Anxiety Disorders: Richter MA

Ravindran AV, da Silva TL, Ravindran LN, Richter MA, Rector NA. · University of Toronto, Ontario, Canada. · Can J Psychiatry. · Pubmed #19497165 No free full text.

Abstract: OBJECTIVE: To provide a review of the evidence-based treatments for obsessive-compulsive spectrum disorders (OCSD), a group of conditions related to obsessive-compulsive disorder (OCD) by phenomenological and etiological similarities, the morbidity of which is increasingly recognized. METHOD: Literature relating to the following disorders: body dysmorphic disorder, hypochondriasis, trichotillomania, onychophagia, psychogenic excoriation, compulsive buying, kleptomania, and pathological gambling, and published between January 1965 and October 2007, was found using PubMed. Included in this review were 107 treatment reports. RESULTS: Serotonin reuptake inhibitors (SRIs) have shown benefits as first-line, short-term treatments for body dysmorphic disorder, hypochondriasis, onychophagia, and psychogenic excoriation, with some benefits in trichotillomania, pathological gambling, and compulsive buying. There are also suggested benefits for several atypical antipsychotics in disorders with a high degree of impulsivity, including trichotillomania and pathological gambling, and to a lesser extent, kleptomania and psychogenic excoriation. Cognitive-behavioural interventions have generally shown evidence for use as first-line treatment across the spectrum, with some variability in degree of benefit. CONCLUSIONS: As in OCD, several conditions in the proposed OCSD benefit from SRIs and (or) cognitive-behavioural interventions. However, the treatment literature is generally limited, and more randomized controlled trials (RCTs) are needed to evaluate individual and combination treatments, for short-term use and as maintenance.

Bottas A, Cooke RG, Richter MA. · Department of Psychiatry, University of Toronto, ON, Canada. · J Psychiatry Neurosci. · Pubmed #15944743 links to  free full text

Abstract: Epidemiologic and neurobiologic evidence suggests that patients with comorbid obsessive-compulsive disorder (OCD) and schizophrenia may represent a special category among patients with schizophrenia. Efforts to examine the neurobiology of this group have focused on neuroimaging studies and neuropsychologic testing. Convergent evidence suggests that there may be a specific pattern of neurobiologic dysfunction in this subgroup of patients accounting for symptom co-expression. This review indicates that future studies should distinguish among (1) apparent obsessive-compulsive symptoms (OCS) that occur only in the context of psychosis and that may overlap with psychotic phenomenology, representing a forme fruste of psychosis; (2) OCS occurring only in the prodromal phase of schizophrenia; (3) neuroleptic-induced OCS or OCD; and (4) OCS or frank OCD occurring concurrently with schizophrenia. We examine the evidence for a putative schizo-obsessive disorder and outline suggestions for identifying OCS in the presence of psychosis.

Arnold PD, Zai G, Richter MA. · Anxiety Disorders Clinic, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada. · Curr Psychiatry Rep. · Pubmed #15260939 No free full text.

Abstract: There is considerable evidence that genetic determinants play a major role in the etiology of anxiety. Investigations into susceptibility genes for anxiety are well underway, particularly for panic disorder and obsessive-compulsive disorder and more broadly defined anxiety-related traits, such as neuroticism and harm avoidance. This review will discuss some of the core issues related to diagnosis and molecular genetic methodology, followed by a review of recent molecular genetic findings for anxiety. The authors will attempt to highlight the numerous convergent and exciting findings. Given the rapid acceleration in knowledge of the human genome, a more definitive understanding of the genetic roots of these complex conditions may be anticipated in the relatively near future.

Arnold PD, Richter MA. · Neurogenetics Section, Centre for Addiction and Mental Health, University of Toronto, Ont. · CMAJ. · Pubmed #11760984 links to  free full text

Abstract: OBSESSIVE-COMPULSIVE DISORDER (OCD) IS A COMMON and debilitating neuropsychiatric disorder. Although it is widely believed to have a genetic basis, no specific genetic factors have been conclusively identified as yet, leading researchers to look for environmental risk factors that may interact with an underlying genetic susceptibility in affected individuals. Recently, there has been increasing interest in a possible link between streptococcal infections and the development of OCD and tic disorders in children. It has been suggested that OCD in some susceptible individuals may be caused by an autoimmune response to streptococcal infections, that is, a similar biological mechanism to that associated with Sydenham's chorea. The term "pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections" (PANDAS) has been used to describe a subset of children with abrupt onset or exacerbations of OCD or tics, or both, following streptococcal infections. Affected children have relatively early symptom onset, characteristic comorbid symptoms and subtle neurological dysfunction. Neuroimaging studies reveal increased basal ganglia volumes, and the proposed cause involves the cross-reaction of streptococcal antibodies with basal ganglia tissue. Vulnerability to developing PANDAS probably involves genetic factors, and elevated levels of D8/17 antibodies may represent a marker of susceptibility to PANDAS. Prophylactic antibiotic treatments have thus far not been shown to be helpful in preventing symptom exacerbations. Intravenous immunoglobulin therapy may be an effective treatment in selected individuals. Further understanding of the role of streptococcal infections in childhood-onset OCD will be important in determining alternative and effective strategies for treatment, early identification and prevention of this common and debilitating psychiatric disorder.

Arnold PD, Macmaster FP, Richter MA, Hanna GL, Sicard T, Burroughs E, Mirza Y, Easter PC, Rose M, Kennedy JL, Rosenberg DR. · Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8. · Psychiatry Res. · Pubmed #19324536 No free full text.

Abstract: In this preliminary study, 16 psychotropic-naïve pediatric patients with obsessive-compulsive disorder (OCD) were studied using magnetic resonance spectroscopy (MRS) and genotyped for six candidate polymorphisms in two glutamate system genes. A significant association was identified between the rs1019385 polymorphism of the glutamate receptor, ionotropic, N-methyl-d-aspartate 2B (GRIN2B) and decreased anterior cingulate cortex (ACC) glutamatergic concentration (Glx) but not with occipital Glx. These results suggest that GRIN2B may be associated with Glx in the ACC, a region consistently implicated in OCD.

Rector NA, Cassin SE, Richter MA, Burroughs E. · Anxiety Disorders Clinic, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada. · J Anxiety Disord. · Pubmed #18619770 No free full text.

Abstract: Cognitive models of obsessive-compulsive disorder (OCD) focus on the role of dysfunctional beliefs and appraisals in conferring risk to the onset and persistence of clinical obsessions. The origins of obsessive beliefs have been proposed to occur within a familial-based developmental context, although little research has examined this empirically. The aim of the present study was to examine the familial cognitive vulnerability for OCD by comparing scores on the Obsessive Beliefs Questionnaire (OBQ) [Obsessive Compulsive Cognitions Working Group (2005). Psychometric validation of the obsessive beliefs questionnaire and interpretation of intrusions inventory-Part 2. Factor analyses and testing of a brief version. Behavior Research and Therapy, 43, 1527-1542] between DSM-IV diagnosed OCD probands, their nonaffected first-degree relatives, and nonaffected controls. First-degree relatives scored significantly higher than controls on the OBQ domain tapping inflated responsibility and overestimation of threat. Further, relatives of early onset OCD probands scored significantly higher than controls on both the inflated responsibility and overestimation of threat domain and the domain tapping perfectionism and intolerance of uncertainty. The results are discussed in relation to the developmental context of cognitive-based vulnerabilities for OCD.

Arnold PD, Sicard T, Burroughs E, Richter MA, Kennedy JL. · Neurogenetics Section, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario M5T 1R8, Canada. · Arch Gen Psychiatry. · Pubmed #16818866 links to  free full text

Abstract: CONTEXT: There is strong evidence from family and twin studies that genetic determinants play an important role in the etiology of obsessive-compulsive disorder (OCD). In the only genome scan of OCD to date that we are aware of, suggestive linkage was reported to the chromosomal region 9p24, a finding that was subsequently replicated. This region contains the gene encoding the neuronal glutamate transporter, SLC1A1. SLC1A1 represents an excellent candidate gene for OCD based on evidence from neuroimaging and animal studies that altered glutamatergic neurotransmission is implicated in the pathogenesis of this disorder. OBJECTIVE: To determine whether sequence variants in SLC1A1 are associated with transmission of the OCD trait. DESIGN: A family-based candidate gene association study. SETTING: A specialized anxiety disorders outpatient clinic. PARTICIPANTS: One hundred fifty-seven white probands with DSM-IV OCD recruited from consecutive referrals and their first-degree relatives (476 individuals in total). INTERVENTION: Nine single nucleotide polymorphisms spanning SLC1A1 were genotyped. Single-locus and haplotype analyses were performed using the Family-Based Association Test and the Transmission Disequilibrium Test. Traits examined included DSM-IV OCD diagnosis and highest lifetime symptom severity as measured using the Yale-Brown Obsessive-Compulsive Scale. Correction for multiple comparisons was performed using permutation tests. RESULTS: After correction for multiple comparisons, 2 variants, rs301434 (chi 2 = 12.04; P = .006) and rs301435 (chi 2 = 9.24; P = .03), located within a single haplotype block were found to be associated with transmission of OCD. Furthermore, a specific 2-marker haplotype within this block was significantly associated with OCD (chi 2 = 12.60; P = .005). This haplotype association was statistically significant in transmissions to male but not female offspring. CONCLUSIONS: Although requiring replication in larger samples, these findings provide preliminary evidence that sequence variation in SLC1A1 is associated with susceptibility to OCD, particularly in males. Furthermore, these results provide support for the role of altered glutamatergic neurotransmission in the pathogenesis of OCD.

Hu XZ, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD, Xu K, Arnold PD, Richter MA, Kennedy JL, Murphy DL, Goldman D. · Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852, USA. · Am J Hum Genet. · Pubmed #16642437 links to  free full text

Abstract: A functional serotonin transporter promoter polymorphism, HTTLPR, alters the risk of disease as well as brain morphometry and function. Here, we show that HTTLPR is functionally triallelic. The L(G) allele, which is the L allele with a common G substitution, creates a functional AP2 transcription-factor binding site. Expression assays in 62 lymphoblastoid cell lines representing the six genotypes and in transfected raphe-derived cells showed codominant allele action and low, nearly equivalent expression for the S and L(G) alleles, accounting for more variation in HTT expression than previously recognized. The gain-of-function L(A)L(A) genotype was approximately twice as common in 169 whites with obsessive-compulsive disorder (OCD) than in 253 ethnically matched controls. We performed a replication study in 175 trios consisting of probands with OCD and their parents. The L(A) allele was twofold overtransmitted to the patients with OCD. The HTTLPR L(A)L(A) genotype exerts a moderate (1.8-fold) effect on risk of OCD, which crystallizes the evidence that the HTT gene has a role in OCD.

Zai G, Arnold PD, Burroughs E, Richter MA, Kennedy JL. · Institute of Medical Science, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. · Psychiatr Genet. · Pubmed #16395130 No free full text.

Abstract: Dysregulation of the immune system has been suggested to play a role in the complex etiology of obsessive-compulsive disorder. In this context, tumor necrosis factor-alpha is considered an interesting candidate for genetic studies as overproduction of tumor necrosis factor-alpha, which may be genetically modulated, can exert neurotoxic effects and influence neural cell growth and proliferation. Moreover, the tumor necrosis factor-alpha gene is located on chromosome 6p21.3, a region that has been found to be weakly associated with obsessive-compulsive disorder in linkage studies. One functional polymorphism, G-308A, has been found within the gene.

Levitan RD, Kaplan AS, Masellis M, Basile VS, Richter MA, Kennedy JL. · Mood and Anxiety Division, Centre for Addiction and Mental Health, University of Toronto, Department of Psychiatry, Canada. · Eur Neuropsychopharmacol. · Pubmed #15944142 No free full text.

Abstract: BACKGROUND: There is significant evidence that eating disorders have an important biological overlap with obsessive-compulsive disorder (OCD), though the specific mediators of this relationship remain unclear. Recent evidence suggests that the G861C polymorphism of the 5HT-1Dbeta receptor gene and the G allele in particular may play a role in OCD. We thus hypothesized that, among a heterogenous group of probands with bulimia nervosa (BN), this same G allele might predict the presence and/or severity of OCD pathology. METHODS: 165 consecutive female probands with BN were genotyped for the G861C polymorphism of the 5HT-1Dbeta receptor gene. Rates of full syndrome OCD, partial syndrome OCD and no OCD were compared across the three genotypic groups defined by this polymorphism. RESULTS: 45 out of 165 BN probands (27.3%) had either full or partial syndrome OCD. In the full sample, there was a significant difference in the distribution of the three diagnostic groups by genotype (chi2=10.07, df=4, p=.039). The G861C polymorphism did not strongly predict which probands had any vs. no OCD pathology. However, among the 45 probands with OCD symptoms, the G861C polymorphism did strongly differentiate full syndrome vs. partial syndrome OCD (chi2=9.26, df=2, p=.01; odds ratio for full syndrome OCD with GG genotype=7.69, 95% CI=1.45-40.9). DISCUSSION: In women with BN, the G861C polymorphism of the 5HT-1Dbeta gene does not appear to be associated with the generation of OCD symptoms; however, it might directly or indirectly be associated with a modulatory effect on syndrome severity in probands otherwise predisposed to OCD. While preliminary and in need of replication in other samples, this is the first association study to suggest how a particular gene might influence OCD pathology in an eating disorder population.

Rector NA, Richter MA, Bagby RM. · Anxiety Disorders Clinic, Mood and Anxiety Program, Centre for Addiction and Mental Health, University of Toronto, Ontario M5T 1R8, Canada. · J Nerv Ment Dis. · Pubmed #15805818 No free full text.

Abstract: Previous research conducted on the five-factor model of personality (FFM) in obsessive-compulsive disorder (OCD) has demonstrated that community and clinical participants score significantly higher than controls on the domains and facets of neuroticism and extraversion and selective facets of agreeableness and conscientiousness. However, studies have yet to examine the extent to which personality traits, as assessed by the FFM, are associated with the specific symptoms of OCD. The purpose of this study was to examine further the personality predictors of obsessive-compulsive symptoms in clinical participants using the facets of the FFM. Patients with a DSM-IV diagnosis of OCD (N = 56) completed the Revised NEO Personality Inventory, the Yale Brown Obsession Compulsion Scale, and the Beck Depression Inventory. Lower scores on openness to ideas were uniquely associated with greater obsession severity, whereas lower openness to actions was uniquely associated with greater compulsive severity. In contrast with past research that has emphasized the association between neuroticism and extraversion and dimensionally rated obsessive-compulsive symptoms, this study demonstrates the specific associations between selective facet traits of openness and clinical obsessions and compulsions. Whereas tendencies toward negative affectivity may confer a nonspecific vulnerability to the development of OCD, facets of openness may impact on the particular expression and severity of obsessive-compulsive symptoms.

Zai G, Arnold P, Burroughs E, Barr CL, Richter MA, Kennedy JL. · Neurogenetics Section, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Canada. · Am J Med Genet B Neuropsychiatr Genet. · Pubmed #15685626 No free full text.

Abstract: Obsessive-compulsive disorder (OCD) is a well-recognized severe neuropsychiatric illness. Genetic factors are believed to be important etiologically. Although historically genetic testing has focused on the serotonergic and dopaminergic systems, there is increasing evidence that the major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), may also be functionally involved. Furthermore the GABA type B receptor 1 (GABBR1) gene has been localized to chromosome 6p21.3 region, which has shown linkage to OCD. We investigated five polymorphisms (A-7265G substitution; C10497G substitution; A33795G substitution in the 3'-UTR; Ser-491-Ser-T1473C transition; Phe-659-Phe-T1977C transition) in the GABBR1 gene in a sample of 159 DSM-IV OCD probands and their families, using the transmission disequilibrium test (TDT). A trend was observed with an over-transmission of -7265A allele at the A-7265G polymorphism and OCD (chi2 = 3.270, P = 0.071). Moreover, the TDT haplotype analysis using TRANSMIT showed a trend toward association with the haplotype of the five polymorphisms together [2.1.1.2.1 (A-7265G.C10497G.Ser-491-Ser.Phe-659-Phe.A33795G)] with a Chi-square value of 3.418, which corresponds to a P-value of 0.065 (overall chi2 = 6.353, 5 df, P = 0.273). Moreover, a trend was observed for the total Yale-Brown obsessive-compulsive scale score in the A-7265G polymorphism (-7265A: z = 1.934, P = 0.053) using the Family-Based Association Test, considering the diagnosis of OCD and then the clinically relevant quantitative phenotypes. The observed trends suggest that further investigations of the role of the GABBR1 gene in OCD are warranted.

Summerfeldt LJ, Kloosterman PH, Antony MM, Richter MA, Swinson RP. · Department of Psychology, Trent University, Peterborough, Ont K9J 7B8, Canada. · Behav Res Ther. · Pubmed #15500815 No free full text.

Abstract: The diverse symptomatology of obsessive-compulsive disorder (OCD) is being increasingly regarded as reducible to a few symptom dimensions. However, prevailing factor-analytically derived models of symptom structure omit a number of the well-recognized "miscellaneous" symptoms of OCD. This study sought to determine whether miscellaneous OCD symptoms, ascertained by the Yale-Brown Obsessive-Compulsive Scale symptom checklist, could be differentially and reliably predicted by four symptom factors (obsessions and checking, symmetry and ordering, contamination and cleaning, and hoarding) in two independent groups of individuals with OCD (n=381 and n=107). Logistic regression analyses were used to determine the association of each of the miscellaneous symptoms with the symptom factors; then a single confirmatory factor analysis was conducted to test the model of associations in the smaller sample. Sixteen (89%) of the 18 symptoms examined were reliably predicted by one (11 items) or two (5 items) of the factors, with obsessions and checking and symmetry and ordering emerging as foremost predictors. The expanded four-factor model showed good fit with data from the second sample. Results are conceptually meaningful, but suggest the inadequacy of groupings based solely upon overt behaviors. These findings may aid clinical understanding of OCD and be of value to studies using symptom factors to guide investigation of its causes and correlates.

Zai G, Bezchlibnyk YB, Richter MA, Arnold P, Burroughs E, Barr CL, Kennedy JL. · Neurogenetics Section, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada. · Am J Med Genet B Neuropsychiatr Genet. · Pubmed #15274043 No free full text.

Abstract: Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric disorder with a strong genetic component, and may involve autoimmune processes. Support for this latter hypothesis comes from the identification of a subgroup of children, described by the term pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS), with onset of OCD symptoms following streptococcal infections. Genes involved in immune response therefore represent possible candidate genes for OCD, including the myelin oligodendrocyte glycoprotein (MOG) gene, which plays an important role in mediating the complement cascade in the immune system. Four polymorphisms in the MOG gene, a dinucleotide CA repeat (MOG2), a tetranucleotide TAAA repeat (MOG4), and 2 intronic single nucleotide polymorphisms, C1334T and C10991T, were investigated for the possibility of association with OCD using 160 nuclear families with an OCD proband. We examined the transmission of alleles of these four polymorphisms with the transmission disequilibrium test (TDT). A biased transmission of the 459-bp allele (allele 2: chi2 = 5.255, P = 0.022) of MOG4 was detected, while MOG2, C1334T, and C10991T showed no statistically significant bias in the transmission of alleles. The transmission of the C1334T.MOG2.C10991T.MOG4 haplotype 1.13.2.2 (chi2 = 6.426, P = 0.011) was also significant. Quantitative analysis using the family-based association test (FBAT) was significant for MOG4 in total Yale-Brown Obsessive-Compulsive Scale severity score (allele 2: z = 2.334, P = 0.020). Further investigations combining genetic, pathological, and pharmacological strategies, are warranted.

Arnold PD, Rosenberg DR, Mundo E, Tharmalingam S, Kennedy JL, Richter MA. · Child Psychiatry Program, Neurogenetics Section, 1st Floor, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, Ontario, Canada M5T 1R8. · Psychopharmacology (Berl). · Pubmed #15083261 No free full text.

Abstract: RATIONALE: Recent investigation suggests that a reversible glutamatergically mediated thalamocortical-striatal dysfunction may serve as a reliable pathophysiological and treatment response marker for obsessive-compulsive disorder (OCD). We postulated that N-methyl- d-aspartate (NMDA) receptors were involved in OCD, and specifically that polymorphisms in the 3' untranslated region of GRIN2B (glutamate receptor, ionotropic, N-methyl- d-aspartate 2B) were associated with OCD in affected families. OBJECTIVES: The objective of this investigation was to test the association between GRIN2B variants and transmission of the OCD trait using a family-based design. METHODS: Using the Family Based Association Test (FBAT), we tested for association with OCD diagnosis in 130 families, and also performed a haplotype analysis. FBAT was additionally used in a subset of 98 families to test for association with the quantitative phenotype of lifetime OCD symptom severity. RESULTS. Under a non-additive model of inheritance, the 5072T/G variant was significantly associated with OCD even after correcting for the number of models tested ( P=0.014). In addition, there was a significant positive association with OCD diagnosis ( P=0.002) for the 5072G-5988T haplotype under the recessive model. CONCLUSIONS: Although preliminary and requiring replication in larger samples, these results provide evidence that GRIN2B may be associated with susceptibility to OCD. Coupled with basic neuroscience and clinical neuroimaging findings in patients with OCD, our results provide new and converging support for the role of altered glutamatergic neurotransmission in the pathogenesis of OCD.

Richter MA, Summerfeldt LJ, Antony MM, Swinson RP. · Anxiety Disorders Clinic, Centre for Addiction and Mental Health, Clarke Division, and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. · Depress Anxiety. · Pubmed #14625876 No free full text.

Abstract: In light of current interest in an obsessive-compulsive spectrum of disorders, this study sought to determine whether comorbidity patterns support the unique relationship hypothesized between these conditions and obsessive-compulsive disorder (OCD). Comparisons were made of lifetime rates of several proposed spectrum conditions in individuals with one of three anxiety disorder principal diagnoses (OCD, social phobia, or panic disorder [PD], N=277). Spectrum conditions examined included tic-related disorders, trichotillomania, skin picking, and eating disorders, with analyses performed on rates both of clinical disorder alone, and clinical and subclinical manifestations jointly. The OCD group was found to differ from both other groups in showing 1) a greater proportion of individuals affected with any lifetime spectrum condition, 2) a greater number of lifetime spectrum conditions affecting each individual, and 3) a greater proportion of individuals having a lifetime history of multiple spectrum conditions. Analyses for specific spectrum conditions indicated differences among the anxiety disorder groups for all spectrum categories except eating disorders, though only in the case of tic-related conditions did OCD differ significantly from both comparison groups. For the other conditions, dissimilar patterns of differences were observed among the three groups, particularly when subclinical manifestations were included. These findings have conceptual and clinical implications, including 1) the salience of tic-related disorders in the OC spectrum, 2) the possibility that the relationship between spectrum conditions and anxiety disorders may take several different forms, and 3) the need for refinement of the hypothesized spectrum.

Masellis M, Rector NA, Richter MA. · Department of Psychiatry, University of Toronto, Toronto, Ontario. · Can J Psychiatry. · Pubmed #12655903 No free full text.

Abstract: OBJECTIVE: An anxiety disorder severely affects the sufferer's quality of life (QOL), and this may be particularly true of those with obsessive-compulsive disorder (OCD). This study examines the differential impact of obsessions, compulsions, and depression comorbidity on the QOL of individuals with OCD. METHOD: Forty-three individuals diagnosed with OCD according to DSM-IV criteria and experiencing clinically significant obsessions and compulsions completed measures of QOL, obsessive-compulsive symptom severity, and depression severity. RESULTS: Obsession severity was found to significantly predict patient QOL, whereas the severity of compulsive rituals did not impact on QOL ratings. Comorbid depression severity was the single greatest predictor of poor QOL, accounting for 54% of the variance. CONCLUSIONS: Given the importance of these symptoms, treatments that directly target obsessions and secondary depression symptoms in OCD are warranted. However, replication of these findings in a prospective cohort study is required, because although the the current study's cross-sectional design allows for the examination of the associations among obsessions, depression, and QOL, it cannot establish their temporal framework (that is, causal relations).

Rector NA, Hood K, Richter MA, Bagby RM. · Mood and Anxiety Program, Centre For Addiction and Mental Health, Toronto, Ontario, Canada. · Behav Res Ther. · Pubmed #12375729 No free full text.

Abstract: Research on individual differences in obsessive-compulsive disorder (OCD) has focused largely on analogue models with participants experiencing sub-clinical obsessions and/or compulsions. Few studies have examined the association between normal, dimensional personality traits and obsessive-compulsive symptomatology in a clinical sample. The purpose of this study was to examine personality differences in patients with a primary diagnosis of OCD (n = 98) or major depression (n = 98) using the domains and facets of the five-factor model of personality (FFM). Patients completed the self-report version of the Revised NEO Personality Inventory (NEO PI-R). When contrasted with community controls (Revised NEO Personality Inventory (NEO-PI-R) and NEO Five-Factor Inventory (NEO-FFI) professional manual, Psychological Assessment Resources, Odessa, FL, 1992), participants with OCD were found to differ across the domains (and facets) of neuroticism, extraversion, and conscientiousness and the facets of openness and agreeableness. Further, when compared to depressed participants, those with OCD were found to be more extraverted, agreeable, conscientious and less neurotic. With the exception of the conscientiousness domain (and facets), these significant differences were maintained even after controlling for depression severity. These results highlight the unique associations between trait domains and facets of the FFM and OCD.

Mundo E, Richter MA, Zai G, Sam F, McBride J, Macciardi F, Kennedy JL. · Neurogenetics Section, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Canada. · Mol Psychiatry. · Pubmed #12192628 links to  free full text

Abstract: Obsessive-Compulsive Disorder (OCD) is a psychiatric condition with strong evidence for a genetic component and for the involvement of genes of the serotonin system. In a recent family-based association study we reported an association between the G allele of the G861C polymorphism of the 5HT1Dbeta receptor gene and OCD. The aim of the present study was to further investigate for the presence of linkage disequilibrium between each of two polymorphisms of the 5HT1Dbeta receptor gene and OCD in a larger sample of OCD families. In a total of 121 families the G861C and the T371G polymorphisms of the 5HT1Dbeta receptor gene were genotyped using standard protocols. The genotyping data were analyzed with a new extension of the Transmission Disequilibrium Test (FBAT). The phenotypes considered in the analyses were the diagnosis of OCD and two quantitative phenotypes related to the diagnosis and clinically relevant, ie, the age at onset and the severity of OCD symptoms. We confirmed the previously found preferential transmission of the G861 allele to the affected subjects (z = 2.262, P = 0.02). No significant association was found between the polymorphism and the quantitative phenotypes considered. These results represent a confirmation of our previous published study and thus, could have important implications for the role of the 5HT1Dbeta receptor gene in the pathogenesis and treatment of OCD. Further genetic investigations on this marker considering additional polymorphisms and other quantitative phenotypes related to OCD are warranted.

Bottas A, Richter MA. · Center for Addiction and Mental Health, Clarke Institute Division, and Department of Psychiatry, University of Toronto, Toronto, Canada. · Pediatr Infect Dis J. · Pubmed #11791105 No free full text.

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Schindler KM, Richter MA, Kennedy JL, Pato MT, Pato CN. · Department of Psychiatry, State University of New York at Buffalo, New York 14214, USA. · Am J Med Genet. · Pubmed #11121168 No free full text.

Abstract: A functional polymorphism in the coding region of the catechol O-methyltransferase (COMT) gene has been reported in previous studies to be associated with obsessive compulsive disorder (OCD), particularly in males [Karayiorgou et al., 1997, 1999]. Using a family-based population analysis, we attempted to replicate these findings in a group of 72 OCD patient/parent trios collected from Buffalo, New York, and Toronto, Canada. Analysis of allele and genotype frequencies using the haplotype relative risk (HRR) and transmission disequilibrium test (TDT) did not identify an association between a particular allele and OCD as had been previously reported. Furthermore, no evidence was found to support the findings of a gender-based association for COMT when the patients and the parents of the same gender were compared. However, our genotype results (n = 72) demonstrate a tendency for association between homozygosity at the COMT locus and OCD (homozygosity analysis: chi(2) = 5.66, P = 0.017; genotypic analysis: chi(2) = 5.78, P = 0.056). Although these findings do not replicate the previous reports, they do provide limited support to demonstrate a trend for homozygosity at the COMT locus in the OCD patients and, in turn, further implicate a potential role for COMT in the genetic etiology of OCD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:721-724, 2000.

Mundo E, Richter MA, Sam F, Macciardi F, Kennedy JL. · Neurogenetics Section, University of Toronto, Ontario, Canada. · Am J Psychiatry. · Pubmed #10873927 links to  free full text

Abstract: OBJECTIVE: Obsessive-compulsive disorder (OCD) is a psychiatric condition for which strong evidence of a genetic component and serotonergic system involvement exists. Recent studies have shown that sumatriptan, a selective ligand of the serotonin (5-HT)(1Dbeta) autoreceptor, modifies OCD symptoms. The aim of this study was to investigate the presence of linkage disequilibrium between the 5-HT(1Dbeta) receptor gene, which has a variant caused by a silent G to C substitution at nucleotide 861 of the coding region, and OCD. METHOD: DNA was collected from 67 probands who met DSM-IV criteria for OCD and from their living parents or siblings. Transmission Disequilibrium Test/sib-Transmission Disequilibrium Test analyses were then conducted with the DNA data. RESULTS: Thirty-two families were informative for the analysis, which showed a preferential transmission of the G allele to the affected subjects. CONCLUSIONS: If the results are confirmed, there may be important implications for the 5-HT(1Dbeta) receptor gene in the pathogenesis and treatment of OCD.

Summerfeldt LJ, Richter MA, Antony MM, Swinson RP. · Psychology Department, St. Joseph's Hospital, Hamilton, Ontario, Canada. · Behav Res Ther. · Pubmed #10204276 No free full text.

Abstract: Although obsessive-compulsive disorder (OCD) has long been a unitary diagnosis, there is much recent interest in its potential heterogeneity, as manifested by symptom subgroups. This study evaluated existing models of symptom structure in a sample of 203 individuals with OCD. Using confirmatory factor analysis, we examined the ability of each model to account for two levels of data: a priori symptom groupings (second-order) and individual symptoms, identified by the Yale-Brown Obsessive Compulsive Scale symptom checklist. Four models were examined: a single-factor, a two-factor (i.e., obsessions and compulsions), and two multidimensional models, comprising three and four factors. Adequate fit was found solely for the four-factor model--specifying obsessions/checking, symmetry/ordering, contamination/cleaning, and hoarding--but only at the second-order level; it did not account for relationships among discrete symptoms. Parameter estimates showed within-factor heterogeneity, as well as overlap between factors, most notably the two representing checking and contamination-related symptoms. The implications of these findings are discussed. Results provide evidence for the multidimensionality of OCD symptoms, but suggest that a comprehensive model has yet to be identified. They also point to the inadequacy of groupings based solely upon overt behavioural similarities (e.g., 'checking'). Recommendations are made for future research.

Zai G, Arnold P, Strauss J, King N, Burroughs E, Richter MA, Kennedy JL. · No affiliation provided · Psychiatr Genet. · Pubmed #16314750 No free full text.

This publication has no abstract.