GUARACI DE LIMA REQUENA
Projetos de Pesquisa
Unidades Organizacionais
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina
6 resultados
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- Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways(2016) CAPPI, C.; BRENTANI, H.; LIMA, L.; SANDERS, S. J.; ZAI, G.; DINIZ, B. J.; REIS, V. N. S.; HOUNIE, A. G.; ROSARIO, M. Conceicao do; MARIANI, D.; REQUENA, G. L.; PUGA, R.; SOUZA-DURAN, F. L.; SHAVITT, R. G.; PAULS, D. L.; MIGUEL, E. C.; FERNANDEZ, T. V.Studies of rare genetic variation have identified molecular pathways conferring risk for developmental neuropsychiatric disorders. To date, no published whole-exome sequencing studies have been reported in obsessive-compulsive disorder (OCD). We sequenced all the genome coding regions in 20 sporadic OCD cases and their unaffected parents to identify rare de novo (DN) single-nucleotide variants (SNVs). The primary aim of this pilot study was to determine whether DN variation contributes to OCD risk. To this aim, we evaluated whether there is an elevated rate of DN mutations in OCD, which would justify this approach toward gene discovery in larger studies of the disorder. Furthermore, to explore functional molecular correlations among genes with nonsynonymous DN SNVs in OCD probands, a protein-protein interaction (PPI) network was generated based on databases of direct molecular interactions. We applied Degree-Aware Disease Gene Prioritization (DADA) to rank the PPI network genes based on their relatedness to a set of OCD candidate genes from two OCD genome-wide association studies (Stewart et al., 2013; Mattheisen et al., 2014). In addition, we performed a pathway analysis with genes from the PPI network. The rate of DN SNVs in OCD was 2.51 x 10(-8) per base per generation, significantly higher than a previous estimated rate in unaffected subjects using the same sequencing platform and analytic pipeline. Several genes harboring DN SNVs in OCD were highly interconnected in the PPI network and ranked high in the DADA analysis. Nearly all the DN SNVs in this study are in genes expressed in the human brain, and a pathway analysis revealed enrichment in immunological and central nervous system functioning and development. The results of this pilot study indicate that further investigation of DN variation in larger OCD cohorts is warranted to identify specific risk genes and to confirm our preliminary finding with regard to PPI network enrichment for particular biological pathways and functions.
- Obsessive-Compulsive Personality Symptoms Predict Poorer Response to Gamma Ventral Capsulotomy for Intractable OCD(2020) COPETTI, Maria Eugenia; LOPES, Antonio C.; REQUENA, Guaraci; JOHNSON, Isaac N. S.; GREENBERG, Benjamin D.; NOREN, Georg; MCLAUGHLIN, Nicole C. R.; SHAVITT, Roseli G.; MIGUEL, Euripedes C.; BATISTUZZO, Marcelo C.; HOEXTER, Marcelo Q.Gamma ventral capsulotomy (GVC) is a radiosurgical procedure which aims to create lesions in the ventral part of the anterior limb of the internal capsule (ALIC). It has been used as a treatment option for patients with intractable obsessive-compulsive disorder (OCD) who do not respond to several first-line treatments attempts. However, changes in personality disorder symptoms after GVC have not been investigated. The aims of this study are to investigate changes in personality disorder symptoms after GVC and to search for baseline personality disorder symptoms that may predict clinical response to GVC. Fourteen treatment-intractable OCD patients who underwent GVC completed the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) at baseline and one year after the procedure. Wilcoxon signed-rank test was performed to investigate personality disorder symptom changes before and after surgery. Linear regression models were utilized to predict treatment response, using baseline personality disorder symptoms as independent variables. We did not observe any quantitative changes in personality disorder symptoms after GVC, compared with baseline. Higher severity of obsessive-compulsive personality disorder symptoms at baseline was correlated with worse treatment response after GVC for OCD (beta = -0.085, t-value = -2.52, p-value = 0.027). These findings advocate for the safety of the GVC procedure in this specific population of intractable OCD patients, in terms of personality disorder symptom changes. They also highlight the importance of taking into account the severity of obsessive-compulsive personality disorder symptoms when GVC is indicated for intractable OCD patients.
- Personality measures after gamma ventral capsulotomy in intractable OCD(2018) PAIVA, Raquel R.; BATISTUZZO, Marcelo C.; MCLAUGHLIN, Nicole C.; CANTERAS, Miguel M.; MATHIS, Maria E. de; REQUENA, Guaraci; SHAVITT, Roseli G.; GREENBERG, Benjamin D.; NOREN, Georg; RASMUSSEN, Steven A.; TAVARES, Hermano; MIGUEL, Euripedes C.; LOPES, Antonio C.; HOEXTER, Marcelo Q.Background: Neurosurgeries such as gamma ventral capsulotomy (GVC) are an option for otherwise intractable obsessive-compulsive disorder (OCD) patients. In general, clinical and neuropsychological status both improve after GVC. However, its consequences on personality traits are not well-studied. The objective of this study was to investigate personality changes after one year of GVC in intractable OCD patients. Methods: The personality assessment was conducted using the Revised NEO Personality Inventory (NEO PI-R) and Cloninger's Temperament and Character Inventory (TCI) in 14 intractable OCD patients before and one year after GVC. Comparisons of personality features between treatment responders (n = 5) and non-responders (n = 9) were performed. Multiple linear regression was also used for predicting changes in clinical and global functioning variables. Results: Overall, no deleterious effect was found in personality after GVC. Responders had a reduction in neuroticism (p = 0.043) and an increase in extraversion (p = 0.043). No significant changes were observed in nonresponders. Increases in novelty seeking and self-directedness, and decreases in persistence and cooperativiness predicted OCD symptom improvement. Similary, improvement in functioning was also predicted by hgher novelty seeking and self-directedness after GVC, whereas better functioning was also associated with lower reward dependence and cooperativeness after surgery. Conclusions: The pattern of changes in personality traits after GVC was generally towards that observed in nonclinical population, and does not raise safety concerns.
conferenceObject Serotonin Reuptake Inhibitor Augmentation with N-Acetylcysteine in Treatment Resistant Obsessive-Compulsive Disorder: A Double-blind Randomized Controlled Trial(2015) COSTA, Daniel L. C.; DINIZ, Juliana B.; JOAQUIM, Marines; ACCIARITO, Ana C.; RODRIGUES, Bernardo; ODA, Eduardo F.; REQUENA, Guaraci; MIGUEL, Euripedes C.; PITTENGER, Christopher; BLOCH, Michael H.; SHAVITT, Roseli G.- Randomized, Double-Blind, Placebo-Controlled Trial of N-Acetylcysteine Augmentation for Treatment-Resistant Obsessive-Compulsive Disorder(2017) COSTA, Daniel L. C.; DINIZ, Juliana B.; REQUENA, Guaraci; JOAQUIM, Marines A.; PITTENGER, Christopher; BLOCH, Michael H.; MIGUEL, Euripedes C.; SHAVITT, Roseli G.Objective: To evaluate the efficacy of serotonin reuptake inhibitor (SRI) augmentation with N-acetylcysteine (NAC), a glutamate modulator and antioxidant medication, for treatment-resistant obsessive-compulsive disorder (OCD). Methods: We conducted a randomized, double-blind, placebo-controlled, 16-week trial of NAC (3,000 mg daily) in adults (aged 18-65 years) with treatment-resistant OCD, established according to DSM-IV criteria. Forty subjects were recruited at an OCD-specialized outpatient clinic at a tertiary hospital (May 2012-October 2014). The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores. To evaluate the variables group, time, and interaction effects for Y-BOCS scores at all time points, we used nonparametric analysis of variance with repeated measures. Secondary outcomes were the severity scores for anxiety, depression, specific OCD symptom dimensions, and insight. Results: Both groups showed a significant reduction of baseline Y-BOCS scores at week 16: the NAC group had a reduction of 4.3 points (25.6 to 21.3), compared with 3.0 points (24.8 to 21.8) for the placebo group. However, there were no significant differences between groups (P =.92). Adding NAC was superior to placebo in reducing anxiety symptoms (P =.02), but not depression severity or specific OCD symptom dimensions. In general, NAC was well tolerated, despite abdominal pain being more frequently reported in the NAC group (n [%]: NAC = 9 [60.0], placebo = 2 [13.3]; P <.01). Conclusions: Our trial did not demonstrate a significant benefit of NAC in reducing OCD severity in treatmentresistant OCD adults. Secondary analysis suggested that NAC might have some benefit in reducing anxiety symptoms in treatment-resistant OCD patients. (C) Copyright 2017 Physicians Postgraduate Press, Inc.
- Adaptive treatment strategies for children and adolescents with Obsessive-Compulsive Disorder: A sequential multiple assignment randomized trial(2018) FATORI, Daniel; PEREIRA, Carlos Alberto de Braganca; ASBAHR, Fernando R.; REQUENA, Guaraci; ALVARENGA, Pedro G.; MATHIS, Maria Alice de; ROHDE, Luis A.; LECKMAN, James F.; MARCH, John S.; POLANCZYK, Guilherme V.; MIGUEL, Euripedes C.; SHAVITT, Roseli G.Objective: This sequential multiple assignment randomized trial (SMART) tested the effect of beginning treatment of childhood OCD with fluoxetine (FLX) or group cognitive-behavioral therapy (GCBT) accounting for treatment failures over time. Methods: A two-stage, 28-week SMART was conducted with 83 children and adolescents with OCD. Participants were randomly allocated to GCBT or FLX for 14 weeks. Responders to the initial treatment remained in the same regimen for additional 14 weeks. Non-responders, defined by less than 50% reduction in baseline Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores, were re-randomized to either switch to or add the other treatment. Assessments were performed at baseline, 7, 14, 21, and 28 weeks. Results: Among the 43 children randomized to FLX who completed the first stage, 15 (41.7%) responded to treatment and 21 non-responders were randomized to switch to (N = 9) or add GCBT (N = 12). Among the 40 children randomized to GCBT who completed the first stage, 18 (51.4%) responded to treatment and 17 non-responders were randomized to switch to (N = 9) or add FLX (N = 8). Primary analysis showed that significant improvement occurred in children initially treated with either FLX or GCBT. Each time point was statistically significant, showing a linear trend of symptom reduction. Effect sizes were large within (0.76-0.78) and small between (-0.05) groups. Conclusions: Fluoxetine and GCBT are similarly effective initial treatments for childhood OCD considering treatment failures over time. Consequently, provision of treatment for childhood OCD could be tailored according to the availability of local resources.