Felipe Filardi da Rocha

Decision-making impairment is related to serotonin transporter promoter polymorphism in a sample of patients with obsessive-compulsive disorder.

OBJECTIVE Decision-making impairment is an important feature of some psychiatric disorders, such as attention-deficit/hyperactivity disorder and substance-use disorders, and is associated with dysfunction of the fronto-subcortical circuit, mainly the orbitofrontal cortex (OFC). Several data reports support significant correlations between decision-making impairment and the serotonin system. Thus, this neurotransmission system may be a major step in some cognitive features, particularly in OCD because serotonin is associated with this disorder. Therefore, the serotonin transporter promoter polymorphism (5-HTTLPR) may be related to the modulation of these cognitive characteristics. In a sample of Caucasian OCD patients, we explored the link between decision-making and the 5-HTTLPR. METHOD We used the Iowa Gambling Task (IGT) to measure decision-making in 49 OCD patients, according to the DSM-IV criteria. All patients were submitted to Y-BOCS, BDI, BAI, the Raven Progressive Matrices, the Continuous Performance Task, and the Trail Making Test. We grouped S- and/or Lg-carriers in view of the fact that these act in a nearly dominant way. RESULTS On IGT, S- and/or Lg-carriers had significantly lower scores on the third, fourth, and fifth blocks. These findings were confirmed after adjusting for clinical and cognitive variables. DISCUSSION Inconclusive findings about the link between OCD and 5-HTTLPR may be better elucidated by studying OCD subgroups that could be more related in some genetic characteristics. Based on our study, low performance on IGT is associated with S- and/or Lg-carriers. CONCLUSION Our results corroborate the hypothesis that the pattern of neuropsychological functioning observed in previous studies may constitute a biological marker or heritable endophenotype of OCD.

Obsessive-compulsive disorder and immunology : A review

Interest in the possibility of an immune-mediated pathophysiology of obsessive-compulsive disorder and related disorders has increased. In the late 1980s, the National Institute of Mental Health reported an increase in obsessive-compulsive symptoms (OCS) in patients with Sydenham chorea (SC). Subsequently, a precipitating streptococcal infection in children with sudden onset of OCS but no chorea led to the coining of PANDAS (Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection). This association has furthered interest in biological measures for immune and genetic susceptibility in non-PANDAS obsessive-compulsive disorder patients (OCD). Furthermore, some studies are trying to demonstrate alterations of immune parameters in OCD patients, with few positive results. In this narrative review, our objective was to describe the immunologic findings in OCD, PANDAS, and their association with SC.

The role of 5-HTTLPR polymorphism in antidepressant-associated mania in bipolar disorder

BACKGROUND The occurrence of mania during antidepressant treatment is a key issue in the clinical management of bipolar disorder (BD). The serotonin transporter gene is a candidate to be associated with antidepressant-associated mania (AAM) in some patients. This gene has a polymorphism within the promoter region (5-HTTLPR) with two allelic forms, the long (L) and the short (S) variants. METHODS We performed a case-control study to compare 5-HTTLPR genotype and allelic frequencies between 43 patients with a DSM-IV diagnosis of BD, with at least one manic/hypomanic episode associated with treatment with proserotonergic antidepressants (AAM+) and 69 unrelated, matched bipolar patients, who had been exposed to proserotonergic antidepressants without development of manic symptoms (AAM-(*)). Furthermore, we performed this comparison between a subgroup of 23 AAM+ patients that, when they presented AAM, were not using mood stabilizer (AAM+(*)) and 25 AAM- patients who used antidepressant without the concomitant use of a mood stabilizer (AAM-(*)). 5-HTTLPR genotyping was performed using PCR. RESULTS No significant differences were found between AAM+ and AAM-. Within the subgroups, our results show that S-carriers (LS+SS Genotypes) are more prone to make a manic/hypomanic episode associated with antidepressant (P=0.017). LIMITATIONS Our study is retrospective. CONCLUSIONS The 5-HTTLPR polymorphism may be considered a predictor of abnormal response to antidepressant in patients with BP, but this action is influenced by the presence of a mood stabilizer. Such observations reinforce that a correct diagnosis of bipolarity before the beginning of the treatment is essential, mainly for S-carriers patients.

Decision-making impairment in obsessive-compulsive disorder as measured by the Iowa Gambling Task

OBJECTIVE This study aims to evaluate the process of decision-making in patients with obsessive-compulsive disorder (OCD) using the Iowa Gambling Task (IGT). In addition, we intend to expand the understanding of clinical and demographic characteristics that influence decision-making. METHOD Our sample consisted of 214 subjects (107 diagnosed with OCD and 107 healthy controls) who were evaluated on their clinical, demographic and neuropsychological features. Moreover, the Iowa Gambling Task (IGT), a task that detects and measures decision-making impairments, was used. RESULTS We found that OCD patients performed significantly worse on the IGT. Furthermore, features such as symptoms of anxiety did not influence IGT performance. CONCLUSION Impaired decision-making seems to be a key feature of OCD. Given that OCD is a complex heterogeneous disorder, homogeneous groups are necessary for an accurate characterization of our findings.

Borderline personality features possibly related to cingulate and orbitofrontal cortices dysfunction due to schizencephaly.

Prefrontal cortex dysfunction has been associated with a series of behavioral symptoms, such as impulsivity and affective instability, which are the defining features of several personality disorders, notably, borderline personality disorder. We report on a 27-year-old patient with schizencephaly in the right frontal lobe (cingulate cortex lesion and secondary orbitofrontal cortex dysfunction) presenting with prominent borderline features and compromise of executive functions, decision-making and attention. We hypothesize that the personality disorder of our patient could be related to cingulate cortex lesion and secondary orbitofrontal cortex dysfunction associated with schizencephaly.

Associations between polymorphic variants of the tryptophan hydroxylase 2 gene and obsessive-compulsive disorder

OBJECTIVE A substantial body of evidence suggests that obsessive-compulsive disorder has a genetic component, and substantial candidate genes for the disorder have been investigated through association analyses. A particular emphasis has been placed on genes related to the serotonergic system, which is likely to play an important role in the pathogenesis of obsessive-compulsive disorder. The gene for tryptophan hydroxylase 2, which is a rate limiting enzyme in serotonin synthesis, is considered an important candidate gene associated with psychiatric disorders. METHOD Our sample consisted of 321 subjects (107 diagnosed with obsessive-compulsive disorder and 214 healthy controls), which were genotyped for eight tagSNPs (rs4448731, rs4565946, rs11179000, rs7955501, rs10506645, rs4760820, rs1487275 and rs10879357) covering the entire human tryptophan hydroxylase 2 gene. Statistical analyses were performed using UNPHASED, version 3.0.12, and Haploview®. RESULTS Single markers, genotype analysis did not show a significant genetic association with obsessive-compulsive disorder. A significant association between the T-C-T (rs4448731, rs4565946, rs10506645) and C-A-T (rs4565946, rs7955501, rs10506645) haplotypes and obsessive-compulsive disorder was observed, as well as a strong linkage disequilibrium between SNPs rs4448731 and rs4565946, and SNPs rs10506645 and 4760820. DISCUSSION Our research has not demonstrated the existence of associations between the eight SNPs of TPH2 and obsessive-compulsive disorder. However, two LD and two haplotypes areas were demonstrated, thus suggesting that more studies in TPH2 are needed to investigate the role of tryptophan hydroxylase 2 variants in obsessive-compulsive disorder.

Produção científica brasileira nas 40 revistas de psiquiatria com maior fator de impacto no ano de 2006

OBJECTIVE: The Brazilian scientific production published in 2006 in the twenty psychiatric journals with high impact factor (IF) according to the Journal of Citation Report (JCR), 2006, was evaluated. METHODS: All articles from 94 journals with an IF higher than the average (n = 40) were selected. We assessed the articles that had at least one author affiliated to a Brazilian institution as well as those with only Brazilian authors or a first/senior author belonging to a Brazilian institution. Secondly, the distribution of the author(s) by state was determined. RESULTS: Among 7996 articles surveyed 96 (1.20%) had at least one author from a Brazilian institution and in eight, the first senior author belonged to a Brazilian institution, not including the 59 publications that were written only by Brazilian authors. The distribution by state showed Sao Paulo as ranking first with 46 articles (47.91%) and absolute predominance of the South-Southeast region (98.95%). CONCLUSION: Although, Brazilian publications on psychiatry had demonstrated apparent quantitative and qualitative growth, scientific production on the subject remains highly concentrated in a few states.

Increased surgical morbidity of psychiatric patients submitted to appendectomy

Referênc ias 1. Vieweg WV, Julius DA, Fernandez A, Beatty-Brooks M, Hettema JM, Pandurangi AK. Posttraumatic stress disorder: clinical features, pathophysiology and treatment. Am J Med. 2006;119(5):383-90. 2. Hamner M, Hunt N, Gee J, Garrell R, Monroe R. PTSD and automatic implatable cardioverter defibril lators. Psychosomatics. 1999;40(1):82-5. 3. Luyster FS, Hughes JW, Waechter D, Josephson R. Resource loss predicts depression and anxiety among patients treated with an implantable cardiover ter defibril lator. Psychosom Med. 2006;68(5):794-800. 4. Neel M. Posttraumatic stress symptomatology in patients with automatic implantable cardioverter defibrillators: nature and intervention. Int J Emerg Ment Health. 2000;2(4):259-63. 5. Baumert J, Schmitt C, Ladwig KH. Psychophysiologic and affective parameters associated with pain intensity of cardiac cardioverter defibrillator shock discharges. Psychosom Med. 2006;68(4):591-7. Dear Editor, The general medical care offered to psychiatric patients tends to be worse than the one offered to the general population. It includes inappropriate management of highly prevalent diseases such as diabetes mellitus and systemic hypertension as well as a significant delay in the diagnosis of emergent clinical and surgical conditions leading to increased morbidity and mortality. In this preliminary report, we aim at presenting our evaluation of the hypothesis that patients with major psychiatric disorders submitted to appendectomy had delayed diagnosis and/or worse outcome when compared to control subjects. We searched for all records of patients over age 18 who underwent a surgical procedure (appendectomy) in a general hospital in the period from May, 2005 to August, 2006, all of them with real appendicitis evidenced by anatomopathologic exam carried out after the surgery. Appendectomy was selected due to the high incidence of appendicitis in the general population. We performed a chart review and the following data were evaluated: 1) the presence of a major psychiatric diagnosis according to DSM-IV criteria; 2) time elapsed from the onset of clinical symptoms to the surgical procedure (in days); 3) length of hospital stay (in days); and 4) number of postoperative complications. Coincidently only female psychiatric patients were identified (n = 10) based on retrospective psychiatric diagnosis (medical record and family information). Three patients had schizophrenia, four patients had recurrent depressive disorder, and three patients had bipolar disorder. The control group was comprised of female patients without current psychiatric disorders and/or receiving psychiatric treatment, who underwent the same surgical procedure at the same period (n = 81). A non-parametric test (Mann-Whitney) was used to compare the values between the groups. The results are shown in Table 1. Increased surgical morbidity of psychiatric patients submitted to appendectomy Morbidade cirúrgica aumentada de pacientes psiquiátricos submetidos à apendectomia

Produção brasileira em periódicos psiquiátricos de alto fator de impacto em 2005

OBJETIVO: Avaliar a producao cientifica brasileira, no ano de 2005, nas 20 revistas de psiquiatria com maior fator de impacto (FI) segundo o Journal of Citation Report (JCR), 2004. METODOS: Do total de 90 periodicos com FI variando de 11,207 ate 0,13, selecionamos todos os artigos dos periodicos com FI acima do percentil 75 (n = 20). Avaliamos, entre esses artigos, quantos apresentavam pelo menos um autor brasileiro, quantos eram compostos por equipe exclusivamente brasileira ou tinham pelo menos o primeiro autor e/ou o autor senior filiado a instituicao nacional. Avaliamos tambem a respectiva distribuicao das publicacoes por estados de acordo com a instituicao de filiacao do(s) autor(es). RESULTADOS: Entre 4.859 artigos avaliados, 54 (1,11%) tinham pelo menos um autor com afiliacao a instituicao brasileira e 22 tinham autor senior brasileiro, excluindo-se as 32 publicacoes compostas exclusivamente por pesquisadores brasileiros. Ao se determinar a distribuicao, por estados, da instituicao de pesquisa a qual esta(ao) vinculado(s) o(s) autor(res) brasileiro(s), Sao Paulo, com 34 publicacoes (55,73%), ficou na primeira posicao, com predominância absoluta do eixo Sudeste-Sul (96,72%). CONCLUSAO: Apesar de as publicacoes brasileiras em psiquiatria terem apresentado aparente crescimento quantitativo e qualitativo, a producao cientifica da area e ainda pequena e altamente concentrada em alguns poucos estados.

Hypomanic episode secondary to sibutramine in a patient with type-I bipolar disorder.

Dear Editor, A possible interaction between sibutramine and hypomanic state is reported in a previously normothymic patient with type-I bipolar disorder (DSM-IV diagnostic criteria). J.G.S. is a 27-year-old single white woman with a five-year history of bipolar type-I disorder. During the last 18 months she remained completely asymptomatic under carbamazepine (1000 mg/daily; blood level: 7.8 mg/L) and risperidone (2 mg/daily). In order to reduce her overweight (body-mass index = 32.40 kg/m2), sibutramine was introduced (10 mg/daily) and was increased to 15 mg/daily after a week. Two weeks later, she presented irritable reactions when her behavior and whereabouts were questioned, increased energy with frenzied activity and pressured speech. Mental status examination did not demonstrate inflated self-esteem, psychomotor excitement or flight of ideas [Young Mania Rating Scale (YMRS) = 15 points; 17-item Hamilton Rating Scale for Depression (HRSD) = 8]. Laboratory work-up, including complete blood count, renal, liver and thyroid function tests, was unremarkable. There was no previous history of substance abuse or another medical disorder. She has an uncle with history of type-I bipolar disorder. Her first manic episode occurred when she was 17 years old, without concomitant use of antidepressants. Since then, she has presented many hospitalizations due to manic and depressive episodes. These episodes occurred seven and three times, respectively, since the onset of the disorder. Mixed episodes never were observed. One of the manic episodes (YMRS = 51 points) occurred after one week under fluoxetine 60 mg/daily and carbamazepine 1000 mg/daily (blood level: 10.0 mg/L) during a depressive state (HRSD = 23). She also used lithium carbonate (600 mg/daily), but the patient complained about intense shivers and sedation under valproic acid (1000 mg/daily). With sibutramine withdrawal, increasing the dosage of carbamazepine to 1200 mg/daily (blood level: 9.0 mg/L) and introduction of clonazepam (1 mg/day), 12 days later, on discharge, her score on the YMRS had dropped to seven. Therefore, we hypothesized that sibutramine may be responsible for the hypomanic symptoms in our bipolar patient due to: 1) the temporal relation between the sibutramine introduction and the onset of hypomanic state; 2) and its remission after drug’s withdrawal.