Aline S. Sampaio

Prenatal, Perinatal, and Postnatal Risk Factors in Obsessive–Compulsive Disorder

BACKGROUND The etiology of obsessive-compulsive disorder (OCD) remains unknown, although it is thought to involve an interaction of genetic and environmental factors. This study aimed to identify prenatal, perinatal, and postnatal risk factors in OCD. METHODS We compared retrospectively 68 OCD patients to 70 control subjects based on responses given on a standardized questionnaire. The questionnaire was designed to evaluate environmental factors, with a special focus on gestation, labor, birth, and early infancy aspects. RESULTS The group of OCD patients had risk factors with greater frequency than the control group. Notable among the significant findings (p < or = 0.001) were edema of the hands, feet, or face and excessive weight gain during gestation; hyperemesis gravidarum; prolonged labor; preterm birth; and jaundice. When socioeconomic class was used as a covariable in the logistic regression analysis, prolonged labor and edema during pregnancy remained statistically significant. CONCLUSIONS Some early risk factors may be associated with the expression of OCD later in life such as edema during pregnancy and prolonged labor. If our findings are confirmed in future studies, greater attention should be given to such factors in predisposed individuals, especially in prenatal care and delivery.

Obsessive-compulsive symptoms and disorder in patients with schizophrenia treated with clozapine or haloperidol.

We conducted a cross-sectional study to compare the prevalence and severity of obsessive-compulsive symptoms (OCSs) and obsessive-compulsive disorder (OCD) in patients with schizophrenia treated with clozapine or haloperidol. Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I disorders-patient edition was used to diagnose schizophrenia and OCD. Sixty subjects, 40 of them using clozapine and 20 using haloperidol, completed the Yale-Brown Obsessive-Compulsive Scale, the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression. The prevalence of OCD in patients taking clozapine was 20%, whereas the prevalence of patients taking haloperidol was 10%, although this difference was not statistically significant (P = .540). However, patients using clozapine showed higher severity of OCSs than patients using haloperidol (P = .027) did. When schizophrenia patients were divided according to the presence or absence of OCD or OCSs, patients with schizophrenia and OCD or OCSs showed higher severity of schizophrenia symptoms when compared to those with schizophrenia without OCD and OCSs (P = .002). A PANSS total score higher than 70 and the use of antidepressants were predictors of the presence of OCSs or OCD. Schizophrenia patients taking clozapine had higher severity scores both in obsessive-compulsive and schizophrenia rating scales. These results may support an association between the exacerbation of obsessive-compulsive phenomena and the use of clozapine.

Comorbid major depression in obsessive-compulsive disorder patients

Although major depressive disorder (MDD) has been consistently considered the most frequent complication of obsessive-compulsive disorder (OCD), little is known about the clinical characteristics of patients with both disorders. This study assessed 815 Brazilian OCD patients using a comprehensive psychiatric evaluation. Clinical and demographic variables, including OCD symptom dimensions, were compared among OCD patients with and without MDD. Our findings showed that prevalence rates of current MDD (32%) and lifetime MDD (67.5%) were similar for both sexes in this study. In addition, patients with comorbid MDD had higher severity scores of OCD symptoms. There was no preferential association of MDD with any particular OCD symptom dimension. This study supports the notion that depressed OCD patients present more severe general psychopathology.

Association between polymorphisms in GRIK2 gene and obsessive-compulsive disorder: a family-based study.

Several studies support a genetic influence on obsessive‐compulsive disorder (OCD) etiology. The role of glutamate as an important neurotransmitter affecting OCD pathophysiology has been supported by neuroimaging, animal model, medication, and initial candidate gene studies. Genes involved in glutamatergic pathways, such as the glutamate receptor, ionotropic, kainate 2 (GRIK2), have been associated with OCD in previous studies. This study examines GRIK2 as a candidate gene for OCD susceptibility in a family‐based approach. Probands had full DSM‐IV diagnostic criteria for OCD. Forty‐seven OCD probands and their parents were recruited from tertiary care OCD specialty clinics from France and USA. Genotypes of single nucleotide polymorphism (SNP) markers and related haplotypes were analyzed using Haploview and FBAT software. The polymorphism at rs1556995 (P= 0.0027; permuted P‐value = 0.03) was significantly associated with the presence of OCD. Also, the two marker haplotype rs1556995/rs1417182, was significantly associated with OCD (P= 0.0019, permuted P‐value = 0.01). This study supports previously reported findings of association between proximal GRIK2 SNPs and OCD in a comprehensive evaluation of the gene. Further study with independent samples and larger sample sizes is required.

TNF-alpha polymorphisms are associated with obsessive-compulsive disorder

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.

Aripiprazole and Tourette syndrome

Dear Editor, Tourette syndrome (TS) is characterized by chronic motor and vocal tics. In the ‘60s, neuroleptics have started to be used on TS and became the most efficient medications. Most used neuroleptics which have been reported in controlled studies or case reports are haloperidol, pimozide, sulpiride, risperidone, olanzapine and ziprazidone.1 Since then, typical neuroleptics have been decreasingly prescribed due to their side-effects. We will present a resistant TS case that responded with aripiprazol, whose mechanism of action differs from both typical and atypical antipsycotics.2 Up to now, there is no publications about aripiprazol on TS. P., 20 years old, male, single, student, born at the countryside of the state of São Paulo and living at the state’s capital, has had his first multiple motor and vocal tics since the age of five. These tics have increasingly worsened causing much suffering for the patient and his family. Additionally, the patient showed obsessive-compulsive symptoms, besides major depressive episode, separation anxiety and panic with agoraphobia. He has unsuccessfully undergone all conventional (haloperidol, pimozide, trifluoperazine, sulpiride, olanzapine, ziprazidone, clonidine, botulinum toxin) and alternative (pergolide, nicotine, clonazepan, reserpine) tics treatments without success. It was added aripiprazol (15 mg/day) to the previous scheme a (sertraline + olanzapine, the latter gradually withdrawn) with tic improvement. Improvement was observed since the second week onwards using the medication and has persisted after three months of continuous treatment with 15 mg/day. The floating nature of tics hampers to assess if the improvement occurred due to the medication or to a remission phase of the disease proper. However, vocal tics, always extremely resistant to pharmacological treatment, decreased significantly, along with the motor tics, when aripiprazol was introduced. In the current model about the pathogenesis of TS which involve cortical-subcortical circuits, it is believed that the increase in the dopaminergic stimulation in the striatal region implies higher release of glutamate in the thalamic-cortical projections, leading to release of involuntary movements.3-4 Aripiprazol has been described as a stabilizer of the dopamin/serotonin system. Its suggested mechanism of action is the partial agonism on D2 receptors, as it binds more to D2 G-protein bound receptors than to those which are not.2 The affinity of the drug for D2 is 4to 20 times lower than that of haloperidol, chlorpromazine or other typical antipsycotics.5 Besides, it shows a partial agonist activity on 5HT1A receptors and antagonism on 5HT2A receptors. Most neocortex 5HT1A receptors are situated in glutamatergic pyramidal neurons. These receptors have a inhibitory action, which would reduce the excitatory glutamatergic output. It is believed that part of the control of tics would stem from this control in the glutamatergic projection pathways. Aripiprazol, therefore, with a profile of side-effects characterized by lower weight gain, lower sedation, absence of prolactine levels elevation and of widening of QT space of electrocardiogram compared to other antipsycotics, becomes an interesting option for TS cases which do not respond to conventional therapies. It has, however, a high cost and needs official support to allow the poorest layers of the population to benefit from its effects. Controlled studies comparing aripiprazol to the conventional treatments for TS are needed.

The drug-naïve OCD patients imaging genetics, cognitive and treatment response study: methods and sample description

OBJECTIVE To describe a protocol that was based on an integrative neurobiological model of scientific investigation to better understand the pathophysiology of obsessive-compulsive disorder and to present the clinical and demographic characteristics of the sample. METHOD A standardized research protocol that combines different methods of investigation (genetics, neuropsychology, morphometric magnetic resonance imaging and molecular neuroimaging of the dopamine transporter) obtained before and after treatment of drug-naïve adult obsessive-compulsive disorder patients submitted to a sequentially allocated 12-week clinical trial with a selective serotonin reuptake inhibitor (fluoxetine) and group cognitive-behavioral therapy. RESULTS Fifty-two treatment-naïve obsessive-compulsive disorder patients entered the clinical trial (27 received fluoxetine and 25 received group cognitive-behavioral therapy). At baseline, 47 blood samples for genetic studies, 50 neuropsychological evaluations, 50 morphometrical magnetic resonance images and 48 TRODAT-1 single-photon emission computed tomography (SPECT) exams were obtained. After 12 weeks, 38 patients completed the protocol (fluoxetine = 20 and GCBT = 18). Thirty-eight neuropsychological evaluations, 31 morphometrical magnetic resonance images and 34 TRODAT-1 SPECT exams were obtained post-treatment. Forty-one healthy controls matched for age, gender, socioeconomic status, level of education and laterality were submitted to the same research procedures at baseline. CONCLUSION The comprehensive treatment response protocol applied in this project allowing integration on genetic, neuropsychological, morphometrical and molecular imaging of the dopamine transporter data in drug-naïve patients has the potential to generate important original information on the neurobiology of obsessive-compulsive disorder, and at the same time be clinically meaningful.

Lack of association of indoleamine 2,3-dioxygenase polymorphisms with interferon-alpha-related depression in hepatitis C

BACKGROUND Major depression is a frequent adverse effect of interferon-alpha (IFN-α) therapy. Although the indoleamine 2,3-dioxygenase (IDO) enzyme seems to be involved in the pathophysiology of IFN-α-induced depression, no pharmacogenetic study has investigated whether variation in the IDO gene modifies vulnerability to this adverse effect. METHODS A cross-sectional study assessing 277 hepatitis C patients recruited in two specialized outpatient clinics of Brazil. They were interviewed with the Mini International Neuropsychiatric Interview (MINI) approximately 1 month after the end of IFN-α plus ribavirin therapy. Genomic DNA of individuals was extracted from venous blood. Three IDO single-nucleotide polymorphisms (SNPs) were genotyped (rs3824259; rs10089084 and rs35099072). RESULTS MINI indicated that 21.3% of the sample met criteria for a major depressive episode during the course of IFN-α therapy. No association with the diagnosis of a major depressive episode during the course of IFN-α therapy was observed genotype or allele-wise (p>0.05). Current major depression and/or current anxiety disorder was significantly associated with IFN-α-related depression (p<0.005). However, gender, age, route of infection, result of the antiviral treatment, past history of substance use disorders, depression or any other psychiatric disorder showed no association with IFN-α-related depression (p>0.05). CONCLUSIONS Our results suggest no influence of the variants in the IDO gene and the diagnosis of interferon-α-related depression in the Brazilian population. Interferon-α-related depression may impose persistent psychopathology on at least 15% of the depressed patients even 2 years after antiviral therapy termination. The cross-sectional design is a limitation of our study, predisposing memory bias. Prospective pharmacogenetic studies are warranted to continue investigation of the impact of IDO polymorphisms on the development of IFN-α-induced depression.

Acute dystonia after injection of pegylated interferon alpha-2b.

I-MIBG uptake may reflect the loss and/or dysfunction of the cardiac postganglionic sympathetic nerve terminals. Olfactory dysfunction and impaired facial expression recognition may reflect the loss and/or dysfunction of the olfactory bulb and the amygdala, respectively. In RBD patients, neurodegeneration may occur more diffusively than that considered previously. Our case study would provide an additional support to the hypothesis that RBD is a manifestation of an evolving synucleinopathy.6 We continue to follow this patient for early detection of any signs of emerging Parkinson’s disease.

A neuropsychological study comparing patients infected with HCV and HBV without psychiatric comorbidities.

Hepatitis C is one of the most common chronic infectious diseases worldwide, with well‐documented extra‐hepatic manifestations, such as a broad number of cognitive deficits. These impairments may be explained by psychiatric comorbidities, which have not been investigated properly in the literature. In order to elucidate a specific hepatitis C virus (HCV) induced cognitive impairment not related to mental disorders, neuropsychological performance of patients infected with HCV was compared with that of patients infected with hepatitis B virus cognitive impairment, especially psychiatric comorbidities. A total of 33 patients infected with HCV and 22 patients infected with HBV were included in the study. There were no significant differences between the two groups with regard to age or years of education. The group of patients infected with HCV performed significantly worse on visuo‐spatial memory tasks after adjusting for years of education and age. There were no significant differences between patients infected with HCV and patients infected with HBV with regards to other neuropsychological functions. The data indicate that patients infected with HCV patients have poorer visuo‐spacial memory performance than patients infected with HBV, suggesting that the cognitive deficit may be specific to HCV infection and not to secondary comorbid psychiatric disorders. J. Med. Virol. 81:1184–1188, 2009.