Navegando por Autor "Lobão-Soares, Bruno"
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Artigo Acute effects of ayahuasca in a juvenile non-human primate model of depression(2018-11-08) Silva, Flávia S. da; Silva, Erick A. S.; Sousa Jr., Geovan M. de; Maia-de-Oliveira, João P.; Soares-Rachetti, Vanessa de Paula; Araújo, Dráulio Barros de; Sousa, Maria Bernardete Cordeiro de; Lobão-Soares, Bruno; Hallak, Jaime; Galvão-Coelho, Nicole L.Objective: The incidence rate of major depression in adolescents reaches approximately 14%. This disorder is usually recurrent, without remission of symptoms even after pharmacological treatment, and persists throughout adult life. Since the effects of antidepressants take approximately 2 weeks to begin, new pharmacological therapies are under continuous exploration. Recent evidence suggests that psychedelics could produce rapid antidepressant effects. In this study, we evaluated the potential antidepressant effects of ayahuasca in a juvenile non-human primate model of depression. Methods: While living with their families, juvenile marmosets (8 males; 7 females) were observed on alternate days for four weeks during a baseline phase. This was followed by 8 weeks of an induced depressive state protocol, the social isolated context (IC), in which the animals were monitored in the first and last weeks. Subsequently, five males and four females were randomly selected for treatment, first with a single administration of saline vehicle (1.67 mL/300 g of body weight, via gavage), followed by a single dose of ayahuasca (1.67 mL/300 g of body weight, via gavage). Both phases lasted 1 week and the animals were monitored daily. A third week of sampling was called the tardive-pharmacological effects phase. In all phases the marmosets were assessed for behavior, fecal cortisol levels, and body weight. Results: After IC, the animals presented typical hypocortisolemia, but cortisol recovered to baseline levels 24 h after an acute dose of ayahuasca; this recovery was not observed in vehicle-treated animals. Additionally, in males, ayahuasca, but not the vehicle, reduced scratching, a stereotypic behavior, and increased feeding. Ayahuasca treatment also improved body weight to baseline levels in both sexes. The ayahuasca-induced behavioral response had long-term effects (14 days). Thus, in this translational juvenile animal model of depression, ayahuasca presented beneficial effects. Conclusions: These results can contribute to the validation of ayahuasca as an antidepressant drug and encourage new studies on psychedelic drugs as a tool for treating mood disorders, including for adolescents with early-onset depression.Artigo Changes in cortisol but not in brain-derived neurotrophic factor modulate the association between sleep disturbances and major depression(2020-04-28) Santiago, Giuliana Travassos Pires; Galvão, Ana Cecília de Menezes; Almeida, Raíssa Nóbrega de; Mota-Rolim, Sergio Arthuro; Palhano-Fontes, Fernanda; Maia-de-Oliveira, João Paulo; Araújo, Dráulio Barros de; Lobão-Soares, Bruno; Galvão-Coelho, Nicole LeiteSleep disturbance is a symptom consistently found in major depression and is associated with a longer course of illness, reduced response to treatment, increased risk of relapse and recurrence. Chronic insomnia has been associated with changes in cortisol and serum brain-derived neurotrophic factor (BDNF) levels, which in turn are also changed in major depression. Here, we evaluated the relationship between sleep quality, salivary cortisol awakening response (CAR), and serum BDNF levels in patients with sleep disturbance and treatment-resistant major depression (n = 18), and in a control group of healthy subjects with good (n = 21) and poor (n = 18) sleep quality. We observed that the patients had the lowest CAR and sleep duration of all three groups and a higher latency to sleep than the healthy volunteers with a good sleep profile. Besides, low CAR was correlated with more severe depressive symptoms and worse sleep quality. There was no difference in serum BDNF levels between groups with distinct sleep quality. Taken together, our results showed a relationship between changes in CAR and in sleep quality in patients with treatment-resistant depression, which were correlated with the severity of disease, suggesting that cortisol could be a physiological link between sleep disturbance and major depression.Artigo Cortisol modulation by ayahuasca in patients with treatment resistant depression and healthy controls(2018-05-08) Galvão, Ana C. de Menezes; Almeida, Raíssa N. de; Silva, Erick A. dos Santos; Freire, Fúlvio A. M.; Palhano-Fontes, Fernanda; Onias, Heloisa; Arcoverde, Emerson; Maia-de-Oliveira, João P.; Araújo, Dráulio Barros de; Lobão-Soares, Bruno; Galvão-Coelho, Nicole L.Major depression is a highly prevalent mood disorder, affecting about 350 million people, and around 30% of the patients are resistant to currently available antidepressant medications. Recent evidence from a randomized controlled trial (RCT) supports the rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression. The aim of this study was to explore the effect of ayahuasca on plasma cortisol and awakening salivary cortisol response, in the same group of treatment-resistant patients (MD) and in healthy volunteers (C). Subjects received a single dose of ayahuasca or placebo (dosing session), and both plasma and awakening salivary cortisol response were measured at baseline (before dosing session) and 48 h after the dosing session. Baseline assessment (D0) showed blunted awakening salivary cortisol response and hypocortisolemia in patients, with respect to healthy controls. Salivary cortisol was also measured during dosing session, and we observed higher increases for both C and MD that ingested ayahuasca than placebo. After 48 h from the dosing session with ayahuasca, patients' awakening salivary cortisol response is similar to the ones detected in controls. No significant changes in plasma cortisol levels were observed 48 h after the sessions. Therefore, these findings point to new evidence on the modulation of salivary cortisol levels as a result of an ayahuasca session, both in healthy and depressive volunteers. Considering that cortisol acts in regulation of distinct physiological pathways, emotional and cognitive processes, it is assumed to be critically involved to the etiology of depression and its regulation seems to be important for the treatment and remission of major depression, ayahuasca use as antidepressant should be further investigated. Moreover, this study highlights the importance of psychedelics in the treatment of human mental disorders.Artigo Effects of yoga respiratory practice (bhastrika pranayama) on anxiety, affect, and brain functional connectivity and activity: a randomized controlled trial(2020-05-21) Novaes, Morgana M.; Palhano-Fontes, Fernanda; Onias, Heloisa; Andrade, Katia C.; Lobão-Soares, Bruno; Arruda-Sanchez, Tiago; Kozasa, Elisa H.; Santaella, Danilo F.; Araújo, Dráulio Barros dePranayama refers to a set of yoga breathing exercises. Recent evidence suggests that the practice of pranayama has positive effects on measures of clinical stress and anxiety. This study explored the impact of a Bhastrika pranayama training program on emotion processing, anxiety, and affect. We used a randomized controlled trial design with thirty healthy young adults assessed at baseline and after 4 weeks of pranayama practices. Two functional magnetic resonance imaging (MRI) protocols were used both at baseline and post-intervention: an emotion task as well as a resting-state acquisition. Our results suggest that pranayama significantly decreased states of anxiety and negative affect. The practice of pranayama also modulated the activity of brain regions involved in emotional processing, particularly the amygdala, anterior cingulate, anterior insula, and prefrontal cortex. Resting-state functional MRI (fMRI) showed significantly reduced functional connectivity involving the anterior insula and lateral portions of the prefrontal cortex. Correlation analysis revealed that changes in connectivity between the ventrolateral prefrontal cortex and the right anterior insula were associated with changes in anxiety. Although it should be noted that these analyses were preliminary and exploratory, it provides the first evidence that 4 weeks of B. pranayama significantly reduce the levels of anxiety and negative affect, and that these changes are associated with the modulation of activity and connectivity in brain areas involved in emotion processing, attention, and awareness.Artigo Hippocampal and cortical communication around micro-arousals in slow-wave sleep(Nature Publishing Group, 2019-04-10) Lima, Gustavo Zampier dos Santos; Lobão-Soares, Bruno; Corso, Gilberto; Belchior, Hindiael Aeraf; Lopes, Sergio Roberto Lopes; Prado, Thiago de Lima; Nascimento, George Carlos do; Araújo, John Fontenele; Ivanov, Plamen Ch.Sleep plays a crucial role in the regulation of body homeostasis and rhythmicity in mammals. Recently, a specific component of the sleep structure has been proposed as part of its homeostatic mechanism, named micro-arousal. Here, we studied the unique progression of the dynamic behavior of cortical and hippocampal local field potentials (LFPs) during slow-wave sleep-related to motor-bursts (micro-arousals) in mice. Our main results comprised: (i) an abrupt drop in hippocampal LFP amplitude preceding micro-arousals which persisted until the end of motor-bursts (we defined as t interval, around 4s) and a similar, but delayed amplitude reduction in cortical (S1/M1) LFP activity occurring at micro-arousal onset; (ii) two abrupt frequency jumps in hippocampal LFP activity: from Theta (6–12 Hz) to Delta (2–4 Hz), also t seconds before the micro-arousal onset, and followed by another frequency jump from Delta to Theta range (5–7 Hz), now occurring at micro-arousal onset; (iii) a pattern of cortico-hippocampal frequency communication precedes micro-arousals: the analysis between hippocampal and cortical LFP fluctuations reveal high coherence during τ interval in a broader frequency band (2–12 Hz), while at a lower frequency band (0.5–2 Hz) the coherence reaches its maximum after the onset of micro-arousals. In conclusion, these novel findings indicate that oscillatory dynamics pattern of cortical and hippocampal LFPs preceding micro-arousals could be part of the regulatory processes in sleep architectureArtigo Modulation of serum brain-derived neurotrophic factor by a single dose of Ayahuasca: observation from a randomized controlled trial(2019-06-04) Almeida, Raíssa Nóbrega de; Galvão, Ana Cecília de Menezes; Silva, Flávia Santos da; Silva, Erick Allan dos Santos; Palhano-Fontes, Fernanda; Maia-de-Oliveira, João Paulo; Araújo, Dráulio Barros de; Lobão-Soares, Bruno; Galvão-Coelho, Nicole LeiteSerotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. Preclinical and clinical studies have suggested that serum brain-derived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls (N = 45) and patients with treatment-resistant depression (N = 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia. Moreover, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca (N = 35) when compared to placebo (N = 34). Furthermore, at D2 just patients treated with ayahuasca (N = 14), and not with placebo (N = 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms. This is the first double-blind randomized placebo-controlled clinical trial that explored the modulation of BDNF in response to a psychedelic in patients with depression. The results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelics as an antidepressant. This trial is registered at http://clinicaltrials.gov (NCT02914769).Artigo Optimizing the detection of nonstationary signals by using recurrence analysis(American Institute of Physics, 2018-08-24) Prado, Thiago de Lima; Lima, Gustavo Zampier dos Santos; Lobão-Soares, Bruno; Nascimento, George Carlos do; Corso, Gilberto; Araújo, John Fontenele; Kurths, Jürgen; Lopes, Sérgio RobertoRecurrence analysis and its quantifiers are strongly dependent on the evaluation of the vicinity threshold parameter, i.e., the threshold to regard two points close enough in phase space to be considered as just one. We develop a new way to optimize the evaluation of the vicinity threshold in order to assure a higher level of sensitivity to recurrence quantifiers to allow the detection of even small changes in the dynamics. It is used to promote recurrence analysis as a tool to detect nonstationary behavior of time signals or space profiles. We show that the ability to detect small changes provides information about the present status of the physical process responsible to generate the signal and offers mechanisms to predict future states. Here, a higher sensitive recurrence analysis is proposed as a precursor, a tool to predict near future states of a particular system, based on just (experimentally) obtained signals of some available variables of the system. Comparisons with traditional methods of recurrence analysis show that the optimization method developed here is more sensitive to small variations occurring in a signal. The method is applied to numerically generated time series as well as experimental data from physiologyArtigo Potential biomarkers of major depression diagnosis and chronicity(2021-09-29) Galvão, Ana Cecília de Menezes; Almeida, Raissa Nobrega; Sousa Júnior, Geovan Menezes de; Leocadio-Miguel, Mário André; Fontes, Fernanda Palhano Xavier de; Araujo, Draulio Barros de; Lobão-Soares, Bruno; Maia-de-Oliveira, João Paulo; Nunes, Emerson Arcoverde; Hallak, Jaime Eduardo Cecilio; Sarris, Jerome; Galvão-Coelho, Nicole LeiteMolecular biomarkers are promising tools to be routinely used in clinical psychiatry. Among psychiatric diseases, major depression disorder (MDD) has gotten attention due to its growing prevalence and morbidity. We tested some peripheral molecular parameters such as serum mature Brain-Derived Neurotrophic Factor (mBDNF), plasma C-Reactive Protein (CRP), serum cortisol (SC), and the salivary Cortisol Awakening Response (CAR), as well as the Pittsburgh sleep quality inventory (PSQI), as part of a multibiomarker panel for potential use in MDD diagnosis and evaluation of disease’s chronicity using regression models, and ROC curve. For diagnosis model, two groups were analyzed: patients in the first episode of major depression (MD: n = 30) and a healthy control (CG: n = 32). None of those diagnosis models tested had greater power than Hamilton Depression Rating Scale-6. For MDD chronicity, a group of patients with treatment-resistant major depression (TRD: n = 28) was tested across the MD group. The best chronicity model (p < 0.05) that discriminated between MD and TRD included four parameters, namely PSQI, CAR, SC, and mBDNF (AUC ROC = 0.99), with 96% of sensitivity and 93% of specificity. These results indicate that changes in specific biomarkers (CAR, SC, mBDNF and PSQI) have potential on the evaluation of MDD chronicity, but not for its diagnosis. Therefore, these findings can contribute for further studies aiming the development of a stronger model to be commercially available and used in psychiatry clinical practiceArtigo Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial(2018-06-15) Palhano-Fontes, Fernanda; Barreto, Dayanna; Onias, Heloisa; Andrade, Katia C.; Novaes, Morgana M.; Pessoa, Jessica A.; Mota-Rolim, Sergio A.; Osório, Flávia L.; Sanches, Rafael; Santos, Rafael G. dos; Tófoli, Luís Fernando; Silveira, Gabriela de Oliveira; Yonamine, Mauricio; Riba, Jordi; Santos, Francisco R.; Silva-Junior, Antonio A.; Alchieri, João C.; Galvão-Coelho, Nicole L.; Lobão-Soares, Bruno; Hallak, Jaime E. C.; Arcoverde, Emerson; Maia-de-Oliveira, João P.; Araújo, Dráulio Barros deBackground Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. Methods To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing. Results We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054). Conclusions To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).Artigo Specific increase of hippocampal delta oscillations across consecutive treadmill runs(2020-06-23) Furtunato, Alan Michel Bezerra; Lobão-Soares, Bruno; Tort, Adriano Bretanha Lopes; Belchior, Hindiael AerafRunning speed affects theta (6–10 Hz) oscillations, the most prominent rhythm in the rat hippocampus. Many reports have found a strong positive correlation between locomotion speed and the amplitude and frequency of theta oscillations. However, less is known about how other rhythms such as delta (0.5–4 Hz) and gamma (25–100 Hz) are affected, and how consecutive runs impact oscillatory activity in hippocampal networks. Here, we investigated whether the successive execution of short-term runs modulates local field potentials (LFPs) in the rat hippocampus. To do this, we trained Long-Evans rats to perform voluntary 15-s runs at 30 cm/s on a treadmill placed on the central stem of an eight-shape maze, in which they subsequently performed a spatial alternation task. We bilaterally recorded CA1 LFPs while rats executed at least 35 runs on the treadmill-maze apparatus. Within running periods, we observed progressive increases in delta band power along with decreases in the power of the theta and gamma bands across runs. Concurrently, the inter-hemispheric phase coherence in the delta band significantly increased, while in the theta and gamma bands exhibited no changes. Delta power and inter-hemispheric coherence correlated better with the trial number than with the actual running speed. We observed no significant differences in running speed, head direction, nor in spatial occupancy across runs. Our results thus show that consecutive treadmill runs at the same speed positively modulates the power and coherence of delta oscillations in the rat hippocampus.