Pedro Gomes de Alvarenga

Gender differences in obsessive-compulsive disorder: a literature review

INTRODUCAO: O transtorno obsessivo-compulsivo (TOC) e um quadro heterogeneo, no qual subtipos tem sido propostos. Estudos anteriores sugerem que genero desempenha papel relevante na expressao fenotipica. O objetivo foi realizar uma revisao convencional da literatura sobre diferencas de genero em relacao a aspectos clinicos e geneticos ou familiares do TOC. METODO: Realizou-se uma revisao convencional da literatura incluindo todos os artigos que investigaram aspectos sociodemograficos, clinicos e geneticos do TOC, de acordo com o genero. A pesquisa foi baseada em publicacoes disponiveis nas bases de dados Medline e PsycInfo nos ultimos 20 anos, usando como palavras-chave: obsessive-compulsive disorder (OCD), e: gender, sex, male, female, demographic characteristics, clinical features, clinical characteristics, genetic, genes, genetics gender OCD, genes OCD, genes OCD males, genes OCD females. RESULTADO: Sessenta e tres artigos de fenotipo e genetica foram selecionados. Na maioria dos estudos, o sexo masculino associou-se mais que o feminino com: ser solteiro, apresentar inicio mais precoce dos sintomas, maior prejuizo social, mais sintomas sexuais, religiosos e de agressao, e mais comorbidade com transtorno de tiques e abuso de substâncias. Pacientes do sexo feminino apresentam mais sintomas de contaminacao/limpeza e mais comorbidade com transtornos alimentares e do controle de impulsos. Estudos geneticos e familiares sao controversos, mas indicam que o genero pode desempenhar um papel na expressao da doenca. CONCLUSAO: Genero e um fator relevante a ser considerado na avaliacao de pacientes com TOC. Sao necessarios mais estudos para determinar se este fator define de fato um grupo homogeneo e particular de TOC.INTRODUCTION Obsessive-compulsive disorder (OCD) is a heterogeneous condition, in which subtypes have been proposed. Previous studies suggested that gender plays a relevant role in OCD phenotypic expression. This study aimed to review the literature on gender differences in clinical, genetic or familial aspects of OCD. METHOD A conventional review was conducted, including all papers that investigated demographic, clinical, and genetic aspects of OCD according to gender. The search was based on data available in Medline and PsycINFO databases in the last 20 years, using as keywords: obsessive-compulsive disorder; and: gender, sex, male, female, demographic characteristics, clinical features, clinical characteristics, genetic, genes, genetics gender OCD, genes OCD, genes OCD males, genes OCD females. RESULTS Sixty three of 487 phenotypical and genetics studies were selected. Most studies indicate that male patients are more likely than females to be single, present early onset of symptoms and chronic course of the disorder, greater social impairment, more sexual-religious and aggressive symptoms, and greater comorbidity with tic and substance use disorders. Female patients present more contamination/cleaning symptoms and greater comorbidity with eating and impulse-control disorders. Genetic and family studies are inconclusive, but suggest that gender may play a role in the disease expression. CONCLUSIONS Gender is a relevant factor that should be taken into account when evaluating OCD patients. More studies are necessary to determine whether in fact it defines a homogeneous and particular group in OCD.

High risk cohort study for psychiatric disorders in childhood: rationale, design, methods and preliminary results.

The objective of this study is to present the rationale, methods, design and preliminary results from the High Risk Cohort Study for the Development of Childhood Psychiatric Disorders. We describe the sample selection and the components of each phases of the study, its instruments, tasks and procedures. Preliminary results are limited to the baseline phase and encompass: (i) the efficacy of the oversampling procedure used to increase the frequency of both child and family psychopathology; (ii) interrater reliability and (iii) the role of differential participation rate. A total of 9937 children from 57 schools participated in the screening procedures. From those 2512 (random =958; high risk =1554) were further evaluated with diagnostic instruments. The prevalence of any child mental disorder in the random strata and high‐risk strata was 19.9% and 29.7%. The oversampling procedure was successful in selecting a sample with higher family rates of any mental disorders according to diagnostic instruments. Interrater reliability (kappa) for the main diagnostic instrument range from 0.72 (hyperkinetic disorders) to 0.84 (emotional disorders). The screening instrument was successful in selecting a sub‐sample with “high risk” for developing mental disorders. This study may help advance the field of child psychiatry and ultimately provide useful clinical information. Copyright

Alcohol use disorders in patients with obsessive–compulsive disorder: The importance of appropriate dual-diagnosis

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.

Randomized Sham Controlled Double-blind Trial of Repetitive Transcranial Magnetic Stimulation for Adults With Severe Tourette Syndrome

BACKGROUND A small proportion of individuals with Tourette syndrome (TS) have a lifelong course of illness that fails to respond to conventional treatments. Open label studies have suggested that low frequency (1-Hz) repetitive transcranial magnetic stimulation (rTMS) targeting the supplementary motor area (SMA) may be effective in reducing tic severity. OBJECTIVE/HYPOTHESIS To examine the efficacy of rTMS over the SMA for TS in a randomized double-blind sham-controlled trial (RCT). METHODS We conducted a two-site RCT-rTMS with 20 adults with severe TS for 3 weeks. Treatment consisted of 15 sessions (1-Hz; 30 min; 1800 pulses per day) of active or sham rTMS at 110% of the motor threshold over the SMA. A subsequent 3 week course of active rTMS treatment was offered. RESULTS Of the 20 patients (16 males; mean age of 33.7 ± 12.2 years), 9 received active and 11 received sham rTMS. After 3 weeks, patients receiving active rTMS showed on average a 17.3% reduction in the YGTSS total tic score compared to a 13.2% reduction in those receiving sham rTMS, resulting in no statistically significant reduction in tic severity (P = 0.27). An additional 3 week open label active treatment for those patients (n = 7) initially randomized to active rTMS resulted in a significant overall 29.7% reduction in tic severity compared to baseline (P = 0.04). CONCLUSION This RCT did not demonstrate efficacy of 3-week SMA-targeted low frequency rTMS in the treatment of severe adult TS. Further studies using longer or alternative stimulation protocols are warranted.

Higher prevalence of obsessive–compulsive spectrum disorders in rheumatic fever

OBJECTIVE This study aims to compare the prevalence of obsessive-compulsive spectrum disorders (OCSD) in psychiatric outpatients with and without a history of rheumatic fever (RF). METHODS An analytical cross-sectional study assessing a large sample of consecutive psychiatric outpatients at a Brazilian private practice was conducted during a 10-year period. Psychiatric diagnoses were made by a senior psychiatrist based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Best-estimate diagnosis procedure was also performed. RESULTS The total sample comprised 678 subjects, 13 of whom (1.92%) presented with a previous history of RF. This group showed a higher prevalence of subclinical obsessive-compulsive disorder (P=.025) and OCSD (P=.007) when compared to individuals with no such history. CONCLUSIONS A previous history of RF was associated with OCSD. These results suggest that clinicians should be encouraged to actively investigate obsessive-compulsive symptoms and related disorders in patients with a positive history of RF.

DBS for Obesity

Obesity is a chronic, progressive and prevalent disorder. Morbid obesity, in particular, is associated with numerous comorbidities and early mortality. In patients with morbid obesity, pharmacological and behavioral approaches often have limited results. Bariatric surgery is quite effective but is associated with operative failures and a non-negligible incidence of side effects. In the last decades, deep brain stimulation (DBS) has been investigated as a neurosurgical modality to treat various neuropsychiatric disorders. In this article we review the rationale for selecting different brain targets, surgical results and future perspectives for the use of DBS in medically refractory obesity.

The Role of Group A β-Hemolytic Streptococcal Infection in Neuropsychiatric Disorders

Kurlan et al1 have brought us reliable information based on an elegant prospective, blinded, case-control study of children who met diagnostic criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS),2 a controversial model of autoimmune neuropsychiatric disorders.3 Their striking finding is that the large majority of psychiatric exacerbations in this subgroup of patients could not be related to the acute group A -hemolytic streptococcal (GABHS) infections, contradicting the hallmark of the PANDAS hypothesis.1 Their findings suggest that obsessive-compulsive disorder (OCD) and Tourette syndrome are complex and heterogeneous conditions that may include subgroups prone to be triggered by a possible array of precipitants, including GABHS infections. Recent studies performed by our group revealed higher frequencies of obsessive-compulsive symptoms4,5 and OCD6 in patients with present or past rheumatic fever (RF) with or without Sydenham chorea. The presence of psychiatric disorders in patients with previous history of RF (not active) suggests that GABHS may trigger OCD and related disorders that may persist throughout life regardless of GABHS reinfections. Recent family studies have reported that obsessivecompulsive–related disorders aggregate more frequently in first-degree relative RF probands when compared with controls.7 Moreover, 2 polymorphisms of the promoter region of the tumor necrosis factor (TNF) gene have been associated with both OCD and RF, which is an interesting finding because TNFis a proinflammatory cytokine involved in RF and several other autoimmune diseases.8 Therefore, it is possible that both obsessive-compulsive–related disorders and RF share a common genetic vulnerability. Consistent with this hypothesis, there was a higher family history of RF in the GABHS group reported by Kurlan et al. In conclusion, GABHS may still have a major role in PANDAS. PANDAS could precipitate an abnormal developmental process that moderates or mediates the expression of the Tourette syndrome/OCD phenotype. This phenotype would be more susceptible to exacerbations by GABHS or other unspecific factors. This moderating or mediating effect of GABHS infections could depend on specific genetic predisposition. Therefore, research into the interface between OCD and RF may also help to clarify this interesting debate on the validity of the PANDAS concept.

An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder

Many studies have attempted to investigate the genetic susceptibility of Attention-Deficit/Hyperactivity Disorder (ADHD), but without much success. The present study aimed to analyze both single-nucleotide and copy-number variants contributing to the genetic architecture of ADHD. We generated exome data from 30 Brazilian trios with sporadic ADHD. We also analyzed a Brazilian sample of 503 children/adolescent controls from a High Risk Cohort Study for the Development of Childhood Psychiatric Disorders, and also previously published results of five CNV studies and one GWAS meta-analysis of ADHD involving children/adolescents. The results from the Brazilian trios showed that cases with de novo SNVs tend not to have de novo CNVs and vice-versa. Although the sample size is small, we could also see that various comorbidities are more frequent in cases with only inherited variants. Moreover, using only genes expressed in brain, we constructed two “in silico” protein-protein interaction networks, one with genes from any analysis, and other with genes with hits in two analyses. Topological and functional analyses of genes in this network uncovered genes related to synapse, cell adhesion, glutamatergic and serotoninergic pathways, both confirming findings of previous studies and capturing new genes and genetic variants in these pathways.

Obsessive-Compulsive Disorder in Childhood

Obsessive-compulsive disorder (OCD) is a common disorder affecting all age ranges. Studies have indicated that OCD is a heterogeneous disorder with many possible subgroups. It has a bimodal age at o

Marcador D8-17: implicações para a neuropsiquiatria

Recent studies suggest that there is a relationship between rheumatic fever (RF) and some neuropsychiatric disorders. Thus, it has been thought that autoimmune mechanisms might be related to the etiology of these neuropsychiatric disorders. It has also been demonstrated that a B cell alloantigen associated to RF is also abnormally overexpressed in patients with such neuropsychiatric disorders. This alloantigen is recognised by a monoclonal antibody known as D8/17. The aim of this article is to introduce the recent work done about D8/17 and its possible implications to the study of neuropsychiatric disorders related or not to RF.