BENY LAFER
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Psiquiatria, Faculdade de Medicina - Docente
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Líder
245 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 245
- The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders(2013) PACCHIAROTTI, Isabella; BOND, David J.; BALDESSARINI, Ross J.; NOLEN, Willem A.; GRUNZE, Heinz; LICHT, Rasmus W.; POST, Robert M.; BERK, Michael; GOODWIN, Guy M.; SACHS, Gary S.; TONDO, Leonardo; FINDLING, Robert L.; YOUNGSTROM, Eric A.; TOHEN, Mauricio; UNDURRAGA, Juan; GONZALEZ-PINTO, Ana; GOLDBERG, Joseph F.; YILDIZ, Aysegul; ALTSHULER, Lori L.; CALABRESE, Joseph R.; MITCHELL, Philip B.; THASE, Michael E.; KOUKOPOULOS, Athanasios; COLOM, Francesc; FRYE, Mark A.; MALHI, Gin S.; FOUNTOULAKIS, Konstantinos N.; VAZQUEZ, Gustavo; PERLIS, Roy H.; KETTER, Terence A.; CASSIDY, Frederick; AKISKAL, Hagop; AZORIN, Jean-Michel; VALENTI, Marc; MAZZEI, Diego Hidalgo; LAFER, Beny; KATO, Tadafumi; MAZZARINI, Lorenzo; MARTINEZ-ARAN, Anabel; PARKER, Gordon; SOUERY, Daniel; OZERDEM, Aysegul; MCELROY, Susan L.; GIRARDI, Paolo; BAUER, Michael; YATHAM, Lakshmi N.; ZARATE, Carlos A.; NIERENBERG, Andrew A.; BIRMAHER, Boris; KANBA, Shigenobu; EL-MALLAKH, Rif S.; SERRETTI, Alessandro; RIHMER, Zoltan; YOUNG, Allan H.; KOTZALIDIS, Georgios D.; MACQUEEN, Glenda M.; BOWDEN, Charles L.; GHAEMI, S. Nassir; LOPEZ-JARAMILLO, Carlos; RYBAKOWSKI, Janusz; HA, Kyooseob; PERUGI, Giulio; KASPER, Siegfried; AMSTERDAM, Jay D.; HIRSCHFELD, Robert M.; KAPCZINSKI, Flavio; VIETA, EduardObjective: The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. Method: An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. Results: There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. Conclusions: Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to moodstabilizing medications.
conferenceObject Increased illness burden in women with co-morbid bipolar and premenstrual dysphoric disorder: data from the large step-BD study(2017) SLYEPCHENKO, A.; FREY, B.; LAFER, B.; NIERENBERG, A. A.; SACHS, G. S.; DIAS, R. S.- Association between prior alcohol use disorders and decreased prefrontal gray matter volumes in bipolar I disorder patients(2011) NERY, Fabiano G.; MATSUO, Koji; NICOLETTI, Mark A.; MONKUL, E. Serap; ZUNTA-SOARES, Giovana B.; HATCH, John P.; LAFER, Beny; SOARES, Jair C.Up to 50% of bipolar disorder (BD) patients present a lifetime diagnosis of alcohol use disorders (AUD). BD patients with comorbid AUD, even when in remission from the AUD, have a poorer outcome and functional impairment than patients with BD alone. The neurobiological abnormalities that potentially characterize this severe subgroup of BD patients are unknown. Our goal was to investigate gray matter (GM) volume abnormalities in BD I patients with comorbid AUD. Twenty-one BD-AUD patients, 21 BD-nonAUD BD patients, and 25 healthy controls (HC), matched by age, gender, and handedness were studied. The BD-AUD patients were in remission from AUD on average for 6.8 years. 3D SPGR MRIs (TR = 25 ms, TE = 5 ms, slice thickness = 1.5 mm) were acquired from all subjects using a 1.5 T GE Signa Imaging System. We used an optimized voxel-based morphometry protocol to compare GM volumes among the groups. BD-AUD patients presented smaller GM volumes in the left medial frontal and the right anterior cingulate gyri compared to BD-nonAUD patients. BDnon-AUD patients did not present GM volume differences compared to HC. These findings provide evidence for an effect of comorbid AUD on regional brain structure of BD I patients and warrant further research on neurobiological aspects of this prevalent and severe comorbidity.
- Low brain-derived neurotrophic factor levels in post-mortem brains of older adults with depression and dementia in a large clinicopathological sample(2018) NUNES, Paula Villela; NASCIMENTO, Camila Fernandes; KIM, Helena Kyunghee; ANDREAZZA, Ana Cristina; BRENTANI, Helena Paula; SUEMOTO, Claudia Kimie; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; GRINBERG, Lea Tenenholz; YONG, Lionel Trevor; JACOB-FILHO, Wilson; LAFER, BenyBackground: Disturbances in peripheral brain-derived neurotrophic factor (BDNF) have been reported in major depressive disorder (MDD). However, there are no studies measuring BDNF levels directly in post-mortem brains of older subjects with MDD and dementia. We aimed to verify if brain BDNF levels were lower in older adults with lifetime history of MDD with and without dementia. Methods: BDNF levels of post-mortem brains from 80 community-dwelling older individuals with lifetime MDD with and without dementia were compared with levels from 80 controls without lifetime MDD. Participants with no reliable close informant, or with prolonged agonal state were excluded. Lifetime MDD was defined as at least one previous episode according to the Structured Clinical Interview for DSM (SCID). Results: BDNF levels were lower in the MDD group with dementia than in participants with dementia and without MDD as confirmed by multivariate analysis adjusted for clinical and cardiovascular risk factors (beta = - 0.106, 95%CI = - 0.204; - 0.009, p = 0.034). No difference was found in the group with MDD without dementia compared with their controls. Limitations: The retrospective assessment of a lifetime history of depression may be subject to information bias and this study only establishes a cross-sectional association between lifetime history of MDD and lower levels of BDNF in patients with dementia. Conclusions: In this community sample of older individuals, lower brain BDNF levels were found in cases with both lifetime MDD and dementia. Low BDNF levels could be a moderator to accelerated brain aging observed in MDD with dementia.
- Physical exercise for bipolar disorder: Time for action COMMENT(2022) LAFER, Beny; NEVES, Lucas Melo; NIERENBERG, Andrew A.
- Morphometric post-mortem studies in bipolar disorder: possible association with oxidative stress and apoptosis(2011) GIGANTE, Alexandre Duarte; YOUNG, Lionel Trevor; YATHAM, Lakshmi N.; ANDREAZZA, Ana Cristina; NERY, Fabiano Goncalves; GRINBERG, Lea Tenenholz; HEINSEN, Helmut; LAFER, BenyDespite extensive research in the last decades, the pathophysiology of bipolar disorder (BD) remains unclear. Access to post-mortem brain tissue of subjects who had BD offers an opportunity to investigate neurobiology and this approach has led to some progress, particularly, due to the availability of more sophisticated molecular and cellular biological methodologies and well characterized brain collections over the past decade. Here we review the findings of morphometric post-mortem studies in BD and interpret them in the context of a potential physiopathological mechanism involving oxidative stress and apoptosis. A review of the literature was conducted to identify post-mortem studies that investigated cellular changes such as number, density and size of neurons and glia, in brains of subjects with BD. We found decreased density of neurons and glia and decreased size of neurons in frontal and subcortical areas of the brain. Based on recent studies that found evidence of increased apoptosis and oxidative stress in BD, we hypothesize that the cell abnormalities described are due to an increase in the apoptotic process that can be triggered, through its intrinsic pathway, by the existence of an exacerbated production of reactive oxygen species and oxidative damage in the disease.
- Can magnetic resonance imaging enhance the assessment of potential new treatments for cognitive impairment in mood disorders? A systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force(2022) MISKOWIAK, Kamilla W.; YALIN, Nefize; SEEBERG, Ida; BURDICK, Katherine E.; BALANZA-MARTINEZ, Vicent; BONNIN, Caterina del Mar; BOWIE, Christopher R.; CARVALHO, Andre F.; DOLS, Annemieke; DOUGLAS, Katie; GALLAGHER, Peter; HASLER, Gregor; V, Lars Kessing; LAFER, Beny; LEWANDOWSKI, Kathryn E.; LOPEZ-JARAMILLO, Carlos; MARTINEZ-ARAN, Anabel; MCINTYRE, Roger S.; PORTER, Richard J.; PURDON, Scot E.; SCHAFFER, Ayal; SUMIYOSHI, Tomiki; TORRES, Ivan J.; RHEENEN, Tamsyn E. Van; YATHAM, Lakshmi N.; YOUNG, Allan H.; VIETA, Eduard; STOKES, Paul R. A.Background Developing treatments for cognitive impairment is key to improving the functioning of people with mood disorders. Neuroimaging may assist in identifying brain-based efficacy markers. This systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force examines the evidence from neuroimaging studies of pro-cognitive interventions. Methods We included magnetic resonance imaging (MRI) studies of candidate interventions in people with mood disorders or healthy individuals, following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE, Cochrane Library, and from inception to 30th April 2021. Two independent authors reviewed the studies using the National Heart, Lung, Blood Institutes of Health Quality Assessment Tool for Controlled Intervention Studies and the quality of neuroimaging methodology assessment checklist. Results We identified 26 studies (N = 702). Six investigated cognitive remediation or pharmacological treatments in mood disorders (N = 190). In healthy individuals, 14 studies investigated pharmacological interventions (N = 319), 2 cognitive training (N = 73) and 4 neuromodulatory treatments (N = 120). Methodologies were mostly rated as 'fair'. 77% of studies investigated effects with task-based fMRI. Findings varied but most consistently involved treatment-associated cognitive control network (CCN) activity increases with cognitive improvements, or CCN activity decreases with no cognitive change, and increased functional connectivity. In mood disorders, treatment-related default mode network suppression occurred. Conclusions Modulation of CCN and DMN activity is a putative efficacy biomarker. Methodological recommendations are to pre-declare intended analyses and use task-based fMRI, paradigms probing the CCN, longitudinal assessments, mock scanning, and out-of-scanner tests.
- Association between history of suicide attempts and family functioning in bipolar disorder(2016) BERUTTI, Mariangeles; DIAS, Rodrigo Silva; PEREIRA, Vivian Alves; LAFER, Beny; NERY, Fabiano G.Objectives: To investigate the association between history of suicide attempts (SA) and family functioning in bipolar disorder (BD) patients. Methods: Thirty-one BD type I patients with lifetime history of SA, 31 BD type I with no lifetime history of SA, participating in the Outpatient Clinic of the Bipolar Disorder Program at the Institute of Psychiatry of the University of Sao Paulo Medical School were recruited for this study. We used the Family Assessment Device (FAD) to evaluate family functioning. We compared these two groups on demographic and clinical variables to identify which variables were associated with family functioning impairment. Fifty-one relatives of the same patients were also asked to complete a FAD. Results: BD patients with SA presented more psychiatric hospitalizations, higher frequency of psychotic symptoms, and higher scores on depressive, manic, and suicidal ideation than BD patients without SA. BD patients with SA presented significantly higher scores in several subscales of the FAD, including Problem Solving (p=0.042), Communication (p=0.009), Roles (p=0.006), and General Functioning (p=0.025), when compared with BD patients without SA. Relatives of BD patients with SA presented significantly higher scores in Communication, Roles, Affective Responsiveness, and General Functioning than relatives of BD patients without SA. Limitations: Cross-sectional study and long time elapsed since last SA. Conclusion: History of SA in BD is associated with worse family functioning in several domains of FAD, including Problem Solving, Communication, Roles, and General Functioning. As suicide attempts are routinely assessed in clinical practice, these findings may help to identify patients with poorer family functioning and may suggest a role for environmental risk factors in suicidal behavior among BD patients.
conferenceObject Inflammatory factors (cytokines and cortisol) across different brain regions in bipolar disorder and their associations with neuropsychiatric symptoms: A post-mortem study(2020) NASCIMENTO, Camila; NUNES, Paula V.; SUEMOTO, Claudia K.; RODRIGUEZ, Roberta D.; LEITE, Renata E. P.; GRINBERG, Lea T.; PASQUALUCCI, Carlos A.; NITRINI, Ricardo; JACOB-FILHO, Wilson; BRENTANI, Helena P.; LAFER, Beny- Initial findings of striatum tripartite model in OCD brain samples based on transcriptome analysis(2019) LISBOA, Bianca C. G.; OLIVEIRA, Katia C.; TAHIRA, Ana Carolina; BARBOSA, Andre Rocha; FELTRIN, Arthur Sant'Anna; GOUVEIA, Gisele; LIMA, Luzia; SANTOS, Ana Cecilia Feio dos; JR, David Correa Martins; PUGA, Renato David; MORETTO, Ariane Cristine; PEREIRA, Carlos Alberto De Braganca; LAFER, Beny; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah De Lucena; FARFEL, Jose Marcelo; GRINBERG, Lea Tenenholz; JACOB-FILHO, Wilson; MIGUEL, Euripedes Constantino; HOEXTER, Marcelo Queiroz; BRENTANI, HelenaObsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and/or compulsions. Different striatal subregions belonging to the cortico-striato-thalamic circuitry (CSTC) play an important role in the pathophysiology of OCD. The transcriptomes of 3 separate striatal areas (putamen (PT), caudate nucleus (CN) and accumbens nucleus (NAC)) from postmortem brain tissue were compared between 6 OCD and 8 control cases. In addition to network connectivity deregulation, different biological processes are specific to each striatum region according to the tripartite model of the striatum and contribute in various ways to OCD pathophysiology. Specifically, regulation of neurotransmitter levels and presynaptic processes involved in chemical synaptic transmission were shared between NAC and PT. The Gene Ontology terms cellular response to chemical stimulus, response to external stimulus, response to organic substance, regulation of synaptic plasticity, and modulation of synaptic transmission were shared between CN and PT. Most genes harboring common and/or rare variants previously associated with OCD that were differentially expressed or part of a least preserved coexpression module in our study also suggest striatum subregion specificity. At the transcriptional level, our study supports differences in the 3 circuit CSTC model associated with OCD.