Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 771
Filtrar
1.
Am J Psychiatry ; 177(10): 965-973, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32660299

RESUMO

OBJECTIVE: Low-dose testosterone has been shown to improve depression symptom severity, fatigue, and sexual function in small studies in women not formally diagnosed with major depressive disorder. The authors sought to determine whether adjunctive low-dose transdermal testosterone improves depression symptom severity, fatigue, and sexual function in women with antidepressant-resistant major depression. A functional MRI (fMRI) substudy examined effects on activity in the anterior cingulate cortex (ACC), a brain region important in mood regulation. METHODS: The authors conducted an 8-week randomized double-blind placebo-controlled trial of adjunctive testosterone cream in 101 women, ages 21-70, with antidepressant-resistant major depression. The primary outcome measure was depression symptom severity as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary endpoints included fatigue, sexual function, and safety measures. The primary outcome of the fMRI substudy (N=20) was change in ACC activity. RESULTS: The participants' mean age was 47 years (SD=14) and their mean baseline MADRS score was 26.6 (SD=5.9). Eighty-seven (86%) participants completed 8 weeks of treatment. MADRS scores decreased in both study arms from baseline to week 8 (testosterone arm: from 26.8 [SD=6.3] to 15.3 [SD=9.6]; placebo arm: from 26.3 [SD=5.4] to 14.4 [SD=9.3]), with no significant difference between groups. Improvement in fatigue and sexual function did not differ between groups, nor did side effects. fMRI results showed a relationship between ACC activation and androgen levels before treatment but no difference in ACC activation with testosterone compared with placebo. CONCLUSIONS: Adjunctive transdermal testosterone, although well tolerated, was not more effective than placebo in improving symptoms of depression, fatigue, or sexual dysfunction. Imaging in a subset of participants demonstrated that testosterone did not result in greater activation of the ACC.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Testosterona/uso terapêutico , Adulto , Idoso , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Resistente a Tratamento/diagnóstico por imagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Neuroimagem Funcional , Giro do Cíngulo/diagnóstico por imagem , Humanos , Hidrocortisona/sangue , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Creme para a Pele , Testosterona/administração & dosagem , Testosterona/sangue , Adulto Jovem
2.
Psychiatry Res Neuroimaging ; 300: 111083, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32298948

RESUMO

There has been a growing interest in the abnormality of networks across the brain in major depressive disorder (MDD). We aimed to investigate the structural covariance networks in patients with first-episode and drug-naïve MDD using structural imaging. A total of 77 patients with first-episode and drug-naïve MDD and 79 healthy subjects (HS) were recruited, from whom high-resolution T1-weighted images were analysed. Incident component analysis was used to calculate the brain networks based on grey matter volume covariance. There were significant differences in salience network, medial temporal lobe network, default mode network and central executive network between MDD and HS (p < 0.05). Further, the disturbance of medial temporal lobe network was significantly correlated with the severity of depressive symptoms (p < 0.05). In conclusion, we found a novel abnormality in the brain network in the medial temporal lobe primarily involving the hippocampus and parahippocampal gyrus in patients with first-episode and treatment-naïve MDD.


Assuntos
Transtorno Depressivo Maior/patologia , Imagem por Ressonância Magnética , Rede Nervosa/patologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Mapeamento Encefálico , Estudos de Casos e Controles , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Masculino , Rede Nervosa/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia
3.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 42(1): 6-13, Jan.-Feb. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1055355

RESUMO

Objective: To test the feasibility and to present preliminary results of a neuroimaging protocol to evaluate adolescent depression in a middle-income setting. Methods: We assessed psychotropic medication-free adolescents (age range 14-16 years) with a diagnosis of major depressive disorder (MDD). Participants underwent a comprehensive clinical evaluation and both structural and functional magnetic resonance imaging (fMRI). In this pilot study, a preliminary single-group analysis of resting-state fMRI (rs-fMRI) data was performed, with a focus on the default mode network (DMN), cognitive control network (CCN), and salience network (SN). Results: The sample included 29 adolescents with MDD (mean age 16.01, SD 0.78) who completed the protocol. Only two participants were excluded due to MRI quality issues (head movement), and were not included in the analyses. The scans showed significant connectivity between the medial prefrontal cortex and posterior cingulate cortex (DMN), the ACC and anterior insula (SN), and the lateral prefrontal cortex and dorsal parietal cortex (CCN). Conclusion: We demonstrated the feasibility of implementing a complex neuroimaging protocol in a middle-income country. Further, our preliminary rs-fMRI data revealed patterns of resting-state connectivity consistent with prior research performed in adolescents from high-income countries.


Assuntos
Humanos , Masculino , Adolescente , Imagem por Ressonância Magnética/métodos , Transtorno Depressivo Maior/diagnóstico por imagem , Neuroimagem/métodos , Controle de Qualidade , Fatores Socioeconômicos , Brasil , Córtex Cerebral/diagnóstico por imagem , Estudos de Viabilidade , Inquéritos e Questionários , Reprodutibilidade dos Testes , Transtorno Depressivo Maior/fisiopatologia , Vias Neurais , Testes Neuropsicológicos
4.
J Clin Psychiatry ; 81(2)2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32078260

RESUMO

OBJECTIVE: Reward deficits and associated striatal circuitry have been implicated in the onset and progression of major depressive disorder (MDD). This work was conducted to clarify how the striatal circuitry is involved in the established risk, acute episodes, and remission of MDD. METHODS: Striatal subregion resting-state functional connectivity (RSFC) was calculated for 29 currently depressed and 28 remitted patients diagnosed with MDD per the Structured Clinical Interview for DSM-IV, 19 first-degree relatives of these patients, and 57 healthy controls (HCs) based on resting-state fMRI data collected between May 2007 and September 2014. RESULTS: Compared with HCs, the other 3 groups showed increased RSFC between left dorsal caudate (DC) and right insula but reduced RSFC between right putamen and left cerebellum. The currently depressed group showed increased FC between right DC and superior frontal gyrus but reduced RSFC between putamen and right anterior cingulate as well as other striatal nuclei compared with the other 3 groups. Although no results were found in ventral striatum (VS) seeds during analysis of covariance, the comparison between currently depressed and remitted patients showed increased RSFC between right superior VS and left inferior frontal gyrus in currently depressed patients at a more linear threshold. Also, both superior and inferior VS showed increased RSFC with superior and inferior frontal gyri but reduced RSFC with cerebellum in relatives compared with HCs. Higher DC-superior frontal gyrus RSFC (r = 0.438, P = .022) was correlated with more severe depression, but lower within-putamen FC was correlated with more severe depression (r = -0.446, P = .02) and retardation (r = -0.465, P = .011). CONCLUSIONS: The findings suggest that reduced VS-frontal, within-putamen, and putamen-cingulate RSFC in currently depressed patients is dependent on current depressive episode and has implications for symptomatic monitoring, while increased caudate-insular and reduced VS-cerebellar RSFC in remitted patients and first-degree relatives might be related to the disease itself and have potential for predicting risk for and recurrence of MDD.


Assuntos
Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Conectoma , Transtorno Depressivo Maior/fisiopatologia , Neostriado/fisiopatologia , Rede Nervosa/fisiopatologia , Recompensa , Estriado Ventral/fisiopatologia , Adulto , Cerebelo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Família , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Neostriado/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Recidiva , Indução de Remissão , Estriado Ventral/diagnóstico por imagem
5.
JAMA Netw Open ; 3(1): e1918377, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899530

RESUMO

Importance: Social and economic costs of depression are exacerbated by prolonged periods spent identifying treatments that would be effective for a particular patient. Thus, a tool that reliably predicts an individual patient's response to treatment could significantly reduce the burden of depression. Objective: To estimate how accurately an outcome of escitalopram treatment can be predicted from electroencephalographic (EEG) data on patients with depression. Design, Setting, and Participants: This prognostic study used a support vector machine classifier to predict treatment outcome using data from the first Canadian Biomarker Integration Network in Depression (CAN-BIND-1) study. The CAN-BIND-1 study comprised 180 patients (aged 18-60 years) diagnosed with major depressive disorder who had completed 8 weeks of treatment. Of this group, 122 patients had EEG data recorded before the treatment; 115 also had EEG data recorded after the first 2 weeks of treatment. Interventions: All participants completed 8 weeks of open-label escitalopram (10-20 mg) treatment. Main Outcomes and Measures: The ability of EEG data to predict treatment outcome, measured as accuracy, specificity, and sensitivity of the classifier at baseline and after the first 2 weeks of treatment. The treatment outcome was defined in terms of change in symptom severity, measured by the Montgomery-Åsberg Depression Rating Scale, before and after 8 weeks of treatment. A patient was designated as a responder if the Montgomery-Åsberg Depression Rating Scale score decreased by at least 50% during the 8 weeks and as a nonresponder if the score decrease was less than 50%. Results: Of the 122 participants who completed a baseline EEG recording (mean [SD] age, 36.3 [12.7] years; 76 [62.3%] female), the classifier was able to identify responders with an estimated accuracy of 79.2% (sensitivity, 67.3%; specificity, 91.0%) when using only the baseline EEG data. For a subset of 115 participants who had additional EEG data recorded after the first 2 weeks of treatment, use of these data increased the accuracy to 82.4% (sensitivity, 79.2%; specificity, 85.5%). Conclusions and Relevance: These findings demonstrate the potential utility of EEG as a treatment planning tool for escitalopram therapy. Further development of the classification tools presented in this study holds the promise of expediting the search for optimal treatment for each patient.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Citalopram/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Eletroencefalografia/estatística & dados numéricos , Aprendizado de Máquina , Adulto , Biomarcadores/análise , Canadá , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Máquina de Vetores de Suporte , Resultado do Tratamento
6.
J Altern Complement Med ; 26(3): 190-197, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31934793

RESUMO

Objective: To determine if a 12-week yoga intervention (YI) was associated with increased gamma aminobutyric acid (GABA) levels and decreased depressive symptoms in participants with major depressive disorder (MDD). Methods: Subjects were randomized to a high-dose group (HDG) of three YIs a week and a low-dose group (LDG) of two YIs a week. Thalamic GABA levels were obtained using magnetic resonance spectroscopy at Scan-1 before randomization. After the assigned 12-week intervention, Scan-2 was obtained, immediately followed by a YI and Scan-3. Beck Depression Inventory II (BDI-II) scores were obtained before Scan-1 and Scan-3. Settings/Location: Screenings and interventions occurred at the Boston University Medical Center. Imaging occurred at McLean Hospital. Subjects: Subjects met criteria for MDD. Intervention: Ninety minutes of Iyengar yoga and coherent breathing at five breaths per minute plus homework. Outcome measures: GABA levels and the BDI-II. Results: BDI-II scores improved significantly in both groups. GABA levels from Scan-1 to Scan-3 and from Scan-2 to Scan-3 were significantly increased in the LDG (n = 15) and showed a trend in the total cohort. Post hoc, participants were divided into two groups based on having an increase in GABA levels at Scan-2. Increases in Scan-2 GABA levels were observed in participants whose mean time between their last YI and Scan-2 was 3.93 ± 2.92 standard deviation (SD) days, but not in those whose mean time between their last YI and Scan-2 was 7.83 ± 6.88 SD. Conclusions: This study tentatively supports the hypothesis that one of the mechanisms through which yoga improves mood is by increasing the activity of the GABA system. The observed increase in GABA levels following a YI that was no longer observed 8 days after a YI suggests that the associated increase in GABA after a YI is time limited such that at least one YI a week may be necessary to maintain the elevated GABA levels.


Assuntos
Exercícios Respiratórios , Transtorno Depressivo Maior , Tálamo/metabolismo , Ioga , Ácido gama-Aminobutírico/análise , Adulto , Ansiedade , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/terapia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tálamo/química , Tálamo/diagnóstico por imagem , Adulto Jovem , Ácido gama-Aminobutírico/metabolismo
7.
Braz J Psychiatry ; 42(1): 6-13, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31389498

RESUMO

OBJECTIVE: To test the feasibility and to present preliminary results of a neuroimaging protocol to evaluate adolescent depression in a middle-income setting. METHODS: We assessed psychotropic medication-free adolescents (age range 14-16 years) with a diagnosis of major depressive disorder (MDD). Participants underwent a comprehensive clinical evaluation and both structural and functional magnetic resonance imaging (fMRI). In this pilot study, a preliminary single-group analysis of resting-state fMRI (rs-fMRI) data was performed, with a focus on the default mode network (DMN), cognitive control network (CCN), and salience network (SN). RESULTS: The sample included 29 adolescents with MDD (mean age 16.01, SD 0.78) who completed the protocol. Only two participants were excluded due to MRI quality issues (head movement), and were not included in the analyses. The scans showed significant connectivity between the medial prefrontal cortex and posterior cingulate cortex (DMN), the ACC and anterior insula (SN), and the lateral prefrontal cortex and dorsal parietal cortex (CCN). CONCLUSION: We demonstrated the feasibility of implementing a complex neuroimaging protocol in a middle-income country. Further, our preliminary rs-fMRI data revealed patterns of resting-state connectivity consistent with prior research performed in adolescents from high-income countries.


Assuntos
Transtorno Depressivo Maior/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Neuroimagem/métodos , Adolescente , Brasil , Córtex Cerebral/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Estudos de Viabilidade , Humanos , Masculino , Vias Neurais , Testes Neuropsicológicos , Controle de Qualidade , Reprodutibilidade dos Testes , Fatores Socioeconômicos , Inquéritos e Questionários
8.
Neuroimaging Clin N Am ; 30(1): 53-63, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31759572

RESUMO

The application of personalized medicine to psychiatry is challenging. Psychoradiology could provide biomarkers based on objective tests in support of the diagnostic classifications and treatment planning. We review potential psychoradiological biomarkers for psychopharmaceutical effects. Although none of the biomarkers reviewed are yet of sufficient clinical utility to inform the selection of a specific pharmacologic compound for an individual patient, there is strong consensus that advanced multimodal approaches will contribute to discovery of novel treatment predictors in psychiatric disorders. Progress has been sufficient to warrant enthusiasm, in which application of neuroimaging-based biomarkers would represent a paradigm shift and modernization of psychiatric practice.


Assuntos
Biomarcadores , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/tratamento farmacológico , Neuroimagem/métodos , Psicotrópicos/uso terapêutico , Transtornos de Ansiedade/diagnóstico por imagem , Transtornos de Ansiedade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Medicina de Precisão , Prognóstico , Psiquiatria/métodos , Radiologia/métodos
9.
Neuroimaging Clin N Am ; 30(1): 85-95, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31759575

RESUMO

Major depression is common and debilitating. Identifying neurobiological subtypes that comprise the disorder and predict clinical outcome are key challenges. Genetic and environmental factors leading to major depression are expressed in neural structure and function. Volumetric decreases in gray matter have been demonstrated in corticolimbic circuits involved in emotion regulation. MR imaging observable abnormalities reflect cytoarchitectonic alterations within a local neuroendocrine milieu with systemic effects. Multivariate pattern analysis offers the potential to identify the neurobiological subtypes and predictors of clinical outcome. It is essential to characterize disease heterogeneity by incorporating data-driven inductive and symptom-based deductive approaches in an iterative process.


Assuntos
Transtorno Depressivo Maior/fisiopatologia , Plasticidade Neuronal , Biomarcadores , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/patologia , Transtorno Depressivo Maior/terapia , Regulação Emocional , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Substância Cinzenta/fisiopatologia , Giro do Cíngulo/patologia , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Neuroimagem , Prognóstico
10.
Adv Exp Med Biol ; 1180: 59-83, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784957

RESUMO

Neuroimaging shed light on the understanding of psychopathological mechanisms underlying major depressive disorder, despite its inconsistent findings. Noninvasive neuroimaging studies have indicated that various behavioral deficits in major depressive disorder are implicated with structural and functional abnormalities in specific brain regions. Moreover, disrupted brain morphological and functional properties may map out the underlying pathways from genetic and environmental factors to the prognosis of depression. Molecular neuroimaging studies have also provided novel method to probe transmitters and metabolites in brain regions rather than simply measuring brain morphological changes. Recent advanced neuroimaging approaches (e.g., pattern recognition) provides great opportunity to probe neuroimaging biomarkers that may contributes to improving diagnostic accuracy and predicting treatment outcomes. In this chapter, we conclude neuroimaging studies in the research field of depression from psychopathological, molecular, genetic/environmental, diagnostic, and therapeutic perspectives.


Assuntos
Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Neuroimagem , Biomarcadores , Humanos
11.
Stereotact Funct Neurosurg ; 97(5-6): 369-380, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31865344

RESUMO

INTRODUCTION: Bilateral anterior capsulotomy (BAC) is an effective surgical procedure for patients with treatment-resistant major depression (TRMD). In this work, we analyze the connectivity of the BAC lesions to identify connectivity "fingerprints" associated with clinical outcomes in patients with TRMD. METHODS: We performed a retrospective study of ten patients following BAC surgery. These patients were divided into "responders" and "non-responders" based on the relative change in the Beck depression inventory (BDI) score after surgery. We generated the dorsolateral prefrontal associative (DLPFC) pathways and the ventromedial prefrontal limbic (vmPFC) pathways going through the anterior limb of the internal capsule and analyzed if the overlap of the BAC lesions with these pathways was associated with either outcome. Finally, we used the BAC lesions of our patients to generate group-averaged connectivity "fingerprints" associated with either outcome. RESULTS: Six patients were responders (≥50% improvement in BDI), four patients were non-responders (<50% improvement). No significant impairments were found in most neuropsychological tests after surgery. The overlap analysis showed that in the responder group, there was less involvement of the DLPFC pathways than the vmPFC pathways (p = 0.001). Conversely, in the non-responder group, there was no significant difference between the involvement of both pathways (p = 0.157). The responder and non-responder connectivity fingerprint showed significant connections with the vmPFC limbic areas. However, the non-responder connectivity fingerprint also showed stronger connectivity to associative areas including the DLPFC and lateral orbitofrontal cortices. CONCLUSIONS: The optimum outcome following BAC surgery in this cohort was associated with interruption of vmPFC pathways and the relative preservation of DLPFC pathways.


Assuntos
Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/cirurgia , Transtorno Depressivo Resistente a Tratamento/diagnóstico por imagem , Transtorno Depressivo Resistente a Tratamento/cirurgia , Cápsula Interna/diagnóstico por imagem , Cápsula Interna/cirurgia , Adulto , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Resistente a Tratamento/psicologia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/cirurgia , Estudos Retrospectivos , Adulto Jovem
12.
Adv Exp Med Biol ; 1192: 159-195, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31705495

RESUMO

This chapter presents an overview of accumulating neuroimaging data with emphasis on translational potential. The subject will be described in the context of three disease states, i.e., schizophrenia, bipolar disorder, and major depressive disorder, and for three clinical goals, i.e., disease risk assessment, subtyping, and treatment decision.


Assuntos
Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Neuroimagem , Psiquiatria , Esquizofrenia/diagnóstico por imagem , Biomarcadores , Tomada de Decisão Clínica , Humanos , Imagem por Ressonância Magnética , Medição de Risco
13.
Depress Anxiety ; 36(11): 1047-1057, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31475432

RESUMO

BACKGROUND: Recent evidence suggests that therapeutic repetitive transcranial magnetic stimulation (TMS) is an effective treatment for pharmacoresistant posttraumatic stress disorder (PTSD) and comorbid major depressive disorder (MDD). We recently demonstrated that response to 5 Hz TMS administered to the dorsolateral prefrontal cortex was predicted by functional connectivity of the medial prefrontal (MPFC) and subgenual anterior cingulate cortex (sgACC). This functionally-defined circuit is a novel target for treatment optimization research, however, our limited knowledge of the structural pathways that underlie this functional predisposition is a barrier to target engagement research. METHODS: To investigate underlying structural elements of our previous functional connectivity findings, we submitted pre-TMS diffusion-weighted imaging data from 20 patients with PTSD and MDD to anatomically constrained tract-based probabilistic tractography (FreeSurfer's TRActs Constrained by UnderLying Anatomy). Averaged pathway fractional anisotropy (FA) was extracted from four frontal white matter tracts: the forceps minor, cingulum, anterior thalamic radiations (ATRs), and uncinate fasciculi. Tract FA statistics were treated as explanatory variables in backward regressions testing the relationship between tract integrity and functional connectivity coefficients from MPFC and sgACC predictors of symptom improvement after TMS. RESULTS: FA in the ATRs was consistently associated with symptom improvement in PTSD and MDD (Bonferroni-corrected p < .05). CONCLUSION: We found that structural characteristics of the ATR account for significant variance in individual-level functional predictors of post-TMS improvement. TMS optimization studies should target this circuit either in stand-alone or successive TMS stimulation protocols.


Assuntos
Transtorno Depressivo Maior/terapia , Transtornos de Estresse Pós-Traumáticos/terapia , Estimulação Magnética Transcraniana/métodos , Substância Branca/fisiologia , Anisotropia , Comorbidade , Corpo Caloso , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Imagem de Difusão por Ressonância Magnética , Feminino , Giro do Cíngulo , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa , Córtex Pré-Frontal , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Resultado do Tratamento , Substância Branca/diagnóstico por imagem
14.
Transl Psychiatry ; 9(1): 236, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537779

RESUMO

Investigations of pathophysiological mechanisms implicated in vulnerability to depression have been negatively impacted by the significant heterogeneity characteristic of psychiatric syndromes. Such challenges are also reflected in numerous null findings emerging from genome-wide association studies (GWAS) of depression. Bolstered by increasing sample sizes, recent GWAS studies have identified genetics variants linked to MDD. Among them, Okbay and colleagues (Nat. Genet. 2016 Jun;48(6):624-33) identified genetic variants associated with three well-validated depression-related phenotypes: subjective well-being, depressive symptoms, and neuroticism. Despite this progress, little is known about psychopathological and neurobiological mechanisms underlying such risk. To fill this gap, a genetic risk score (GRS) was computed from the Okbay's study for a sample of 88 psychiatrically healthy females. Across two sessions, participants underwent two well-validated psychosocial stressors, and performed two separate tasks probing reward learning both before and after stress. Analyses tested whether GRS scores predicted anhedonia-related phenotypes across three units of analyses: self-report (Snaith Hamilton Pleasure Scale), behavior (stress-induced changes in reward learning), and circuits (stress-induced changes in striatal reward prediction error; striatal volume). GRS scores were negatively associated with anhedonia-related phenotypes across all units of analyses but only circuit-level variables were significant. In addition, the amount of explained variance was systematically larger as variables were putatively closer to the effects of genes (self-report < behavior < neural circuitry). Collectively, findings implicate anhedonia-related phenotypes and neurobiological mechanisms in increased depression vulnerability, and highlight the value of focusing on fundamental dimensions of functioning across different units of analyses.


Assuntos
Anedonia/fisiologia , Depressão/genética , Transtorno Depressivo Maior/genética , Adulto , Encéfalo/diagnóstico por imagem , Condicionamento Operante/fisiologia , Depressão/diagnóstico por imagem , Depressão/psicologia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/psicologia , Feminino , Predisposição Genética para Doença , Humanos , Imagem por Ressonância Magnética , Fenótipo , Escalas de Graduação Psiquiátrica , Recompensa , Adulto Jovem
15.
Transl Psychiatry ; 9(1): 234, 2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31534117

RESUMO

Repetitive negative thinking (RNT) is a maladaptive response to sadness and a transdiagnostic risk-factor. A critical challenge hampering attempts to promote more adaptive responses to sadness is that the between-person characteristics associated with the tendency for RNT remain uncharacterized. From the perspective of the impaired disengagement hypothesis, we examine between-person differences in blood-oxygen-level-dependent (BOLD) functional networks underlying cognitive conflict signaling, self-referential thought, and cognitive flexibility, and the association between sadness and RNT in daily life. We pair functional magnetic resonance imaging with ambulatory assessments deployed 10 times per day over 4 consecutive days measuring momentary sadness and RNT from 58 participants (40 female, mean age = 36.69 years; 29 remitted from a lifetime episode of Major Depression) in a multilevel model. We show that RNT increases following sadness for participants with higher than average between-network connectivity of the default mode network and the fronto-parietal network. We also show that RNT increases following increases in sadness for participants with lower than average between-network connectivity of the fronto-parietal network and the salience network. We also find that flexibility of the salience network's pattern of connections with brain regions is protective against increases in RNT following sadness. Our findings highlight the importance of functional brain networks implicated in cognitive conflict signaling, self-referential thought, and cognitive flexibility for understanding maladaptive responses to sadness in daily life and provide support for the impaired disengagement hypothesis of RNT.


Assuntos
Encéfalo/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Pessimismo , Ruminação Cognitiva/fisiologia , Adulto , Mapeamento Encefálico , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/psicologia , Emoções/fisiologia , Feminino , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Masculino
16.
Nat Hum Behav ; 3(12): 1319-1331, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31548678

RESUMO

The efficacy of antidepressant treatment for depression is controversial due to the only modest superiority demonstrated over placebo. However, neurobiological heterogeneity within depression may limit overall antidepressant efficacy. We sought to identify a neurobiological phenotype responsive to antidepressant treatment by testing pretreatment brain activation during response to, and regulation of, emotional conflict as a moderator of the clinical benefit of the antidepressant sertraline versus placebo. Using neuroimaging data from a large randomized controlled trial, we found widespread moderation of clinical benefits by brain activity during regulation of emotional conflict, in which greater downregulation of conflict-responsive regions predicted better sertraline outcomes. Treatment-predictive machine learning using brain metrics outperformed a model trained on clinical and demographic variables. Our findings demonstrate that antidepressant response is predicted by brain activity underlying a key self-regulatory emotional capacity. Leveraging brain-based measures in psychiatry will forge a path toward better treatment personalization, refined mechanistic insights and improved outcomes.


Assuntos
Antidepressivos de Segunda Geração/metabolismo , Antidepressivos/metabolismo , Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/tratamento farmacológico , Antidepressivos/uso terapêutico , Antidepressivos de Segunda Geração/uso terapêutico , Encéfalo/efeitos dos fármacos , Ensaios Clínicos como Assunto , Depressão , Transtorno Depressivo Maior/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética/métodos , Neuroimagem/métodos , Resultado do Tratamento
17.
Brain Imaging Behav ; 13(6): 1766-1779, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31414234

RESUMO

Individuals with major depression show impaired control of attention and emotions. Both processes are conceptually similar and might share common mechanisms. The current study aims to examine attention control and its association with cognitive emotion regulation in depression. 26 patients with a history of major depression (14 females) and 26 healthy controls (14 females) performed an emotional face-word Stroop task and a cognitive emotion regulation task while undergoing fMRI. Patients and controls showed a similar behavioral performance in both tasks. Across groups, participants who were less distracted from happy faces by the incongruent word "sadness" (Stroop task) were better at regulating their happiness (emotion regulation task). Notably, both the Stroop and emotion regulation task recruited the left supramarginal gyrus. Additionally, only patients showed a relative attentional disengagement from positive compared to negative stimuli in the Stroop task. Attention control and cognitive emotion regulation capabilities appear to be linked at both the behavioral and neural level. Shared mechanisms suggest that emotional disturbances in depression may be improved by interventions that target attention control, particularly regarding the processing of positive stimuli.


Assuntos
Atenção , Encéfalo/patologia , Cognição , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/patologia , Regulação Emocional , Adulto , Feminino , Felicidade , Humanos , Imagem por Ressonância Magnética , Masculino , Testes Neuropsicológicos
18.
Transl Psychiatry ; 9(1): 197, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434867

RESUMO

Major depression is a frequent and severe disorder, with a combination of psycho- and pharmacotherapy most patients can be treated. However, ~20% of all patients suffering from major depressive disorder remain treatment resistant; a subgroup might be treated with deep brain stimulation (DBS). We present two trials of DBS to the superolateral medial forebrain bundle (slMFB DBS; FORESEE I and II). The goal was to identify informed features that allow to predict treatment response. Data from N = 24 patients were analyzed. Preoperative imaging including anatomical sequences (T1 and T2) and diffusion tensor imaging (DTI) magnetic resonance imaging sequences were used together with postoperative helical CT scans (for DBS electrode position). Pathway activation modeling (PAM) as well as preoperative structural imaging and morphometry was used to understand the response behavior of patients (MADRS). A left fronto-polar and partly orbitofrontal region was identified that showed increased volume in preoperative anatomical scans. Further statistical analysis shows that the volume of this "HUB-region" is predictive for later MADRS response from DBS. The HUB region connects to typical fiber pathways that have been addressed before in therapeutic DBS in major depression. Left frontal volume growth might indicate intrinsic activity upon disconnection form the main emotional network. The results are significant since for the first time we found an informed feature that might allow to identify and phenotype future responders for slMFB DBS. This is a clear step into the direction of personalized treatments.


Assuntos
Estimulação Encefálica Profunda , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/terapia , Lobo Frontal/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Resistente a Tratamento/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Humanos , Terapia de Campo Magnético , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
19.
Transl Psychiatry ; 9(1): 191, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431610

RESUMO

Several studies have shown that electroconvulsive therapy (ECT) results in increased hippocampal volume. It is likely that a multitude of mechanisms including neurogenesis, gliogenesis, synaptogenesis, angiogenesis, and vasculogenesis contribute to this volume increase. Neurotrophins, like vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) seem to play a crucial mediating role in several of these mechanisms. We hypothesized that two regulatory SNPs in the VEGF and BDNF gene influence the changes in hippocampal volume following ECT. We combined genotyping and brain MRI assessment in a sample of older adults suffering from major depressive disorder to test this hypothesis. Our results show an effect of rs699947 (in the promotor region of VEGF) on hippocampal volume changes following ECT. However, we did not find a clear effect of rs6265 (in BDNF). To the best of our knowledge, this is the first study investigating possible genetic mechanisms involved in hippocampal volume change during ECT treatment.


Assuntos
Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia , Hipocampo/diagnóstico por imagem , Regiões Promotoras Genéticas , Fator A de Crescimento do Endotélio Vascular/genética , Idoso , Idoso de 80 Anos ou mais , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/genética , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/genética , Resultado do Tratamento
20.
Brain Stimul ; 12(6): 1600-1602, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31402180

RESUMO

BACKGROUND: Accurate identification of cranial midline structures is essential for many targeting techniques that use repetitive transcranial magnetic stimulation (rTMS), including the Beam F3 method used for depression treatment. OBJECTIVE: Evaluate whether a novel, laser-sighted device will assist with more accurate identification of the cranial midline relative to standard scalp-based measurement procedures. METHODS: Three trained TMS technicians performed repeated scalp-based measurements to identify the inion and vertex on five subjects (n = 54 measurements). Measurements were compared to points identified with the midline localizer device and the true midline as defined by MRI midline structures. RESULTS: Use of the midline localizer was more accurate for midline identification than technician measurement (p = 0.00025) and the ratio of localizing the midline within 5 mm was higher (78% versus 54%, p = 0.008). CONCLUSION: Use of a laser-sighted midline localizer device can improve the accuracy of scalp measurements associated with target localization for rTMS treatment protocols.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Imagem por Ressonância Magnética/métodos , Estimulação Magnética Transcraniana/métodos , Adulto , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Feminino , Humanos , Imagem por Ressonância Magnética/instrumentação , Masculino , Couro Cabeludo , Estimulação Magnética Transcraniana/instrumentação , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA