These patients occasionally reported that the need to check over and over sometimes seemed to just "click off" or end. They were often identified as perfectionists with overly meticulous and critical parents. They would sometimes need to check and recheck the status of some event or object despite the absence of identifiable feared consequences. Patients presenting with sexual or aggressive obsessions often had a strict religious
upbringing. Although compulsive hoarding was common, it rarely dominated the symptom picture and this behavior was often ego syntonic.
Insel (1990a) suggested that there are four general phenomenological presentations in OCD. The most common was that of patients with contamination obsessions and
The second most common group of patients were those with obsessional doubt who often engage in compulsive checking. These patients have an intense struggle between the
uncertainty they experience and the need to recheck something. Paradoxically, the more they check, the more uncertain they often become. Guilt is often prominent in this group of patients. The third presentation described by Insel consisted of those patients with relatively pure
obsessions, often of a sexual or aggressive nature. These patients tended to be highly secretive. The fourth group were those patients with primary obsessional slowness who experienced little resistance and little anxiety. They would spend inordinate amounts of time in activities of daily
living which precluded effective functioning.
Khanna, Kaliaperumal, and Channabasavanna (1990) performed a cluster analysis on the form and content of
obsessions and compulsions of 410 OCD patients. Checking and washing emerged as the two primary clusters. Henderson and Pollard (1988), in their small sample of 14 OCD patients identified in a community sample, found that the most
prevalent symptomatology involved checking compulsions and suggested that washers may be more commonly seen in clinics. Rachman and Hodgson (1980) suggested that men and women tend to develop different forms of OCD. Eighty-six percent of their washers were women whereas checkers had a more balanced sex distribution.
Liebowitz and Hollander (1991) suggested that OCD as currently defined may encompass pathophysiologically
heterogeneous subtypes. Rasmussen and Eisen (1991), however, found few differences between phénoménologie subgroups on demographic variables, course of illness, comorbidity, or other clinical features. They noted that the symptom picture typically changes over the course of time for any individual such that one type of symptom will be replaced by another. Although there is apparent diversity in the content of
obsessions and compulsions, these authors suggested that the underlying form of the disorder is generally consistent
across phénoménologie presentation. All subgroups with the exception of those with obsessional slowing describe anxiety as the dominant affective symptom. Most OCD patients fear that they will be responsible for something terrible that will happen to themselves or others. Insel (1990a),
commenting upon the observation that the symptom picture changes over the course of their illness, also proposed that the various presentations are different faces of the same disorder rather than representing subsyndromes.
Many studies have concluded that there is a high
frequency of other disorders coexisting with OCD. Rasmussen and Eisen (1991) found that 57% of the OCD patients in their sample had at least one other DSM-III-R diagnosis on
admission and an even higher percentage had a lifetime history of another Axis I disorder. Almost a third of their
patients met criteria for major depressive episode on admission. The next most common concurrent diagnoses were simple phobia, social phobia, eating disorders, alcohol abuse, panic disorder, and Tourette's syndrome. The frequency of lifetime major depression was 67%.
Approximately 10% of the patients had psychotic features associated with their primary OCD.
Austin et al. (1990) found that 39% of their sample of OCD patients reported a lifetime history of panic attacks. Half of these patients developed OCD before the onset of panic attacks. The two symptom complexes waxed and waned independently of each other over the course of time. The prevalence rates for simple phobias and social phobias were 20% and 14%, respectively. Over 60% of the patients had had at least one major depressive episode in their lifetime. Karno et al.(1988) found that over half of the subjects in their study with lifetime occurrence of both depression and OCD reported the onset of OCD before the onset of the
affective disorder.
There has been debate about the relationship between OCD and schizophrenia. Some researchers have thought OCD to be closely related to the psychoses (Flor-Henry, 1979,
198 3). However, follow-up studies have shown that few OCD probands go on to develop schizophrenia and most researchers currently think the two disorders are independent (Rasmussen & Eisen, 1990b). The clinical presentation of OCD has been
compared with a number of other disorders including body dysmorphic disorder, trichotillomania, and compulsive sex, eating, gambling, or self-mutilation, as well as various other disorders of impulse control (Jenike, 1990a) .
Baer et al. (1990) assessed 96 patients with OCD for DSM-III personality disorder diagnoses and found that 52% of the subjects met criteria for at least one personality
disorder. Mixed, dependent, and histrionic personality
disorders were most frequently diagnosed. Many studies have concluded that OCD and obsessive-compulsive personality disorder are largely independent disorders (Baer et al., 1990; Joffe, Swinson, & Regan, 1988; Poliak, 1987). Swedo and Rapoport (1989), however, have suggested that there is
"a complex and important relationship between the two" (p.
28) which is evident developmentally. Liebowitz and Hollander (1991) have noted that distinctions between subclinical OCD features and obsessive-compulsive personality traits are not clearly drawn.
The Biological Basis and Neural Substrate of Obsessive- Compulsive Disorder
Overview of suspected anatomv.
Converging neurobiological evidence, to be reviewed below, suggests that the neural substrate of OCD may primarily involve components of cortical-basal
ganglia-thalamocortical circuitry. This section will provide a brief overview of this neuroanatomy.
Rosvold and Szwarcbart (1964) had early on proposed the concept of a cortical-subcortical frontal-lobe system on the basis of anatomical and functional relationships between prefrontal cortex and the striatum (caudate nucleus and
putamen). DeLong and Georgopoulos (1981) proposed that there were motor and association (or complex) loops, which funnel and integrate diverse inputs as they course through the basal ganglia projecting back up to prefrontal cortex.
Alexander, DeLong, and Strick (1986) subsequently reviewed the evidence for five parallel cortical-basal ganglia-thalamocortical circuits and suggested that there are likely a number of others. Each of these circuits funnel diverse cortical (and subcortical) input through the basal ganglia and project, via thalamic nuclei, to separate areas of the frontal cortex thereby partially closing the
circuits. The striatal target of the motor circuit is the putamen. This circuit eventually projects, via other basal ganglia and thalamic nuclei, to the supplemental motor area. The striatal target of the oculomotor circuit is a central portion of the body of the caudate nucleus which eventually projects back to the frontal eye fields. The dorsolateral prefrontal circuit converges on the dorsolateral head of the caudate nucleus through to the tail. This circuit eventually projects back to the dorsolateral prefrontal cortex. The
lateral orbital frontal circuit converges on the ventromedial caudate nucleus from head to tail and
eventually projects back to the lateral orbital frontal cortex. The anterior cingulate circuit, with inputs which may include projections from the posterior medial
orbitofrontal cortex, courses through ventral
striatopallidal structures and eventually projects back to the anterior cingulate.
Heimer and Wilson (1975) introduced the concept of the ventral striatopallidal system, which is generally thought to include the nucleus accumbens, olfactory tubercle, and ventral aspects of the striatum and pallidum (Haber, Lynd, Klein, & Groenewegen, 1990; Heimer & Wilson, 1975; Nauta,
1986; Parent, 1986). The ventral striatopallidal system has extensive connections with such "limbic system" structures as the amygdala, hippocampal formation, lateral habenula, orbital frontal cortex, anterior cingulate, as well as
temporal association cortices, several thalamic nuclei, the ventral tegmental area (VTA), substantia nigra, midbrain tegmentum, and dorsal raphe' nuclei- Further details about cortical-basal ganglia-thalamocortical circuitry, including the functional neuroanatomy, will be reviewed in later
sections.
Genetics, associated disease states, lesion studies, and neurological soft signs.
Although there is clearly a genetic component involved in the etiology of OCD as indicated by concordance rates for monozygotic twins, heritability estimates, and the
clustering of OCD within families, there is far from complete genetic determination of the disorder (Pauls, Raymond, & Robertson, 1991; Rasmussen & Tsuang, 1986a). Heritability estimates indicate that about half of the
phenotypic variance may be due to genetic factors (Pauls et al., 1991). A number of authors have suggested that there is an abnormally high incidence of birth trauma or other early developmental insults in OCD (Capstick & Seldrup, 1977; Flor-Henry, 1983; Grimshaw, 1964). Conversely, the
puerperium is also a period of risk for the onset of OCD (Sichel, Cohen, Dimmock, & Rosenbaum, 1993).
Several studies have reported the presence of what are often considered soft neurological signs in OCD. Insel,
Donnelly, Lalakea, Alterman, and Murphy (1983) reported that OCD patients often complain that they are clumsy and
nonmechanical. Behar et al. (1984), following
neurodevelopmental examination of 7 OCD patients, reported a high frequency of age-inappropriate synkinesias and left hemibody signs including abnormalities of tone, reflexes, and posture. Flor-Henry (1983), in a review of the
literature, concluded that OCD subjects have an unusually high incidence of left-handedness.
Denckla (1989) reported that 44 of 54 OCD patients, aged 6 to 20, had significantly more total neurological soft signs (mean = 6.2) than did normal controls (mean = 1.5). Fine motor coordination impairment accounted for most of the difference in total soft signs. There were also major
subgroups of subjects with left-sided findings,
neurodevelopmental immaturity (i.e., timed-task slowness, extraneous overflow movements, inattentiveness, and
impulsivity), and choreiform syndrome.
Hollander et al. (1990) examined 41 adult OCD patients and 20 controls with 20 tasks designed to assess four areas: fine motor coordination, involuntary movements, sensory function, and visuospatial function. A comparison of the first half of the OCD patients with the second half revealed that the findings were consistent. OCD subjects had
significantly more soft signs (mean = 5.31) compared with controls (mean = 1.40) including abnormalities of fine motor coordination, involuntary movements, and visuospatial
findings. OCD subjects also had a significant increase in left-sided findings. Hymas, Lees, Bolton, Epps, and Head
(1991) studied OCD patients with obsessional slowness and found subtle neurological abnormalities including loss of motor fluency, hesitancy of initiation of limb movements,
speech and gait abnormalities, cogwheel rigidity, complex repetitive movements, and tics.
Nickoloff, Radant, Reichler, and Hommer (1991) found an increased number of neurologic soft signs in their sample of OCD subjects but these subjects did not exhibit impaired performance of oculomotor function which included several measures of smooth pursuit and saccadic function. Tien, Pearlson, Machlin, Bylsma, and Hoehn-Saric (1992), however, did find that OCD subjects had a significantly greater rate of inaccurate saccades on a goal-guided antisaccade task although there were no differences in reaction time,
saccadic velocity, or accuracy on a visually-guided saccade task. Most of the abnormal findings were among male
patients.
Many disease states or neurologic conditions have been found to be associated with OCD. Wise and Rapoport (1989) reported upon von Economo's description of the
postencephalitic disorders, of which postencephalitic
Parkinson's is likely the most well known, subsequent to the outbreak of viral encephalitis lethargica in 1916-1917.
Although von Econome documented an array of focal lesions caused by this neurotoxin, the basal ganglia were
prominently affected. Many of these patients had pronounced tics, obsessions and compulsions, von Econome thought that the driven, compulsive aspect of these patients' behavior indicated that the lesions responsible for such symptoms were within diencephalic and mesencephalic areas rather than cerebral cortex.
Several studies have reported that the incidence of OCD in patients with Gilles de la Tourette's syndrome ranges from 32% to 90% which is considerably higher than what would be expected (Comings & Comings, 1987; Frankel et al., 1986; Nee et al., 1980, 1982; Pauls, Towbin, Leckman, Zahner, & Cohen, 1986; Pitman et al., 1987). Tourette's patients have a higher than expected incidence of first degree relatives with OCD, irrespective of whether the Tourette proband has OCD (Pauls et al., 1986). About 20% of OCD subjects have chronic motor tics (Jenike, 1989; Swedo, Rapoport, Leonard, Lenane, & Cheslow, 1989). A substantial body of evidence implicates the basal ganglia and related cortical and thalamic structures in the pathophysiology of Tourette's syndrome (Cummings & Frankel, 198 5; Leckman, Knorr,
Rasmussen, & Cohen, 1991). Many of the movement disorders such as tics have clear or suspected pathophysiology of the basal ganglia (Weiner and Lang, 1989).
There has as yet been no autopsy study of primary OCD (OCD not secondary to some other disorder) reported in the literature. There have been only a few autopsy studies of Tourette's Syndrome, the most intriguing of which is the single case study reported by Haber, Kowall, Vonsattel,
Bird, and Richardson (1986). In this study, there was found to be a striking and total absence of woolly fibres which normally react immunologically positive for the dynorphin A neuropeptide in the dorsal part of the external segment of
the globus pallidus. Also, there was only very faint
staining in the ventral pallidum for this peptide. Haber et al. reported that the dynorphin-immunoreactive fibres in the pallidum arise from striatal neurons and note that the
observed phenomenon may be the result of several factors involving the synthesis, metabolism, or transport of this peptide. Haber (personal communication, November 18, 1993) and associates have found this effect in a further four of five autopsy studies of Tourette's syndrome brains. Notably, such a lesion could potentially affect any number of the cortical-basal ganglia-thalamocortical circuits all of which traverse the pallidum.
Sydenham's chorea, a disorder primarily seen in
prepubertal girls and occurring in 10-30% of children with rheumatic fever, is characterized by sudden involuntary jerking movements of the extremities which implicates
dysfunction of the basal ganglia (Swedo, Rapoport, Cheslow et al., 1989). Post mortem studies of Sydenham's chorea have reported perivascular cellular infiltration and neuronal degeneration most pronounced in the striatum (Wise &
Rapoport, 1989). Husby, van de Ryn, Zabriskie, Abdin, and Williams (1976) reported that 50% of patients with
postrheumatic chorea have specific antibodies to caudate and subthalamic nuclei, suggesting that there may be some
An association between Sydenham's chorea and OCD has long been noted (Chapman, Pilkey, & Gibbons, 1958; Grimshaw,
1964). Swedo, Rapoport, Cheslow, et al. (1989) have
recently reported a systematic study of children and
adolescents who had either Sydenham's chorea or rheumatic fever without chorea. Those subjects with Sydenham's chorea had significantly greater obsessionality scores on the
Leyton Obsessional Inventory - Child Version. Three of the 2 3 Sydenham's chorea subjects but none of the 14 rheumatic fever without chorea subjects met diagnostic criteria for OCD. It has also been reported that there is a close
parallel between the onset and remission of choreiform movements and OCD symptoms in this disorder (Rapoport, 1991).
OCD has been associated with various other central nervous system (CNS) disorders and lesions. OCD
symptomatology has occasionally been observed in patients with Huntington's disease (Cummings & Cunningham, 1992) and Parkinson's disease (Hardie, Lees, & Stern, 1984; Tomer, Levin, & Weiner, 1993) , two diseases with well documented lesions affecting the basal ganglia. It is unknown whether such an association may represent any significant elevation of incidence from what may be predicted from base rates of the respective disorders although a review of psychiatric
interviews with over 300 patients with Huntington's
OCD and related obsessive-compulsive phenomena in this population (Rapoport, 1990).
Numerous cases of OCD involving lesions of the basal ganglia associated with anoxic or toxic encephalopathy
(Laplane et al., 1989; Pulst, Walsh, & Romero, 1983;
Weilburg, 1989), vascular infarcts (Croisile, Tourniarie, & Confavreux, 1989; Williams, Owen, & Heath, 1988), or of unknown etiology (Tonkonogy & Barreira, 1989) have been
reported. Some of these studies will be discussed more fully in subsequent sections.
Minsk! (1933) reported on a patient with OCD who had a left frontal tumor whereas Seibyl, Krystal, Goodman, and Price (1989) reported the case of a patient with a right frontal lesion. Eslinger and Damasio (1985) reported on a patient with onset of symptomatology strikingly similar to OCD (although no such diagnosis was made) following
resection of a bilateral orbitalfrontal meningioma. There have been a number of reports of OCD developing after
traumatic head injury (Drummond & Gravestock, 1988; Jenike & Brandon, 1988; Khanna, 1988; McKeon, McGuffin, & Robinson, 1984).
Comparisons between the forced thinking sometimes
experienced ictally in seizure disorder patients as well as the interictal behavioral syndrome described by Bear and Fedio (1977) and the symptomatology of OCD have been made
have been a few case reports of an association between OCD and partial complex seizures (Kanner, Morris, Stagno,
Chelune, & Luders, 1993).
Neuropsvchopharmacoloqical studies.
Most pharmaceutical agents which reduce anxiety, depression or psychosis are not effective in treating OCD
(Insel & Winslow, 1990). The only agents which have been found to be effective in double-blind placebo controlled studies are all potent serotonergic reuptake inhibitors which include clomipramine, fluvoxamine, fluoxetine, and sertraline (Clomipramine Collaborative Study Group, 1991; Greist, 1990; Jenike, 1990c; Winslow & Insel, 1990). The average symptomatic improvement, as measured by OCD rating scales or the proportion of patients considered responders, is approximately 50% but relapse is usually seen if
treatment is discontinued (Liebowitz & Hollander, 1991). Anti-obsessional effects are independent of anti-depressant effects (Insel & Winslow, 1990). Notably, psychological treatment of OCD primarily involving exposure and response prevention has been demonstrated to be approximately as effective as pharmacological intervention but gains made using this treatment modality seem to be more long lasting once treatment is discontinued (Foa, Steketee, & Ozarow, 1985).
It had initially been thought that the mechanism of action of clomipramine was to prolong the action of
serotonin (5HT) at the receptor and, therefore, that OCD involved a serotonergic deficiency (Yarayura-Tobias, Turner, Michelson, & Jacob, 1976). However, more recently, there is evidence that the mechanism of action may be a down-
regulation of serotonergic receptors with chronic administration (Liebowitz & Hollander, 1991) but the pharmacodynamic mechanism producing symptom improvement remains unclear (Barr, Goodman, Price, McDougle & Charney, 1992). Notably, there is not yet any evidence as to
specifically which areas of the brain in OCD have any
serotonergic abnormality. It may be pertinent that there is a dense serotonergic innervation of the basal ganglia
(Molliver, 1987). Insel & Winslow (1990) caution that it is fallacious to deduce the cause of OCD from mechanisms of treatment. Other neurotransmitters and pharmacologic agents continue to be investigated (Austin et al., 1991; Hollander et al., 1991; Lemus & Robinson, 1991; Swedo & Rapoport,
1992) .
The characteristic exaggerated concern about harm to self or others and difficulty in feeling certain in OCD, has been contrasted with the impulsivity and diminished concern over the consequences of one's actions, characteristic of psychopaths or violent suicides. In contrast with the evidence for possibly elevated 5-HT responsivity in OCD,
there is evidence for decreased 5-HT responsivity in
psychopathic and violent suicidal individuals (Brown et al., 1982; Virkkunen, Nuutila, Goodwin, & Linnoila, 1987). Stein, Hollander, and Liebowitz (1993) have recently reviewed the strong evidence for the involvement of serotonin in the spectrum of impulse control disorders which suggests that serotonergic underactivity is related to impulsivity whereas overactivity is related to behavioral inhibition.
Imaging studies.
Seven of nine structural imaging studies of OCD have reported differences between OCD subjects and normal
controls. Most notably, Luxenberg et al. (1988) found
significantly smaller caudate but not lentiform nuclei in a computerized tomography (CT) study of primary OCD. Laplane et al. (1989), in a CT and magnetic resonance imaging (MRI) study of patients with brain damage related to anoxic or toxic encephalopathy, five of whom met criteria for OCD, found bilateral basal ganglia lesions, primarily of the lentiform nuclei (especially the pallidum) but also often involving the caudate. Weilburg et al. (1989) presented the case of a psychology graduate student with onset of OCD in his teens who showed CT abnormalities suggestive of a
putamenal infarct and MRI findings of marked decrease in the volume of the head of the caudate and markedly narrowed
(1989) reported the case of a woman with severe compulsive hand-washing and contamination fears who showed progressive bilateral caudate atrophy on MRI. Contrary to the usually reported finding of decreased volume in basal ganglia nuclei, Scarone et al. (1992) found increased size of the right caudate nucleus with MRI in OCD subjects. Garber, Ananth, Chiu, Griswold, and Oldendorf (1989) reported MRI findings indicative of right frontal white matter
abnormalities in OCD subjects although none of the findings were considered significant radiologic evidence of
neurologic disease.
There have been at least 20 functional imaging studies of OCD reported in the literature, almost all of which
indicate abnormalities of blood flow or metabolic rates in regions of the basal ganglia and/or the prefrental cortex. In a series of studies using positron emission tomography
(PET), Baxter and associates at UCLA (Baxter et al., 1987, 1988, 1989, 1992) have found increased metabolic rates bilaterally for OCD subjects in the head of the caudate nuclei and orbital frontal cortex compared with normal
controls. Notably, the analysis of the data by this research group greatly reduced the probability of Type I errors.
Baxter et al., (1987) found that successful pharmacological treatment resulted in a significant
bilateral increase in metabolic rate of the caudate relative to the rate of the ipsilateral hemisphere. This relative
rate was then significantly elevated compared with controls although there had not been such a difference before
treatment. In another study (Baxter et al., 1992),
successful pharmacological or behavioral treatment resulted in a significant decrease in the metabolic rate of the right head of the caudate nucleus. There was a nonsignificant
trend for such a relative decrease in the left caudate. Changes were not observed in the metabolic rate of the orbitalfrontal area in either of these studies. Baxter et al. (1992) note that in the earlier study most of the OCD subjects also had a major depression. Previous studies have documented lowered metabolic rates in the caudate nuclei of depressed patients (Baxter et al., 1985). Baxter et al.
(1992) suggested that the earlier finding of increased
relative rates of metabolism following successful treatment in OCD subjects was likely due to the lifting of the
depression in that sample of subjects.
There have been several PET studies of OCD conducted at the National Institutes of Mental health (NIMH)
laboratories. Nordhal et al. (1989) found elevated metabolic rates bilaterally in the orbital gyri but not in the caudate nuclei. These researchers also found increased rates in the anterior cingulate and lateral prefrental areas as well as
in some other disparate regions. OCD symptom severity was related to orbital metabolic rates. In a follow-up study
pharmacological treatment, a reduction in the normalized (regional metabolic rate/global gray metabolism) metabolic rate of the left caudate and the orbital frontal cortex was observed as well as an increase in the right anterior
putamen.
In another study, increased metabolic rates in the left orbital, bilaterally in the prefrental and anterior cingulate as well as other disparate regions were found
(Swedo, Schapiro, et al., 1989). There were no significant differences in the caudate or lenticular nuclei although the rates for OCD subjects were higher than in normals in the same areas. Swedo et al. (1992) later rescannned 13 of the subjects from the previous study, after at least one year of pharmacotherapy, and found a significant decrease in
normalized orbitofrontal metabolism bilaterally.
Hindus, Nyman, Mogard, Meyerson, and Ericson (1991) reported on a PET study in which OCD subjects were scanned before and after psychosurgery for alleviation of their symptomatology. Surgery was clinically beneficial and there was a reduction of metabolic rates postoperatively in the orbital gyri and caudate nuclei although OCD subjects had lower metabolic rates preoperatively than controls. A number of possibilities were suggested to explain this later
finding including small sample size and areas of interest that were scanned. However, the favored explanation was that this group of severe intractable OCD subjects who received
psychosurgery had "burned out" and were no longer resisting symptoms which accounted for the lower orbital rates. This and related hypotheses will be examined further in the discussion of models of OCD.
Sawle, Hymas, Lees, and Frackowiak (1991), in a PET study, found focal hypermetabolism in the orbital frontal cortex, premotor cortex, and midfrontal cortex of OCD subjects with obsessional slowing but there were no
significant differences, as compared with normal controls, for the caudate, putamen, or medial frontal cortex- It was suggested that the increased activity in premotor and
midfrontal areas was related to the subjects' internal preparation for movement.
There have been a number of regional cerebral blood flow (rCBF) studies of OCD. Zohar et al. (1989) studied OCD subjects using the xenon 133 inhalation technique under
three conditions: relaxation, imaginai flooding, and in vivo exposure to the feared stimuli. The rCBF increased slightly in temporal cortex with imaginai flooding but decreased significantly in virtually every cortical area (prefrontal, precentral, parietal, temporal, posterior) with in vivo
exposure. Subjective and peripheral autonomic measures of anxiety were highest during the in vivo exposure. It was suggested that higher level cortical processing may be shut down with the onset of obsessional urges.
Rubin, Villanueva, Ananth, Trajmar, and Mena (1992) measured rCBF with the xenon 133 inhalation technique and regional cerebral uptake of technetium 99m d,1-hexamethyl propyleneamine oxime (Tc-HMPAO) by single-photon emission computed tomography (SPECT) in OCD subjects and normal controls. There were no significant differences between
groups on rCBF measures in any of the several cortical areas visualized nor a combined measure of rCBF in the basal
ganglia and thalamus. SPECT revealed increased uptake in OCD patients in the high dorsal parietal cortex bilaterally, the left posterofrental cortex, and the orbital frontal cortex bilaterally. There was reduced uptake in OCD patients in the head of the caudate nucleus bilaterally,
Machlin et al. (1991) also studied OCD subjects using Tc-HMPAO uptake and found elevated medial-frontal but normal orbital-frontal perfusion rates in the OCD subjects.
Successful pharmacological treatment resulted in reduced medial hyperfrontality (Hoehn-Saric, Pearlson, Harris, Machlin, & Camargo, 1991). Hamlin, Swayne, and Liebowitz
(1989) reported a single case study of a patient with severe OCD and obsessional slowing. SPECT revealed decreased tracer deposition in the right basal ganglia and adjacent anterior right temporal lobe which returned to normal values
following successful pharmacological treatment.
Rubin et al. (1992) discussed the differences between their study and that of Machlin et al. (1991) which may have
resulted in the disparity of findings. Of particular import, their study used a scanner with a much higher resolution and OCD subjects were individually matched with normal controls rather than controls being group-matched. Possible
explanations for disparity of results from different PET studies, related to the technology of PET imaging, have been addressed by Baxter and associates (Baxter, Schwartz, Guze, Bergamn, and Szuba, 1990a; Baxter, Schwartz, & Guze, 1991). The possibility of differences related to progressive
neurobiological changes in the disorder will be discussed further in the models section.
Electrohvsioloqical studies.
Electroencephalographic studies have generally found abnormalities in less than 10% of OCD patients (Insel et al., 1983) and have not revealed findings indicative of any specific pathological process (Turner, Beidal, & Nathan, 1985). However, two studies will be mentioned. Flor-Henry, Yeudall, Koles, and Howarth (1979) found evidence of
bilateral frontal, left greater than right, and left
temporal EEG abnormalities in unmedicated OCD subjects. A more recent study found reduced EEG power confined to the delta and beta bandwidths which was considered indicative of some frontal (delta) and posterior (beta) abnormalities
(Kuskowski et al., 1993). In addition, measures of relative activity for homologous areas of each hemisphere revealed
that OCD subjects had reduced EEG power in right hemisphere sites.
Event related potential (ERP) studies have indicated increased cortical arousal and especially left frontal dysfunction (Shagass, Roemer, Straumanis, & Josiassen, 1984). Abnormalities of N200 and P300 components (shorter latencies and smaller amplitudes) have been found with OCD subjects which are more marked with increasing complexity of information processing required (.Ciesieliski, Beech, &
Gordon, 1981; Beech, Ciesielski, & Gordon, 1983; Towey et al., 1990). Malloy, Rasmussen, Braden, and Haier (1989) measured visual ERFs in a go-no go task and found
significantly smaller P300 amplitudes in orbital frontal areas during the presentation of the no go stimulus in OCD subjects.
Electrical stimulation of the anterior cingulate gyrus has been reported to result in integrated motor behavior, some of which has a forced obsessional quality (Talairach et al., 1973). Grey-Walter (1966) had earlier concluded on the basis of a large number of electrical stimulation studies that overactivity in the frontotemporal system resulted in affective disturbance (especially anxiety) whereas
overactivity of the cingulate system led to obsessive- compulsive and ritualistic behavior.
The results of various psychosurgical procedures have provided further evidence for the neural substrate of OCD. Lewin (1973), in a review of 182 cases, cited dramatic evidence of mixed depressive-obsessional cases where, in turn, the depressive and then the obsessive symptoms
resolved after bilateral sequential orbital and cingulate lesions. Flor-Henry (1975), in his review of the literature, also concluded that anterior cingulotomies were the most effective procedure in treating OCD. Tippin and Henn (1982) reviewed studies involving 110 OCD patients in which
modified leukotomy led to improvement in 81% of patients, half of whom were in complete remission. In this procedure, the medial 2 to 3 cm of white matter, coming through the anterior cingulate, was severed which was thought to act by disrupting thalamofrental tracts. O*Callaghan and Carroll
(1982), in their review, concluded that lesions of the cingulate gyrus and lower medial quadrant of the frontal lobe were generally the most useful. Khanna (1988) concluded that procedures which resulted in isolation of the frontal cortex have generally been found to be effective.
Wise and Rapoport (1989), in their review of 29 published reports of psychosurgical treatment with OCD, reported that although no studies were ideal, the best documented were those using anterior capsulotomy or
cingulotomy. Anterior capsulotomy involves bilateral basal lesions of the anterior limb of the internal capsule which
interrupts frontal cingulate projections as well as
reciprocal connections of orbital frontal with dorsomedial and related thalamic nuclei. The target zone for the lesion lies within the striatum, adjacent to the caudate nuclei. Cingulotomy involves lesions of the anterior portion of the cingulate gyrus, interrupting fibres between cingulate gyrus and frontal lobes and other efferent projections of the
anterior cingulate. Jenike (1990b) cited a review of over 325 cases of bilateral anterior internal capsulotomy by Hindus (1986) in which 70% of patients experienced a significant reduction in target symptoms.
Ballantine et al. (1987) reported the results of a retrospective study of 198 patients who had received bilateral cingulate lesions for various psychiatric disorders. Although 25% of the OCD patients were functionally well following this operation, 50% of nonobsessive anxiety disorder patients were also functionally well. It was suggested that anterior
cingulotomy is more effective in the relief of anxiety than in the relief of obsessive-compulsive symptomatology.
Chiocca and Martuzza (1990), in a review of the literature, reported that there are currently four psychosurgical
procedures used to treat OCD: anterior cingulotomy, subcaudate tractotomy, limbic leukotomy, and anterior capsulotomy. Subcaudate tractotomy involves bilateral stereotactic lesions in the rostral part of the orbital
cortex ventral to the head of the caudate nucleus, a region which coincides with the substantia innominata. Although it was initially believed that this operation resulted in
interrruption of tracts connecting frontal cortex with the hypothalamus and amygdala, it may also have interrupted frontal-striatal pathways. Limbic leukotomy was defined as combined bilateral lesions in the lower medial quadrant of the orbitofrontal areas and bilateral lesions of the
anterior cingulate bundle. Chiocca and Martuzza (1990) concluded that anterior cingulotomy and subcaudate
tractotomy led to improvement in approximately half of the reported cases, limbic leukotomy in over 80% of cases, and anterior capsulotomy led to improvement in 50 to 7 0% of cases.
Summary of the evidence for the neural substrate in obsessive-compulsive disorder.
In summary, there is considerable evidence from several sources that there is a biological basis of OCD and that some specific neural substrate may mediate symptomatology. Such evidence has led to the widely held opinion that OCD is the model neuropsychiatrie disorder (Barr et al., 1992). Although there has been inconsistency in the findings of various studies concerning precisely what structures are involved, several lines of converging neurobiological evidence suggest that the neural substrate of OCD may
primarily involve components of cortical-basal ganglia- thalamocortical circuitry. The evidence for involvement of the basal ganglia and orbitofrontal areas may be the
strongest although other structures are also implicated.
Neuropsychological Investigations of Obsessive-Compulsive Disorder
There have been several neuropsychological
investigations of OCD, almost all of which have purported to document specific deficits indicative of some pattern of abnormal brain functioning. Interpretations of test deficits have variously been attributed to dysfunction of the
dominant hemisphere, the nondominant hemisphere, the frontal lobes, and subcortical components of frontal system
circuitry, the basal ganglia.
Dominant hemispheric dysfunction.
Some researchers have concluded that there is evidence for dominant hemispheric dysfunction in OCD. Flor-Henry, Yeudall, Koles, and Howarth (1979) administered an expanded Halstead-Reitan test battery (Reitan & Wolfson, 1985) to OCD subjects and normal controls. OCD subjects had impaired
performance on the Aphasia Screening Test (Reitan, 1979), the Purdue Pegboard (Tiffin, 1968), Colored Progressive Matrices (Raven, 1947), a Symbol Gestalt test, the Category
Test (Reitan & Wolfson, 1985), minute estimation, the
Tactual Performance Test (TFT) (Reitan & Wolfson, 1985), and the Wechsler Adult Intelligence Scale (Wais) (Wechsler,
1955) digit span and digit symbol subtests. There was notably no typical profile of abnormal test results and there was much variability. However, the results were
interpreted as indicating bilateral frontal dysfunction, left greater than right, according to rules of
interpretation provided by Reitan (1959) and Royce, Yeudall, and Bock (1976). Rapoport et al. (1981), in a descriptive study of nine adolescent OCD subjects, found a lack of left ear advantage in a dichotic listening task which was
suggestive of dominant hemisphere dysfunction.
Ludlow, Bassaich, Connor, and Rapoport (1989) explored the possibility of language impairment in adolescent OCD subjects in detail. A large number of measures were
administered including an adaptation of the Neurosensory Center Comprehensive Examination for Aphasia (Spreen &
Benton, 1969), The Token Test (DeRenzi & Vignolo, 1962), the Reporters Test (DeRenzi, 1978), the Boston Naming Test
(Borod, Goodglass, & Kaplan, 1980), subtests of the Goldman- Fristoe-Woodcock Auditory Skills Battery (Goldman, Fristoe, & Woodcock, 1974), and a dichotic listening task for speech syllables. It was concluded that there was no primary
impairment in language function and specific deficits that were documented did not resemble any known pattern of
aphasia. There were no significant relationships between measures of symptom severity and linguistic testing.
Ludlow et al. (1989) noted that each of the tasks that OCD subjects had difficulty with required mental
manipulation of knowledge in one form or another. It was suggested that the results of the current study as well as previous studies have demonstrated that differences between OCD subjects and normal controls is more marked with
increasing task complexity and that OCD subjects have difficulty in adopting efficient information processing strategies. Other researchers have also suggested that OCD subjects have particular difficulty with tasks involving mental manipulation and processing of complex information
(Gordon, 1985; Liebowitz & Hollander, 1991).
Nondominant hemispheric dvsfunction.
Several studies have concluded that there may be
nondominant hemispheric dysfunction in OCD, largely on the basis of deficits in various aspects of nonverbal processing ability. Insel et al. (1983) found that more than half of their sample of OCD subjects scored in the impaired range on the Tactual Performance Test. Diamond, Albrecht and Borison
(1988) found abnormalities on a complex figure test.
Hollander et al. (1990) found that OCD subjects performed more poorly than controls on a cube drawing task, and that the number of errors on the Benton Visual Retention Test
(Benton, 1974) was significantly correlated with the total number of neurological soft signs.
Zielinski, Taylor and Juzwin (1991) studied a select sample of OCD patients, nine of 21 who were being treated with psychoactive medication at the time of testing. No significant differences in test performance were found between those OCD subjects receiving medication and those who were not. In comparison with normal controls, OCD subjects had mild difficulty with the span of immediate recall on the Corsi blocks (Corsi, 1972), OCD subjects had difficulty learning the repeating sequence on the Corsi blocks and often reported feeling overwhelmed by this task. Although there was no difference between groups on the number of figures recalled on The Kimura Recurring Figures
(Kimura, 1963) for either immediate or delayed conditions, OCD subjects had more false positives. OCD subjects also made more errors on nonsense figures than on geometric
designs. Notably, the Recurring Figures Test was included in this test battery because Poulos and Wilkinson (1984) had
suggested that visual imagery may be important in the ability to recall prior actions, a problem that may be
involved in checking behavior of OCD subjects,
Zielinski et al. (1991) found that OCD subjects made more errors on a short form of the Raven's Standard
Progressive Matrices (Raven, 1986) but these were on the easier items of the test. There were no difference between
groups on any of the several measures of the California Verbal Learning Test (Delis, Kramer, Kaplan, Ober, & Fridlund, 1987) except that the OCD subjects had more intrusions. OCD subjects did not perform more poorly than normal controls on measures of phonemic word fluency, Design Fluency (Jones-Gotman & Milner, 1977), sustained attention and vigilance as measured with a continuous performance test, or number of categories achieved or total errors on the Wisconsin Card Sorting Test (WCST) (Berg, 1948). Ratings of OCD symptom severity and neuropsychological performance did not significantly correlate and neither state nor trait anxiety were significantly related to neuropsychological performance. Results of this study were interpreted
primarily in terms of nondominant hemispheric dysfunction. Although corrections for multiple statistical comparisons was not made, it was argued that there was a consistent pattern of visual-spatial deficits.
Boone, Ananth, Philpott, Kaur, and Djenderedjian (1991) studied medication free OCD subjects who had never required medication on a regular basis. OCD subjects had a minimum total score of ten on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) (Goodman & Price, 1990) but the mean ratings on this scale were not reported. As such, this OCD sample may have been only mildly affected. A battery of tests designed to assess frontal lobe ability, memory and
