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1.
Psychol Med ; 53(5): 2017-2030, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-34749836

RESUMO

BACKGROUND: Accumulating evidence suggests that alterations in inflammatory biomarkers are important in depression. However, previous meta-analyses disagree on these associations, and errors in data extraction may account for these discrepancies. METHODS: PubMed/MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from database inception to 14 January 2020. Meta-analyses of observational studies examining the association between depression and levels of tumor necrosis factor-α (TNF-α), interleukin 1-ß (IL-1ß), interleukin-6 (IL-6), and C-reactive protein (CRP) were eligible. Errors were classified as follows: incorrect sample sizes, incorrectly used standard deviation, incorrect participant inclusion, calculation error, or analysis with insufficient data. We determined their impact on the results after correction thereof. RESULTS: Errors were noted in 14 of the 15 meta-analyses included. Across 521 primary studies, 118 (22.6%) showed the following errors: incorrect sample sizes (20 studies, 16.9%), incorrect use of standard deviation (35 studies, 29.7%), incorrect participant inclusion (7 studies, 5.9%), calculation errors (33 studies, 28.0%), and analysis with insufficient data (23 studies, 19.5%). After correcting these errors, 11 (29.7%) out of 37 pooled effect sizes changed by a magnitude of more than 0.1, ranging from 0.11 to 1.15. The updated meta-analyses showed that elevated levels of TNF- α, IL-6, CRP, but not IL-1ß, are associated with depression. CONCLUSIONS: These findings show that data extraction errors in meta-analyses can impact findings. Efforts to reduce such errors are important in studies of the association between depression and peripheral inflammatory biomarkers, for which high heterogeneity and conflicting results have been continuously reported.


Assuntos
Depressão , Interleucina-6 , Humanos , Depressão/epidemiologia , Inflamação/metabolismo , Biomarcadores , Proteína C-Reativa , Fator de Necrose Tumoral alfa
2.
Sci Rep ; 11(1): 12105, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103606

RESUMO

Cognitive complaints after chemotherapy are common in breast cancer patients, but the neural bases for these complaints remain unclear. This pilot study explored resting-state functional connectivity (FC) as a marker of subtle cognitive changes in breast cancer patients who experience cognitive complaints. Chemotherapy-treated (n = 20, at least 6 months off therapy) and untreated (n = 17, disease-control) female breast cancer patients with cognitive complaints and healthy controls (n = 20) were recruited. The FC of the right dorsolateral prefrontal cortex was calculated, and any correlations between this FC and neuropsychological assessments were determined. Chemotherapy-treated patients with cognitive complaints displayed increased FC between the right dorsolateral prefrontal cortex and both the contralateral cerebellar lobule VII and the cerebellar vermis XI, compared to the disease-control and healthy-control groups, despite unimpaired neuropsychological performance. The increased FC was negatively correlated with executive function and attention in breast cancer survivors with cognitive complaints. Our pilot study findings provide evidence that cerebellar-cortical FC changes may be a pathophysiological basis for chemotherapy-related cognitive complaints. In addition, the FC changes have the potential to reflect minor or compensated cognitive function impairment in breast cancer patients.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/complicações , Neoplasias da Mama/fisiopatologia , Cerebelo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Transtornos Cognitivos/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico , Sobreviventes de Câncer , Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Cognição , Disfunção Cognitiva/fisiopatologia , Função Executiva/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Projetos Piloto , Córtex Pré-Frontal
3.
Drug Saf ; 43(6): 539-547, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32034700

RESUMO

INTRODUCTION: Theoretically, benzodiazepines (BZDs) can narrow the iridocorneal angle and induce acute angle-closure glaucoma (AACG). However, little evidence exists regarding this association. OBJECTIVE: The objective of this study was to assess whether the use of BZDs is associated with the risk of AACG. METHODS: We conducted a population-based case-crossover study using the nationwide claims database of the National Health Insurance Service in Korea. Patients with newly diagnosed AACG-between 1 January 2013 and 31 December 2016-who had received at least one BZD prescription prior to AACG diagnosis were enrolled. The date of AACG diagnosis was set as the index date. We assessed BZD use by each patient during a 30-day case period prior to the index date and three consecutive control periods that preceded this date. We used conditional logistic regression that adjusted for concomitant medications to determine the odds ratio for the use of BZDs in the case period compared with that in the control period in patients with incident AACG. RESULTS: Of the 11,093 patients with incident AACG, 6709 received a prescription for BZD prior to diagnosis. BZD use was associated with an increased risk of AACG [adjusted odds ratio (aOR) = 1.40; 95% confidence interval (CI) 1.27-1.54]. AACG risk was similar for short-acting (aOR = 1.40, 95% CI 1.24-1.57) and long-acting BZDs (aOR = 1.33, 95% CI 1.18-1.50). CONCLUSION: We found that BZD use was associated with AACG risk in the Korean population. Clinicians should carefully monitor the occurrence of visual disturbance in BZD-treated patients.


Assuntos
Benzodiazepinas/efeitos adversos , Glaucoma de Ângulo Fechado/induzido quimicamente , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzodiazepinas/administração & dosagem , Estudos Cross-Over , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Glaucoma de Ângulo Fechado/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , República da Coreia , Adulto Jovem
4.
PLoS One ; 14(2): e0211957, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30753205

RESUMO

The early identification and prevention of dementia is important for reducing its worldwide burden and increasing individuals' quality of life. Although several dementia prediction models have been developed, there remains a need for a practical and precise model targeted to middle-aged and Asian populations. Here, we used national Korean health examination data from adults (331,126 individuals, 40-69 years of age, mean age: 52 years) from 2002-2003 to predict the incidence of dementia after 10 years. We divided the dataset into two cohorts to develop and validate of our prediction model. Cox proportional hazards models were used to construct dementia prediction models for the total group and sex-specific subgroups. Receiver operating characteristics curves, C-statistics, calibration plots, and cumulative hazards were used to validate model performance. Discriminative accuracy as measured by C-statistics was 0.81 in the total group (95% confidence interval (CI) = 0.81 to 0.82), 0.81 in the male subgroup (CI = 0.80 to 0.82), and 0.81 in the female subgroup (CI = 0.80 to 0.82). Significant risk factors for dementia in the total group were age; female sex; underweight; current hypertension; comorbid psychiatric or neurological disorder; past medical history of cardiovascular disease, diabetes mellitus, or hypertension; current smoking; and no exercise. All identified risk factors were statistically significant in the sex-specific subgroups except for low body weight and current hypertension in the female subgroup. These results suggest that public health examination data can be effectively used to predict dementia and facilitate the early identification of dementia within a middle-aged Asian population.


Assuntos
Demência/epidemiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Saúde Pública , República da Coreia/epidemiologia , Medição de Risco , Fatores de Risco , Inquéritos e Questionários
5.
Psychiatry Investig ; 14(4): 400-406, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28845165

RESUMO

OBJECTIVE: Sleep disturbance is common in the elderly, which is result from multi-factorial causes encompassing socio-demographic, behavioral, and clinical factors. We aimed to identify factors associated with insomnia among the elderly in a rural community in South Korea, a country with a rapidly growing aged population. METHODS: This cross-sectional study used the data from the second wave of the Korean Social life, Health and Ageing Project, which is a cohort study of individuals living in a typical rural community in South Korea. Socio-demographic, behavioral, and clinical characteristics were obtained through face-to-face interviews. Various factors suspected to be associated with insomnia were compared between elderly participants with and without insomnia, and multiple logistic regression analyses were conducted to identify independent risk factors for insomnia. RESULTS: We found that 32.4% of 509 participants (72.8±7.7 years old) had insomnia. Female sex [odds ratio (OR)=2.19], low education level (OR=2.44), current smoking (OR=2.26), number of chronic diseases (OR=2.21 for 2-3 chronic diseases; OR=2.06 for 4 or more chronic diseases), and depression (OR=2.53) were independently associated with insomnia. CONCLUSION: We found that sex, education, chronic disease, and depression independently increase the risk of insomnia of the elderly in a Korean rural community. To overcome the elderly's insomnia, interventions should target modifiable factors such as depression. To promote active aging, longitudinal studies of factors associated with insomnia among the elderly should be performed in different regions and communities.

6.
Neuroreport ; 28(2): 82-86, 2017 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-27906773

RESUMO

Neuroinflammation has been raised as a candidate of unifying pathogenesis and a target of a disease-modifying strategy for Alzheimer's disease (AD). Aminoacyl-tRNA synthetase complex (ARS)-interacting multifunctional protein 1 (AIMP1) is a cytokine that is known to amplify the actions of tumor necrosis factor-α and to be involved in microglial activation and neuronal death. In this respect, AIMP1 could be a plausible target for the treatment of AD. Therefore, we aimed to examine whether anti-AIMP1 antibody could exert therapeutic effects against cognitive impairment using 3xTg-AD mice. Through the passive avoidance test, we found that an intraperitoneal injection of anti-AIMP1 antibody over 4 weeks was effective in protecting memory function in 3xTg-AD mice (16 weeks old). In addition, to address the translational implications of AIMP1, we measured blood AIMP1 levels in patients with AD (n=22), mild cognitive impairment (n=25), and normal cognition (n=23). Blood AIMP1 levels were associated negatively with global cognitive function and were significantly higher in individuals with a higher degree of medial temporal lobe atrophy, which is one of the representative clinical markers of AD. Our results suggested a possible association of AIMP1 with AD pathogenesis, as well as the potential of the anti-AIMP1 antibody as a novel therapeutic option for AD.


Assuntos
Doença de Alzheimer/complicações , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/prevenção & controle , Citocinas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Animais , Anticorpos/uso terapêutico , Aprendizagem da Esquiva/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/etiologia , Entrevista Psiquiátrica Padronizada , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Mutação/genética , Presenilina-1/genética , Teste de Desempenho do Rota-Rod , Proteínas tau/genética
7.
Sleep Med ; 27-28: 72-79, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27938923

RESUMO

BACKGROUND: Disturbed sleep has been associated with increased insulin resistance and elevated inflammation. Although there is growing body of evidence that activation of inflammatory pathways plays a crucial role in the development of insulin resistance, the mediational model whereby sleep disturbances influence inflammation that drives insulin resistance has not been fully assessed in general population studies with objectively measured sleep. This study aimed to examine associations between objectively measured sleep, inflammatory markers, and insulin resistance simultaneously and in a mediational analysis, thereby offering insights into the possible causal model. METHODS: Cross-sectional data collected from 2004 to 2009 during the Midlife Development in the United States II biomarker project were used. The study population included 374 community-based participants (138 men and 236 women) who completed seven nights of wrist actigraphy. Multiple regressions controlling for age and statistically significant variables in univariate regressions were performed to evaluate the associations between actigraphy-assessed sleep measures, inflammatory cytokines, and insulin resistance. RESULTS: The regression models showed that in women, higher sleep onset latency (SOL) was associated with higher insulin resistance after controlling for age, smoking, obesity, diabetes, depression, and inflammatory cytokines. Higher SOL was also associated with higher interleukin (IL)-6 and C-reactive protein (CRP) levels in women, but no association was found in men. Using mediation models in women, the association between SOL and insulin resistance was partially explained by the indirect effect of inflammatory cytokines. CONCLUSION: A combination of inflammation and other unidentified pathways may contribute to the relationship between disturbed sleep and glucose homeostasis.


Assuntos
Citocinas/sangue , Inflamação/fisiopatologia , Resistência à Insulina/fisiologia , Caracteres Sexuais , Sono/fisiologia , Actigrafia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Homeostase/fisiologia , Humanos , Inflamação/complicações , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Tempo , Estados Unidos
8.
Artigo em Inglês | MEDLINE | ID: mdl-27343360

RESUMO

The rate of hippocampal neurogenesis declines with aging. This is partly explained by decreased neural responsiveness to various cues stimulating metabolism. AMP-activated protein kinase (AMPK), a pivotal enzyme regulating energy homeostasis in response to metabolic demands, showed the diminished sensitivity in peripheral tissues during aging. AMPK is also known to be involved in neurogenesis. We aimed to see whether AMPK reactivity is also blunted in the aged hippocampus, and thus is associated with aging-related change in neurogenesis. Following subchronic (7days) intraperitoneal and acute intracerebroventricular (i.c.v.) administration of either 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR; AMPK activator) or saline (sham) to young (16-week-old) and old (72-week-old) mice, we measured changes in AMPK activity, brain-derived neurotrophic factor (BDNF) expression or neurogenesis in the hippocampus. AICAR-induced changes in AMPK activity were observed in the hippocampus of young mice after acute i.c.v. injection. However, neither subchronic nor acute treatment induced significant changes in AMPK activity in old mice. Intriguingly, directions of AICAR-induced changes in AMPK activity were opposite between the hippocampus (decrease) and skeletal muscle (increase). ATP levels were inversely correlated with hippocampal AMPK activity, suggesting that the higher energy levels achieved by AICAR treatment might deactivate neuronal AMPK in young mice. The blunted response of AMPK to AICAR in old age was also indicated by the observations that the levels of neurogenesis and BDNF expression were significantly changed only in young mice upon AICAR treatment. Our findings suggest that the blunted response of neuronal AMPK in old age might be responsible for aging-associated decline in neurogenesis. Therefore, in addition to activation of AMPK, recovering its sensitivity may be necessary to enhance hippocampal neurogenesis in old age.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Envelhecimento/patologia , Hipocampo/enzimologia , Hipocampo/fisiopatologia , Neurogênese/fisiologia , Trifosfato de Adenosina/metabolismo , Envelhecimento/efeitos dos fármacos , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Bromodesoxiuridina/metabolismo , Proteínas do Domínio Duplacortina , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Neurogênese/efeitos dos fármacos , Neuropeptídeos/metabolismo , Ribonucleotídeos/farmacologia
9.
Neuropsychobiology ; 73(2): 81-91, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27002982

RESUMO

OBJECTIVE: Donepezil, a widely prescribed drug for Alzheimer's disease (AD), is now considered to have multimodal actions beyond cholinesterase inhibition. We aimed to see whether donepezil enhances mitochondrial biogenesis and relevant signaling pathways since mitochondrial dysfunction is a key feature of the hypometabolic AD brain. METHODS: As a metabolic gauge, AMP-activated protein kinase (AMPK) was investigated as a tentative mediator of neurometabolic action of donepezil. Changes in phospho-AMPK levels, mitochondrial biogenesis, and ATP levels were measured upon donepezil treatment using neuroblastoma cells, primary cultured neurons and ex vivo hippocampal tissue of adult mice. RESULTS: Donepezil dose-dependently increased mitochondrial biogenesis and ATP levels as well as expression of PGC-1α and NRF-1 in neuroblastoma cells. Donepezil dose-dependently activated AMPK; however, inhibition of AMPK abolished the observed effects of donepezil, indicating that AMPK is a key mediator of donepezil's action. Notably, mitochondrial biogenesis upon donepezil treatment was mainly observed within dendritic regions of primary cultured hippocampal neurons. Levels of synaptic markers were also increased by donepezil. Finally, AMPK- dependent mitochondrial biogenesis by donepezil was confirmed in organotypic hippocampal tissue. CONCLUSIONS: Our findings indicate that AMPK/PGC-1α signaling is involved in beneficial actions of donepezil on neurometabolism. Pharmacological activation of AMPK might be a promising approach to counteract AD pathogenesis associated with brain hypometabolism.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Inibidores da Colinesterase/farmacologia , Hipocampo/efeitos dos fármacos , Indanos/farmacologia , Mitocôndrias/efeitos dos fármacos , Biogênese de Organelas , Piperidinas/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Linhagem Celular Tumoral , Dendritos/efeitos dos fármacos , Dendritos/metabolismo , Donepezila , Relação Dose-Resposta a Droga , Feminino , Hipocampo/metabolismo , Humanos , Masculino , Camundongos Endogâmicos ICR , Mitocôndrias/metabolismo , Fator 1 Nuclear Respiratório/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Técnicas de Cultura de Tecidos
10.
J Psychosom Res ; 80: 53-7, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26721548

RESUMO

OBJECTIVES: The Montreal Cognitive Assessment (MoCA) is a useful screening tool for mild cognitive impairment. We aimed to know whether the full MoCA and subsets of the full test are effective for detecting HIV-associated neurocognitive disorder (HAND). METHODS: We examined the socio-demographic, clinical, functional, and neuropsychological levels of 194 HIV-infected patients. We compared total scores and scores from each cognitive domain of MoCA between patients with and without HAND. We also examined the utility of subsets of the full test using a few selective domains. The diagnostic accuracies of MoCA and subset composition were evaluated. RESULTS: The total scores of MoCA (P<0.001) and scores from Trail Making Test-B (P=0.020), attention domain (P=0.005), and immediate (P=0.003) and delayed recall (P=0.002) differed between patients with and without HAND. A subset composed of Trail Making Test-B, rescored serial subtraction, and immediate/delayed recall showed a 69.2% accuracy. CONCLUSIONS: Our results suggest that the MoCA and its subsets alone are not sufficient in screening for HAND. Further studies will be needed to develop a simpler and easier screening tool for HAND based on this study.


Assuntos
Complexo AIDS Demência/diagnóstico , Complexo AIDS Demência/psicologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Testes Neuropsicológicos , Adulto , Atenção , Transtornos Cognitivos/etiologia , Função Executiva , Feminino , Infecções por HIV/psicologia , Humanos , Testes de Linguagem , Masculino , Programas de Rastreamento , Memória de Curto Prazo , Rememoração Mental , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores Socioeconômicos , Teste de Sequência Alfanumérica
11.
Psychiatry Res ; 234(3): 292-7, 2015 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-26602611

RESUMO

The biological underpinnings of the psychological factors characterizing chronic fatigue syndrome (CFS) have not been extensively studied. Our aim was to evaluate alterations of resting-state functional connectivity in CFS patients. Participants comprised 18 women with CFS and 18 age-matched female healthy controls who were recruited from the local community. Structural and functional magnetic resonance images were acquired during a 6-min passive-viewing block scan. Posterior cingulate cortex seeded resting-state functional connectivity was evaluated, and correlation analyses of connectivity strength were performed. Graph theory analysis of 90 nodes of the brain was conducted to compare the global and local efficiency of connectivity networks in CFS patients with that in healthy controls. The posterior cingulate cortex in CFS patients showed increased resting-state functional connectivity with the dorsal and rostral anterior cingulate cortex. Connectivity strength of the posterior cingulate cortex to the dorsal anterior cingulate cortex significantly correlated with the Chalder Fatigue Scale score, while the Beck Depression Inventory (BDI) score was controlled. Connectivity strength to the rostral anterior cingulate cortex significantly correlated with the Chalder Fatigue Scale score. Global efficiency of the posterior cingulate cortex was significantly lower in CFS patients, while local efficiency showed no difference from findings in healthy controls. The findings suggest that CFS patients show inefficient increments in resting-state functional connectivity that are linked to the psychological factors observed in the syndrome.


Assuntos
Mapeamento Encefálico , Síndrome de Fadiga Crônica/fisiopatologia , Giro do Cíngulo/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Descanso/fisiologia , Adulto , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Síndrome de Fadiga Crônica/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia
12.
Neuroreport ; 26(7): 424-8, 2015 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-25839176

RESUMO

Reduced glucose metabolism has been implicated as a pathophysiology of depressive disorder. Normalization of such impaired neurometabolism has been related to the therapeutic actions of antidepressant medication. However, the molecular mechanism underlying the neurometabolic actions of antidepressants has not been fully understood. Given that AMP-activated protein kinase (AMPK) is a master switch for energy homeostasis, we aimed to determine whether selective serotonin reuptake inhibitor paroxetine enhances energy metabolism by activating AMPK in neuroblastoma cells. We found that paroxetine dose dependently increased mitochondrial biogenesis, which involves the AMPK-peroxisome proliferator-activated receptor-γ coactivator-1α pathway. In addition, paroxetine-induced AMPK activation increases glucose uptake and ATP production. These neurometabolic effects of paroxetine were suppressed by cotreatment with compound C (CC), an AMPK inhibitor. These findings suggest a possibility that modulation of the AMPK pathway might be a previously unrecognized mechanism underlying the neurometabolic action of antidepressants. Further study is warranted to examine the region-specific and time-specific effects of AMPK modulation by antidepressants on mood-related behaviors.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antidepressivos/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Paroxetina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Trifosfato de Adenosina/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Metabolismo Energético/efeitos dos fármacos , Glucose/metabolismo , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fatores de Transcrição/metabolismo
13.
J Alzheimers Dis ; 42(2): 421-33, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24898638

RESUMO

Discovery of biomarkers in peripheral blood is a crucial step toward the early diagnosis and repetitive monitoring of treatment response for Alzheimer's disease (AD). Metabolomics is a promising technology that can identify unbiased biomarkers. To explore potential blood biomarkers for AD via metabolic profiling with high-resolution magic angle spinning nuclear magnetic resonance techniques, we identified changes in peripheral blood metabolomic profiles in response to amyloid-ß (Aß)-induced neuroinflammation and co-treatment with gallate, a phytochemical known to have anti-neuroinflammatory properties. Alzheimer's-like (AL) model mice were produced by intracerebroventricular infusion of Aß and compared with normal control mice with infusion of vehicle. AL mice were treated with either gallate (treated AL mice) or vehicle (untreated AL mice). Metabolomic analyses of both whole blood and plasma showed a clear separation between untreated AL mice and the other two groups, with levels of several metabolites involved in energy metabolism, including pyruvate and creatine, being significantly reduced in untreated AL mice compared with control and treated AL mice. Gallate treatment suppressed Aß-induced overproduction of the inflammatory cytokine tumor necrosis factor-α in the hippocampus and normalized plasma levels of the affected metabolites. These results suggest that plasma levels of several metabolites could be indicative of both brain pathology and therapeutic responses, supporting the possibility of a close relationship between central neuroinflammation and systemic metabolic disturbance. These findings also suggest the potential of NMR-based metabolomics as a method to identify novel plasma biomarkers for AD, which could be confirmed by future translational research with human patients.


Assuntos
Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/complicações , Encefalite/sangue , Encefalite/etiologia , Fator de Necrose Tumoral alfa/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Encefalite/tratamento farmacológico , Encefalite/patologia , Ácido Gálico/uso terapêutico , Células HEK293 , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Endogâmicos ICR , Análise Multivariada , Fragmentos de Peptídeos/toxicidade , Análise de Componente Principal , Ácido Pirúvico/sangue , Transfecção , Trítio
14.
J Psychosom Res ; 77(1): 76-80, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24913346

RESUMO

OBJECTIVE: Coping with cancer is an important determinant of psychological morbidity, quality of life, and treatment adherence in cancer patients. The aim of this study was to elucidate the association between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and coping response to stress in patients diagnosed with advanced gastric cancer. METHODS: Ninety-one subjects (60 males, 31 females) recently diagnosed with advanced gastric cancer were recruited. Coping style and distress level were examined using the Mini-Mental Adjustment to Cancer (Mini-MAC) scale and Hospital Anxiety and Depression Scale, and genotyping was evaluated. To examine the temporal stability of the Mini-MAC scores, a 6-week follow-up evaluation was conducted in 72 patients, after completion of two chemotherapy cycles. RESULTS: Coping style to cancer significantly differed between the Met carriers of BDNF Val66Met and the Val/Val homozygotes. The Met carriers were significantly more anxious than the Val/Val homozygotes. CONCLUSION: The present findings suggest that the BDNF Val66Met polymorphism may be involved in individual coping responses to cancer. The Met allele of BDNF Val66Met may be predictive of an anxious coping style in patients with advanced cancer.


Assuntos
Adaptação Psicológica , Fator Neurotrófico Derivado do Encéfalo/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/patologia , Neoplasias Gástricas/psicologia , Alelos , Ansiedade/genética , Feminino , Seguimentos , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética
15.
Asian Pac J Cancer Prev ; 13(3): 1003-10, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22631628

RESUMO

BACKGROUND: This study examined the influence of body mass index (BMI), subjective body perception (SBP), and the differences between BMI and SBP influence on smoking among women. METHODS: This study used the Korea National Health and Nutrition Examination Survey IV-2, 3 2008-2009. A urinary cotinine test was administered to 5485 women at least 19 years of age. Individuals whose cotinine level was at least 50 ng/mL were categorized as smokers. A multiple logistic regression analysis was performed to estimate the extent to which body-related variables affect female smoking. RESULTS: Women with a lower BMI who perceived themselves to be normal or very fat were 2.09 times (1.14-3.83) more likely to smoke than women with a normal BMI and SBP. Women who were never married with a low BMI and thin SBP were 3.11 times (1.47-6.55) more likely to smoke than women with a normal BMI and SBP. Married women with a high BMI who considered themselves very fat were 0.63 times (0.43-0.94) less likely to smoke than women with a normal BMI and SBP. In contrast, divorced and widowed women with a low or normal BMI who considered themselves very fat were 26.1 times (1.35-507.3) more likely to smoke. CONCLUSIONS: Discrepancies between the objective physical condition (BMI) and the subjective body image (SBP) influence the female smoking rate. To reduce the number of female smokers, public education on the association between smoking behavior and weight issues is needed, especially among women with low BMI and distorted weight perception.


Assuntos
Imagem Corporal , Índice de Massa Corporal , Cotinina/urina , Fumar/epidemiologia , Adulto , Idoso , Peso Corporal , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade , República da Coreia/epidemiologia , Adulto Jovem
16.
Psychoneuroendocrinology ; 37(9): 1569-76, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22459275

RESUMO

Cancer patients, who have to adapt to a long treatment process with multiple stressful events, show various stress responses. Genetic components may contribute to individual differences in stress response and risk for development of stress-related psychiatric problems. The present study aimed to investigate the influence of FK506 binding protein 5 (FKBP5) gene polymorphisms regulating the hypothalamic-pituitary-adrenal (HPA) axis on individual distress levels in cancer patients faced with similar stressful situation. The present study used a prospective design to elucidate predictors of distress. A total of 130 patients (90 males, 40 females) who were newly diagnosed with advanced gastric cancer and supposed to receive first-line chemotherapy were initially assessed, and a six-week follow-up assessment occurred for 93 patients (63 males, 30 females) after two cycles of chemotherapy. Distress levels and coping patterns were measured by the Hospital Anxiety and Depression Scale (HADS) and Mini-Mental Adjustment to Cancer (Mini-MAC) scale. For genetic factors, three single nucleotide polymorphisms of FKBP5 rs1360780, rs9296158 and rs9470080 were genotyped. For HADS-anxiety, FKBP5 rs9296158 had a significant group-by-time interaction (p=0.015), and rs9470080 and rs1360780 had a marginally significant interaction (p=0.023, p=0.038, respectively). For HADS-depression, rs9470080 and rs9296158 had a marginally significant group-by-time interaction (p=0.026, p=0.032, respectively). In addition, a step-wise linear regression analysis showed that FKBP5 rs9470080 and rs9296158 were significant predictors of anxiety and depression after prolonged stress exposure in cancer patients. Our findings indicate that the genetic factors regulating the HPA axis such as FKBP5 gene polymorphisms may play a crucial role in anxiety and depression following prolonged stress exposure.


Assuntos
Ansiedade/genética , Depressão/genética , Neoplasias Gástricas/complicações , Estresse Psicológico/genética , Proteínas de Ligação a Tacrolimo/genética , Adaptação Psicológica , Adulto , Idoso , Alelos , Ansiedade/complicações , Ansiedade/fisiopatologia , Depressão/complicações , Depressão/fisiopatologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/fisiopatologia , Polimorfismo de Nucleotídeo Único , Escalas de Graduação Psiquiátrica , Neoplasias Gástricas/fisiopatologia , Neoplasias Gástricas/psicologia , Estresse Psicológico/complicações , Estresse Psicológico/fisiopatologia
17.
Support Care Cancer ; 20(9): 2177-82, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22134442

RESUMO

BACKGROUND: Nearly 50% of women with breast cancer show depressive symptoms after diagnosis and treatment. The purpose of this study was to clarify how psychosocial factors (body image, sexuality, and social relationships) and genetic factors (functional polymorphism of the serotonin transporter-linked promoter region) influence depression. METHODS: The participants were categorized by DSM-IV diagnoses; scored according to their depressive symptoms, body image and social and sexual function (BIRS), self-esteem, and quality of life; and genotyped by functional polymorphism of the serotonin transporter promoter. RESULTS: Patients with depressive symptoms showed low self-esteem, poor body image, relationship problems, and low quality of life. Genotype frequencies did not differ between two groups categorized by the presence or absence of depressive symptoms. However, the patients with the short allele of the 5-HTTLPR had significantly higher HAM-D scores (F = 7.59, p = 0.047). CONCLUSION: The results suggest that psychosocial factors related to breast cancer treatment such as body image, self-esteem, and interpersonal relationship influence the development of depressive symptoms. The 5-HTTLPR may be associated with the severity of depressive symptoms rather than susceptibility to the development of depressive symptoms.


Assuntos
Imagem Corporal/psicologia , Neoplasias da Mama/psicologia , Depressão/psicologia , Polimorfismo Genético , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Sexualidade/psicologia , Alelos , Feminino , Técnicas de Genotipagem , Humanos , Pessoa de Meia-Idade , República da Coreia , Autoimagem , Inquéritos e Questionários
18.
Psychoneuroendocrinology ; 37(3): 358-65, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21813245

RESUMO

Metabolic and cognitive disorders are closely related. However, the molecular mechanism underlying this association is still elusive. Given the importance of energy metabolism in neuronal cells, AMP-activated protein kinase (AMPK), a master switch of energy metabolism, could be an independent factor affecting cognitive as well as metabolic functions. Therefore, we examined the relationship between the AMPK γ2 gene, the PRKAG2 -26C/T polymorphism and cognitive impairment or diabetes in 1609 subjects aged from 60 to 80. We performed multivariate logistic regression analyses with adjustment for age, gender, education, smoking, alcohol, depression, waist circumference, APOE e4, and stroke history. We found a significant association between the -26C/T polymorphism (CC vs. CT/TT) and cognitive impairment (OR, 1.6; 95% CI, 1.1-2.3). Moreover, this polymorphism (CC/CT vs. TT) was also related to the presence of diabetes (OR, 1.8; 95% CI, 1.2-2.8). Importantly, the relationship with cognitive impairment was still significant in non-diabetic individuals (OR, 1.6; 95% CI, 1.1-2.4). Further analyses with a subpopulation (n=611) revealed that CC homozygotes relative to T-allele carriers had significantly better performances in verbal memory and attentional tasks. These findings collectively support a hypothesis that AMPK has a role not only in metabolic functioning but also in cognitive functioning in humans. Extended longitudinal study with a larger number of samples is warranted.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Transtornos Cognitivos/genética , Diabetes Mellitus/genética , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Estudos de Associação Genética/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Desempenho Psicomotor
19.
Gen Hosp Psychiatry ; 33(3): 246-52, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21601721

RESUMO

OBJECTIVES: This study primarily aimed to investigate the prevalence and associated factors of psychological distress among Korean cancer patients. Its secondary objective was to classify mental illnesses among cancer patients with significant psychological distress. METHODS: We administered the Modified Distress Thermometer (MDT), Hospital Anxiety and Depression Scale (HADS), and Center for Epidemiologic Studies-Depression Scale (CES-D) to consecutive, newly diagnosed cancer patients and conducted subsequent psychiatric interviews. A multiple logistic regression produced a discriminate profile of individuals with psychological distress. RESULTS: Among 295 participants, 85 (28.8%) were identified as patients with psychological distress. Female gender [odds ratio (OR)=1.97], low educational level (OR=2.25) and low performance status (OR=4.10) were significantly associated with this condition. Among the 38 patients with psychological distress who received psychiatric assessment, the most common mental illness was adjustment disorder (n=23, 69.7%). CONCLUSION: The results of this study showed that approximately one-third of the cancer patients suffered from psychological distress. We recommend that physicians focus on the psychological status of female cancer patients with low levels of education and poor performance status.


Assuntos
Neoplasias/psicologia , Estresse Psicológico/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Entrevista Psicológica , Entrevistas como Assunto , Modelos Logísticos , Masculino , Transtornos Mentais , Pessoa de Meia-Idade , Razão de Chances , República da Coreia/epidemiologia , Adulto Jovem
20.
Psychooncology ; 17(6): 592-7, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17957732

RESUMO

Mental adjustment and coping affect the physical outcome and survival as well as quality of life in cancer patients. The Mini-Mental Adjustment to Cancer (Mini-MAC) scale is a new refined, economical and reliable self-rating instrument measuring cognitive and behavioral responses to cancer. The aim of this study was to evaluate the psychometric properties of the Mini-MAC in Korean cancer patients. A total of 208 cancer patients recruited from the Yonsei Cancer Center were assessed with the Mini-MAC and the Hospital Anxiety and Depression Scale (HADS). Principal component analysis with varimax rotation for the Korean version of Mini-MAC (K-Mini-MAC) confirmed four factors. Three had psychometric properties similar to Helpless-Hopeless (HH), Anxious Preoccupation (AP) and Cognitive Avoidance (CA) of the original Mini-MAC. A novel factor, named Positive Attitude, included items of both Fatalism (FA) and Fighting Spirit (FS) from the original version. The five subscales from the original version (AP, HH, FS, FA and CA) and Positive Attitude had acceptable internal reliabilities in our sample (Cronbach's alpha coefficient 0.50-0.86; correlation coefficient of test-retest 0.68-0.88). For the validity, significant interscale correlation was observed in the original five subscales and Positive Attitude. Each subscale including Positive Attitude was also significantly related to Depression and Anxiety of HADS. As a whole, the K-Mini-MAC was a reliable, valid and acceptable tool for Korean cancer patients. These findings can provide information about the cross-cultural validity of Mini-MAC scale's factor structure. Cultural differences were also discussed.


Assuntos
Adaptação Psicológica , Comparação Transcultural , Neoplasias/psicologia , Inventário de Personalidade/estatística & dados numéricos , Papel do Doente , Atividades Cotidianas/psicologia , Adulto , Idoso , Ansiedade/diagnóstico , Ansiedade/psicologia , Aprendizagem da Esquiva , Neoplasias da Mama/psicologia , Neoplasias Colorretais/psicologia , Cultura , Mecanismos de Defesa , Feminino , Desamparo Aprendido , Humanos , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Psicometria/estatística & dados numéricos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Tradução
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