RICARDO ALBERTO MORENO
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Médico
16 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 16
- Bcl-2 rs956572 Polymorphism is Associated with Increased Anterior Cingulate Cortical Glutamate in Euthymic Bipolar I Disorder(2013) SOEIRO-DE-SOUZA, Marcio Gerhardt; SALVADORE, Giacomo; MORENO, Ricardo Alberto; OTADUY, Maria Concepcion Garcia; CHAIM, Kalil T.; GATTAZ, Wagner F.; ZARATE JR., Carlos A.; MACHADO-VIEIRA, RodrigoB-cell lymphoma 2 (Bcl-2) is an important regulator of cellular plasticity and resilience. In bipolar disorder (BD), studies have shown a key role for a Bcl-2 gene single-nucleotide polymorphism (SNP) rs956572 in the regulation of intracellular calcium (Ca2+) dynamics, Bcl-2 expression/levels, and vulnerability to cellular apoptosis. At the same time, Bcl-2 decreases glutamate (Glu) toxicity in neural cells. Abnormalities in Glu function have been implicated in BD. In magnetic resonance spectroscopy (MRS) studies, anterior cingulated cortex (ACC) Glu levels have been reported to be increased in bipolar depression and mania, but no study specifically evaluated ACC Glu levels in BD-euthymia. Here, we compared ACC Glu levels in BD-euthymia compared with healthy subjects using H-1-MRS and also evaluated the selective role of the rs956572 Bcl-2 SNP in modulating ACC Glu and Glx (sum of Glu and glutamine) in euthymic-BD. Forty euthymic subjects with BD type 1 and forty healthy controls aged 18-40 were evaluated. All participants were genotyped for Bcl-2 rs956572 and underwent a 3-Tesla brain magnetic resonance imaging examination including the acquisition of an in vivo PRESS single voxel (2 cm(3)) H-1-MRS sequence to obtain metabolite levels from the ACC. Euthymic-BD subjects had higher Glu/Cre (creatine) and Glx/Cre compared with healthy controls. The Bcl-2 SNP AA genotype was associated with elevated ACC Glu/Cre and Glx/Cre ratio in the BD group but not in controls. The present study reports for the first time an increase in ACC Glu/Cre and Glx/Cre ratios in BD-euthymia. Also, Bcl-2 AA genotype, previously associated with lower Bcl-2 expression and increase intracellular Ca2+, showed to be associated with increased ACC Glu and Glx levels in euthymic-BD subjects. The present findings reinforce a key role for glutamatergic system dysfunction in the pathophysiology of BD, potentially involving modulatory effects by Bcl-2 in the ACC. Neuropsychopharmacology (2013) 38, 468-475; doi:10.1038/npp.2012.203; published online 17 October 2012
- Lithium-associated anterior cingulate neurometabolic profile in euthymic Bipolar I disorder: A H-1-MRS study(2018) SOEIRO-DE-SOUZA, Marcio Gerhardt; OTADUY, Maria Concepcion Garcia; MACHADO-VIEIRA, Rodrigo; MORENO, Ricardo Alberto; NERY, Fabiano G.; LEITE, Claudia; LAFER, BenyObjective: In the treatment of Bipolar disorder (BD), achieving euthymia is highly complex and usually requires a combination of mood stabilizers. The mechanism of action in stabilizing mood has not been fully elucidated, but alterations in N-Acetylaspartate (NAA), Myo-Inositol (mI) and Choline (Cho) have been implicated. Proton magnetic resonance spectroscopy (H-1-MRS) is the gold standard technique for measuring brain NAA, Cho and mI in vivo. The objective of this study was to investigate the association of lithium use in BD type I and brain levels of NAA, mI and Cho in the (anterior cingulate cortex) ACC. Methods: 129 BD type I subjects and 79 healthy controls (HC) were submitted to a 3-Tesla brain magnetic resonance imaging scan (H-1-MRS) using a PRESS ACC single voxel (8cm(3)) sequence. Results: BD patients exhibited higher NAA and Cho levels compared to HC. Lithium prescription was associated with lower mI (combination + monotherapy) and higher NAA levels (monotherapy). Conclusion: The results observed add to the knowledge about the mechanisms of action of mood stabilizers on brain metabolites during euthymia. Additionally, the observed decrease in mI levels associated with lithium monotherapy is an in vivo finding that supports the inositol-depletion hypothesis of lithium pharmacodynamics.
conferenceObject GAD1 POLYMORPHISMS ARE ASSOCIATED WITH GLUTAMATERGIC ACTIVITY IN THE ANTERIOR CINGULATE IN BIPOLAR I DISORDER(2017) SOEIRO-DE-SOUZA, Marcio; MACHADO-VIEIRA, Rodrigo; MORENO, Ricardo; CHILE, Thais; GOUVEIA, Gisele; PASTORELLO, Bruno; LEITE, Claudia; HENNING, Anke; OTADUY, Maria Concepcion; VALLADA, Homero- Creativity and executive function across manic, mixed and depressive episodes in bipolar I disorder(2011) SOEIRO-DE-SOUZA, Marcio Gerhardt; DIAS, Vasco Videira; BIO, Danielle Soares; POST, Robert M.; MORENO, Ricardo A.Introduction: Creativity is a complex construct involving affective and cognitive components. Bipolar Disorder (BD) has been associated with creativity and is characterized by a wide range of affective and cognitive symptoms. Although studies of creativity in BD have tended to focus on creativity as a trait variable in medicated euthymic patients, it probably fluctuates during symptomatic states of BD. Since creativity is known to involve key affective and cognitive components, it is plausible to speculate that cognitive deficits and symptoms present in symptomatic BD could interfere with creativity. Material and methods: Sixty-seven BD type I patients medication free, age 18-35 years and experiencing a maniac, mixed, or depressive episodes, were assessed for creativity, executive functioning, and intelligence. Results: Manic and mixed state patients had higher creativity scores than depressive individuals. Creativity was influenced by executive function measures only in manic patients. Intelligence did not influence creativity for any of the mood episode types. Conclusion: We propose that creativity in BD might be linked to the putative hyperdopaminergic state of mania and be dependent on intact executive function. Future studies should further explore the role of dopaminergic mechanisms in creativity in BD.
- Altered brain creatine cycle metabolites in bipolar I disorder with childhood abuse: A H-1 magnetic resonance spectroscopy study(2021) BIO, Danielle Soares; MORENO, Ricardo Alberto; GARCIA-OTADUY, Maria Concepcion; NERY, Fabiano; LAFER, Beny; SOEIRO-DE-SOUZA, Marcio GerhardtBackground: Childhood abuse (CA) is a risk factor for a number of psychiatric disorders and has been associated with higher risk of developing bipolar disorders (BD). CA in BD has been associated with more severe clinical outcomes, but the neurobiological explanation for this is unknown. Few studies have explored in vivo measurement of brain metabolites using proton magnetic resonance spectroscopy (1H-MRS) in CA and no studies have investigated the association of CA severity with brain neurometabolites in BD. Objective: To investigate whether CA severity is associated with changes in anterior cingulate cortex (ACC) neurometabolite profile in BD and HC subjects. Methods: Fifty-nine BD I euthymic patients and fifty-nine HC subjects were assessed using the Childhood Trauma Questionnaire (CTQ) and underwent a 3-Tesla 1H-MRS scan. Severity of childhood abuse (physical, sexual and emotional) and its association with levels of brain metabolites was analyzed within each group. Results: BD patients had higher total scores on the CTQ and higher severity rates of sexual and physical abuse compared to HC subjects. Greater severity of physical and sexual abuse was associated with increased ACC PCr level and lower Cr/PCr ratio in the BD group only. Conclusion: Sexual and physical abuse in BD patients, but not in HC subjects, appeared to be associated with creatine metabolism in the ACC, which can influence neuronal mitochondrial energy production. Further studies should investigate whether this is the mechanism underlying the association between CA and worse clinical outcomes in BD.
- Early improvement of psychotic symptoms with lithium monotherapy as a predictor of later response in mania(2012) SOUSA, Rafael T. de; BUSNELLO, Joao V.; FORLENZA, Orestes V.; ZANETTI, Marcus V.; SOEIRO-DE-SOUZA, Marcio G.; BILT, Martinus T. van de; MORENO, Ricardo A.; ZARATE JR., Carlos A.; GATTAZ, Wagner F.; MACHADO-VIEIRA, RodrigoAlthough lithium has been the first line agent in the treatment of bipolar disorder (BD), few studies have evaluated lithium's efficacy in mania with psychosis and its association with later response. Furthermore, given the widespread concern about antipsychotic side effects, answering a question about whether lithium alone can manage to treat both psychotic and non-psychotic mania seems a very relevant one. The present study addresses the antipsychotic efficacy of lithium monotherapy in acute mania and early improvement of psychotic symptoms as a predictor of later response of manic symptoms. Forty-six patients presenting a manic episode (32 with psychotic features and 14 subjects without psychotic features) were treated for 4 weeks with lithium monotherapy and evaluated weekly using the Young Mania Rating Scale (YMRS). Subjects with rapid cycling, substance abuse/dependence, or mixed episodes were excluded. The overall antimanic efficacy of lithium in psychosis vs. non-psychosis groups was evaluated. In addition, early improvement of psychotic symptoms and its prediction of subsequent response (>50% decrease in total YMRS scores) or remission were evaluated. Lithium showed a similar efficacy in both psychosis and non-psychosis mania. Early improvement of psychotic symptoms was associated with clinical response and remission at endpoint.
- Association of the COMT Met(158) allele with trait impulsivity in healthy young adults(2013) SOEIRO-DE-SOUZA, Marcio Gerhardt; STANFORD, Matthew S.; BIO, Danielle Soares; MACHADO-VIEIRA, Rodrigo; MORENO, Ricardo AlbertoDopamine (DA) is considered to be an important neurotransmitter in the control of impulsive behavior, however, its underlying mechanisms have not been fully elucidated. Catechol-O-methyltransferase (COMT) is a key enzyme in the catabolism of DA within the prefrontal cortex (PFC) and has been suggested to play a role in the mediation of impulsive behavior. The COMT single nucleotide polymorphism (SNP) rs4680 (Val(158)Met) Met allele has been shown to decrease COMT enzyme activity and is associated with improved PFC cognitive function (intelligence and executive functions). Studies have associated the rs4680 genotype with impulsivity as a symptom in attention deficit hyperactivity disorder and substance abuse. However, only a few studies have assessed the effects of rs4680 on impulsiveness in healthy subjects, the results of which remain controversial. The Barratt Impulsiveness Scale (BIS-11) was applied to 82 healthy volunteers (including 42 females) who were genotyped for COMT rs4680. Subjects carrying the Met/Met genotype scored higher for the BIS-11 second-order factor Non-planning than carriers of the Val/Val genotype. No interaction between gender*genotype was detected. Age, gender and education had no effect on the results. The COMT rs4680 Met/Met genotype was associated with higher impulsivity on the BIS-11 second-order factor Non-planning. These results suggest that COMT enzyme activity may be important in the regulation of impulsiveness among young adults. Further studies involving larger samples should be conducted to confirm the results of the present study.
- Physical activity as an adjuvant therapy for depression and influence on peripheral inflammatory markers: A randomized clinical trial(2022) FERNANDES, Beatriz Monteiro; SIQUEIRA, Cristiana Carvalho; VIEIRA, Rodrigo Machado; MORENO, Ricardo Alberto; SOEIRO-DE-SOUZA, Marcio GerhardtIntroduction: Regular exercise is recommended for people with major depressive disorder (MDD) by major treatment guidelines (e.g. the NICE guideline, 2009). In addition, an effect of antidepressant (AD) treatment on pro-inflammatory markers has been reported. However, it remains unclear whether physical activity as an adjuvant to AD treatment increases clinical response rates and is associated with levels of inflammatory markers. Methods: A four-week single-blind clinical trial involving forty people with major MDD, divided into an AD group (sertraline) and AD + exercise (40 min/day, four times weekly for four weeks) group was conducted. Peripheral inflammatory markers (IL-12, IL-10, IL-8, IL-6, IL-1 beta, TNF-alpha) and cortisol were collected at baseline and at endpoint. Results: We observed a significant decrease in cortisol levels over time, but this change did not differ between the AD and AD + exercise groups. None of the other inflammatory markers showed a significant change in level during the trial. Also, most of the individuals who achieved remission were from the AD + exercise group. Conclusion: Although our study failed to find that the association of physical activity as an adjunct to antide-pressants promotes a change in cortisol or interleukins in people with MDD, we found that cortisol seems to be the most sensitive biomarker to antidepressant treatment. Further studies involving larger samples of, longer duration and with other classes of antidepressants and types of exercise should be conducted to better elucidate the link between inflammatory markers and depression.
- The CACNA1C risk allele rs1006737 is associated with age-related prefrontal cortical thinning in bipolar I disorder(2017) SOEIRO-DE-SOUZA, M. G.; LAFER, B.; MORENO, R. A.; NERY, F. G.; CHILE, T.; CHAIM, K.; LEITE, C. da Costa; MACHADO-VIEIRA, R.; OTADUY, M. C. G.; VALLADA, H.Calcium channels control the inflow of calcium ions into cells and are involved in diverse cellular functions. The CACNA1C gene polymorphism rs1006737 A allele has been strongly associated with increased risk for bipolar disorder (BD) and with modulation of brain morphology. The medial prefrontal cortex (mPFC) has been widely associated with mood regulation in BD, but the role of this CACNA1C polymorphism in mPFC morphology and brain aging has yet to be elucidated. One hundred seventeen euthymic BD type I subjects were genotyped for CACNA1C rs1006737 and underwent 3 T three-dimensional structural magnetic resonance imaging scans to determine cortical thickness of mPFC components (superior frontal cortex (sFC), medial orbitofrontal cortex (mOFC), caudal anterior cingulate cortex (cACC) and rostral anterior cingulate cortex (rACC)). Carriers of the CACNA1C allele A exhibited greater left mOFC thickness compared to non-carriers. Moreover, CACNA1C A carriers showed age-related cortical thinning of the left cACC, whereas among A non-carriers there was not an effect of age on left cACC cortical thinning. In the sFC, mOFC and rACC (left or right), a negative correlation was observed between age and cortical thickness, regardless of CACNA1C rs1006737 A status. Further studies investigating the direct link between cortical thickness, calcium channel function, apoptosis mechanism and their underlying relationship with aging-associated cognitive decline in BD are warranted.
- The impact of limbic system morphology on facial emotion recognition in bipolar I disorder and healthy controls(2013) BIO, Danielle Soares; SOEIRO-DE-SOUZA, Marcio Gerhardt; OTADUY, Maria Concepcion Garcia; MACHADO-VIEIRA, Rodrigo; MORENO, Ricardo AlbertoIntroduction: Impairments in facial emotion recognition (FER) have been reported in bipolar disorder (BD) subjects during all mood states. This study aims to investigate the impact of limbic system morphology on FER scores in BD subjects and healthy controls. Material and methods: Thirty-nine euthymic BD I (type I) subjects and 40 healthy controls were subjected to a battery of FER tests and examined with 3D structural imaging of the amygdala and hippocampus. Results: The volume of these structures demonstrated a differential pattern of influence on FER scores in BD subjects and controls. In our control sample, larger left and right amygdala demonstrated to be associated to less recognition of sadness faces. In BD group, there was no impact of amygdala volume on FER but we observed a negative impact of the left hippocampus volume in the recognition of happiness while the right hippocampus volume positively impacted on the scores of happiness. Conclusion: Our results indicate that amygdala and hippocampus volumes have distinct effects on FER in BD subjects compared to controls. Knowledge of the neurobiological basis of the illness may help to provide further insights on the role of treatments and psychosocial interventions for BD. Further studies should explore how these effects of amygdala and hippocampus volumes on FER are associated with social networks and social network functioning.