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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- Emotional reactivity to valence-loaded stimuli are related to treatment response of neurocognitive therapy(2016) VANDERHASSELT, Marie-Anne; RAEDT, Rudi De; NAMUR, Victoria; VALIENGO, Leandro C. L.; LOTUFO, Paulo A.; BENSENOR, Isabela M.; BAEKEN, Chris; BOGGIO, Paulo S.; BRUNONI, Andre R.Emotional Context Insensitivity (ECI) is a psychological feature observed in depressed patients characterized by a decreased emotional reactivity when presented to positive- and negative valence-loaded stimuli. Given that fronto-cingulate-limbic circuits are implicated in abnormal reactivity to valence-loaded stimuli, neurocognitive treatments engaging the prefrontal cortex may be able to modulate this emotional blunting observed in MDD. Therefore, our goal was to evaluate emotional reactivity in depressed patients before and after a combination of neurocognitive interventions that engage the prefrontal cortex (cognitive control training and/or transcranial direct current stimulation). In line with the premises of the ECI framework, before the start of the antidepressant intervention, patients showed blunted emotional reactivity after exposure to negative valence-loaded stimuli. This emotional reactivity pattern changed after 9 sessions of the intervention: positive affect decreased and negative affect increased after watching a series of negative valence-loaded stimuli (i.e. images). Interestingly, higher emotional reactivity (as indexed by a larger increase in negative affect after watching the valence-loaded stimuli) at baseline predicted reductions in depression symptoms after the intervention. On the other hand, higher emotional reactivity (as indexed by a decrease in positive affect) after the intervention was marginally associated with reductions in depression symptoms. To conclude, emotional reactivity increased after the neurocognitive antidepressant intervention and it was directly associated to the degree of depression improvement.
- Cognitive outcomes of TMS treatment in bipolar depression: Safety data from a randomized controlled trial(2018) MYCZKOWSKI, Martin L.; FERNANDES, Adriano; MORENO, Marina; VALIENGO, Leandro; LAFER, Beny; MORENO, Ricardo A.; PADBERG, Frank; GATTAZ, Wagner; BRUNONI, Andre R.Background: Bipolar depression (BD) is a highly prevalent condition associated with marked cognitive deficits that persist even in the euthymic phase of the illness. Pharmacological treatments for BD might further aggravate cognitive impairment, highlighting the need of developing interventions that present cognitive safety. In this study, we evaluated the cognitive effects of H1-coil (deep) transcranial magnetic stimulation (TMS) in patients with treatment-resistant bipolar depression. Methods: Fourty-three patients were randomized to receive 20 sessions of active (55 trains, 18 Hz, 120% resting motor threshold intensity) or sham rTMS within a double-blind, sham-controlled trial. A battery of 20 neuropsychological assessments, grouped in 6 domains (attention and processing speed, working memory and executive function, inhibitory control, language, immediate verbal memory, and long-term verbal memory) was performed at baseline and after 4 and 8 weeks of trial onset. Depressive symptoms were assessed with the 17 item Hamilton Rating Scale for Depression. Results: Cognitive improvement was shown for all cognitive domains. It occurred regardless of intervention group and depression improvement. For the language domain, greater improvement was observed in the sham group over time. No correlations between depression (at baseline or during treatment) and cognitive improvement were found. Limitations: Absence of healthy control group. Conclusion: The results of this exploratory study provide evidence on the cognitive safety of H1-coil TMS for BD patients. Putative pro-cognitive effects of rTMS in BD were not observed and thus should be further investigated.
- Cognitive control therapy and transcranial direct current stimulation for depression: A randomized, double-blinded, controlled trial(2014) BRUNONI, A. R.; BOGGIO, P. S.; RAEDT, R. De; BENSENOR, I. M.; LOTUFO, P. A.; NAMUR, V.; VALIENGO, L. C. L.; VANDERHASSELT, M. A.Background: Based on findings that major depressive disorder (MDD) is associated to decreased dorsolateral prefrontal cortical (DLPFC) activity; interventions that increase DLPFC activity might theoretically present antidepressant effects. Two of them are cognitive control therapy (CCT), a neurocognitive intervention that uses computer-based working memory exercises, and transcranial direct current stimulation (tDCS), which delivers weak, electric direct currents over the scalp. Methods: We investigated whether tDCS enhanced the effects of CCT in a double-blind trial, in which participants were randomized to sham tDCS and CCT (n=17) vs. active tDCS and CCT (n=20). CCT and tDCS were applied for 10 consecutive workdays. Clinicaltrials.gov identifier: NCT01434836. Results: Both CCT alone and combined with tDCS ameliorated depressive symptoms after the acute treatment period and at follow-up, with a response rate of approximately 25%. Older patients and those who presented better performance in the task throughout the trial (possibly indicating greater engagement and activation of the DLPFC) had greater depression improvement in the combined treatment group. Limitations: Our exploratory findings should be further confirmed in prospective controlled trials. Discussion: CCT and tDCS combined might be beneficial for older depressed patients, particularly for those who have cognitive resources to adequately learn and improve task performance over time This combined therapy might be specifically relevant in this subgroup that is more prone to present cognitive decline and prefrontal cortical atrophy.
- 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.
- Plasma levels of soluble TNF receptors 1 and 2 after tDCS and sertraline treatment in major depression: Results from the SELECT-TDCS trial(2015) BRUNONI, Andre R.; MACHADO-VIEIRA, Rodrigo; SAMPAIO-JUNIOR, Bernardo; VIEIRA, Erica L. M.; VALIENGO, Leandro; BENSENOR, Isabela M.; LOTUFO, Paulo A.; CARVALHO, Andre F.; CHO, Hyong Jin; GATTAZ, Wagner F.; TEIXEIRA, Antonio L.Background: The cytokine hypothesis of depression postulates that the pathophysiology of this illness incorporates an increased production of pro-inflammatory cytokines, which leads to an over activation of the hypothalamic-pituitary-adrenal axis as well as monoaminergic disturbances. Nevertheless, it remains unclear whether the amelioration of depressive symptoms could decrease cytokine levels. Notwithstanding antidepressant drug therapy might exert anti-inflammatory effects, the effects of non-invasive neuromodulatory approaches like transcranial direct current stimulation (tDCS) on pro-inflammatory cytokine networks are largely unknown. Methods: We evaluated, in the Set-Leanne vs. Eleciric Curreni Therapy for TreaLing Depression Clinical SLudy (SELECT-TDCS) fetal, whether the plasma levels of the soluble TNF recepLors 1 and 2 (sTNFRs) changed tiller anLiclepressanL LreaLmeni in a sample of 73 anLidepressanL-free paLienis with unipolar depressive disorder in an episode of aL leasL mocleraLe inLensiLy. Results: Although boat LDCS and set-Leanne exerLed anLiclepressanL effecfs. the plasma levels of sTNFRs did noi change over Lime regardless of Lhe infervenLion and clinical response. Also, baseline sTNFRs levels did noL predicL anLiclepressanL response. Limitations: Our negative findings could be a type LI error, as this trial did not use an equivalence design. Conclusions: To conclude, in this novel placebo-controlled trial prospectively evaluating the changes of sTNFRs in depressed patients, we found that these molecules are not surrogate biomarkers of treatment I esponse of tDCS, whose antidepressant effects occurred regardless of normalization of immunological activity.