LEANDRO DA COSTA LANE VALIENGO
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject Plasma Cortisol in First Episode Drug-Naive Mania: Differential Levels in Euphoric Versus Irritable Mood(2012) VALIENGO, Leandro L.; SOEIRO-DE-SOUZA, Marcui G.; MARQUES, Andrea H.; JURUENA, Mario F.; ANDREAZZA, Ana C.; GATTAZ, Wagner F.; MACHADO-VIERA, RodrigoBackground: Dysregulation of HPA axis have been widely described in subjects with bipolar disorder (BD), including changes in cortisol levels during mood episodes and euthymia. However, most of the studies were done with medicated BD patients with variable length of illness, which was shown to interfere on peripheral cortisol levels. Therefore, the present study aims to evaluate plasma cortisol levels in drug-naïve BD subjects during the first manic episode, as well as investigate the relationship between plasma cortisol levels and manic symptomatology. Methods: Twenty-six drug-naïve patients were enrolled meeting criteria for a first manic episode in bipolar I disorder. Severity of mania was assessed using the Young Mania Rating Scale (YMRS). The control group included 27 healthy subjects matched by age and gender. Cortisol was quantified using a direct radioimmunoassay. Results: Plasma cortisol levels were decreased during first manic episode compared to healthy controls. Higher cortisol levels were positively associated with the presence of irritability (dysphoria), while elated mania showed lower cortisol levels compared to controls. Conclusions: Higher cortisol in dysphoric mania compared to predominantly elated/euphoric mania may indicate a clinical and neurobiological polymorphic phenomenon, potentially involving a higher biological sensitivity to stress in the presence of irritable mood. The present findings highlight the importance to dd a dimensional approach to the traditional categorical diagnosis for future neurobiological studies in BD.- Plasma cortisol in first episode drug-naive mania: Differential levels in euphoric versus irritable mood(2012) VALIENGO, Leandro L.; SOEIRO-DE-SOUZA, Marcio G.; MARQUES, Andrea H.; MORENO, Doris H.; JURUENA, Mario F.; ANDREAZZA, Ana Cristina; GATTAZ, Wagner F.; MACHADO-VIEIRA, RodrigoBackground: Dysregulation of HPA axis has been widely described in subjects with bipolar disorder (BD), including changes in cortisol levels during mood episodes and euthymia. However, most of the studies were done with medicated BD patients with variable length of illness, which was shown to interfere on peripheral cortisol levels. Therefore, the present study aims to evaluate plasma cortisol levels in drug-naive BD subjects during the first manic episode, as well as investigate the relationship between plasma cortisol levels and manic symptomatology. Methods: Twenty-six drug-naive patients were enrolled meeting criteria for a first manic episode in bipolar I disorder. Severity of mania was assessed using the Young Mania Rating Scale (YMRS). The control group included 27 healthy subjects matched by age and gender. Cortisol was quantified using a direct radioimmunoassay. Results: Plasma cortisol levels were decreased during first manic episode compared to healthy controls. Higher cortisol levels were positively associated with the presence of irritability (dysphoria), while elated mania showed lower cortisol levels compared to controls. Limitation: Data including larger samples are lacking. Conclusion: Higher cortisol in dysphoric mania compared to predominantly elated/euphoric mania may indicate a clinical and neurobiological polymorphic phenomenon, potentially involving a higher biological sensitivity to stress in the presence of irritable mood. The present findings highlight the importance to add a dimensional approach to the traditional categorical diagnosis for future neurobiological studies in BD.
conferenceObject Sertraline vs. Electrical Current Therapy for Treating Depression Clinical Trial (SELECT TDCS): Results from a Factorial, Randomized, Controlled Trial(2012) BRUNONI, Andre; VALIENGO, Leandro; BACCARO, Alessandra; ZANAO, Tamires; OLIVEIRA, Janaina Farias de; GOULART, Alessandra; LOTUFO, Paulo; BOGGLE, Paulo; BENSENOR, Isabela; FREGNI, FelipeBackground: Non-invasive brain stimulation has been increasingly used as an intervention for major depressive disorder (MDD). Methods: Randomized, factorial, double-blinded, controlled trial. Participants were randomized to sertraline/placebo and active/sham tDCS. They presented moderate to severe medication-free, nonpsychotic, unipolar, major depressivedisorder. They received 6-week treatment of 2mA anodal left dorsolateral prefrontal tDCS (twelve 30-min sessions: 10 consecutive sessions plus two extra sessions every other week) and sertraline (50mg/day). The primary outcome was the Montgomery-Asberg depression scale (MADRS) score changes at the end of treatment (6-week). A difference of at least 3 points in scores was consideredclinically relevant. Secondary outcomes were remission and response rates, and other depression scales. Results : At six weeks (primary outcome), the combined treatment was superior to sham tDCS - placebo (mean difference= 11.5 points; 95% CI=6.03 to 17.1; p<0.01) to sham tDCS -sertraline (mean 8.5; 95% CI=2.96 to 14.03; p<0.01) and to active tDCS - placebo (mean 5.9; 95%=CI 0.36 to 11.43). TDCS and sertraline alone were not different between each other (mean 2.6; 95% CI=8.13 to -2.9; p=0.35). Secondary efficacy analyses mainly confirmed these findings. Adverse effects were not significantly different when comparing groups, althoughfive of seven episodes of treatment-emergent (hypo)mania were observed in the combined treatment. Conclusions: In MDD, combination of tDCS and sertraline increases the efficacy of each treatment alone. Efficacy/safety did not differ between them.- A systematic review and meta-analysis of heart rate variability in epilepsy and antiepileptic drugs(2012) LOTUFO, Paulo A.; VALIENGO, Leandro; BENSENOR, Isabela M.; BRUNONI, Andre R.Purpose: Epilepsy is associated with near-fatal and fatal arrhythmias, and sudden unexpected death in epilepsy (SUDEP) is partly related to cardiac events. Dysfunction of the autonomous nervous system causes arrhythmias and, although previous studies have investigated the effects of epilepsy on the autonomic control of the heart, the results are still mixed regarding whether imbalance of sympathetic, vagal, or both systems is present in epilepsy, and also the importance of anticonvulsant treatment on the autonomic system. Therefore, we aimed to investigate epilepsy and its treatment impact on heart rate variability (HRV), assessed by sympathetic and parasympathetic activity expressed as low-frequency (LF) and high-frequency (HF) power spectrum, respectively. Method: We performed a systematic review from the first date available to July 2011 in Medline and other databases; key search terms were ""epilepsy''; ""anticonvulsants''; ""heart rate variability''; ""vagal''; and ""autonomous nervous system.'' Original studies that reported data and/or statistics of at least one HRV value were included, with data being extracted by two independent authors. We used a random-effects model with Hedges's g as the measurement of effect size to perform two main meta-analyses comparing LF and HF HRV values in (1) epilepsy patients versus controls; (2) patients receiving versus not receiving treatment; and (3) well-controlled versus refractory patients. Secondary analyses assessed other time-and frequency-domain measurements (nonlinear methods were not analyzed due to lack of sufficient data sets). Quality assessment of each study was verified and also meta-analytic techniques to identify and control bias. Meta-regression for age and gender was performed. Key Findings: Initially, 366 references were identified. According to our eligibility criteria, 30 references (39 studies) were included in our analysis. Regarding HF, epilepsy patients presented lower values (g -0.69) than controls, with the 95% confidence interval (CI) ranging from -1.05 to -0.33. No significant differences were observed for LF (g -0.18; 95% CI -0.71 to 0.35). Patients receiving treatment presented HF values to those not receiving treatment (g -0.05; 95% CI -0.37 to 0.27), with a trend for having higher LF values (g 0.1; 95% CI -0.13 to 0.33), which was more pronounced in those receiving antiepileptic drugs (vs. vagus nerve stimulation). No differences were observed for well-controlled versus refractory patients, possibly due to the low number of studies. Regression for age and gender did not influence the results. Finally, secondary time-domain analyses also showed lower HRV and lower vagal activity in patients with epilepsy, as shown by the standard deviation of normal-to-normal interval (SDNN) and the root mean square of successive differences (RMSSD) indexes, respectively. Significance: We confirmed and extended the hypothesis of sympathovagal imbalance in epilepsy, as showed by lower HF, SDNN, and RMSSD values when compared to controls. In addition, there was a trend for higher LF values in patients receiving pharmacotherapy. As lower vagal (HF) and higher sympathetic (LF) tone are predictors of morbidity and mortality in cardiovascular samples, our findings highlight the importance of investigating autonomic function in patients with epilepsy in clinical practice. Assessing HRV might also be useful when planning therapeutic interventions, as some antiepileptic drugs can show hazardous effects in cardiac excitability, potentially leading to cardiac arrhythmia.