PEDRO GOMES DE ALVARENGA

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LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina

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  • article 39 Citação(ões) na Scopus
    Obsessive-compulsive symptoms are associated with psychiatric comorbidities, behavioral and clinical problems: a population-based study of Brazilian school children
    (2016) ALVARENGA, Pedro G.; ROSARIO, Maria C. do; CESAR, Raony C.; MANFRO, Gisele G.; MORIYAMA, Tais S.; BLOCH, Michael H.; SHAVITT, Roseli G.; HOEXTER, Marcelo Q.; COUGHLIN, Catherine G.; LECKMAN, James F.; MIGUEL, Euripedes C.
    Pediatric-onset obsessive-compulsive disorder (OCD) is underdiagnosed, and many affected children are untreated. The present study seeks to evaluate the presence and the clinical impact of OCD and obsessive-compulsive symptoms (OCS) in a large sample of school-age children. In Phase I, we performed an initial screening using the Family History Screen (FHS). In Phase II, we identified an ""at-risk"" sample, as well as a randomly selected group of children. A total of 2,512 children (6-12 years old) were assessed using the FHS, the Development and Well-Being Assessment (DAWBA), the Strengths and Difficulties Questionnaire (SDQ), and the Child Behavior Checklist (CBCL). Data analyses included descriptive and multivariate analytical techniques. 2,512 children (mean age: 8.86 +/- A 1.84 years; 55.0 % male) were categorized into one of the three diagnostic groups: OCD (n = 77), OCS (n = 488), and unaffected controls (n = 1,947). There were no significant socio-demographic differences (age, gender, socioeconomic status) across groups. The OCS group resembled the OCD on overall impairment, including school problems and delinquent behaviors. However, the OCD group did have significantly higher rates of several comorbid psychiatric disorders, including separation anxiety, generalized anxiety, and major depressive disorder, than OCS or unaffected controls. Moreover, the OCD group also scored higher than the SDQ, as well as on each of CBCL items rated by the parent. Our findings suggest that there is a psychopathological continuum between OCS and OCD in school-aged children. The presence of OCS is associated with functional impairment, which needs further investigation in longitudinal studies.
  • article 20 Citação(ões) na Scopus
    The Child Behavior Checklist-Obsessive-Compulsive Subscale Detects Severe Psychopathology and Behavioral Problems Among School-Aged Children
    (2017) SAAD, Laura O.; ROSARIO, Maria C. do; CESAR, Raony C.; BATISTUZZO, Marcelo C.; HOEXTER, Marcelo Q.; MANFRO, Gisele G.; SHAVITT, Roseli G.; LECKMAN, James F.; MIGUEL, Euripedes C.; ALVARENGA, Pedro G.
    Objective: The aims of this study were (1) to assess obsessive-compulsive symptoms (OCS) dimensionally in a school-aged community sample and to correlate them with clinical and demographical variables; (2) to determine a subgroup with significant OCS ""at-risk for OCD'') using the Child Behavior Checklist (CBCL-OCS) and (3) to compare it with the rest of the sample; (4) To review the CBCL-OCS subscale properties as a screening tool for pediatric OCD. Methods: Data from the Brazilian High Risk Cohort were analyzed. The presence and severity of OCS were assessed through the CBCL-OCS subscale. DSM-IV psychiatric diagnoses were obtained by the Developmental and Well-Being Assessment. Behavioral problems were assessed using the Strengths and Difficulties Questionnaire, the Youth Strengths Inventory, and the CBCL internalizing and externalizing behavior subscales. Results: A total of 2512 (mean age: 8.86 +/- 1.84 years; 55.0% male) children were included. Moderate correlations were found between OCS severity and functional impairment (r = 0.36, p < 0.001). Children with higher levels of OCS had higher rates of psychiatric comorbidity and behavioral problems (p < 0.001). A score of 5 or higher in the CBCL-OCS scale determined an ""at-risk for OCD'' subgroup, comprising 9.7% of the sample (n = 244), with behavioral patterns and psychiatric comorbidities (e.g., tics [odds ratios, OR = 6.41, p < 0.001]), anxiety disorders grouped [OR = 3.68, p < 0.001] and depressive disorders [OR = 3.0, p < 0.001] very similar to those described in OCD. Sensitivity, specificity, positive predictive value, and negative predictive value of the CBCL-OCS for OCD diagnosis were, respectively, 48%, 91.5%; 15.1%, and 98.2%. Conclusions: The dimensional approach suggests that the presence of OCS in children is associated with higher rates of comorbidity, behavioral problems, and impairment. The ""at-risk for OCD'' group defined by the CBCL revealed a group of patients phenotypically similar to full blown OCD.
  • article 51 Citação(ões) na Scopus
    Obsessive-compulsive symptom dimensions correlate to specific gray matter volumes in treatment-naive patients
    (2012) ALVARENGA, Pedro G.; ROSARIO, Maria C. do; BATISTUZZO, Marcelo C.; DINIZ, Juliana B.; SHAVITT, Roseli G.; DURAN, Fabio L. S.; DOUGHERTY, Darin D.; BRESSAN, Rodrigo A.; MIGUEL, Euripedes C.; HOEXTER, Marcelo Q.
    Background: Clinical and sociodemographic findings have supported that OCD is heterogeneous and composed of multiple potentially overlapping and stable symptom dimensions. Previous neuroimaging investigations have correlated different patterns of OCD dimension scores and gray matter (GM) volumes. Despite their relevant contribution, some methodological limitations, such as patient's previous medication intake, may have contributed to inconsistent findings. Method: Voxel-based morphometry was used to investigate correlations between regional GM volumes and symptom dimensions severity scores in a sample of 38 treatment-naive OCD patients. Several standardized instruments were applied, including an interview exclusively developed for assessing symptom dimensions severity (DY-BOCS). Results: Scores on the ""aggression"" dimension were positively correlated with GM volumes in lateral parietal cortex in both hemispheres and negatively correlated with bilateral insula, left putamen and left inferior OFC. Scores on the ""sexual/religious"" dimension were positively correlated with GM volumes within the right middle lateral OFC and right DLPFC and negatively correlated with bilateral ACC. Scores on the ""hoarding"" dimension were positively correlated with GM volumes in the left superior lateral OFC and negatively correlated in the right parahippocampal gyrus. No significant correlations between GM volumes and the ""contamination"" or ""symmetry"" dimensions were found. Conclusions: Building upon preexisting findings, our data with treatment-naive OCD patients have demonstrated distinct GM substrates implicated in both cognitive and emotion processing across different OCS dimensions.
  • conferenceObject
    Subtle Neurocognitive Deficits Associated With Obsessive-Compulsive Symptoms During Childhood: A Latent Class Analysis Applied in a Brazilian High Risk Cohort
    (2017) BATISTUZZO, Marcelo; HOEXTER, Marcelo; VATTIMO, Eduardo; ALVARENGA, Pedro; SHAVITT, Roseli; TEIXEIRA, Lorenna; ROSARIO, Maria Conceicao do; MIGUEL, Euripedes; SALUM, Giovanni
  • article 10 Citação(ões) na Scopus
    Reduced Prefrontal Activation in Pediatric Patients With Obsessive-Compulsive Disorder During Verbal Episodic Memory Encoding
    (2015) BATISTUZZO, Marcelo Camargo; BALARDIN, Joana Bisol; MARTIN, Maria da Graca Morais; HOEXTER, Marcelo Queiroz; BERNARDES, Elisa Teixeira; BORCATO, Sonia; SOUZA, Marina de Marco e; QUERIDO, Cicero Nardini; MORAIS, Rosa Magaly; ALVARENGA, Pedro Gomes de; LOPES, Antonio Carlos; SHAVITT, Roseli Gedanke; SAVAGE, Cary R.; AMARO JR., Edson; MIGUEL, Euripedes C.; POLANCZYK, Guilherme V.; MIOTTO, Eliane C.
    Objective: Patients with obsessive-compulsive disorder (OCD) often present with deficits in episodic memory, and there is evidence that these difficulties may be secondary to executive dysfunction, that is, impaired selection and/or application of memory-encoding strategies (mediation hypothesis). Semantic clustering is an effective strategy to enhance encoding of verbal episodic memory (VEM) when word lists are semantically related. Self-initiated mobilization of this strategy has been associated with increased activity in the prefrontal cortex, particularly the orbitofrontal cortex, a key region in the pathophysiology of OCD. We therefore studied children and adolescents with OCD during uncued semantic, clustering strategy application in a VEM functional magnetic resonance imaging (fMRI)-encoding paradigm. Method: A total of 25 pediatric patients with OCD (aged 8.1-17.5 years) and 25 healthy controls (HC, aged 8.1-16.9) matched for age, gender, handedness, and IQ were evaluated using a block design VEM paradigm that manipulated semantically related and unrelated words. Results: The semantic clustering strategy score (SCS) predicted VEM performance in HC (p <.001, R-2 = 0.635), but not in patients (p =.099). Children with OCD also presented hypoactivation in the dorsomedial prefrontal cortex (cluster-corrected p <.001). Within-group analysis revealed a negative correlation between Yale-Brown Obsessive Compulsive Scale scores and activation of orbitofrontal cortex in the group with OCD. Finally, a positive correlation between age and SCS was found in HC (p = .001, r = 0.635), but not in patients with OCD (p = .936, r = 0.017). Conclusion: Children with OCD presented altered brain activation during the VEM paradigm and absence of expected correlation between SCS and age, and between SCS and total words recalled. These results suggest that different neural mechanisms underlie self-initiated semantic clustering in OCD.
  • article 31 Citação(ões) na Scopus
    Assessment of Safety and Outcome of Lateral Hypothalamic Deep Brain Stimulation for Obesity in a Small Series of Patients With Prader-Willi Syndrome
    (2018) FRANCO, Ruth R.; FONOFF, Erich T.; ALVARENGA, Pedro G.; ALHO, Eduardo J. L.; LOPES, Antonio Carlos; HOEXTER, Marcelo Q.; BATISTUZZO, Marcelo C.; PAIVA, Raquel R.; TAUB, Anita; SHAVITT, Roseli G.; MIGUEL, Euripides C.; TEIXEIRA, Manoel J.; DAMIANI, Durval; HAMANI, Clement
    IMPORTANCE Deep brain stimulation (DBS) has been investigated for treatment of morbid obesity with variable results. Patients with Prader-Willi syndrome (PWS) present with obesity that is often difficult to treat. OBJECTIVE To test the safety and study the outcome of DBS in patients with PWS. DESIGN, SETTING, AND PARTICIPANTS This case series was conducted in the Hospital das Clinicas, University of Sao Paulo, Brazil. Four patients with genetically confirmed PWS presenting with severe obesity were included. EXPOSURE Deep brain stimulation electrodes were bilaterally implanted in the lateral hypothalamic area. After DBS implantation, the treatment included the following phases: titration (1-2 months), stimulation off (2 months), low-frequency DBS (40 Hz; 1 month), washout (15 days), high-frequency DBS (130 Hz; 1 month), and long-term follow-up (6 months). MAIN OUTCOMES AND MEASURES Primary outcome measures were adverse events recorded during stimulation and long-term DBS treatment. Secondary outcomes consisted of changes in anthropometric measures (weight, body mass index [calculated as weight in kilograms divided by height in meters squared], and abdominal and neck circumference), bioimpedanciometry, and calorimetry after 6 months of treatment compared with baseline. The following evaluations and measurements were conducted before and after DBS: clinical, neurological, psychiatric, neuropsychological, anthropometry, calorimetry, blood workup, hormonal levels, and sleep studies. Adverse effects were monitored during all follow-up visits. RESULTS Four patients with PWS were included (2 male and 2 female; ages 18-28 years). Baseline mean (SD) body mass index was 39.6 (11.1). Two patients had previous bariatric surgery, and all presented with psychiatric comorbidity, which was well controlled with the use of medications. At 6 months after long-term DBS, patients had a mean 9.6% increase in weight, 5.8% increase in body mass index, 8.4% increase in abdominal circumference, 4.2% increase in neck circumference, 5.3% increase in the percentage of body fat, and 0% change in calorimetry compared with baseline. Also unchanged were hormonal levels and results of blood workup, sleep studies, and neuropsychological evaluations. Two patients developed stimulation-induced manic symptoms. Discontinuation of DBS controlled this symptom in 1 patient. The other required adjustments in medication dosage. Two infections were documented, 1 associated with skin picking. CONCLUSIONS AND RELEVANCE Safety of lateral hypothalamic area stimulation was in the range of that demonstrated in patients with similar psychiatric conditions receiving DBS. In the small cohort of patients with PWS treated in our study, DBS was largely ineffective.
  • article 14 Citação(ões) na Scopus
    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.