Anxiety Disorders: Miguel EC

Bandelow B, Zohar J, Hollander E, Kasper S, Möller HJ, Anonymous00037, Zohar J, Hollander E, Kasper S, Möller HJ, Bandelow B, Allgulander C, Ayuso-Gutierrez J, Baldwin DS, Buenvicius R, Cassano G, Fineberg N, Gabriels L, Hindmarch I, Kaiya H, Klein DF, Lader M, Lecrubier Y, Lépine JP, Liebowitz MR, Lopez-Ibor JJ, Marazziti D, Miguel EC, Oh KS, Preter M, Rupprecht R, Sato M, Starcevic V, Stein DJ, van Ameringen M, Vega J. · Department of Psychiatry and Psychotherapy, University of Gottingen, Gottingen, Germany. · World J Biol Psychiatry. · Pubmed #18949648 No free full text.

Abstract: In this report, which is an update of a guideline published in 2002 (Bandelow et al. 2002, World J Biol Psychiatry 3:171), recommendations for the pharmacological treatment of anxiety disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are presented. Since the publication of the first version of this guideline, a substantial number of new randomized controlled studies of anxiolytics have been published. In particular, more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs. The recommendations, developed by the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-traumatic Stress Disorders, a consensus panel of 30 international experts, are now based on 510 published randomized, placebo- or comparator-controlled clinical studies (RCTs) and 130 open studies and case reports. First-line treatments for these disorders are selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and the calcium channel modulator pregabalin. Tricyclic antidepressants (TCAs) are equally effective for some disorders, but many are less well tolerated than the SSRIs/SNRIs. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of substance abuse disorders. Potential treatment options for patients unresponsive to standard treatments are described in this overview. Although these guidelines focus on medications, non-pharmacological were also considered. Cognitive behavioural therapy (CBT) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders, OCD, and PTSD to support them being recommended either alone or in combination with the above medicines.

Torres AR, Ferrão YA, Miguel EC. · No affiliation provided · Rev Bras Psiquiatr. · Pubmed #15962131 links to  free full text

This publication has no abstract.

Prado HS, Rosário MC, Lee J, Hounie AG, Shavitt RG, Miguel EC. · Department of Psychiatry at the University of São Paulo Medical School, São Paulo, Brazil. · CNS Spectr. · Pubmed #18496480 links to  free full text

Abstract: INTRODUCTION: A variety of subjective experiences have been reported to be associated with the symptom expression of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). First described in TS patients, these subjective experiences have been defined in different ways. There is no consensus in the literature on how to best define subjective experiences. This lack of consensus may hinder the understanding of study results and prevents the possibility of including them in the search for etiological factors associated with OCD and TS. METHODS: The objective of this article was to review the descriptions of subjective experiences in the English-language literature from 1980-2007. This meta-analytic review was carried out using the English-language literature from 1980-2007 available on MEDLINE, PsycINFO, and the Cochrane Library databases using the following search terms: premonitory urges, sensory tics, "just-right" perceptions, sensory phenomena, sensory experiences, incompleteness, "not just-right" phenomena, obsessive-compulsive disorder and TS, including OCD and/or TS, in all combination searches. We also searched for the references cited in each article previously found that referred to the aforementioned terms. Thirty-one articles were included in the study. RESULTS: Subjective experiences, in particular, the sensory phenomena, were important phenotypic variables in the characterization of the tic-related OCD subtype and were more frequent in the early-onset OCD subtype. There is a paucity of studies using structured interviews to assess sensory phenomena, their epidemiology and the etiological mechanisms associated with sensory phenomena. CONCLUSION: The current review provides some evidence that sensory phenomena can be useful to identify more homogenous subgroups of OCD and TS patients and should be included as important phenotypic variables in future clinical, genetic, neuroimaging, and treatment-response studies.

de Mathis MA, Diniz JB, do Rosário MC, Torres AR, Hoexter M, Hasler G, Miguel EC. · Department of Psychiatry, University of São Paulo Medical School, Brazil. · CNS Spectr. · Pubmed #17008820 links to  free full text

Abstract: The clinical presentation of obsessive-compulsive disorder (OCD) varies not only across patients but over the course of the disorder. This diversity indicates that OCD is a heterogeneous disorder, which may have an important impact on psychopathological, longitudinal, genetic, and treatment research. To better understand OCD heterogeneity, more homogeneous phenotypic descriptions are necessary to delimiting clinically meaningful subgroups of patients. Besides phenotypic descriptions, another method of delimiting OCD patient subgroups includes the search for endophenotypes (extended phenotypes) based on neurophysiological, immunological, genetic, neuropsychological, or neuroanatomic (neuroimaging) paradigms. This article will describe some strategies that deal with OCD heterogeneity, including the identification of more homogeneous phenotypical categories, an improved understanding of obsessive-compulsive symptom dimensions and how to use them as quantitative traits, and broadening the diagnostic boundaries of OCD to include other related conditions. The relevance and limitations of each approach are also discussed. Since the etiological mechanisms associated with the expressions of OCD are unknown, there is probably not one but several heuristic strategies to search for more homogeneous OCD subgroup, that combined may provide the most fruitful results.

Shavitt RG, Hounie AG, Rosário Campos MC, Miguel EC. · Department of Psychiatry, University of São Paulo Medical School, Rua Dr. Ovidio Pires de Campos, Sao Paulo 05430-010, Brazil. · Psychiatr Clin North Am. · Pubmed #16650718 No free full text.

Abstract: This article has focused on TS, and the relationship between TS and OCD has been addressed from different perspectives. In patients who have OCD, the presence of TS seems to have some impact in the clinical manifestation of OCD symptoms. One of the main features of tic-related OCD is the frequent presence of sensory phenomena preceding the compulsions, in the absence of obsessions. Genetic epidemiologic studies provide consistent evidence for the association between TS and OCD. Although no major loci have been identified so far, family and segregation analysis studies support the assumption that genes play a major role in the etiology of TS and related disorders. Genes interact with environmental factors,which can modulate the expression of TS or OCD and determine the onset of these disorders. Neuroimaging studies suggest that the pathophysiology of TS encompasses projections of primary, secondary, and somato sensory cortex to the putamen, dorsolateral caudate nucleus, and globus pallidus,whereas the pathophysiology of OCD involves more ventral structures,such as orbitofrontal-caudate-thalamic-cortical areas. Current treatment strategies for TS include education, behavioral therapy, pharmacotherapy,and support from patients associations. Alfa-adrenergic agents such as guanfacine and clonidine are first-choice treatments for TS; typical antipsychotics are more effective but are troublesome because of their long-term side-effect profiles. For comorbid TS plus OCD, each condition should be treated with its respective first-line option. Nonetheless, for patients who have tic-related OCD who are unresponsive to monotherapy with serotonin reuptake inhibitors, augmentation of serotonin reuptake inhibitors with atypical antipsychotics may be of benefit. Despite important advances, re-search is needed to clarify further the biologic and behavioral aspects of TS and its relationship with the frequently associated conditions, with particular attention to their management and prognosis.

Hounie AG, do Rosario-Campos MC, Diniz JB, Shavitt RG, Ferrão YA, Lopes AC, Mercadante MT, Busatto GF, Miguel EC. · Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil. · Adv Neurol. · Pubmed #16536350 No free full text.

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Miguel EC, Leckman JF, Rauch S, do Rosario-Campos MC, Hounie AG, Mercadante MT, Chacon P, Pauls DL. · Department of Psychiatry, University of São Paulo Medical School, Rua Dr. Ovídio Pires de Campos, s/n, 05403-010, São Paulo, SP, Brazil. · Mol Psychiatry. · Pubmed #15611786 No free full text.

Abstract: Obsessive-compulsive disorder (OCD) clinical presentation is remarkably diverse, and can vary both within and across patients over time. This variability in the phenotypic expression has led to the hypothesis that OCD is a heterogeneous disorder and that this heterogeneity obscures the findings of clinical, natural history and treatment response studies and complicates the search for vulnerability genes. A complete understanding of what comprises OCD and the underlying etiological mechanisms will require a dramatic change in how the disorder is conceptualized. In this review, several different approaches that may represent the first steps in this reconceptualization are discussed. These approaches include (1) narrowing the phenotype to identify categorically defined more homogeneous and mutually exclusive subtypes of OCD, (2) considering OC symptom dimensions as quantitative components of the more complex OCD phenotype and (3) broadening the phenotype to include other etiologically related conditions. A combined dimensional approach within distinctive subgroups is proposed as probably the most effective in helping to identify the heritable components of OCD. By identifying heritable components of OCD, it should be possible to find genes for these separate components. The review continues with the illustration of the possible role of some epigenetic risk and protective factors in the OCD presentation and the relevance of examining associated traits and/or endophenotypes to enhance our ability to understand the genetic basis of OCD. To conclude, we discuss the variability in treatment outcome and the significance of the development of specific pharmacological and/or behavioral based therapies tailored to each of these phenotypes.

Lopes AC, de Mathis ME, Canteras MM, Salvajoli JV, Del Porto JA, Miguel EC. · Projeto Transtorno do Espectro Obsessivo-Compulsivo, Departamento de Psiquiatria, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil. · Rev Bras Psiquiatr. · Pubmed #15057843 links to  free full text

Abstract: Responses to pharmacotherapy and psychotherapy in obsessive-compulsive disorder (OCD) range from 60 to 80% of cases. However, a subset of OCD patients do not respond to adequately conducted treatment trials, leading to severe psychosocial impairment. Stereotactic surgery can be indicated then as the last resource. Five surgical techniques are available, with the following rates of global post-operative improvement: anterior capsulotomy (38-100%); anterior cingulotomy (27-57%); subcaudate tractotomy (33-67%); limbic leucotomy (61-69%), and central lateral thalamotomy/anterior medial pallidotomy (62.5%). The first technique can be conducted as a standard neurosurgery, as radiosurgery or as deep brain stimulation. In the standard neurosurgery neural circuits are interrupted by radiofrequency. In radiosurgery, an actinic lesion is provoked without opening the brain. Deep brain stimulation consists on implanting electrodes which are activated by stimulators. Literature reports a relatively low prevalence of adverse events and complications. Neuropsychological and personality changes are rarely reported. However, there is a lack of randomized controlled trials to prove efficacy and adverse events/complication issues among these surgical procedures. Concluding, there is a recent development in the neurosurgeries for severe psychiatric disorders in the direction of making them more efficacious and safer. These surgeries, when correctly indicated, can profoundly alleviate the suffering of severe OCD patients.

Miguel EC, Shavitt RG, Ferrão YA, Brotto SA, Diniz JB. · Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil. · J Psychosom Res. · Pubmed #12842231 No free full text.

Abstract: Obsessive-compulsive disorder (OCD) constitutes an etiologically heterogeneous set of conditions, including a subtype that seems etiologically related to Tourette syndrome (TS). In order to treat OCD patients optimally, the clinician needs to integrate educational, psychological and pharmacological approaches. The most effective psychological intervention is cognitive-behavior therapy (CBT). Drug treatment includes clomipramine and all selective serotonin reuptake inhibitors (SSRIs). A subgroup of OCD patients, however, shows no significant improvement. Few studies suggest that the presence of tics is associated to a worse treatment response to SSRIs and that such patients benefit from combined therapy of serotonin-reuptake inhibitors plus neuroleptics. Independently of the presence of tics, there are several different augmentation strategies for resistant cases with drugs that interfere in the dopamine, serotonin, opioid and gonadal hormone systems. In addition, new therapies are now being tested against presumed postinfectious autoimmune processes. Finally, new developments are promising in neural circuit-based therapies, including neurosurgery for refractory patients.

Miguel EC, do Rosário-Campos MC, Shavitt RG, Hounie AG, Mercadante MT. · Department of Psychiatry, University of São Paulo Medical School, São Paulo, SP, Brazil. · Adv Neurol. · Pubmed #11530446 No free full text.

This publication has no abstract.

O'Sullivan RL, Mansueto CS, Lerner EA, Miguel EC. · Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA. · Psychiatr Clin North Am. · Pubmed #10986729 No free full text.

Abstract: Multiple approaches to characterization of TTM have been developed, including categoric definitions and dimensional considerations. When TTM is viewed in the context of other disorders with common comorbidities and overlapping similar phenomenologies, such as OCD, body dysmorphic disorder, skin picking, TS, and olfactory reference syndrome, clinical approaches to assessment and differential diagnosis are more complex. This article presents a general overview of TTM included as a background for a heuristic clinical framework for assessing obsessive-compulsive spectrum disorders. A comprehensive behavioral model of TTM as a template is presented in the context of a broader, phenomenologic approach to assessment of several other disorders. These additional conditions were chosen on clinical grounds because they seem to share some phenomenologic characteristics with TTM. It is hoped that combining a phenomenologic approach to the differentiation of repetitive behaviors (as has been valuable in advancing the understanding of repetitive behaviors in TS and OCD), coupled with a paradigmatic comprehensive behavioral assessment and treatment model of TTM, may foster the validation of such approaches for other putative obsessive-compulsive spectrum disorders. Also, the relative intensity and frequency ascribed to the various behavioral and phenomenologic components of the conditions depicted represent clinical impressions, with varying degrees of empiric support, and require objective validation. This approach is meant to serve as a point of departure for clinical assessment of these complex, interesting, and sometimes incompletely diagnosed and inadequately treated conditions. It is hoped that empiric validation or refutation of this conceptualization will stimulate additional research and provide clinicians with a general framework for assessing patients suffering from these difficult conditions. For more information about trichotillomania, contact The Trichotillomania Learning Center (TLC), 1215 Mission Street, Santa Cruz, CA 95060 (831-457-1004; www.trich.org).

Cecconi JP, Lopes AC, Duran FL, Santos LC, Hoexter MQ, Gentil AF, Canteras MM, Castro CC, Norén G, Greenberg BD, Rauch SL, Busatto GF, Miguel EC. · Department of Psychiatry, University of São Paulo Medical School (FMUSP), São Paulo, SP, Brazil. · Neurosci Lett. · Pubmed #18835422 No free full text.

Abstract: OBJECTIVE: The purpose of this study was to investigate regional structural abnormalities in the brains of five patients with refractory obsessive-compulsive disorder (OCD) submitted to gamma ventral capsulotomy. METHODS: We acquired morphometric magnetic resonance imaging (MRI) data before and after 1 year of radiosurgery using a 1.5-T MRI scanner. Images were spatially normalized and segmented using optimized voxel-based morphometry (VBM) methods. Voxelwise statistical comparisons between pre- and post-surgery MRI scans were performed using a general linear model. Findings in regions predicted a priori to show volumetric changes (orbitofrontal cortex, anterior cingulate gyrus, basal ganglia and thalamus) were reported as significant if surpassing a statistical threshold of p<0.001 (uncorrected for multiple comparisons). RESULTS: We detected a significant regional postoperative increase in gray matter volume in the right inferior frontal gyri (Brodmann area 47, BA47) when comparing all patients pre and postoperatively. CONCLUSIONS: Our results support the current theory of frontal-striatal-thalamic-cortical (FSTC) circuitry involvement in OCD pathogenesis. Gamma ventral capsulotomy is associated with neurobiological changes in the inferior orbitofrontal cortex in refractory OCD patients.

Meira-Lima I, Shavitt RG, Miguita K, Ikenaga E, Miguel EC, Vallada H. · Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil. · Genes Brain Behav. · Pubmed #15005715 No free full text.

Abstract: Family and twin studies have supported a strong genetic factor in the etiology of obsessive-compulsive disorder (OCD), although the precise mechanism of inheritance is unclear. Clinical and pharmacological studies have implicated the serotonergic and dopaminergic systems in disease pathogenesis. In this cross-sectional study, we have examined the allelic and genotypic frequencies of a Val-158-Met substitution in the COMT gene, a 44-base pair (bp) length variation in the regulatory region of the serotonin transporter gene (5-HTTLPR) and the T102C and C516T variants in the serotonin receptor type 2A (5HT2A) gene in 79 OCD patients and 202 control subjects. There were no observed differences in the frequencies of allele and genotype between patients and control groups for the COMT, the 5HTTLPR and the T102C 5HT2A gene polymorphisms. In contrast, a statistically significant difference between OCD patients and controls was observed on the genotypic distribution (chi(2) = 16.7, 2df, P = 0.0002) and on the allelic frequencies (chi(2) = 15.8, 1df, P = 0.00007) for the C516T 5HT2A gene polymorphism. The results suggest that the C516T variant of the 5HT2A gene may be one of the genetic risk factors for OCD in our sample. However, further studies using larger samples and family based methods are recommended to confirm these findings.

Batistuzzo MC, Taub A, Nakano E, D'Alcante CC, de Mathis ME, Hoexter MQ, Miguel EC, Lopes AC. · Department & Institute of Psychiatry, Clinical Hospital, University of Sao Paulo Medical School (FMUSP), Sao Paulo-SP, Brazil. · Neurocase. · Pubmed #19274575 No free full text.

Abstract: OBJECTIVE: To compare the performance of patients with obsessive-compulsive disorder (OCD) refractory to conventional treatments to healthy controls according to the Frontal Systems Behaviour Scale (FrSBe), comparing the scale scores within each group (Self or Family) and correlating FrSBe with Y-BOCS, DY-BOCS, tic disorder and age of first symptoms. METHOD: Twenty OCD patients and 20 healthy controls were assessed using the FrSBe, a scale designed to evaluate frontal syndromes. RESULTS: The patients had higher scores when compared with the control group (p value < .001) in terms of total score on the scale for both profile forms (Self and Family). In addition, there was a significant difference between the scores reported by the patients and their respective relatives. However, no correlation was observed between the scale and the other variables. CONCLUSIONS: The scale was able to clearly differentiate patients with OCD from healthy controls. This finding suggests that the FrSBe can be used not only in neurologic patients but also in psychiatric cases such as refractory OCD.

Seixas AA, Hounie AG, Fossaluza V, Curi M, Alvarenga PG, De Mathis MA, De Mathis ME, Vallada H, Pauls D, de Bragança Pereira CA, Miguel EC. · Department of Psychiatry, University of São Paulo Medical School, Brazil. · CNS Spectr. · Pubmed #19179939 links to  free full text

Abstract: INTRODUCTION: Findings suggest that obsessive-compulsive disorder (OCD) and related disorders, referred to as obsessive-compulsive spectrum disorders (OCSDs), are more common in patients with rheumatic fever (RF). OBJECTIVES: To determine whether RF or Sydenham's chorea increases the probability of anxiety disorders in the relatives of individuals with RF with and without SC. METHODS: This was a case-control family study in which 98 probands and 389 first-degree relatives (FDRs) were assessed using structured psychiatric interviews. A Poisson regression model was used to determine whether the presence of any disorder in one family member influences the rate of disorders in the remaining family members. RESULTS: Generalized anxiety disorder (GAD) occurred more frequently in the FDRs of RF probands than in those of control probands (P=.018). The presence of RF, GAD, or separation anxiety disorder in one family member significantly increased the chance of OCSDs in another member of the family. CONCLUSION: We found familial aggregation among RF, GAD, and OCSDs. Clinicians should be aware of the possible familial relationship between GAD and OCSDs in their RF patients and their family members, which may suggest a genetic component between them. Further studies on OCD should include anxiety disorders to better define OCD spectrum.

Duran FL, Hoexter MQ, Valente AA, Miguel EC, Busatto GF. · Department and Institute of Psychiatry, Clinical Hospital, University of São Paulo Medical School, SP, Brazil. · Neurosci Lett. · Pubmed #19150484 No free full text.

Abstract: Neurobiological models support an involvement of white matter tracts in the pathophysiology of obsessive-compulsive disorder (OCD), but there has been little systematic evaluation of white matter volumes in OCD using magnetic resonance imaging (MRI). We investigated potential differences in the volume of the cingulum bundle (CB) and anterior limb of internal capsule (ALIC) in OCD patients (n=19) relative to asymptomatic control subjects (n=15). White matter volumes were assessed using a 1.5T MRI scanner. Between-group comparisons were carried out after spatial normalization and image segmentation using optimized voxel-based morphometry. Correlations between regional white matter volumes in OCD subjects and symptom severity ratings were also investigated. We found significant global white matter reductions in OCD patients compared to control subjects. The voxel-based search for regional abnormalities (with covariance for total white matter volumes) showed no specific white matter volume deficits in brain portions predicted a priori to be affected in OCD (CB and ALIC). However, large clusters of significant positive correlation with OCD severity scores were found bilaterally on the ALIC. These findings provide evidence of OCD-related ALIC abnormalities and suggest a connectivity dysfunction within frontal-striatal-thalamic-cortical circuits. Further studies are warranted to better define the role of such white matter alterations in the pathophysiology of OCD, and may provide clues for a more effectively targeting of neurosurgical treatments for OCD.

Torresan RC, Ramos-Cerqueira AT, de Mathis MA, Diniz JB, Ferrão YA, Miguel EC, Torres AR. · Department of Neurology, Psychology and Psychiatry, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, SP, Brazil. · Compr Psychiatry. · Pubmed #19059516 No free full text.

Abstract: Previous studies have shown differences in clinical features of obsessive-compulsive disorder (OCD) between men and women, including mean age at onset of obsessive-compulsive symptoms (OCS), types of OCS, comorbid disorders, course, and prognosis. The aim of this study was to compare male and female Brazilian patients with OCD on several demographic and clinical characteristics. Three hundred thirty outpatients with OCD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV], criteria) who sought treatment at 3 Brazilian public universities and at 2 private practice clinics in the city of São Paulo were evaluated. The assessment instruments used were the Yale-Brown Obsessive-Compulsive Scale to evaluate OCD severity and symptoms, the Beck Depression and Anxiety Inventories, the Yale Global Tic Severity Scale, and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I Disorders to assess psychiatric comorbidity. Fifty-five percent of the patients (n = 182) were men who were significantly more likely than women to be single and to present sexual, religious, and symmetry obsessions and mental rituals. They also presented earlier onset of OCS and earlier symptom interference in functioning, and significantly more comorbid tic disorders and posttraumatic stress disorder. Women, besides showing significantly higher mean scores in the Beck Depression and Anxiety Inventories, were more likely to present comorbid simple phobias, eating disorders in general and anorexia in particular, impulse control disorders in general, and compulsive buying and skin picking in particular. No significant differences were observed between sexes concerning family history of OCS or OCD, and global symptoms severity, either in obsession or compulsive subscale. The present study confirms the presence of sex-related differences described in other countries and cultures. The fact that the OCS start earlier and probably have a worse impact in men can eventually lead to more specific and efficacious treatment approaches for these patients.

Hazen EP, Reichert EL, Piacentini JC, Miguel EC, do Rosario MC, Pauls D, Geller DA. · Clinical Research Program in Pediatric Psychopharmacology, Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA. · Ann Clin Psychiatry. · Pubmed #19034751 No free full text.

Abstract: INTRODUCTION: Marked intolerance or intrusive re-experiencing of ordinary sensory stimuli that in turn drive functionally impairing compulsive behaviors are occasionally seen in young children with OCD. METHODS: We describe a number of children with DSM-IV OCD ascertained from a family genetic study of pediatric OCD, whose intolerance of ordinary sensory stimuli created significant subjective distress and time-consuming ritualistic behavior that was clinically impairing. RESULTS: In each case, these sensory symptoms were the primary presenting symptoms and were experienced in the absence of intrusive thoughts, images, or ideas associated with "conventional" OCD symptoms. CONCLUSIONS: These symptoms suggest abnormalities in sensory processing and integration in at least a subset of OCD patients. Recognition of these sensory symptoms and sensory-driven behaviors as part of the broad phenotypic variation in children with OCD could help clinicians more easily identify OCD patients and facilitate treatment.

Gentil AF, de Mathis MA, Torresan RC, Diniz JB, Alvarenga P, do Rosário MC, Cordioli AV, Torres AR, Miguel EC. · Department & Institute of Psychiatry, Clinical Hospital, University of São Paulo Medical School, São Paulo, R. Dr. Ovidio Pires de Campos, 485, 3o andar, CEAPESQ, sala 7, CEP 05403-010, São Paulo, SP, Brazil. · Drug Alcohol Depend. · Pubmed #19004577 No free full text.

Abstract: OBJECTIVE: To evaluate the prevalence and clinical associated factors of alcohol use disorders (AUD) comorbidity in a large clinical sample of patients with obsessive-compulsive disorder (OCD). METHODS: A cross-sectional study including 630 DSM-IV OCD patients from seven Brazilian university services, comparing patients with and without AUD comorbidity. The instruments of assessment used were a demographic and clinical questionnaire including evaluation of suicidal thoughts and acts and psychiatric treatment, the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I), the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Brown Assessment of Beliefs Scale, the Beck Depression and Anxiety Inventories and the Clinical Global Impression Scale. Current or past alcohol and other psychoactive substances use, abuse and dependence were assessed using the SCID-I (section E) and corroborated by medical and familial history questionnaires. RESULTS: Forty-seven patients (7.5%) presented AUD comorbidity. Compared to OCD patients without this comorbidity they were more likely to be men, to have received previous psychiatric treatment, to present lifetime suicidal thoughts and attempts and to have higher scores in the hoarding dimension. They also presented higher comorbidity with generalized anxiety and somatization disorders, and compulsive sexual behavior. Substance use was related to the appearance of the first O.C. symptoms and symptom amelioration. CONCLUSIONS: Although uncommon among OCD treatment seeking samples, AUD comorbidity has specific clinical features, such as increased risk for suicidality, which deserve special attention from mental health professionals. Future studies focused on the development of specific interventions for these patients are warranted.

Corchs F, Corregiari F, Ferrão YA, Takakura T, Mathis ME, Lopes AC, Miguel EC, Bernik M. · Department and Institute of Psychiatry, Medical School, Universidade de São Paulo, SP, Brazil. · Rev Bras Psiquiatr. · Pubmed #18833426 links to  free full text

Abstract: OBJECTIVE: Comorbidity with personality disorders in obsessive-compulsive patients has been widely reported. About 40% of obsessive-compulsive patients do not respond to first line treatments. Nevertheless, there are no direct comparisons of personality traits between treatment-responsive and non-responsive patients. This study investigates differences in personality traits based on Cloninger's Temperament and Character Inventory scores between two groups of obsessive-compulsive patients classified according to treatment outcome: responders and non-responders. METHOD: Forty-four responsive and forty-five non-responsive obsessive-compulsive patients were selected. Subjects were considered treatment-responsive (responder group) if, after having received treatment with any conventional therapy, they had presented at least a 40% decrease in the initial Yale-Brown Obsessive Compulsive Scale score, had rated "better" or "much better" on the Clinical Global Impressions scale; and had maintained improvement for at least one year. Non-responders were patients who did not achieve at least a 25% reduction in Yale-Brown Obsessive Compulsive Scale scores and had less than minimal improvement on the Clinical Global Impressions scale after having received treatment with at least three selective serotonin reuptake inhibitors (including clomipramine), and at least 20 hours of cognitive behavioral therapy. Personality traits were assessed using Temperament and Character Inventory. RESULTS: Non-responders scored lower in self-directedness and showed a trend to score higher in persistence than responders did. CONCLUSION: This study suggests that personality traits, especially self-directedness, are associated with poor treatment response in obsessive-compulsive patients.

Miguel EC, Ferrão YA, Rosário MC, Mathis MA, Torres AR, Fontenelle LF, Hounie AG, Shavitt RG, Cordioli AV, Gonzalez CH, Petribú K, Diniz JB, Malavazzi DM, Torresan RC, Raffin AL, Meyer E, Braga DT, Borcato S, Valério C, Gropo LN, Prado Hda S, Perin EA, Santos SI, Copque H, Borges MC, Lopes AP, Silva ED, Anonymous00017. · Clinical Hospital, Department of Psychiatry, Institute of Psychiatry, Universidade de São Paulo, São Paulo, SP, Brazil. · Rev Bras Psiquiatr. · Pubmed #18833417 links to  free full text

Abstract: OBJECTIVE: To describe the recruitment of patients, assessment instruments, implementation, methods and preliminary results of The Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders, which includes seven university sites. METHOD: This cross-sectional study included a comprehensive clinical assessment including semi-structured interviews (sociodemographic data, medical and psychiatric history, disease course and comorbid psychiatric diagnoses), and instruments to assess obsessive-compulsive (Yale-Brown Obsessive-Compulsive Scale and Dimensional Yale-Brown Obsessive-Compulsive Scale), depressive (Beck Depression Inventory) and anxious (Beck Anxiety Inventory) symptoms, sensory phenomena (Universidade de São Paulo Sensory Phenomena Scale), insight (Brown Assessment Beliefs Scale), tics (Yale Global Tics Severity Scale) and quality of life (Medical Outcome Quality of Life Scale Short-form-36 and Social Assessment Scale). The raters' training consisted of watching at least five videotaped interviews and interviewing five patients with an expert researcher before interviewing patients alone. The reliability between all leaders for the most important instruments (Structured Clinical Interview for DSM-IV, Dimensional Yale-Brown Obsessive-Compulsive Scale, Universidade de São Paulo Sensory Phenomena Scale) was measured after six complete interviews. RESULTS: Inter-rater reliability was 96%. By March 2008, 630 obsessive-compulsive disorder patients had been systematically evaluated. Mean age (+/-SE) was 34.7 (+/-0.51), 56.3% were female, and 84.6% Caucasian. The most prevalent obsessive compulsive symptom dimensions were symmetry and contamination. The most common comorbidities were major depression, generalized anxiety and social anxiety disorder. The most common DSM-IV impulsive control disorder was skin picking. CONCLUSION: The sample was composed mainly by Caucasian individuals, unmarried, with some kind of occupational activity, mean age of 35 years, onset of obsessive-compulsive symptoms at 13 years of age, mild to moderate severity, mostly of symmetry, contamination/cleaning and comorbidity with depressive disorders. The Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders has established an important network for standardized collaborative clinical research in obsessive-compulsive disorder and may pave the way to similar projects aimed at integrating other research groups in Brazil and throughout the world.

Hounie AG, Cappi C, Cordeiro Q, Sampaio AS, Moraes I, Rosário MC, Palácios SA, Goldberg AC, Vallada HP, Machado-Lima A, Nakano E, Kalil J, Pauls D, Pereira CA, Guilherme L, Miguel EC. · Department of Psychiatry, Institute of Psychiatry, Clinical Hospital, University of São Paulo (USP), Brazil. · Neurosci Lett. · Pubmed #18639610 No free full text.

Abstract: INTRODUCTION: Several lines of evidence support an immunologic involvement in obsessive-compulsive disorder (OCD): the increased prevalence of OCD in patients with rheumatic fever (RF), and the aggregation of obsessive-compulsive spectrum disorders among relatives of RF probands. Tumor necrosis factor alpha is a proinflammatory cytokine involved in RF and other autoimmune diseases. Polymorphisms in the promoter region of the TNFA gene have been associated with RF. Given the association between OCD and RF, the goal of the present study was to investigate a possible association between polymorphisms within the promoter region of TNFA and OCD. MATERIALS AND METHODS: Two polymorphisms were investigated: -308 G/A and -238 G/A. The allelic and genotypic frequencies of these polymorphisms were examined in 111 patients who fulfilled DSM-IV criteria for OCD and compared with the frequencies in 250 controls. RESULTS: Significant associations were observed between both polymorphisms and OCD. For -238 G/A, an association between the A allele and OCD was observed (chi(2)=12.05, p=0.0005). A significant association was also observed between the A allele of the -308 G/A polymorphism and OCD (chi(2)=7.09, p=0.007). Finally, a haplotype consisting of genotypes of these two markers was also examined. Significant association was observed for the A-A haplotype (p=0.0099 after correcting for multiple testing). DISCUSSION: There is association between the -308 G/A and -238 G/A TNFA polymorphisms and OCD in our Brazilian sample. However, these results need to be replicated in larger samples collected from different populations.

de Mathis MA, do Rosario MC, Diniz JB, Torres AR, Shavitt RG, Ferrão YA, Fossaluza V, de Bragança Pereira CA, Miguel EC. · Department of Psychiatry, University of Sao Paulo Medical School, Rua Dr. Ovídio Pires de Campos, 785, 05403-010 São Paulo, SP, Brazil. · Eur Psychiatry. · Pubmed #18329252 No free full text.

Abstract: PURPOSE: This study investigates the influence of age at onset of OCS on psychiatric comorbidities, and tries to establish a cut-off point for age at onset. METHODS: Three hundred and thirty OCD patients were consecutively recruited and interviewed using the following structured interviews: Yale-Brown Obsessive Compulsive Scale; Yale Global Tic Severity Scale and the Structured Clinical Interview for DSM-IV. Data were analyzed with regression and cluster analysis. RESULTS: Lower age at onset was associated with a higher probability of having comorbidity with tic, anxiety, somatoform, eating and impulse-control disorders. Longer illness duration was associated with lower chance of having tics. Female gender was associated with anxiety, eating and impulse-control disorders. Tic disorders were associated with anxiety disorders and attention-deficit/hyperactivity disorder. No cut-off age at onset was found to clearly divide the sample in homogeneous subgroups. However, cluster analyses revealed that differences started to emerge at the age of 10 and were more pronounced at the age of 17, suggesting that these were the best cut-off points on this sample. CONCLUSIONS: Age at onset is associated with specific comorbidity patterns in OCD patients. More prominent differences are obtained when analyzing age at onset as an absolute value.

Miguita K, Cordeiro Q, Siqueira-Roberto J, Shavitt RG, Castillo JC, Castillo AR, Miguel EC, Vallada H. · Department and Institute of Psychiatry Progene LIM-23, University of São Paulo Medical School, São Paulo, SP, Brazil. · Arq Neuropsiquiatr. · Pubmed #18094849 links to  free full text

Abstract: Family, twin and segregation analysis have provided evidences that genetic factors are implicated in the susceptibility for obsessive-compulsive disorder (OCD). Several lines of research suggest that the dopaminergic system may be involved in the pathophysiology of OCD. Thus, the aim of the present study was to investigate a possible association between a polymorphism located in intron 8 of the dopamine transporter gene (SLC6A3) and OCD in a Brazilian sample composed by 208 patients and 865 healthy controls. No statistical differences were observed in allelic and genotype distributions between cases and controls. No association was also observed when the sample was divided according to specific phenotypic features such as gender, presence of tic disorders, co-morbidity, and age at onset of obsessive-compulsive symptoms (OCS). Our results suggest that the intron 8 VNTR of the SLC6A3 investigated in this study is not related to the susceptibility for OCD in our Brazilian sample.

Chacon P, Rosario-Campos MC, Pauls DL, Hounie AG, Curi M, Akkerman F, Shimabokuro FH, de Mathis MA, Lopes AC, Hasler G, Miguel EC. · Department of Psychiatry, University of São Paulo School of Medicine, São Paulo, Brazil. · Am J Med Genet B Neuropsychiatr Genet. · Pubmed #17440931 No free full text.

Abstract: Obsessive-compulsive disorder (OCD) is a heterogeneous disorder of unknown etiology. Phenotypic studies of affected sib-pairs (SPs) may help to characterize familial components of the phenotype. To determine whether SPs affected with OCD are similar in age at onset of obsessive-compulsive symptoms (OCS), symptom dimensions and presence of tic disorders (TDs). Forty OCD siblings ranging from 13 to 59 years old were evaluated by expert psychiatrists or psychologists. Families with two or more siblings affected with OCD were recruited from several OCD clinics in Brazil. The Yale Brown Obsessive-Compulsive Scale Checklist was used to assess OCS and the severity of OCD. The OCD diagnoses were made according to the DSM-IV. The chi-square test was used to assess concordance of TD presence within SPs based on the TD frequency reported in the literature (30%). There were significantly more siblings with early-onset OCS than with late-onset OCS (P = 0.002). Age at onset of OCS correlated positively and significantly between the two members of each SP (P = 0.005). Fourteen patients (35%) were diagnosed with TDs. There was no concordance of the TD presence within the SPs. When both were male, there was a significant sibling correlation in the contamination obsessions/cleaning compulsions dimension (ICC = 0.74; P = 0.002). Similarly, when both siblings were female, they were comparable in the hoarding obsessions/compulsions dimension (ICC = 0.76; P = 0.01). Familial factors seem to contribute to specific OCD phenotypic components such as age at onset of OCS and specific dimensions. The obvious influence of gender is as yet unexplained.