The co-occurrence of obsessive-compulsive symptoms (OCS) and psychotic illness has been a challenge for clinicians and investigators for more than a century. Over the past decade, interest in this area has burgeoned because of recognition of higher-than-chance comorbidity rates of schizophrenia and OCD.
The co-occurrence of obsessive-compulsive symptoms (OCS) and psychotic illness has been a challenge for clinicians and investigators for more than a century.1 Over the past decade, interest in this area has burgeoned because of recognition of higher-than-chance comorbidity rates of schizophrenia and obsessive-compulsive disorder (OCD), and observations of appearance or exacerbation of OCS during treatment of schizophrenia with atypical antipsychotics.2-6 Emerging neurobiological and genetic evidence suggests that persons with comorbid OCD and schizophrenia may represent a special category of the schizophrenic population.
The evidence for a putative schizo-obsessive disorder is examined and practical treatment suggestions for this subgroup of patients are outlined in this article.7-9
Comorbidity between OCD and schizophrenia
The lifetime prevalence for schizophrenia is 1% and for OCD it is 2% to 3%.10 Comorbidity rates for OCD in the schizophrenia population are substantially higher than what would be expected to occur randomly. In the schizophrenic population, the reported prevalence of clinically significant OCS and of OCD ranges from 10% to 52% and from 7.8% to 26%, respectively.11-23
The higher-than-expected comorbidity rate for OCD and schizophrenia suggests a nonrandom association and possibly an integral relation between these 2 conditions.9 The question is whether this comorbid group with schizo-obsessive disorder represents a more severely ill group with greater brain dysfunction that could, in part, be caused by common neurodevelopmental predisposing factors, or whether the 2 conditions are part of a more complex syndrome that represents a distinct diagnostic entity. The answer could be clarified in part if neurobiological studies were to demonstrate a distinct neuroanatomical substrate in this comorbid group rather than the summation or superimposition of neurobiological lesions observed in the separate disorders.9
Clinical and research challenges
Recent studies have aimed to reduce bias and
confounding that were often inherent in older studies. Newer studies have used such methods as randomization, prospective and cross-sectional study designs, standardized diagnostic criteria, validated diagnostic tools, age-matched control groups, and stratification of patient populations according to phase of illness to increase the validity of study results.
Notwithstanding these efforts to enhance diagnostic clarity and study validity, the distinction between obsessions and delusions is often difficult to discern.9 Paradoxically, DSM-IV allows for the OCD specifier “with poor insight.” This stands in contrast to the definition of an obsession as being recognized by the individual as foreign to him or her (ie, ego-dystonic), and implies the presence of insight. Insel and Akiskal24 proposed that “OCD represents a psychopathological spectrum varying along a continuum of insight,” and that this “obsessional delusion” does not signify a schizophrenia diagnosis. Complicating the matter further is the observation of perceptual disturbances that mimic various types of hallucinations or pseudohallucinations in some persons with OCD.25
Whether obsessions can be accurately detected in the presence of psychosis remains a matter of debate.9 To date, there is no universally accepted method of detecting OCD in the presence of schizophrenia, although most contemporary study designs have used the Structured Clinical Interview for DSM-IV Axis I psychiatric disorders and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS).26,27 In attempts to ascertain the reliability and validity of the Y-BOCS in this comorbid subgroup, de Haan and colleagues28 examined the properties of this psychometric tool in patients with recent-onset schizophrenia and comorbid OCS. These investigations found good internal consistency and interrater reliability in this population. However, their findings concerning the divergent validity against depressive and negative symptoms were inconsistent.
Although the phenomenological delineations between obsessions and delusions often remain unclear, there is substantial evidence that OCS in schizophrenia represents more than just an expression of enduring psychosis.9 This evidence includes observations that conventional antipsychotic medications appear to be of limited use in the treatment of OCS in schizophrenia, the persistence of OCS even after successful treatment of the psychotic symptoms, and the effectiveness of serotonin reuptake inhibitors in the treatment of OCS in patients with schizophrenia.29-33
Clinical relevance of OCS in schizophrenia
Early investigators concluded that the presence of OCS confers protection against cognitive deficits, functional impairment, and negative symptoms associated with schizophrenia.34,35 Psychodynamic theories postulated that obsessions constitute a defense against psychosis and prevent progression of the disease. However, more recent studies that used rigorous methods have not tended to replicate these earlier findings.36 Instead, recent studies have found that this comorbid group is burdened by a greater magnitude of cognitive deficits, negative and positive symptoms, neurological soft signs, distress, dysfunction, hopelessness, depression, suicidal ideation, and suicide attempts. A few studies have not replicated some of these findings.19,20,37-48
Pedigree and genetic studies
Pedigree and genetic studies have not found any familial relationship or shared etiology between OCD and schizophrenia in their pure forms. However, specific genotypes of polymorphisms of the same gene may differentially confer risk for the 2 disorders.
The catechol-O-methyltransferase (COMT) gene is a candidate gene for schizophrenia because of its role in the breakdown of dopamine in the prefrontal cortex. Zinkstok and colleagues49 found that the COMT high activity Val allele is associated with more OCS in young patients with schizophrenia, whereas patients with the Met/Met genotype had the lowest Y-BOCS scores. These results support the hypothesis that the COMT Val-Met polymorphism may be a modifier gene for the symptoms of schizophrenia.49
Poyurovsky and colleagues50 examined familial aggregation of schizophrenia spectrum disorders and obsessive-compulsive–associated disorders in schizophrenia probands with and without OCD. They found that relatives of OCD-schizophrenia probands had significantly higher morbid risks for OCD-schizophrenia and obsessive-compulsive personality disorder (OCPD); they also found a trend toward higher morbid risk for OCD. When morbid risks for OCD, OCPD, and OCD-schizophrenia were pooled, the significant between-group differences became robust. These data suggest a genetic contribution to the expression of OCS in individuals with schizophrenia. In addition, they lend support for the validity of a putative schizo-obsessive diagnostic entity.50
Neurobiology of the schizo-obsessive subgroup
Considerable work has been done to reveal the neurobiological basis of both schizophrenia and OCD.9 This research has focused primarily on elucidating key neurotransmitter systems, structural and functional neuroanatomy, and neuropsychology. However, there is very limited published research that focuses specifically on neurobiological features unique to this putative schizo-obsessive subtype.
Neurotransmitter systems. There is a paucity of published research on unique neurotransmitter involvement in the schizo-obsessive subtype group.
However, serotonin and dopamine have most consistently emerged as the principal neurotransmitters of interest in both disorders.9 The dopamine hypothesis in schizophrenia has long been regarded as the fundamental neurochemical premise; however, the superior efficacy of the serotonin-dopamine receptor antagonists in the treatment of schizophrenia also supports the importance of the serotonergic system in the pathophysiology of this disorder and may reflect the modulation of dopaminergic systems by serotonin.51,52
Conversely, in OCD a somewhat opposing picture has emerged with respect to neurotransmitter involvement.9 The serotonin hypothesis of OCD is supported by successful treatment of the disorder with serotonin reuptake inhibitors, pharmacological challenge studies, and cerebrospinal fluid neurotransmitter metabolite studies.53 However, several lines of evidence suggest that serotonin is not the sole neurotransmitter involved in OCD. Considerable evidence supports the additional role of the dopaminergic system in this disorder.51,53-57 Preclinical evidence of dopamine’s reciprocal modulatory effects on the serotonin system and successful treatment of refractory OCD with adjunctive dopamine receptor antagonists and serotonin-dopamine receptor antagonists have provided support for the dopamine-serotonin hypothesis of OCD.51,53,56,57
There is a lack of neurotransmitter data in the overlap group. However, one study examined the differences in whole blood serotonin concentrations in healthy volunteers versus patients with OCD, in persons with schizophrenia with and without OCS, and in clozapine-treated schizophrenia in patients with and without clozapine-induced OCS. This study found that the groups with OCD, schizophrenia with OCS, and clozapine-treated schizophrenia with OCS had significantly lower levels of whole blood serotonin than did the healthy volunteers and the schizophrenia-only groups.58
Neuroanatomy and neurocircuitry. In contrast to the abundance of neuroimaging studies investigating structural brain abnormalities in persons with OCD and schizophrenia separately, there is a dearth of such studies examining the comorbid subgroup. However, the considerable overlap in the neurocircuitry and specific anatomical structures implicated in each disorder may account for symptom coexpression in this subgroup of patients.52,59,60 The functional circuitry implicated in the pathophysiology of OCD is generally believed to involve a cortico-striatal-thalamic-cortical circuit.61 Specific structures implicated in this pathway include the basal ganglia, orbitofrontal cortex, and anterior cingulate cortex.62
In schizophrenia, the dorsolateral prefrontal cortex circuit contains anatomical substrates similar to those of the OCD orbitofrontal circuit.52 Thus, the specific neuroanatomical sites identified by structural and functional neuroimaging studies performed in each of these disorders independently show considerable over-lap in implicated structures, including the basal ganglia, thalamus, anterior cingulum, orbitofrontal cortex, and regions of the temporal cortex, although some of these findings are controversial.59,60
Neuroimaging studies suggest the presence of specific neuroanatomical abnormalities in the overlap group that may differ from what is observed in the individual disorders. One MRI study of patients with juvenile-onset schizophrenia with OCS found significantly smaller left hippocampi in this group than in schizophrenia-only and control groups.63 In addition, there was an inverse correlation between illness duration and frontal lobe size in the comorbid group but not in the schizophrenia-only group.
Another MRI study of patients with juvenile-onset schizophrenia demonstrated significant enlargement of the anterior horn of the lateral ventricle and the third ventricle in patients with OCS compared with patients who did not have OCS.64 In a different study of patients with schizophrenia and various degrees of OCS, functional MRI found that one subgroup exhibited a negative correlation between activation of the left dorsolateral prefrontal cortex and OCS severity.65
Taken together, these findings suggest greater neuroanatomical dysfunction in the comorbid subgroup. Whether these findings reflect a specific pattern of dysfunction unique to this comorbid subgroup or a more severe form of illness with greater brain dysfunction is thus far unclear. The question warrants further study.
Several studies have compared the profiles of neurocognitive deficits in patients with schizophrenia without OCS with those of the schizo-obsessive subgroup. Most, but not all, of these studies have revealed more severe neuropsychological impairments in the comorbid subgroup.66 Compared with their schizophrenia-only counterparts, the comorbid subgroup demonstrated greater impairment in nonverbal memory, cognitive shifting abilities, visuospatial skills, and executive function as measured by performance on the Wisconsin Card Sorting Test.30,37,38,67,68
Epidemiological and biological data strongly suggest an integral relationship between OCD and schizophrenia in the comorbid subgroup of patients. The epidemiological data strongly suggest a unique relationship between these 2 disorders, given the marked degree of comorbidity that has been consistently observed and which appears to represent more than just a spurious association. Although pedigree and genetic studies of this overlap group are limited, preliminary findings suggest intriguing genetic influences on comorbid symptom expression.
The neurobiological data on each disorder suggest the involvement of common brain regions and neurotransmitter systems. However, more neuroimaging studies in the overlap group are required to determine whether specific structural abnormalities unique to this putative subtype are present Neuropsychological testing has generally revealed more severe impairment among patients in this comorbid group, which suggests a specific and active interaction between these 2 disease processes, but it has not identified a unique pattern of impairment.9
Hence, despite the growing body of evidence that supports the existence of a specific epidemiological, genetic, and neurobiological relationship between these 2 disorders, the association remains poorly understood. The question of whether this overlap group represents a distinct diagnostic entity or comorbid disorders that result from a greater magnitude of brain involvement, common neurodevelopmental predisposing factors, or other confounding factors is impossible to answer definitively on the basis of existing knowledge.
Further neurobiological and genetic research that focuses specifically on this comorbid group is essential to clarify the nature of this proposed diagnostic entity. The current literature suggests that this comorbid subgroup probably carries a greater overall illness burden and that these patients have more distress and impairment and worse outcomes-including the possibility of higher suicide risk. These clinical issues highlight the importance of identification and treatment of OCS in schizophrenia (Table) while the biological underpinnings continue to be elucidated.
Drug Mentioned in This Article
1. Berrios GE. Obsessive-compulsive disorder: its conceptual history in France during the 19th century. Compr Psychiatry. 1989;30:283-295.
2. Khullar A, Chue P, Tibbo P. Quetiapine and obsessive-compulsive symptoms (OCS): case report and review of atypical antipsychotic-induced OCS. J Psychiatry Neurosci. 2001;26:55-59.
3. Alevizos B, Lykouras L, Zervas IM, Christodoulou GN. Risperidone-induced obsessive-compulsive symptoms: a series of six cases. J Clin Psychopharmacol. 2002;22:461-467.
4. de Haan L, Beuk N, Hoogenboom B, et al. Obsessive-compulsive symptoms during treatment with olanzapine and risperidone: a prospective study of 113 patients with recent-onset schizophrenia or related disorders. J Clin Psychiatry. 2002;63:104-107.
5. Lykouras L, Zervas IM, Gournellis R, et al. Olanzapine and obsessive-compulsive symptoms. Eur Neuropsychopharmacol. 2000;10:385-387.
6. Ghaemi SN, Zarate CA Jr, Popli AP, et al. Is there a relationship between clozapine and obsessive-compulsive disorder? A retrospective chart review. Compr Psychiatry. 1995;36:267-270.
7. Hwang MY, Hollander E. Schizo-obsessive disorders. Psychiatr Ann. 1993;23:396-401.
8. Zohar J. Is there room for a new diagnostic subtype: the schizo-obsessive subtype? CNS Spectr. 1997;2:49-50.
9. Bottas A, Cooke RG, Richter MA. Comorbidity and pathophysiology of obsessive-compulsive disorder in schizophrenia: is there evidence for a schizo-obsessive subtype of schizophrenia? J Psychiatry Neurosci. 2005;30:187-193.
10. Sadock BJ, Sadock VA, eds. Kaplan and Sadock’s Comprehensive Textbook of Psychiatry [CD-ROM]. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2000.
11. Fenton WS, McGlashan TH. The prognostic significance of obsessive-compulsive symptoms in schizophrenia. Am J Psychiatry. 1986;143:437-441.
12. Bland RC, Newman SC, Orn H. Schizophrenia: lifetime co-morbidity in a community sample. Acta Psychiatr Scand. 1987;75:383-391.
13. Berman I, Kalinowski SM, Berman SM, et al. Obsessive and compulsive symptoms in chronic schizophrenia. Compr Psychiatry. 1995;36:6-10.
14. Porto L, Bermanzohn P, Pollack S, et al. A profile of obsessive-compulsive symptoms in schizophrenia. CNS Spectr. 1997;2:21-25.
15. Fabisch K, Fabisch H, Langs G, et al. Incidence of obsessive-compulsive phenomena in the course of acute schizophrenia and schizoaffective disorder. Eur Psychiatry. 2001;16:336-341.
16. Craig T, Hwang M, Bromet E. Obsessive-compulsive and panic symptoms in patients with first- admission psychosis. Am J Psychiatry. 2002;159: 592-598.
17. Eisen JL, Beer DA, Pato MT, et al. Obsessive-compulsive disorder in patients with schizophrenia or schizoaffective disorder. Am J Psychiatry. 1997;154: 271-273.
18. Poyurovsky M, Hramenkov S, Isakov V, et al. Obsessive-compulsive disorder in hospitalized patients with chronic schizophrenia. Psychiatry Res. 2001; 102:49-57.
19. Poyurovsky M, Fuchs C, Weizman A. Obsessive-compulsive disorder in patients with first-episode schizophrenia. Am J Psychiatry. 1999;156:1998-2000.
20. Tibbo P, Kroetsch M, Chue P, Warneke L. Obsessive-compulsive disorder in schizophrenia. J Psychiatr Res. 2000;34:139-146.
21. Ohta M, Kokai M, Morita Y. Features of obsessive-compulsive disorder in patients primarily diagnosed with schizophrenia. Psychiatry Clin Neurosci. 2003; 57:67-74.
22. Nechmad A, Ratzoni G, Poyurovsky M, et al. Obsessive-compulsive disorder in adolescent schizophrenia patients. Am J Psychiatry. 2003;160:1002-1004.
23. KrÃ¼ger S, BrÃ¤unig P, HÃ¶ffler J, et al. Prevalence of obsessive-compulsive disorder in schizophrenia and significance of motor symptoms. J Neuropsychiatry Clin Neurosci. 2000;12:16-24.
24. Insel TR, Akiskal HS. Obsessive-compulsive disorder with psychotic features: a phenomenologic analysis. Am J Psychiatry. 1986;143:1527-1533.
25. Fontenelle LF, Lopes AP, Borges MC, et al. Auditory, visual, tactile, olfactory, and bodily hallucinations in patients with obsessive-compulsive disorder. CNS Spectr. 2008;13:125-130.
26. First M, Spitzer R, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV Axis I Disorders-Administration Booklet. Washington, DC: American Psychiatric Press; 1994:70-73.
27. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale, I: development, use, and reliability. Arch Gen Psychiatry. 1989;46:1006-1011.
28. de Haan L, Hoogeboom B, Beuk N, et al. Reliability and validity of the Yale-Brown Obsessive-Compulsive Scale in schizophrenia patients. Psychopharmacol Bull. 2006;39:25-30.
29. Poyurovsky M, Dorfman-Etrog P, Hermesh H, et al. Beneficial effect of olanzapine in schizophrenic patients with obsessive-compulsive symptoms. Int Clin Psychopharmacol. 2000;15:169-173.
30. Berman I, Merson A, Viegner B, et al. Obsessions and compulsions as a distinct cluster of symptoms in schizophrenia: a neuropsychological study. J Nerv Ment Dis. 1998;186:150-156.
31. Berman I, Sapers BL, Chang HH, et al. Treatment of obsessive-compulsive symptoms in schizophrenic patients with clomipramine. J Clin Psychopharmacol. 1995;15:206-210.
32. Poyurovsky M, Isakov V, Hromnikov S, et al. Fluvoxamine treatment of obsessive-compulsive symptoms in schizophrenic patients: an add-on open study. Int Clin Psychopharmacol. 1999;14:95-100.
33. Reznik I, Sirota P. An open study of fluvoxamine augmentation of neuroleptics in schizophrenia with obsessive and compulsive symptoms. Clin Neuropharmacol. 2000;23:157-160.
34. Rosen I. The clinical significance of obsessions in schizophrenia. J Ment Sci. 1957;103:773-785.
35. Stengel E. A study on some clinical aspects of the relationship between obsessional neurosis and psychotic reaction types. J Ment Sci. 1945;91:166-187.
36. Dowling FG, Pato MT, Pato CN. Comorbidity of obsessive-compulsive and psychotic symptoms: a review. Harv Rev Psychiatry. 1995;3:75-83.
37. Lysaker PH, Marks KA, Picone JB, et al. Obsessive and compulsive symptoms in schizophrenia: clinical and neurocognitive correlates. J Nerv Ment Dis. 2000;188:78-83.
38. Lysaker PH, Bryson GJ, Marks KA, et al. Association of obsessions and compulsions in schizophrenia with neurocognition and negative symptoms. J Neuropsychiatry Clin Neurosci. 2002;14:449-453.
39. Ongur D, Goff DC. Obsessive-compulsive symptoms in schizophrenia: associated clinical features, cognitive function and medication status. Schizophr Res. 2005;75:349-362.
40. Rajkumar RP, Reddy YC, Kandavel T. Clinical profile of “schizo-obsessive” disorder: a comparative study. Compr Psychiatry. 2008;49:262-268.
41. Mukhopadhay K, Krishnaiah R, Taye T, et al. Obsessive-compulsive disorder in UK clozapine-treated schizophrenia and schizoaffective disorder: a cause for clinical concern. J Psychopharmacol. 2009;23:6-13.
42. Sevincok L, Akoglu A, Arslantas H. Schizo-obsessive and obsessive-compulsive disorder: comparison of clinical characteristics and neurological soft signs. Psychiatry Res. 2006;145:241-248.
43. Lysaker PH, Whitney KA, Davis LW. Obsessive-compulsive and negative symptoms in schizophrenia: associations with coping preference and hope. Psychiatry Res. 2006;141:253-259.
44. de Hann L, Hoogenboom B, Beuk N, et al. Obsessive-compulsive symptoms and positive, negative and depressive symptoms in patients with recent- onset schizophrenic disorders. Can J Psychiatry. 2005;50:519-524.
45. Sevincok L, Akoglu A, Kokcu F. Suicidality in schizophrenic patients with and without obsessive-compulsive disorder. Schizophr Res. 2007;90:198-202.
46. OngÃ¼r D, Goff DC. Obsessive-compulsive symptoms in schizophrenia: associated clinical features, cognitive function and medication status. Schizophr Res. 2005;75:349-362.
47. Byerly M, Goodman W, Acholonu W, et al. Obsessive compulsive symptoms in schizophrenia: frequency and clinical features. Schizophrenia Res. 2005;76:309-316.
48. Poyurovsky M, Faragian S, Pashinian A, et al. Neurological soft signs in schizophrenia patients with obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci. 2007;19:145-150.
49. Zinkstok J, van Nimwegen L, van Amelsvoort T, et al. Catechol-O-methyltransferase gene and obsessive-compulsive symptoms in patients with recent-onset schizophrenia: preliminary results. Psychiatry Res. 2008;157:1-8.
50. Poyurovsky M, Kriss V, Weisman G, et al. Familial aggregation of schizophrenia-spectrum disorders and obsessive-compulsive associated disorders in schizophrenia probands with and without OCD. Am J Med Genet B Neuropsychiatr Genet. 2005;133B:31-36.
51. Kapur S, Remington G. Serotonin-dopamine interaction and its relevance to schizophrenia. Am J Psychiatry. 1996;153:466-476.
52. Tibbo P, Warneke L. Obsessive-compulsive disorder in schizophrenia: epidemiologic and biologic overlap. J Psychiatry Neurosci. 1999;24:15-24. 53. Stein DJ. Neurobiology of the obsessive-compulsive spectrum disorders. Biol Psychiatry. 2000;47: 296-304.
54. McDougle CJ, Goodman WK, Leckman JF, Price LH. The psychopharmacology of obsessive compulsive disorder. Implications for treatment and pathogenesis. Psychiatr Clin North Am. 1993;16:749-766.
55. Goodman WK, McDougle CJ, Price LG, et al. Beyond the serotonin hypothesis: a role for dopamine in some forms of obsessive-compulsive disorder? J Clin Psychiatry. 1990;51(suppl):S36-S43.
56. McDougle CJ, Goodman WK, Leckman JF, et al. Haloperidol addition in fluvoxamine-refractory obsessive- compulsive disorder: a double-blind placebocontrolled study in patients with and without tics. Arch Gen Psychiatry. 1994;51:302-308.
57. McDougle CJ, Epperson CN, Pelton GH, et al. A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive- compulsive disorder. Arch Gen Psychiatry. 2000;57:794-801.
58. Ma N,Tan LW,Wang Q, et al. Lower levels of whole blood serotonin in obsessive-compulsive disorder and in schizophrenia with obsessive-compulsive symptoms. Psychiatry Res. 2007;150:61-69.
59. Adler CM, Strakowski SM. Boundaries of schizophrenia. Psychiatr Clin North Am. 2003;26:1-23.
60. Gross-Isseroff R, Hermesh H, Zohar J,Weizman A. Neuroimaging communality between schizophrenia and obsessive compulsive disorder: a putative basis for schizo-obsessive disorder? World J Biol Psychiatry. 2003;4:129-134.
61. Stein DJ. Obsessive-compulsive disorder. Lancet. 2002;360:397-405.
62. Graybiel AM, Rauch SL. Toward a neurobiology of obsessive-compulsive disorder. Neuron. 2000;28: 343-347.
63. Aoyama F, Iida J, Inoue M, et al. Brain imagingin childhood- and adolescent-onset schizophrenia associated with obsessive-compulsive symptoms.Acta Psychiatr Scand. 2000;102:32-37.
64. Iida J, Matumura K,Aoyama F. Cerebral MRI findings in childhood-onset schizophrenia, comparison of patients with prodromal obsessive-compulsive symptoms and those without symptoms. Recent Prog Child Adolesc Psychiatry. 1998;2:75-83.
65. Levine JB, Gruber SA, Baird AA,Yurgelun-Todd D. Obsessive-compulsive disorder among schizophrenic patients: an exploratory study using functional magnetic resonance imaging data. Compr Psychiatry. 1998;39:308-311.
66. Borkowska A, PilaczyÃ±ska 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.
67. 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.
68. 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.
69. Koran LM, Hanna, GL, Hollander E, et al; American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007;164(suppl 7):5-53.
70. Chiao-Li K, Cheng-Fang Y, Cheng-Chung C, et al. Obsessive-compulsive symptoms associated with clozapine and risperidone treatment: three case reports and review of the literature. Kaohsiung J Med Sci. 2004;20:295-301