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Obsessive-Compulsive Disorder: Boundary Issues

Naomi A. Fineberg, MBBS, MA, MRCPsych, Sanjaya Saxena, MD, Joseph Zohar, MD, PhD, and Kevin J. Craig, MBBCh, MPhil, MRCPsych


CNS Spectr. 2007;12(5):359-364,367-375

Faculty Affiliations and Disclosures

Dr. Fineberg is visiting professor at the Postgraduate School of Medicine at the University of Hertfordshire and consultant psychiatrist at Queen Elizabeth II Hospital in Welwyn Garden City, United Kingdom, and senior research fellow in the Department of Psychiatry in the School of Clinical Medicine at the University of Cambridge in the UK. Dr. Saxena is associate professor in the Department of Psychiatry at the University of California, San Diego School of Medicine in La Jolla. Dr. Zohar is professor of psychiatry at Chaim Sheba Medical Center in Tel-Hashomer, Israel. Dr. Craig is clinical research associate in the Behavioural and Clinical Neuroscience Institute at the University of Cambridge and honorary consultant psychiatrist at Addenbrooke’s Hospital in Cambridge. 

Disclosures: Dr. Fineberg receives grant/research funding from Cephalon, GlaxoSmithKline, and Lundbeck and is on the speaker’s bureaus of AstraZeneca and Lundbeck. Drs. Saxena and Zohar do not have an affiliation with or financial interest in any organization that might pose a conflict of interest. Dr. Craig receives grant/research support from GlaxSmithKline.

Funding/Support: Dr. Saxena receives support from National Institute of Mental Health grant 5R01 MH69433-03.

Submitted for publication: March 13, 2007; Accepted for publication: April 4, 2007.

Please direct all correspondence to: Naomi A. Fineberg, MBBS, MA, MRCPsych, University of Hertfordshire, Postgraduate School of Medicine, Queen Elizabeth II Hospital, Welwyn Garden City,  UK AL7 4HQ; Tel: 44-0-1707365085; E-mail:

Focus Points

• Obsessive-compulsive spectrum disorders (OCSDs) share similarities with many psychiatric disorders.
• An endophenotype model will allow improved differentiation of OCSDs.
• Dopaminergic dysregulation in corticostriatal circuits seems central to OCSDs.


The boundaries between obsessive-compulsive disorder (OCD) and other neuropsychiatric disorders remain unresolved and may well differ from one disorder to another. Endophenotypes are heritable, quantitative traits hypothesized to more closely represent genetic risk for complex polygenic mental disorders than overt symptoms and behaviors. They may have a role in identifying how closely these disorders are associated with another and with other mental disorders with which they share major comorbidity. This review maps the nosological relationships of OCD to other neuropsychiatric disorders, using OCD as the prototype disorder and endophenotype markers, such as cognitive, imaging, and molecular data as well as results from demographic, comorbidity, family, and treatment studies. Despite high comorbidity rates, emerging evidence suggests substantial endophenotypic differences between OCD and anxiety disorders, depression, schizophrenia, and addictions, though comparative data is lacking and the picture is far from clear. On the other hand, strong relationships between OCD, Tourette syndrome, body dysmorphic disorder, hypochondriasis, grooming disorders, obsessive-compulsive personality disorder, and pediatric autoimmune neuropsychiatric disorders associated with streptococcus are likely. Studies designed to delineate the cause, consequences, and common factors are a challenging but essential goal for future research in this area.


The current debate about where obsessive-compulsive disorder (OCD) best belongs in psychiatric classification has highlighted an interesting paradox. While OCD is currently classified by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision1 as an anxiety disorder, a growing corpus of literature has emphasized the role of corticostriatally mediated control and reward systems in the pathophysiology of OCD.2 The focus has, thus, shifted from learning models in which anxiety-driven obsessions entrain neutralizing compulsions to an emphasis on the primacy of obsessional thoughts and compulsive behaviors as disorders of basal ganglia dysregulation. Moreover, the serotonin (5-HT) hypothesis for OCD,3 derived largely from clinical psychopharmacologic response data, has not been satisfactorily substantiated by a growing body of molecular imaging and genetic evidence that points to dopaminergic dysfunction as a candidate etiological factor.4-6 In turn, this has prompted the move toward conceptualizing OCD as a prototype disorder for a group of “obsessive-compulsive spectrum disorders” (OCSDs),7 for which failures of behavioral (cognitive and motor) inhibition constitute a key characteristic.

In the DSM-IV-TR, OCD is categorized as an anxiety disorder. A central role for anxiety in mediating symptoms was argued: obsessions were considered to contribute to escalating anxiety and compulsions performed to avoid or reduce this anxiety.8 Moreover, the observation that OCD frequently coexisted with other anxiety disorders (simple phobia [22%], social phobia [18%], and panic disorder [12%])9,10 was thought to reflect a common etiological basis. In contrast to the DSM-IV-TR, the International Statistical Classification of Diseases, Tenth Edition recognizes anxiety with and without autonomic arousal to be common, but not essential features of OCD, and separates OCD from other anxiety disorders, placing it as a separate illness within with the group of neurotic, stress-related, and somatoform disorders.

Mental disorders can be difficult to define on the basis of phenomenological grounds, owing to substantial overlap between the content and form of symptoms across so many disorders.11 The comorbidity argument is also limited by diagnostic systems based on phenotypic symptoms (similarities in phenomenology and comorbidity rates could argue equally well for inclusion of OCD into affective disorders, psychotic disorders, and, even, addiction). Endophenotypes, representing measurable intermediate markers on the pathway between the phenotype and the distal genotype, have been proposed to be more biologically meaningful than phenotypes and have so far shown promise in identifying specific inherited aspects of non-psychiatric illness, such as heart disease.12 Arguably, the identity and relationship between OCD and other neuropsychiatric disorders may be better understood by mapping the disorders across a number of key endophenotypic domains, including outcomes on tests of neurocognition, brain imaging, and molecular mechanisms.13 By so doing, an endophenotype profile or “grid” for each individual disorder can be constructed (Table 1) and used as a benchmark against which the other disorders can be compared.

The aim of this review is to map out the nosological boundaries of OCD. Using OCD as the prototypic disorder and applying the endophenotype-grid model as systematically as possible within the limitations of available data, we will attempt to identify important cognitive, imaging, and molecular findings that link or distinguish OCD from other neuropsychiatric disorders, including anxiety disorders, depression, schizophrenia, and putative obsessive-compulsive spectrum disorders (OCSDs), such as body dysmorphic disorder (BDD), hypochondriasis, grooming disorders, Tourette syndrome (TS), obsessive-compulsive personality disorder (OCPD), and poststreptococcal neuropsychiatric syndromes.

Comparison Between Obsessive-Compulsive Disorder and Other Mental Disorders

Obsessive-Compulsive Disorder Versus Axis I Disorders: Anxiety Disorders


Whereas in clinical samples the gender ratio of OCD is roughly equal, females predominate in community populations (~1.5:1), though not to the same extent as in other anxiety disorders (2–3:1), perhaps reflecting greater illness severity in males. Males predominated in a sample of clinical cases of early-onset OCD,10 whereas in the large-scale epidemiological analysis by Wittchen and Jacoby15 there was an equal gender ratio in individuals 35–49 years of age, but females predominated in the 18–34 years of age and 50–65 years of age ranges. Lochner and colleagues16 compared clinical and genetic data across gender and found that males with OCD showed an earlier onset and a trend toward more tics and poorer outcome, different symptom profiles, and different genetic polymorphisms. The meta-analytic study by Pooley and colleagues6 also identified sexual dimorphism in relation to catechol-O-methyltransferase (COMT) gene polymorphisms, implying that gender contributes to the clinical and biological heterogeneity of OCD. The earlier age of onset and stable course of OCD also differentiates OCD from other anxiety disorders ( Table 2).


In epidemiological samples, comorbid OCD is twice as common (1.4%) as non-comorbid OCD (0.7%).17 Table 3 shows the disorders that most commonly coexist in individuals with clinical cases of OCD. Although comorbidity with anxiety disorders is relatively common,9 Richter and colleagues18 found greater lifetime rates of comorbid OCSDs, such as tic disorders, BDD, trichotillomania, skin-picking, and eating disorders in OCD patients (37%), compared with patients with panic disorder and social anxiety disorder, suggesting specificity for co-segregation of OCSDs above anxiety disorders in general.

Family Studies

Family studies19 have shown that, in families with an OCD proband, there are higher than expected rates of anxiety disorders, including panic disorder, generalized anxiety disorder (GAD), agoraphobia, separation anxiety, and recurrent major depressive disorder (MDD), implying either a common cause or a consequential link. In some studies,20,21 GAD and agoraphobia occurred more frequently, even in case relatives who did not have OCD, suggesting that these disorders share a familial etiology. However, other studies found no increased rate of anxiety disorders in unaffected relatives of OCD patients compared with relatives of controls, calling into question the idea of a familial association between OCD and anxiety disorders. In a study by Carter and colleagues,20 rates of panic disorder, GAD, and MDD were higher only among case relatives with OCD but not in those without OCD, leading the authors to suggest that anxiety and depression may have occurred in these relatives as a consequence of having OCD, rather than due to a shared inherited etiology.


Functional brain imaging research has led to a greater understanding of the neurobiological mediation of OCD. Various positron emission tomography (PET) studies of OCD22 have found elevated glucose metabolic rates in the orbitofrontal cortex, anterior cingulate gyrus, caudate nuclei, and thalamus that normalize with response to treatment. Interventions that provoke OCD symptoms have been found to increase activity in these same brain regions.23-26 These and other findings2,27 have led to the theory that the symptomatic expression of OCD is mediated by hyperactivity along specific, frontal-subcortical circuits connecting the orbitofrontal cortex, ventromedial caudate, globus pallidus, and the medial dorsal nucleus of the thalamus.

In contrast to OCD, the brain circuits most often found to be dysfunctional in anxiety disorders are thought to involve the amygdala, which processes the emotional response to threat, the hippocampus, which is involved in fear conditioning, and more diffuse pathways subserving attention and arousal.28 Abnormal activation of the amygdala and hippocampus has been reported in social anxiety disorder, both in emotion-processing29 and symptom-provocation studies.30,31 In contrast, most symptom-provocation studies in OCD have not found the amygdala to be abnormally activated (see Saxena and colleagues22 for review). Few imaging studies32 have directly compared OCD with other anxiety disorders on tests of neuronal circuitry. Lucey and colleagues33 compared OCD patients with groups of patients with panic disorder, posttraumatic stress disorder (PTSD), and healthy controls and found significant differences between OCD patients and the other three groups in cerebral blood flow to the caudate nuclei. Overall, neuroimaging research indicates that the pathophysiology of OCD differs from that of other anxiety disorders.28,32

By the same token, few studies have directly compared OCD with anxiety disorders on neurocognitive tasks. Individuals with OCD were more impaired than those with panic disorder on a range of executive tasks in four studies.34-37 GAD patients were included in one study and did not separate from controls.34 Social anxiety disorder patients showed similar or worse impairment than OCD on some executive tasks,34,38 suggesting a closer relationship between these two disorders (Table 4).


The robust selectivity of the pharmacotherapeutic response for serotonergic agents has distinguished OCD from depression and anxiety disorders, for which a wider range of medications are known to be effective and has implicated 5-HT in the mechanism of the treatment effect.39 Randomized controlled trials of anxiolytic drugs, such as benzodiazepines40 and buspirone,41,42 do not show efficacy in treating OCD. Anxiogenic challenges, such as yohimbine,43 sodium lactate, caffeine, carbon dioxide,44 and pentagastrin and cholecystokinin,45 do not exacerbate OCD symptoms.

Although the OCD phenotype shows some overlap with anxiety disorders in terms of shared symptoms, comorbidities, and family history, important differences, including age of onset, gender bias, differing functional neuroanatomy, and neuropsychological deficits cast question on its membership of the anxiety disorders group.46

Obsessive-Compulsive Disorder Versus Depression

Depression and anxiety frequently overlap. Lifetime prevalence rates for comorbid mood disorders in OCD are reported as high as in MDD (66%), dysthymia (26%), and bipolar disorder (10%).9,10 Comorbid MDD usually follows the onset of OCD and, like OCD, responds selectively to selective serotonin reuptake inhibitors (SSRIs). Comorbid depression is also characterized by different symptoms and imaging profiles from non-comorbid MDD,22 hinting it may be integral to OCD.47

OCD often starts in childhood and runs a chronic course, while depression has a peak age of onset in adulthood and tends to be episodic. Episodic OCD, with complete inter-episodic recovery, has been reported in up to 25% cases48 and is thought to share a possible association with bipolar affective disorder.49 OCD can be distinguished from MDD by its selective pharmacotherapeutic response to SSRIs,39 including the tricyclic antidepressant clomipramine and SSRIs. These drugs are effective even when depression is rigorously excluded in the reference population, implying a specific anti-obsessional effect. Antidepressant drugs lacking these properties, such as other tricyclics (eg, amitriptyline, nortriptyline, etc.) and monoamine oxidase inhibitors (clorgyline, phenelzine, etc.) have been found to be ineffective for OCD.50 Studies investigating lithium and electroconvulsive therapy have also not produced positive findings.39 

The treatment effect is slow and gradual in OCD, with a linear, incremental pattern of improvement that also appears different from depression. Dose-finding studies51-53 have suggested that higher doses are required (eg, citalopram 60 mg/day, fluoxetine 60 mg/day, paroxetine 60 mg/day, and sertraline 200 mg/day) than those usually used to treat depression or anxiety disorders.39 Unlike depression and social anxiety disorder,54 tryptophan depletion does not seem to precipitate the reemergence of symptoms in SSRI-treated cases of OCD55 or changes in cortisol sectretion,56 casting doubt on the essential role of 5-HT in the mechanism of treatment effect.

Trait-like deficits in cognitive flexibility and motor inhibition have been consistently demonstrated in non-depressed patients with OCD and their unaffected relatives.57 It has been suggested that these deficits may represent distinct neuropathology of the lateral orbitofrontal-subcortical circuit in OCD.2,27 Similarly, patients with bipolar disorder and MDD show deficits in cognitive flexibility58,59 and attentional set shifting.60 In affective disorders, as with OCD, these deficits seem to be trait-like, in that they remain when patients are euthymic and are also found in euthymic first-degree relatives.61 These findings, along with anatomical studies in bipolar patients suggest overlapping pathology in the lateral prefrontal cortex. Conversely, the deficits in motor inhibition on tests, such as the stop signal reaction-time task, found to be associated with OCD62 do not seem to occur in depression, whereas verbal learning has been identified as a state marker for depression and bipolar disorder60 but remains intact in OCD.

The relationship between OCD and depression is complex. Areas of convergence include comorbidity, response to serotonergic treatment, deficits in cognitive flexibility, and attentional set shifting. On the other hand, OCD has an earlier onset, a different mechanism of response to SSRIs, a different pattern of structural and functional brain abnormalities, and impairments in motor inhibition that distinguish it from affective disorders (Table 2). However, there may be a common underlying factor leading to vulnerability to both disorders (eg, trait neuroticism or abnormal 5-HT neurocircuitry) that explains the high level of comorbidity and unusual profile of the comorbid disorder.

Obsessive-Compulsive Disorder Versus Schizophrenia

In the past, OCD was thought to have more in common with psychotic disorders than we recognize today. For a long time, European psychiatrists held that anxiety, depression, and repetitive behavior were less important than the delusional qualities, magical rituals, psychosocial disability, absence of insight, persistence of certain themes (religion, sex, and violence), hallucinatory experiences, and motor disorders in the understanding of OCD.63

Like OCD, schizophrenia develops in early adulthood, runs a chronic course, and shows roughly equal gender ratios in clinical cohorts. Co-occurrence of OCD, bizarre grooming, and hoarding in schizophrenia is well recognized.64,65 It remains unclear whether the observed overrepresentation of obsessive-compulsive symptoms (OCS) in schizophrenia reflects true comorbidity, more severe illness, or distinct neuropsychological substrates unique to this group.


There is convergent evidence that schizophrenia involves dysfunction of the dorsolateral prefrontal cortex,66-70 whereas OCD involves overactivity of the orbitofrontal cortex22,23-26,71 and perhaps also some parts of the dorsolateral prefrontal cortex.2 Deficits in working memory and “cortical hypofrontality,” which characterize schizophrenia, are not found in OCD.

Numerous studies14,72-74 have compared the profiles of neurocognitive deficits in patients with schizophrenia only versus patients with both schizophrenia and OCD or OCS. Most, but not all, of these studies have revealed more severe neuropsychological impairments in the patients with both conditions (Table 5). Several studies14,72,73 have reported greater impairment of executive function, as measured by performance on the Wisconsin Card Sorting Test, in patients with schizophrenia and OCS than in those with schizophrenia only. A recent study comparing executive function in patients with both schizophrenia and OCD with that in patients with schizophrenia only or OCD only suggested that rather than having a unique pattern of neuropsychological deficits, the group with both conditions was more impaired than the other two groups across several neuropsychological domains.74 Preliminary results from another study by Poyurovsky and colleagues (M. Poyurovsky, MD, written communication, 2006), which attempted to match subjects for degree of illness severity, demonstrated abnormal results on the Wisconsin Card Sorting Test for those with schizophrenia only and schizophrenia with OCD, but not OCD only, and impairment on the Iowa Gambling Task for those with schizophrenia with OCD and OCD only, but not schizophrenia only. These findings support a “pathophysiological double jeopardy” in the overlap group.


Family and genetic studies have not found any familial relationship or shared etiology between OCD and schizophrenia. Interestingly, specific genotypes of polymorphisms of the same gene may differentially confer risk for the two disorders. The COMT gene contains a functional polymorphism (Val75 Met) that determines high and low activity of this enzyme, which impacts cognition and psychiatric illness. Homozygosity for the low-activity (Met) allele is associated with a three- to four-fold reduction of the COMT enzyme activity compared with homozygotes for the high-activity valine (Val) variant, resulting in reduced degradation of synaptic catecholamines in individuals with the Met allele. Recent evidence suggests6,76 an association between the Met allele and males with OCD. Met75 alleles may also be associated with an advantage in memory and attention but have also been linked with increased pain sensitivity and hoarding.77,78 Conversely, those with Val75 alleles have increased COMT activity and lower prefrontal extracellular dopamine compared with those with the Met substitution. Val homozygotes perform poorly on measures of working memory and have an increased incidence of schizophrenia. However, Val75 alleles may be associated with an advantage in the processing of aversive stimuli, set switching, and cognitive flexibility where rapid disengagement from stimuli is beneficial. Thus, Val alleles may confer protection against OCD and pain susceptibility, while Met alleles may confer protection against schizophrenia (although the data remain controversial).79

In summary, OCS are common in schizophrenia and there are clear similarities in terms of natural history and endophenotypic factors (Table 2). Both conditions respond to antipsychotics,80 although only as an adjunct to SSRI treatment in the case of SSRI-resistant OCD. But the disorders differ considerably in phenomenology, neurobiology, genetics, and treatment response. Important differences in COMT polymorphisms that may confer reciprocal cognitive vulnerability to OCD or schizophrenia merit further exploration across these disorders.

Obsessive-Compulsive Disorder Versus Addictive Disorders

Compulsive behavior has much in common with addictive disorders. A central feature in both is the loss of control over behavior, which significantly impairs everyday functioning. However, in contrast to compulsive drug use, the compulsions of OCD are not inherently pleasurable to perform. Moreover, the compulsions of substance dependence are driven by craving rather than obsessive fears. Drug addiction has been characterized as a transition from voluntarily initiated recreational drug use to a maladaptive pattern of compulsive drug-seeking and uncontrolled drug intake.81 Chronic drug users experience compulsions in the form of intense urges to consume the drug, which they fail to resist, even in face of the adverse consequences precipitated by further drug use.

Brain imaging studies have found some overlap in dopaminergic abnormalities in the two conditions. Studies using PET in medication-naïve OCD patients4,82 and chronic drug users,83,84 have revealed reduced levels of dopamine (D)2 receptors in the striatum in both patient groups compared with healthy volunteers. These data are compatible with the notion that compulsive and addictive behaviors may be driven by abnormal function of the same underlying brain systems, namely the ascending dopaminergic projections into fronto-striatal circuitry.85 PET radioligand studies in medication-naïve OCD patients86 have also shown higher dopamine transporter binding in the striatum. These data are consistent with a model of compulsive and addictive behavior sharing dopamine overactivity in ascending pathways involving D2/3 receptors. On the other hand, OCD is characterized by increased orbitofrontal corticostriatal activity,22,23-26,71,91 whereas substance use disorders are typically associated with decreased orbitofrontal activity.92

Chronic drug use is harmful to the brain, and can be associated with a range of neuroadaptive and neurotoxic effects in the prefrontal cortex and limbic system.93 One putative effect of these changes is a progressive breakdown of inhibitory control implemented by this circuitry.94 There is significant overlap in impaired performance in measures of inhibitory control between chronic drug users95,96 and OCD.62

In conclusion, different forms of compulsive behavior are central to OCD and addictive disorders. Dopaminergic dysfunction in fronto-striatal circuits has been found in both, as has impaired performance on neurocognitive tests of behavioral inhibition. However, baseline abnormalities in brain function differ markedly between the conditions. Furthermore, there is no familial or genetic association between OCD and substance use disorders, and they differ greatly in their psychopharmacology. Dopaminergic drugs can both exacerbate and remediate compulsive behaviours in the context of several therapeutic areas. Compulsive gambling is considered a behavioural addiction. It shares many characteristics with substance addiction, and a suggested comorbidity with OCSDs.97-99 A survey of cases of compulsive gambling, induced by dopamine agonist medications in Parkinson’s disease revealed a close link between occurrence of gambling and D3 preferent medications.100 Conversely, a selective D3 antagonist SB-277011-A has been shown to successfully attenuate drug-seeking behaviour on a rodent model.101  The behaviourally opposite effects of agonist and antagonist drugs acting at D2/D3 receptors may thus be understood in terms of their opposing modulatory effects on fronto-striatal systems.

Obsessive-Compulsive Disorder Versus Hypochondriasis, Body Dysmorphic Disorder, and Grooming Disorders.

Obsessional fears and compulsive checking are central features of hypochondriasis and BDD. Grooming disorders, such as trichotillomania, skin-picking, and nail-biting, are characterized by a loss of motor control over irresistible urges and are associated with a prior build-up of tension that is temporarily relieved by enacting the behavior. There is significant comorbidity in clinical cohorts between patients with OCD as a primary diagnosis and these disorders (eg, trichotillomania [12.9%], hypochondriasis [8.2%] and BDD [12.9%]).102 Of those with a primary diagnosis of BDD, 30% also fulfilled criteria for OCD.103  In TTM females outnumber males by three to one.104 These disorders seem to share a specific familial relationship with OCD. Bienvenu and colleagues105 found increased rates of hypochondriasis, BDD, and grooming disorders in families of OCD probands relative to controls. However, there was no familial association between eating disorders or impulse control disorders and OCD.106

In contrast to OCD, these disorders have higher rates of poor insight, over-valued ideation, delusions, and ideas of reference.107,108 While hypochondriasis and BDD have a similar profile of selective responsivity to high-dose SSRIs109,110 and cognitive-behavioral therapy (CBT) utilizing exposure- and response-prevention techniques.111,112 Of those with a primary diagnosis of BDD, 30% also fulfilled criteria for OCD.103 In trichotillomania, females outnumber males by 3:1.104 These disorders seem to share a specific familial relationship with OCD. Moreover, the CBT method with the best results for trichotillomania and skin-picking is habit reversal rather than exposure and response prevention.113,114 

Trichotillomania and hypochondriasis may also differ significantly from OCD in their neurobiology and pathophysiology. A neurocognitive study comparing trichotillomania with OCD115 suggested more limited and specific failures of behavioral inhibition in the former using tests sensitive to cortical function. In contrast to OCD, where the major neuroimaging findings have implicated the caudate and orbitofrontal cortex, imaging studies in trichotillomania have reported decreased activity and volume in the putamen28,116 and cerebellum.117,118 Rauch and colleagues119 reported enlarged white matter volume and altered asymmetry in the caudate nucleus—an area implicated in OCD—in patients with BDD. A study by van den Heuvel and colleagues120 compared OCD with hypochondriasis and panic disorder using an emotional Stroop task. Although all disease groups showed activation of the amygdala relative to controls, only OCD showed decreased performance on color related words, which was accompanied by activation of posterior brain regions, and a specific neural response in mainly ventrolateral brain regions and the amygdala. In contrast, patients with panic disorder and hypochondriasis displayed no interference for incongruent versus congruent words but showed a more generalized attentional bias for negative stimuli (panic-related and OCD words), involving both ventral and dorsal brain regions. Patients with panic disorder also showed amygdala activation limited to panic-related words. Thus, while there is evidence that these body-focused symptoms cluster together in patients with OCD, they seem to have different cognitive substrates.121,122

Obsessive-Compulsive Disorder Versus Tourette Syndrome

Tics are involuntary movements or vocalizations driven by premonitory urges. They constitute the core feature of TS, a relatively rare juvenile-onset disorder that emerges in childhood (2–18 years of age) and affects males more than females in a ratio of 1.5–3:1. In contrast to tics, the compulsions of OCD are goal-directed and aimed at preventing or reducing distress or a dreaded event. TS and chronic tic disorders are frequently comorbid with OCD and associated with symmetry and hoarding compulsions in particular.123-125 TS occurs in roughly 7% of patients with OCD as a primary diagnosis.9 Conversely OCS are common in patients with TS, with rates as high as 50% in children.126 Tic disorders, including TS, are also more common in first-degree relatives of patients with OCD106 and vice versa.127 Juvenile-onset OCD with symmetry and hoarding symptoms, male gender, and the presence of tics has been proposed as a poor prognosis subtype of OCD.128,129 Leckman and colleagues130 found evidence for at least three subsets of OCD with differing family histories: OCD with a family history of tic disorders, OCD with a family history of OCD, and OCD with no family history of tics or OCD. The close relationship between TS and OCD has also been reflected in candidate gene studies.127,131 Zhang and colleagues132 investigated compulsive hoarding (a subtype of OCD) in a study of 77 sibling pairs concordant for TS. Hoarding in TS was associated with regions on chromosomes 4q, 5q, and17q. However, sibling pairs were not concordant for the hoarding phenotype, suggesting a separate etiology.

Converging evidence suggests that TS involves abnormal corticostriatal circuitry. TS has been associated with small striatal volumes.133 Functional imaging studies using PET and functional magnetic resonance imaging have implicated corticostriatal pathways similar to OCD.134,135 A cognitive study136 comparing  TS with OCD found that both showed deficits in set shifting tasks compared with controls. However, there were also important differences between the cognitive profiles of the two groups in the areas of recognition memory and decision-making.

TS is associated with increased dopaminergic innervation in the striatum.137-139 Dopamine receptor antagonists are effective in the treatment of the disorder,140-142 while dopamine agonists exacerbate it.143 SSRIs also have a role in treating the OCS associated with TS.144 Although dopamine antagonists are currently considered ineffective as monotherapy in OCD, they are effective as adjuncts to SSRIs in SSRI-resistant cases.

There are significant overlaps between early-onset SSRI-resistant OCD and TS in terms of phenomenology, comorbidity, family history, functional imaging, and pharmacologic treatment. This overlap supports the argument for juvenile-onset, male, tic-related OCD as a clinically relevant subgroup.128

Obsessive-Compulsive Disorder and Axis II Disorders

In clinical cohorts, up to 75% of individuals with OCD meet criteria for at least one comorbid Axis II (personality) disorder.145 Several clinical studies have shown a predominance of cluster C personality disorders (avoidant, dependent, OPCD).145-152 Norman and colleagues153 reported that 35% to 50% of OCD patients have schizotypal traits, reinforcing the view that there is an association between OCD and schizophrenic-spectrum symptoms. Among those with OCD, the prevalence of individual categories of Axis II disorder seems to vary between the sexes. Males with OCD are more likely to meet diagnostic criteria for antisocial,149 schizotypal,149 or OCPD,154 while borderline and dependent disorders appear more frequently among females.149 

Clinical cohorts may be biased by the effects of the comorbid personality disorder on their likelihood to present for treatment for OCD. In an epidemiological sample,155 OCD was associated with antisocial personality disorder in 10% of cases. However, this was the only type of personality disorder assessed in that survey. In a community study by Nestadt and colleagues,156 compulsive, borderline, and histrionic were the only categories of personality disorder significantly associated with OCD.

Obsessive-Compulsive Disorder Versus Obsessive-Compulsive Personality Disorder

The fundamental symptoms of OCPD comprise orderliness and perfectionism. Conscientiousness, indecisiveness, and rigidity have also been considered integral at times. Samuels and colleagues152 reported that OCPD stood out from other Axis II disorders by being overrepresented in never married high school graduates, drawing parallels with the high celibacy rates reported for individuals with OCD. Some OCPD features seem indistinguishable from OCD (eg, hoarding). However, hoarding severity does not correlate with the severity of OCPD symptoms,157 and, of the eight diagnostic criteria for DSM-IV-TR OCPD, hoarding was found to have the lowest specificity and predictive value.158 In addition, the obsessional fears and repetitive behaviors that characterize OCD distinguish it from OCPD.

Family studies have found that relatives of OCD patients patients also frequently had obsessional personality traits. However, the occurrence of personality traits in relatives of non-OCD control groups were not reported.159 Some studies48,146,147,159-162 that used standardized personality disorder assessment instruments found a relatively high comorbidity of Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised OCPD in OCD patients, ranging from 16% to 44%. In contrast, other similar studies found a low co-occurrence (2% to 6%)151,163,164 and a high frequency of avoidant, dependent, and passive-aggressive personality disorders (classified with OCPD in the  DSM-III-R “anxious” cluster). Schizoid, schizotypal, paranoid, histrionic, narcissistic, and borderline personality disorders have also been reported by multiple studies to be present in individuals with OCD.

In a carefully controlled community study,152 DSM-IV-TR OCPD was found in around 32% of OCD probands, compared with 6% of control probands, and in 12% of case relatives, compared to 6% of control relative. Of personality disorders, only OCPD occurred significantly more often than expected in the case relatives, suggesting a shared heritability linking the two disorders. Case relatives also scored significantly higher on dimensional scale measures of neuroticism, including anxiety, self-consciousness, and vulnerability to stress, suggesting a common inherited temperament.

Although most studies have suggested that OCPD occured more frequently in cases of OCD than in non-OCD controls, OCPD as defined by DSM-IV-TR criteria was not found in most OCD cases. Thus, OCPD is not a prerequisite for OCD. The issue of underreporting is relevant, not least because of the secretiveness and lack of insight associated with OCPD and problems with the categorical DSM-IV-TR “threshold model,” which may miss relevant cases. It may be more appropriate to consider, instead, individual OCPD traits or dimensions. Eisen and colleagues165 investigated the traits most commonly occurring in OCD cases with comorbid OCPD. Preoccupation with details, rigidity, reluctance to delegate, and perfectionism all occurred in roughly one third of cases. These comorbid cases had higher compulsion scores, were more socially impaired and had earlier onset of illness than uncomplicated OCD. Interestingly, there were no gender differences. Two factors within OCD (hoarding and symmetry) have been reported to be more frequently associated with OCPD.148 Suggestions that “incompleteness” rather than “harm avoidance” is the core cognitive feature separating this group from the other forms of OCD, and that these comorbid patients are more treatment-refractory, need to be confirmed in controlled studies.

There have been no studies investigating brain abnormalities in uncomplicated OCPD. Irle and colleagues166 retrospectively assessed the long-term outcome in 16 refractory cases of OCD who had undergone neurosurgery involving ventromedial frontal leucotomy performed in 1970. Three patients with comorbid OCPD had improved significantly less. These findings hint that OCPD may be associated with a more refractory form of OCD that might involve different neural pathways.

There have been no studies specifically examining neurocognitive function in OCPD. A study of university students identified associations between performance deficits on measures of frontal executive function and obsessive-compulsive traits.167 OCD is associated with prominent executive dysfunction involving fronto-striatal circuitry.115 A preliminary, unpublished analysis by the authors suggested similar executive impairments in OCD cases with and without OCPD, but the OCPD-positive group were significantly more impaired on measures of cognitive flexibility.

OCPD ovelaps with OCD on many phenomenological factors. Converging evidence from family studies points to a link between OCPD, neuroticism and OCD. Endophenotypic evidence is, however, still scanty. Further exploration of this relationship using imaging and neurocognitive probes is indicated.

Obsessive-Compulsive Disorder and Axis III Disorders

OCSDs are more frequent in patients with active or prior rheumatic fever.168 The prominence of OCS in rheumatic fever, systemic lupus erythematosus,169 and Sydenham’s chorea has prompted studies into the possibility of an autoimmune form of OCD. There is still both debate and interest in the hypothesis that streptococcal infections may lead to OCD and/or tic disorders in childhood without concomitant chorea.170 Coined pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS),171 the symptoms of these disorders can include OCD, tics, and attention-deficit/hyperactivity disorder (ADHD). Clinically, symptoms usually appear suddenly following a group A ß-hemolytic streptococcal infection and run a fluctuating course with exacerbations. Males are more likely to develop poststreptococcal OCD-like symptoms and at an earlier age than females.171,172 Family studies173 have demonstrated similar rates of OCD in family members of probands with PANDAS and probands with childhood-onset OCD. Fore example, a recent family study by Hounie and colleagues173 found significantly higher rates of OCSDs among first-degree relatives of probands with rheumatic fever compared with controls.

The proposed mediators of PANDAS are anti-basal ganglia antibodies. In a study by Dale and colleagues174 positive anti-basal ganglia antibodies binding (as seen in Sydenham’s chorea) was found in 42% of a cohort of 50 children with OCD compared with 2% to 10% of control groups (P<.001 in all comparisons), supporting the hypothesis that central nervous system autoimmunity may have a role in a significant subgroup of cases of OCD. Further study is required to examine whether the antibodies concerned are pathogenic or coincidental.

With circumstantial evidence of PANDAS accumulating slowly, there are few studies addressing possible differences in the endophenotype (apart from immunological biomarkers). Similarly, little is known about the differences between Sydenham’s chorea, PANDAS, and TS in terms of psychiatric symptoms.175 A study by Asbahr and colleagues176 reported similar symptom clusters (violent thoughts and contamination obsession) in patients with Sydenham’s chorea and primary OCD. The symptom clusters differed significantly from those who had tic disorders, in whom a preponderance of symmetry and ordering obsessions was found. The authors suggested that this may be due to a shared neurological substrate in the case of OCD and Sydenham’s chorea that differs from OCS in tic disorders. Apart from the temporal correlation between ß-hemolytic streptococcal infection and the emergence of symptoms, it does not seem likely that PANDAS can be reliably differentiated from ideopathic OCD on phenomenology alone.

Like OCD, OCSDs caused by PANDAS respond to standard treatment with SSRIs and CBT.177 Trials of antibiotic therapy and/or prophylaxis170 have shown some promising results but are hindered by small sample sizes. It is unclear whether symptoms remit after acute exacerbations or progress to chronic OCD.


The studies reviewed in this article cover a wide range of methods, from epidemiology, through family studies to neuroimaging, genetics, and neurocognition. All lend support to the validity of an obsessive-compulsive spectrum of disorders discrete from anxiety disorders. OCD might be considered a prototype for this spectrum of disorders, though all OCSDs share compulsive behavior and failures in behavioral inhibition as an endophenotype. The question of which other disorders should be included within the spectrum is an empirical one requiring further work. OCD seems to share a closer relationship with BDD, grooming disorders, OCPD, TS, and PANDAS in terms of comorbidity, family history, and cognitive failures and may thus be considered part of the same category. Juvenile-onset, male, tic-related OCD with associated symmetry/order/repeating/touching compulsions and poor response to SSRIs may represent a distinct subtype or variant of OCD. Studies designed to delineate cause, consequence, and common factors are a challenging but essential area for future research.

Despite high comorbidity rates, emerging evidence suggests substantial endophenotypic differences between OCD and anxiety disorders, depression, schizophrenia, and addictions, though comparative data is lacking and the picture is far from clear. Comorbidity rates are higher for other OCSDs than for disorders such as anxiety and depression. Similarly, family studies have not shown increased risk of anxiety disorders in unaffected relatives. Finally, the few cognitive and neuroimaging studies that have directly compared anxiety with OCD have indicated more differences than similarities.

Although OCD and addictions share endophenotypic similarities, such as impaired behavioral inhibition and abnormal dopamine signalling in fronto-striatal pathways, they seem phenotypically and neurobiologically different, with lower than expected comorbidity rates and no familial or genetic association.178 Grouping these disorders in terms of compulsive behavior has facilitated research into cognitive endophenotypes and helped to distinguish this spectrum of disorders from anxiety and depression.

Future studies that systematically investigate different OCD subgroups, compare OCD with OCSDs, and compare OCD to other major mental disorders and their first-degree relatives, using a standardized battery of endophenotype markers, may help clarify the overlap and the boundaries between these disorders. These studies will inevitably require collaborative expertise integrating diverse fields (eg, clinical, neuroimaging, pharmacologic challenge, biological markers, neuropsychology, and genetics).


1. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. text rev. Washington, DC: American Psychiatric Association; 2000.
2. Chamberlain SR, Blackwell AD, Fineberg NA, Robbins TW, Sahakian BJ. The neuropsychology of obsessive compulsive disorder: the importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers. Neurosci Biobehav Rev. 2005;29:399-419.
3. Insel TR, Mueller EA, Alterman I, Linnoila M, Murphy DL. Obsessive-compulsive disorder and serotonin: is there a connection? Biol Psychiatry. 1985;20:1174-1188.
4. Denys D, van der Wee N, Janssen J, De Geus F, Westenberg HG. Low level of dopaminergic D2 receptor binding in obsessive-compulsive disorder. Biol Psychiatry. 2004;55:1041-1045.
5. Denys D, Van Nieuwerburgh F, Deforce D, Westenberg H. Association between the dopamine D(2) receptor TaqI A2 allele and low activity COMT allele with obsessive-compulsive disorder in males. Eur Neuropsychopharmacol. 2006;16:446-450.
6. Pooley EC, Fineberg NA, Harrison PJ. The met158 allele of catechol-O-methyltransferase (COMT) is associated with obsessive-compulsive disorder in men: case-control study and meta-analysis. Biol Psychiatry. In press.
7. Hollander E, Wong CM. Obsessive-compulsive spectrum disorders. J Clin Psychiatry. 1995;56(suppl 4):3-6.
8. Marks I. Fears, Phobias and Rituals: Panic, Anxiety, and Their Disorders. New York, NY: Oxford University Press; 1987.
9. Pigott TA, L’Heureux F, Dubbert B, Bernstein S, Murphy DL. Obsessive compulsive disorder: comorbid conditions. J Clin Psychiatry. 1994;55(suppl):15-27.
10. Rasmussen SA, Eisen JL. Epidemiology of obsessive compulsive disorder. J Clin Psychiatry. 1990;51(suppl):10-13.
11. Shapiro AK, Shapiro E. Evaluation of the reported association of obsessive-compulsive symptoms or disorder with Tourette’s disorder. Compr Psychiatry. 1992;33:152-165.
12. Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry. 2003;160:636-645.
13. Hollander E, Kim S, Khanna S, Pallanti S. Obsessive-compulsive disorder and obsessive-compulsive spectrum disorders: diagnostic and dimensional issues. CNS Spectr. 2007;12(2 suppl 3):5-13.
14. Hwang MY, Morgan JE, Losconzcy MF. Clinical and neuropsychological profiles of obsessive-compulsive schizophrenia: a pilot study. J Neuropsychiatry Clin Neurosci. 2000;12:91-94.
15. Wittchen HU, Jacobi F. Size and burden of mental disorders in Europe—a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol. 2005;15:357-376.
16. Lochner C, Hemmings SM, Kinnear CJ, et al. Gender in obsessive-compulsive disorder: clinical and genetic findings. Eur Neuropsychopharmacol. 2004;14:105-113.
17. Hollander E, Greenwald S, Neville D, Johnson J, Hornig CD, Weissman MM. Uncomplicated and comorbid obsessive-compulsive disorder in an epidemiologic sample. Depress Anxiety. 1996;4:111-119.
18. Richter MA, Summerfeldt LJ, Antony MM, Swinson RP. Obsessive-compulsive spectrum conditions in obsessive-compulsive disorder and other anxiety disorders. Depress Anxiety. 2003;18:118-127.
19. Nestadt G, Samuels J, Riddle MA, et al. The relationship between obsessive-compulsive disorder and anxiety and affective disorders: results from the Johns Hopkins OCD Family Study. Psychol Med. 2001;31:481-487.
20. Carter AS, Pollock RA, Suvak MK, Pauls DL. Anxiety and major depression comorbidity in a family study of obsessive-compulsive disorder. Depress Anxiety. 2004;20:165-174.
21. Fyer AJ, Lipsitz JD, Mannuzza S, Aronowitz B, Chapman TF. A direct interview family study of obsessive-compulsive disorder. I. Psychol Med. 2005;35:1611-1621.
22. Saxena S. Neuroimaging and the pathophysiology of obsessive-compulsive disorder. In: Fu CH, Senior C, Russell TA, Weinberger D, Murray R, eds. Neuroimaging in Psychiatry.  London, UK: Martin Dunitz; 2003:191-224.
23. Breiter HC, Rauch SL, Kwong KK, et al. Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder. Arch Gen Psychiatry. 1996;53:595-606.
24. Cottraux J, Gerard D, Cinotti L, et al. A controlled positron emission tomography study of obsessive and neutral auditory stimulation in obsessive-compulsive disorder with checking rituals. Psychiatry Res.1996:60:101-112.
25. McGuire PK, Bench CJ, Frith CD, Marks IM, Frackowiak RS, Dolan RJ. Functional anatomy of obsessive-compulsive phenomena. Br J Psychiatry. 1994;164:459-468.
26. Rauch SL, Jenike MA, Alpert NM, et al. Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography. Arch Gen Psychiatry. 1994;51:62-70.
27. Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Review Neurosci. 1986;9:357-381.
28. Kent JM, Rauch SL. Neurocircuitry of anxiety disorders. Curr Psychiatry Rep. 2003;5:266-273.
29. Schneider F, Weiss U, Kessler C, et al. Subcortical correlates of differential classical conditioning of aversive emotional reactions in social phobia. Biol Psychiatry. 1999;45:863-871.
30. Stein MB, Goldin PR, Sareen J, Zorrilla LT, Brown GG. Increased amygdala activation to angry and contemptuous faces in generalized social phobia. Arch Gen Psychiatry. 2002;59:1027-1034.
31. Tillfors M, Furmark T, Marteinsdottir I, Fredrikson M. Cerebral blood flow during anticipation of public speaking in social phobia: a PET study. Biol Psychiatry. 2002;52:1113-1119.
32. Mataix-Cols D, van den Heuvel OA. Common and distinct neural correlates of obsessive-compulsive and related disorders. Psychiatr Clin North Am. 2006;29:391-410.
33. Lucey JV, Costa DC, Adshead G, et al. Brain blood flow in anxiety disorders: OCD, panic disorder with agoraphobia, and post-traumatic stress disorder on 99mTcHMPAO single photon emission tomography (SPET). Br J Psychiatry. 1997;171:346-350.
34. Airaksinen E, Larsson M, Forsell Y. Neuropsychological functions in anxiety disorders in population-based samples: evidence of episodic memory dysfunction. J Psychiatr Res. 2005;39:207-214.
35. Boldrini M, Del Pace L, Placidi GP, et al. Selective cognitive deficits in obsessive-compulsive disorder compared to panic disorder with agoraphobia. Acta Psychiatr Scand. 2005;111:150-158.
36. Clayton IC, Richards JC, Edwards CJ. Selective attention in obsessive-compulsive disorder. J Abnorm Psychol. 1999;108:71-75.
37. Purcell R, Maruff P, Kyrios M, Pantelis C. Neuropsychological deficits in obsessive-compulsive disorder: a comparison with unipolar depression, panic disorder, and normal controls. Arch Gen Psychiatry. 1998;55:415-423.
38. Cohen Y, Lachenmeyer JR, Springer C. Anxiety and selective attention in obsessive-compulsive disorder. Behav Res Ther. 2003;41:1311-1323.
39. Fineberg NA, Gale TM. Evidence-based pharmacotherapy of obsessive-compulsive disorder. Int J Neuropsychopharmacol. 2005;8:107-129.
40. Crockett BA, Churchill E, Davidson JR. A double-blind combination study of clonazepam with sertraline in obsessive-compulsive disorder. Ann Clin Psychiatry. 2004;16:127-132.
41. Grady TA, Pigott TA, L’Heureux F, Hill JL, Bernstein SE, Murphy DL. Double-blind study of adjuvant buspirone for fluoxetine-treated patients with obsessive-compulsive disorder. Am J Psychiatry. 1993;150:819-821.
42. McDougle CJ, Goodman WK, Leckman JF, et al. Limited therapeutic effect of addition of buspirone in fluvoxamine-refractory obsessive-compulsive disorder. Am J Psychiatry. 1993;150:647-649.
43. Rasmussen SA, Goodman WK, Woods SW, Heninger GR, Charney DS. Effects of yohimbine in obsessive compulsive disorder. Psychopharmacology (Berl). 1987;93:308-313.
44. Griez E, de Loof C, Pols H, Zandbergen J, Lousberg H. Specific sensitivity of patients with panic attacks to carbon dioxide inhalation. Psychiatry Res. 1990;31:193-199.
45. de Leeuw AS, Den Boer JA, Slaap BR, Westenberg HG. Pentagastrin has panic-inducing properties in obsessive compulsive disorder. Psychopharmacology (Berl). 1996;126:339-344.
46. Bartz JA, Hollander E. Is obsessive-compulsive disorder an anxiety disorder? Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:338-352.
47. Fineberg NA, Fourie H, Gale TM, Sivakumaran T. Comorbid depression in obsessive compulsive disorder (OCD): symptomatic differences to major depressive disorder. J Affect Disord. 2005;87:327-330.
48. Ravizza L, G. Maina G, Bogetto F. Episodic and chronic obsessive-compulsive disorder. Depress Anxiety. 1997;6:154-158.
49. Perugi G, Toni C, Frare F, Travierso MC, Hantouche E, Akiskal HS. Obsessive-compulsive-bipolar comorbidity: a systematic exploration of clinical features and treatment outcome. J Clin Psychiatry. 2002;63:1129-1134.
50. Hoehn-Saric R, Ninan P, Black DW, et al. Multicenter double-blind comparison of sertraline and desipramine for concurrent obsessive-compulsive and major depressive disorders. Arch Gen Psychiatry. 2000;57:76-82.
51. Montgomery SA, Kasper S, Stein DJ, Bang Hedegaard K, Lemming OM. Citalopram 20 mg, 40 mg and 60 mg are all effective and well tolerated compared with placebo in obsessive-compulsive disorder. Int Clin Psychopharmacol. 2001;16:75-86.
52. Tollefson GD, Rampey AH Jr, Potvin JH, et al. A multicenter investigation of fixed-dose fluoxetine in the treatment of obsessive-compulsive disorder. Arch Gen Psychiatry. 1994;51:559-567.
53. Wheadon DE, Bushnell W, Steiner M. A fixed dose comparison of 20, 40 or 60mg paroxetine to placebo in the treatment of obsessive compulsive disorde. Poster presented at: annual meeting of the American College of Neuropsychopharmacology. December 1993. Honalulu, HI.
54. Argyropoulos SV, Hood SD, Adrover M, et al. Tryptophan depletion reverses the therapeutic effect of selective serotonin reuptake inhibitors in social anxiety disorder. Biol Psychiatry. 2004;56:503-509.
55. Barr LC, Goodman WK, McDougle CJ, et al. Tryptophan depletion in patients with obsessive-compulsive disorder who respond to serotonin reuptake inhibitors. Arch Gen Psychiatry. 1994;51:309-317.
56. Vielhaber K, Riemann D, Feige B, Kuelz A, Kirschbaum C, Voderholzer U. Impact of experimentally induced serotonin deficiency by tryptophan depletion on saliva cortisol concentrations. Pharmacopsychiatry. 2005;38:87-94.
57. Chamberlain SR, Fineberg NA, Menzies LA, et al. Impaired cognitive flexibility and motor inhibition in unaffected first-degree relatives of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007;164:335-338.
58. Bearden CE, Hoffman KM, Cannon TD. The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review. Bipolar Disord. 2001;3:106-150.
59. Veiel HO. A preliminary profile of neuropsychological deficits associated with major depression. J Clin Exp Neuropsychol. 1997;19:587-603.
60. Clark L, Iversen SD, Goodwin GM. Sustained attention deficit in bipolar disorder. Br J Psychiatry. 2002;180:313-319.
61. Clark L, Sarna A, Goodwin GM. Impairment of executive function but not memory in first-degree relatives of patients with bipolar I disorder and in euthymic patients with unipolar depression. Am J Psychiatry. 2005;162:1980-1982.
62. Chamberlain SR, Fineberg NA, Blackwell AD, Robbins TW, Sahakian BJ. Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania. Am J Psychiatry. 2006:163:1282-1284.
63. Berrios GE. Obsessive compulsive disorders. In:  Berrios GE, Porter R, eds. A History of Clinical Psychiatry: The Origin and History of Psychiatric Disorders. London, UK: Athlone Press; 1995;573-598.
64. Luchins DJ, Goldman MB, Lieb M, Hanrahan P. Repetitive behaviors in chronically institutionalized schizophrenic patients. Schizophr Res. 1992;8:119-123.
65. Tracy JI, de Leon J, Qureshi G, McCann EM, McGrory A, Josiassen RC. Repetitive behaviors in schizophrenia: a single disturbance or discrete symptoms? Schizophr Res. 1996;20:221-229.
66. Abbruzzese M, Ferri S, Scarone S. The selective breakdown of frontal functions in patients with obsessive-compulsive disorder and in patients with schizophrenia: a double dissociation experimental finding. Neuropsychologia. 199;35:907-912.
67. Cavallaro R, Cavedini P, Mistretta P, et al. Basal-corticofrontal circuits in schizophrenia and obsessive-compulsive disorder: a controlled, double dissociation study. Biol Psychiatry. 2003;54:437-443.
68. Goldstein JM, Goodman JM, Seidman LJ, et al. Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging. Arch Gen Psychiatry. 1999;56:537-547.
69. Meador-Woodruff JH, Haroutunian V, Powchik P, Davidson M, Davis KL, Watson SJ. Dopamine receptor transcript expression in striatum and prefrontal and occipital cortex. Focal abnormalities in orbitofrontal cortex in schizophrenia. Arch Gen Psychiatry. 1997;54:1089-1095.
70. Silbersweig DA, Stern E, Frith C, et al. A functional neuroanatomy of hallucinations in schizophrenia. Nature. 1995;378:176-179.
71. Saxena S, Rauch SL. Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder. Psychiatr Clin North Am. 2000;23:563-586.
72. Lysaker PH, Bryson GJ, Marks KA, Greig TC, Bell MD. Association of obsessions and compulsions in schizophrenia with neurocognition and negative symptoms. J Neuropsychiatry Clin Neurosci. 2002;14:449-453.
73. Lysaker PH, Marks KA, Picone JB, Rollins AL, Fastenau PS, Bond GR. Obsessive and compulsive symptoms in schizophrenia: clinical and neurocognitive correlates. J Nerv Ment Dis. 2000;188:78-83.
74. Whitney KA, Fastenau PS, Evans JD, Lysaker PH. Comparative neuropsychological function in obsessive-compulsive disorder and schizophrenia with and without obsessive-compulsive symptoms. Schizophr Res. 2004;69:75-83.
75. Irle E, Exner C, Thielen K, Weniger G, Ruther E. Obsessive-compulsive disorder and ventromedial frontal lesions: clinical and neuropsychological findings. Am J Psychiatry. 1998;155:255-263.
76. Karayiorgou M, Altemus M, Galke BL, et al. Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder. Proc Natl Acad Sci U S A. 1997;94:4572-4575.
77. Lochner C, Kinnear CJ, Hemmings SM, et al. Hoarding in obsessive-compulsive disorder: clinical and genetic correlates. J Clin Psychiatry. 2005;66:1155-1160.
78. Zubieta JK Heitzeg MM, Smith YR, et al. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science. 2003;299:1240-1243.
79. Stein DJ, Newman TK, Savitz J, Ramesar R. Warriors versus worriers: the role of COMT gene variants. CNS Spectr. 2006;11:745-748.
80. Fineberg NA, Gale TM, Sivakumaran T. A review of antipsychotics in the treatment of obsessive compulsive disorder. J Psychopharmacol. 2006;20:97-103.
81. Everitt BJ, Robbins TW. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci. 2005;8:1481-1489.
82. Hesse SU, Muller U, Lincke T, et al. Serotonin and dopamine transporter imaging in patients with obsessive-compulsive disorder. Psychiatry Res. 2005;140:63-72.
83. Volkow ND, Chang L, Wang GJ, et al. Higher cortical and lower subcortical metabolism in detoxified methamphetamine abusers. Am J Psychiatry. 2001;158:383-389.
84. Volkow ND, Fowler JS, Wang GJ, et al. Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers. Synapse. 1993;14:169-177.
85. Volkow ND, Fowler JS. Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cereb Cortex. 2000;10:318-325.
86. van der Wee NJ, Stevens H, Hardeman JA, et al. Enhanced dopamine transporter density in psychotropic-naive patients with obsessive-compulsive disorder shown by [123I]{beta}-CIT SPECT. Am J Psychiatry. 2004;161:2201-2206.
87. Berman I, Merson A, Viegner B, Losonczy MF, Pappas D, Green AI. Obsessions and compulsions as a distinct cluster of symptoms in schizophrenia: a neuropsychological study. J Nerv Ment Dis. 1998;186:150-156.
88. Borkowska A, Pilaczynska E, Rybakowski JK. The frontal lobe neuropsychological tests in patients with schizophrenia and/or obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci. 2003;15:359-362.
89. Ongur D, Goff DC. Obsessive-compulsive symptoms in schizophrenia: associated clinical features, cognitive function and medication status. Schizophr Res. 2005;75:349-362.
90. Hermesh H, Weizman A, Gur S, et al. Alternation learning in OCD/schizophrenia patients. Eur Neuropsychopharmacol. 2003;13:87-91.
91. Baxter LR Jr, Phelps ME, Mazziotta JC, Guze BH, Schwartz JM, Selin CE. Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls. Arch Gen Psychiatry. 1987;44:211-218.
92. Volkow ND, Fowler JS, Wang GJ, Swanson JM. Dopamine in drug abuse and addiction: results from imaging studies and treatment implications. Mol Psychiatry. 2004;9:557-569.
93. Wilson JM, Kalasinsky KS, Levey AI, et al. Striatal dopamine nerve terminal markers in human, chronic methamphetamine users. Nat Med. 1996;2:699-703.
94. Nestler EJ. Molecular basis of long-term plasticity underlying addiction. Nat Rev Neurosci. 2001;2:119-128.
95. Fillmore MT, Rush CR. Impaired inhibitory control of behavior in chronic cocaine users. Drug Alcohol Depend. 2002;66:265-273.
96. Moeller FG, Dougherty DM, Barratt ES, et al. Increased impulsivity in cocaine dependent subjects independent of antisocial personality disorder and aggression. Drug Alcohol Depend. 2002;68:105-111.
97. Grant JE, Brewer JA, Potenza MN. The neurobiology of substance and behavioral addictions. CNS Spectr. 2006;11:924-930.
98. Potenza MN, Leung HC, Blumberg HP, et al. An FMRI Stroop task study of ventromedial prefrontal cortical function in pathological gamblers. Am J Psychiatry. 2003;160:1990-1994.
99. Siever LJ, Buchsbaum MS, New AS, et al. d,l-fenfluramine response in impulsive personality disorder assessed with [18F]fluorodeoxyglucose positron emission tomography. Neuropsychopharmacology. 1999;20:413-423.
100. Dodd ML, Klos KJ, Bower JH, Geda YE, Josephs KA, Ahlskog JE. Pathological gambling caused by drugs used to treat Parkinson disease. Arch Neurol. 2005;62:1377-1381.
101. Di Ciano P, Underwood RJ, Hagan JJ, Everitt BJ. Attenuation of cue-controlled cocaine-seeking by a selective D3 dopamine receptor antagonist SB-277011-A. Neuropsychopharmacology. 2003;28:329-338.
102. du Toit PL, van Kradenburg J, Niehaus D, Stein DJ. Comparison of obsessive-compulsive disorder patients with and without comorbid putative obsessive-compulsive spectrum disorders using a structured clinical interview. Compr Psychiatry. 2001;42:291-300.
103. Gunstad J, Phillips KA. Axis I comorbidity in body dysmorphic disorder. Compr Psychiatry. 2003:44:270-276.
104. Chamberlain SR, Menzies L, Sahakian BJ, Fineberg NA. Lifting the veil on trichotillomania. Am J Psychiatry. 2007;164:568-574.
105. Bienvenu OJ, Samuels JF, Riddle MA, et al. The relationship of obsessive-compulsive disorder to possible spectrum disorders: results from a family study. Biol Psychiatry. 2000;48:287-293.
106. Grados MA, Riddle MA, Samuels JF, et al. The familial phenotype of obsessive-compulsive disorder in relation to tic disorders: the Hopkins OCD family study. Biol Psychiatry. 2001;50:559-565.
107. Fontenelle LF, Telles LL, Nazar BP, et al. A sociodemographic, phenomenological, and long-term follow-up study of patients with body dysmorphic disorder in Brazil. Int J Psychiatry Med. 2006;36:243-259.
108. Phillips KA, Pinto A, Menard W, Eisen JL, Mancebo M, Rasmussen SA. Obsessive-compulsive disorder versus body dysmorphic disorder: a comparison study of two possibly related disorders. Depress Anxiety. 2006 Oct 13; [Epub ahead of print] .
109. Heimann SW. SSRI for body dysmorphic disorder. J Am Acad Child Adolesc Psychiatry. 1997;36:868.
110. Perkins RJ. SSRI antidepressants are effective for treating delusional hypochondriasis. Med J Aust. 1999;170:140-141.
111. Barsky AJ, Ahern DK. Cognitive behavior therapy for hypochondriasis: a randomized controlled trial. JAMA. 2004;291:464-470.
112. Castle DJ, Rossell S, Kyrios M. Body dysmorphic disorder. Psychiatr Clin North Am. 2006;29:521-538.
113. Ninan PT, Rothbaum BO, Marsteller FA, Knight BT, Eccard MB. A placebo-controlled trial of cognitive-behavioral therapy and clomipramine in trichotillomania. J Clin Psychiatry. 2000;61:47-50.
114. Rapp JT, Miltenberger RG, Long ES, Elliott AJ, Lumley VA. Simplified habit reversal treatment for chronic hair pulling in three adolescents: a clinical replication with direct observation. J Appl Behav Anal. 1998;31:299-302.
115 Chamberlain SR, Blackwell AD, Fineberg NA, Robbins TW, Sahakian BJ. Strategy implementation in obsessive-compulsive disorder and trichotillomania. Psychol Med. 2006;36:91-97.
116. O’Sullivan RL, Rauch SL, Breiter HC, et al. Reduced basal ganglia volumes in trichotillomania measured via morphometric magnetic resonance imaging. Biol Psychiatry. 1997;42:39-45.
117. Keuthen NJ, Makris N, Schlerf JE, et al. Evidence for reduced cerebellar volumes in trichotillomania. Biol Psychiatry. 2007;61:374-381.
118. Swedo SE, Rapoport JL, Leonard HL, Schapiro MB, Rapoport SI, Grady CL. Regional cerebral glucose metabolism of women with trichotillomania. Arch Gen Psychiatry. 1991;48:828-833.
119. Rauch SL, Shin LM, Dougherty DD, Alpert NM, Fischman AJ, Jenike MA. Predictors of fluvoxamine response in contamination-related obsessive compulsive disorder: a PET symptom provocation study. Neuropsychopharmacology. 2002;27:782-791.
120. van den Heuvel OA, Veltman DJ, Groenewegen HJ, et al. Disorder-specific neuroanatomical correlates of attentional bias in obsessive-compulsive disorder, panic disorder, and hypochondriasis. Arch Gen Psychiatry. 2005;62:922-933.
121. Carey P, Seedat S, Warwick J, van Heerden B, Stein DJ. SPECT imaging of body dysmorphic disorder. J Neuropsychiatry Clin Neurosci. 2004;16:357-359.
122. Stein DJ. Neurobiology of the obsessive-compulsive spectrum disorders. Biol Psychiatry. 2000;47:296-304.
123. Baer L. Factor analysis of symptom subtypes of obsessive compulsive disorder and their relation to personality and tic disorders. J Clin Psychiatry. 1994;55(suppl):18-23.
124. Leckman JF, Grice DE, Boardman J, et al. Symptoms of obsessive-compulsive disorder. Am J Psychiatry. 1997;154:911-917.
125. Mataix-Cols D, Rauch SL, Manzo PA, Jenike MA, Baer L. Use of factor-analyzed symptom dimensions to predict outcome with serotonin reuptake inhibitors and placebo in the treatment of obsessive-compulsive disorder. Am J Psychiatry. 1999;156:1409-1416.
126. Park S, Como PG, Cui L, Kurlan R. The early course of the Tourette’s syndrome clinical spectrum. Neurology. 1993;43:1712-1715.
127. Pauls DL, Towbin KE, Leckman JF, Zahner GE, Cohen DJ. Gilles de la Tourette’s syndrome and obsessive-compulsive disorder. Evidence supporting a genetic relationship. Arch Gen Psychiatry. 1986;43:1180-1182.
128. Rosario-Campos MC, Leckman JF, Mercadante MT, et al. Adults with early-onset obsessive-compulsive disorder. Am J Psychiatry. 2001;158:1899-1903.
129. Samuels J, Bienvenu OJ 3rd, Riddle MA, et al. Hoarding in obsessive compulsive disorder: results from a case-control study. Behav Res Ther. 2002;40:517-528.
130. Leckman JF, Zhang H, Alsobrook JP, Pauls DL. Symptom dimensions in obsessive-compulsive disorder: toward quantitative phenotypes. Am J Med Genet. 2001;105:28-30.
131. Pauls DL, Leckman JF, Towbin KE, Zahner GE, Cohen DJ. A possible genetic relationship exists between Tourette’s syndrome and obsessive-compulsive disorder. Psychopharmacol Bull. 1986;22:730-733.
132. Zhang H, Leckman JF, Pauls DL, et al. Genomewide scan of hoarding in sib pairs in which both sibs have Gilles de la Tourette syndrome. Am J Hum Genet. 2002;70:896-904.
133. Peterson BS, Thomas P, Kane MJ, et al. Basal Ganglia volumes in patients with Gilles de la Tourette syndrome. Arch Gen Psychiatry. 2003;60:415-424.
134. Braun AR, Randolph C, Stoetter B, et al. The functional neuroanatomy of Tourette’s syndrome: an FDG-PET Study. II: relationships between regional cerebral metabolism and associated behavioral and cognitive features of the illness. Neuropsychopharmacology. 1995;13:151-168.
135. Stern E, Silbersweig DA, Chee KY, et al. A functional neuroanatomy of tics in Tourette syndrome. Arch Gen Psychiatry. 2000;57:741-748.
136. Watkins LH, Sahakian BJ, Robertson MM, et al. Executive function in Tourette’s syndrome and obsessive-compulsive disorder. Psychol Med. 2005;35:571-582.
137. Albin RL, Koeppe RA, Bohnen NI, et al. Increased ventral striatal monoaminergic innervation in Tourette syndrome. Neurology. 2003;61:310-315.
138. Albin RL, Mink JW. Recent advances in Tourette syndrome research. Trends Neurosci. 2006;29:175-182.
139. Freeman CP, Trimble MR, Deakin JF, et al. Fluvoxamine versus clomipramine in the treatment of obsessive compulsive disorder: a multicenter, randomized, double-blind, parallel group comparison. J Clin Psychiatry. 1994;55:301-305.
140. Gilbert D. Treatment of children and adolescents with tics and Tourette syndrome. J Child Neurol. 2006;21:690-700.
141. Gilbert DL, Bansal AS, Sethuraman G, et al. Association of cortical disinhibition with tic, ADHD, and OCD severity in Tourette syndrome. Mov Disord. 2004;19:416-425.
142. Gilbert DL, Wang Z, Sallee FR, et al. Dopamine transporter genotype influences the physiological response to medication in ADHD. Brain. 2006;129:2038-2046.
143. Goodman WK, McDougle CJ, Price LH, et al. Beyond the serotonin hypothesis: a role for dopamine in some forms of obsessive compulsive disorder? J Clin Psychiatry. 1990;51(suppl):36-43.
144. George MS, Trimble MR, Ring HA, Sallee FR, Robertson MM. Obsessions in obsessive-compulsive disorder with and without Gilles de la Tourette’s syndrome. Am J Psychiatry. 1993;150:93-97.
145. Bejerot S, Ekselius L, von Knorring L. Comorbidity between obsessive-compulsive disorder (OCD) and personality disorders. Acta Psychiatr Scand. 1998;97:398-402.
146. Baer L, Jenike MA. Personality disorders in obsessive compulsive disorder. Psychiatr Clin North Am. 1992;15:803-812.
147. Diaferia G, Bianchi I, Bianchi ML, Cavedini P, Erzegovesi S, Bellodi L. Relationship between obsessive-compulsive personality disorder and obsessive-compulsive disorder. Compr Psychiatry. 1997;38:38-42.
148. Mataix-Cols D, Baer L, Rauch SL, Jenike MA. Relation of factor-analyzed symptom dimensions of obsessive-compulsive disorder to personality disorders. Acta Psychiatr Scand. 2000;102:199-202.
149. Matsunaga H, Kiriike N, Matsui T, et al. Gender differences in social and interpersonal features and personality disorders among Japanese patients with obsessive-compulsive disorder. Compr Psychiatry. 2000;41:266-272.
150. Matsunaga H, Kiriike N, Miyata A, et al. Personality disorders in patients with obsessive-compulsive disorder in Japan. Acta Psychiatr Scand. 1998;98:128-134.
151. Mavissakalian M, Hamann MS, Jones B. Correlates of DSM-III personality disorder in obsessive-compulsive disorder. Compr Psychiatry. 1990;31:481-489.
152. Samuels J, Nestadt G, Bienvenu OJ, et al. Personality disorders and normal personality dimensions in obsessive-compulsive disorder. Br J Psychiatry. 2000;177:457-462.
153. Norman RM, Davies F, Malla AK, Cortese L, Nicholson IR. Relationship of obsessive-compulsive symptomatology to anxiety, depression and schizotypy in a clinical population. Br J Clin Psychol. 1996;3:553-566.
154. Thomsen PH, Mikkelsen HU. Development of personality disorders in children and adolescents with obsessive-compulsive disorder. A 6- to 22-year follow-up study. Acta Psychiatr Scand. 1993;87:456-462.
155 Kolada JL, Bland RC, Newman SC. Epidemiology of psychiatric disorders in Edmonton. Obsessive-compulsive disorder. Acta Psychiatr Scand Suppl. 1994;376:24-35.
156. Nestadt G, Samuels JF, Romanoski AJ, Folstein MF, McHugh PR. Obsessions and compulsions in the community. Acta Psychiatr Scand. 1994;89:219-224.
157. Black DW, Noyes R Jr, Pfohl B, Goldstein RB, Blum N. Personality disorder in obsessive-compulsive volunteers, well comparison subjects, and their first-degree relatives. Am J Psychiatry. 1993;150:1226-1232.
158. Alnaes R, Torgersen S. DSM-III symptom disorders (Axis I) and personality disorders (Axis II) in an outpatient population. Acta Psychiatr Scand. 1988;78:348-355.
159. Pfohl B, Black DW, Noyes R, Coryell WH, Barrash J. Axis I and Axis II comorbidity findings: implications for validity. In: Oldham JM, ed. Personality Disorders: New Perspectives on Diagnostic Validity. Washington, DC: American Psychiatric Press. 1990:147-161.
160. Stanley MA, Turner SM, Borden JW. Schizotypal features in obsessive-compulsive disorder. Compr Psychiatry. 1990;31:511-518.
161. Baer L, Jenike MA, Ricciardi JN 2nd, et al. Standardized assessment of personality disorders in obsessive-compulsive disorder. Arch Gen Psychiatry. 1990;47:826-830.
162. Joffe RT, Swinson RP, Regan JJ. Personality features of obsessive-compulsive disorder. Am J Psychiatry. 1988;145:1127-1129.
163. Eisen JL. Obsessive compulsive personality disorder: its treatment and relationship to OCD. Paper presented at: annual meeting of American Psychiatric Association. May 2004; New York, NY.
164. Dinn WM, Harris CL, Aycicegi A, Greene P, Andover MS. Positive and negative schizotypy in a student sample: neurocognitive and clinical correlates. Schizophr Res. 2002;56:171-185.
165. Mercadante MT, Busatto GF, Lombroso PJ, et al. The psychiatric symptoms of rheumatic fever. Am J Psychiatry. 2000;157:2036-2038.
166. Slattery MJ, Dubbert BK, Allen AJ, Leonard HL, Swedo SE, Gourley MF. Prevalence of obsessive-compulsive disorder in patients with systemic lupus erythematosus. J Clin Psychiatry. 2004;65:301-306.
167. Murphy TK, Sajid MW, Goodman WK. Immunology of obsessive-compulsive disorder. Psychiatr Clin North Am. 2006;29:445-469.
168. Swedo SE, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998;155:264-271.
169. Carapetis JR, Currie BJ. Rheumatic chorea in northern Australia: a clinical and epidemiological study. Arch Dis Child. 1999;80:353-358.
170. Hounie AG, Pauls DL, do Rosario-Campos MC, et al. Obsessive-compulsive spectrum disorders and rheumatic fever: a family study. Biol Psychiatry. 2007;61:266-272.
171. Dale RC, Heyman I, Giovannoni G, Church AW. Incidence of anti-brain antibodies in children with obsessive-compulsive disorder. Br J Psychiatry. 2005;187:314-319.
172. Arnold PD, Richter MA. Is obsessive-compulsive disorder an autoimmune disease? CMAJ. 2001;165:1353-1358.
173. Asbahr FR, Garvey MA, Snider LA, Zanetta DM, Elkis H, Swedo SE. Obsessive-compulsive symptoms among patients with Sydenham chorea. Biol Psychiatry. 2005;57:1073-1076.
174. Storch EA, Murphy TK, Geffken GR, et al. Cognitive-behavioral therapy for PANDAS-related obsessive-compulsive disorder: findings from a preliminary waitlist controlled open trial. J Am Acad Child Adolesc Psychiatry. 2006;45:1171-1178.
175. Bejerot S, Humble M. Low prevalence of smoking among patients with obsessive-compulsive disorder. Compr Psychiatry. 1999;40:268-272.
176. Szechtman H, Sulis W, Eilam D. Quinpirole induces compulsive checking behavior in rats: a potential animal model of obsessive-compulsive disorder (OCD). Behav Neurosci. 1998;112:1475-1485.
177. Steketee G, Frost R. Compulsive hoarding: current status of the research. Clin Psychol Rev. 2003;23:905-927.
178. Grilo CM McGlashan TH, Morey LC, et al. Internal consistency, intercriterion overlap and diagnostic efficiency of criteria sets for DSM-IV schizotypal, borderline, avoidant and obsessive-compulsive personality disorders. Acta Psychiatr Scand. 2001;104:264-272.



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