PEDRO GOMES DE ALVARENGA

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Projetos de Pesquisa
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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 49 Citação(ões) na Scopus
    Obsessive-compulsive symptom dimensions in a population-based, cross-sectional sample of school-aged children
    (2015) ALVARENGA, Pedro G.; CESAR, Raony C.; LECKMAN, James F.; MORIYAMA, Tais S.; TORRES, Albina R.; BLOCH, Michael H.; COUGHLIN, Catherine G.; HOEXTER, Marcelo Q.; MANFRO, Gisele G.; POLANCZYK, Guilherme V.; MIGUEL, Euripedes C.; ROSARIO, Maria C. do
    Background: Obsessive-compulsive disorder can be expressed as four potentially overlapping obsessive-compulsive symptom (OCS) dimensions (OCSD) (""symmetry/ordering"", ""contamination/cleaning"", ""aggressive/sexual/religious"" and ""collecting/hoarding""). In clinical samples, some dimensions are more familial and associated with increased psychiatric comorbidity and malfunctioning. However, data concerning OCS and OCSD are scarce in non-clinical samples, particularly among children. The present study aims to estimate: (1) the prevalence and sex/age distribution of OCS/OCSD in a community-based sample of schoolchildren; (2) the association between OCS and additional clinical factors; and (3) the degree of familial aggregation of OCS/OCSD. Methods: OCS and OCSD were evaluated in 9937 Brazilian school-children (6-12 years-old) and their biological relatives using the Family History Screen. Data analyses included gradient estimated equations and post-hoc tests. Results: We included data on 9937 index-children, 3305 siblings (13-18 years-old), and 16,218 parents. Biological mothers were the informants in 87.6% of the interviews. OCS were present in 14.7% of the index-children; 15.6% of their siblings; 34.6% of their mothers and 12.1% of their fathers. The prevalence of OCS and each of the OCSD gradually increased from ages 6 to 12 years. Overall, OCS in children were associated with the presence of other psychiatric symptoms, as well as behavioral/school impairment. OCS and each of the four OCSD aggregated significantly within families. Conclusions: OCS are prevalent and associated with psychiatric symptoms and clinical impairment among school-aged children. OCSD aggregate within families in a dimension-specific fashion. These findings suggest a natural continuum between OCS and OCD with regard to their dimensional character.
  • article 16 Citação(ões) na Scopus
    Lateral hypothalamic activity indicates hunger and satiety states in humans
    (2017) TALAKOUB, Omid; PAIVA, Raquel R.; MILOSEVIC, Matija; HOEXTER, Marcelo Q.; FRANCO, Ruth; ALHO, Eduardo; NAVARRO, Jessie; PEREIRA JR., Jose F.; POPOVIC, Milos R.; SAVAGE, Cary; LOPES, Antonio C.; ALVARENGA, Pedro; DAMIANI, Durval; TEIXEIRA, Manoel J.; MIGUEL, Euripides C.; FONOFF, Erich T.; BATISTUZZO, Marcelo C.; HAMANI, Clement
    Lateral hypothalamic area (LHA) local field potentials (LFPs) were recorded in a Prader-Willi patient undergoing deep brain stimulation (DBS) for obesity. During hunger, exposure to food-related cues induced an increase in beta/low-gamma activity. In contrast, recordings during satiety were marked by prominent alpha rhythms. Based on these findings, we have delivered alpha-frequency DBS prior to and during food intake. Despite reporting an early sensation of fullness, the patient continued to crave food. This suggests that the pattern of activity in LHA may indicate hunger/satiety states in humans but attest to the complexity of conducting neuromodulation studies in obesity.
  • 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.
  • 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 6 Citação(ões) na Scopus
    Low frequency fluctuation of brain spontaneous activity and obsessive compulsive symptoms in a large school-age sample
    (2018) HOEXTER, Marcelo Q.; BIAZOLI JR., Claudinei E.; ALVARENGA, Pedro G.; BATISTUZZO, Marcelo C.; SALUM, Giovanni A.; GADELHA, Ary; PAN, Pedro M.; ANES, Mauricio; MANCINI-MARTINS, Leticia; MOURA, Luciana M.; SORIANO-MAS, Caries; AQUILLA, Marco A. G. Del'; ARNARO JR., Edson; ROHDE, Luis A.; JACKOWSKI, Andrea P.; BRESSAN, Rodrigo A.; MIGUEL, Euripedes C.; ROSARIO, Maria C. do; SATO, Joao R.
    Background: The present study was designed to explore alterations in brain dynamics at rest that are associated with Obsessive Compulsive Symptoms (OCS) in childhood by measuring low frequency fluctuation of spontaneous brain activity in a large school community sample from a developing country. Method: Resting state functional magnetic resonance imaging data were collected in a sample of 655 children and adolescents (6-15 years old) from the brazilian 'High Risk Cohort Study for Psychiatric Disorders (HRC)'. OCS were assessed using items from the Compulsion and Obsessions section of the Development and Well-Being Assessment (DAWBA). The correlation between the fractional amplitude of low frequency fluctuations (fALFF) and the number of OCS were explored by using a general linear model, considering fALFF as response variable, OCS score as regressor and age, gender and site as nuisance variables. Results: The number of OCS was positively correlated with the fALFF coefficients at the right sensorimotor cortex (pre-motor, primary motor cortex and post-central gyrus) and negatively correlated with the fALFF coefficients at the insula/superior temporal gyrus of both hemispheres. Our results were specific to OCS and not due to associations with overall psychopathology. Conclusions: Our results suggest that brain spontaneous activity at rest in the sensorimotor and insular/superior-temporal cortices may be involved in OCS in children. These findings need independent replication and future studies should determine whether brain spontaneous activity changes within these regions might be predictors of risk for obsessive-compulsive disorder latter in life.