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1.
Medicine (Baltimore) ; 100(8): e24581, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663067

RESUMO

ABSTRACT: Major depressive disorder (MDD) is a common disease with both affective and cognitive disorders. Alterations in metabolic systems of MDD patients have been reported, but the underlying mechanisms still remains unclear. We sought to identify abnormal metabolites in MDD by metabolomics and to explore the association between differential metabolites and neurocognitive dysfunction.Plasma samples from 53 MDD patients and 83 sex-, gender-, BMI-matched healthy controls (HCs) were collected. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was then used to detect metabolites in those samples. Two different algorithms were applied to identify differential metabolites in 2 groups. Of the 136 participants, 35 MDD patients and 48 HCs had completed spatial working memory test. Spearman rank correlation coefficient was applied to explore the relationship between differential metabolites and working memory in these 2 groups.The top 5 metabolites which were found in sparse partial least squares-discriminant analysis (sPLS-DA) model and random forest (RF) model were the same, and significant difference was found in 3 metabolites between MDD and HCs, namely, gamma-glutamyl leucine, leucine-enkephalin, and valeric acid. In addition, MDD patients had higher scores in spatial working memory (SWM) between errors and total errors than HCs. Valeric acid was positively correlated with working memory in MDD group.Gamma-glutamyl leucine, leucine-enkephalin, and valeric acid were preliminarily proven to be decreased in MDD patients. In addition, MDD patients performed worse in working memory than HCs. Dysfunction in working memory of MDD individuals was associated with valeric acid.


Assuntos
Transtorno Depressivo Maior/sangue , Memória de Curto Prazo/fisiologia , Navegação Espacial/fisiologia , Adolescente , Adulto , Fatores Etários , Algoritmos , Índice de Massa Corporal , Cromatografia Líquida , Transtorno Depressivo Maior/fisiopatologia , Dipeptídeos/sangue , Encefalina Leucina/sangue , Feminino , Humanos , Masculino , Metabolômica , Pessoa de Meia-Idade , Ácidos Pentanoicos/sangue , Escalas de Graduação Psiquiátrica , Fatores Sexuais , Espectrometria de Massas em Tandem , Adulto Jovem
2.
J Couns Psychol ; 67(4): 523-535, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32614232

RESUMO

The therapeutic alliance is one of the most consistent predictors of therapeutic change, including symptom reduction and improvement in wellbeing and quality of life, across a variety of mental health interventions. Yet, little is known about its biological mechanisms. Oxytocin (OT) has been suggested as a biological mechanism by which bonds are formed and strengthened across species. This article is intended to demonstrate the potential of OT as a biomarker of therapeutic change in psychotherapy and counseling psychology, especially of the therapeutic alliance. We delineate three main potential paths of investigation based on the most recent research on OT in parent-child and romantic partner dyads. For each path, we provide a detailed explanation for whom, when, and how OT should be measured. Each path is illustrated using data collected in a randomized controlled trial of psychotherapy for major depressive disorder. These illustrations demonstrate the great potential of OT as a biomarker of (a) trait-like characteristics of the patients and the therapists, (b) the processes of therapeutic change, and (c) the dyadic synchrony between patients and their therapists. The potential clinical contribution of OT as a biomarker for each of these three paths is further demonstrated using a case study. Practical suggestions and directions for future research are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Aconselhamento/métodos , Ocitocina/sangue , Psicoterapia/métodos , Aliança Terapêutica , Biomarcadores/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Maior/terapia , Feminino , Humanos , Masculino , Relações Profissional-Paciente , Qualidade de Vida/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
3.
BMC Psychiatry ; 20(1): 333, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32580709

RESUMO

BACKGROUND: The alterations of biological markers are thought to be effective tools to understand the pathophysiology and management of major depressive disorder (MDD). A lot of researches has implied many markers for depression, but any of them fully discovered the association between the markers and depression. The present study investigated the serum levels of amino acids and non-enzymatic antioxidants in major depression, and also explained their association with depression. METHODS: This study examined 247 MDD patients and 248 healthy controls (HCs) matched by age and sex. The Hamilton Depression Rating Scale (Ham-D) was used to all the participants to measure the severity of depression. Quantification of serum amino acids, vitamin A and E were carried out using the HPLC system whereas vitamin C levels were measured by UV-spectrophotometer. All the statistical analysis was performed by SPSS statistical software (version 23.0). The independent sample t-test, the Mann-Whitney U test, and the Fisher's exact test were applied to detect the group differences where a Bonferroni correction applied to the p value. RESULTS: It was observed that serum levels of four amino acids (methionine, phenylalanine, tryptophan, and tyrosine) along with three non-enzymatic antioxidants (vitamin A, E, and C) were significantly dropped in MDD patients compared to HCs (Cohen's d (d): - 0.45, - 0.50, - 0.68, - 0.21, - 0.27, - 0.65, and - 0.24, respectively). Furthermore, Ham-D scores of cases were negatively correlated with serum levels of methionine (r = - 0.155, p = 0.015) and tyrosine (r = - 0.172, p = 0.007). CONCLUSION: The present study suggests that lowered serum methionine, phenylalanine, tryptophan, tyrosine, and non-enzymatic antioxidants are associated with depression. The reduction of these parameters in MDD patients may be the consequence, and not the cause, of major depression.


Assuntos
Aminoácidos/sangue , Antioxidantes/análise , Transtorno Depressivo Maior/sangue , Adolescente , Adulto , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
BMC Psychiatry ; 20(1): 208, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32384884

RESUMO

BACKGROUND: IGF-1 is an essential neurotrophin produced peripherally and in the brain. Impairments in the brain IGF-1 concentrations might be responsible for some aspects of major depressive disorder (MDD) pathogenesis, whereas peripheral IGF-1 could have the marker value. We aimed: 1) to compare serum IGF-1 levels in MDD patients and healthy controls (HC); 2) to elucidate possible associations between changes in IGF-1 expression and crucial characteristics of the current depressive episode, MDD course; 3) to evaluate IGF-1 dynamics after 8 weeks` vortioxetine treatment. METHODS: Seventy-eight MDD patients (according to DSM-5) and 47 HC were enrolled. Serum IGF-1, psychopathological (MADRS, CGI) and neuropsychological parameters (PDQ-5, RAVLT, TMT-B, DSST) were analyzed in all subjects at admission and 48 patients after 8 weeks` vortioxetine treatment. AUC-ROCs were calculated to determine if the value of serum IGF-1 could separate MDD patients from HC. Multiple regression models were performed to explore relationships between IGF-1 and depressive episode's symptoms. RESULTS: MDD patients had significantly higher serum IGF-1 levels than HC (228 (183-312) ng/ml vs 153 (129-186) ng/ml, p < 0.0001). IGF-1 had a good diagnostic value for predicting MDD in the whole sample with AUC of 0.820 (p < 0.0001). For a cutoff of 178.00 ng/ml, the sensitivity and specificity were 83 and 71%, respectively, and the number needed to misdiagnose was 5, indicating that only 1 of 5 tests give an invalid result. Among MADRS items, only reported sadness, inner tension, and concentration difficulties were significantly positively associated with serum IGF-1 concentrations. Vortioxetine treatment significantly attenuated IGF-1 levels and improved all psychopathological, neuropsychological parameters. CONCLUSIONS: Significant associations between IGF-1 levels and hypothymia, anxiety, and cognitive disturbances may indicate a pathogenic role of IGF-1 for the mentioned symptoms. We assume that the activity of the cerebral-hepatic axis increases in response to insufficient IGF-1 brain expression in MDD patients, whereas, vortioxetine treatment restores cerebral IGF-1 concentrations and, consequently, decreases its compensatory production by the liver. TRIAL REGISTRATION: registered at ClinicalTrials.gov (NCT03187093). First posted on 14th June 2017.


Assuntos
Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Fator de Crescimento Insulin-Like I/metabolismo , Vortioxetina/uso terapêutico , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Transtorno Depressivo Maior/sangue , Método Duplo-Cego , Feminino , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Reprodutibilidade dos Testes , Resultado do Tratamento
5.
J Neuroimmunol ; 344: 577250, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32344162

RESUMO

The properties of CD4+CD25hi T regulatory cells (Tregs), and interleukin (IL)-2 pathway were investigated in major depressive disorder (MDD) patients treated with or without selective serotonin reuptake inhibitor (SSRI). The frequencies of FOXP3 and pSTAT5 in peripheral Tregs were found to be diminished in untreated patients (SSRI-) versus HCs (p < .001 for both), while their percentages were increased in treated patients (SSRI+) versus untreated patients (p < .001 and p = .04). The proliferation of CD4+ T cells was higher in SSRI-MDD patients versus HCs (p = .03). The SSRI-MDD patients showed a lower concentration of supernatant TGF-ß than HCs (p = .001), while the production of TGF-ß was enhanced in SSRI+MDD versus SSRI-MDD patients (p = .003). The number of CD45RA-expressing Tregs, the expression of JAK1 and JAK3, and the levels of IL-2 and IL-10 were similar between the patients and HCs. The study results showed that untreated patients have an impaired IL-2 signaling pathway and defective Tregs, and SSRI treatment may improve the Tregs function.


Assuntos
Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Linfócitos T Reguladores/metabolismo , Adulto , Células Cultivadas , Feminino , Humanos , Interleucina-2/sangue , Masculino , Inibidores de Captação de Serotonina/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos
6.
BMC Psychiatry ; 20(1): 145, 2020 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245436

RESUMO

BACKGROUND: Major depressive disorder and bipolar disorder are prevalent and debilitating psychiatric disorders that are difficult to distinguish, as their diagnosis is based on behavioural observations and subjective symptoms. Quantitative protein profile analysis might help to objectively distinguish between these disorders and increase our understanding of their pathophysiology. Thus, this study was conducted to compare the peripheral protein profiles between the two disorders. METHODS: Serum samples were collected from 18 subjects with major depressive disorder and 15 subjects with bipolar disorder. After depleting abundant proteins, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and label-free quantification were performed. Data-dependent acquisition data were statistically analysed from the samples of 15 subjects with major depressive disorder and 10 subjects with bipolar disorder who were psychotropic drug-free. Two-sided t-tests were performed for pairwise comparisons of proteomes to detect differentially-expressed proteins (DEPs). Ingenuity Pathway Analysis of canonical pathways, disease and functions, and protein networks based on these DEPs was further conducted. RESULTS: Fourteen DEPs were significant between subjects with major depressive disorder and those with bipolar disorder. Ras-related protein Rab-7a (t = 5.975, p = 4.3 × 10- 6) and Rho-associated protein kinase 2 (t = 4.782, p = 8.0 × 10- 5) were significantly overexpressed in subjects with major depressive disorder and Exportin-7 (t = -4.520, p = 1.5 × 10- 4) was significantly overexpressed in subjects with bipolar disorder after considering multiple comparisons. Bioinformatics analysis showed that cellular functions and inflammation/immune pathways were significantly different. CONCLUSIONS: Ras-related protein Rab-7a, Rho-associated protein kinase 2, and Exportin-7 were identified as potential peripheral protein candidates to distinguish major depressive disorder and bipolar disorder. Further large sample studies with longitudinal designs and validation processes are warranted.


Assuntos
Transtorno Bipolar/sangue , Proteínas Sanguíneas/metabolismo , Transtorno Depressivo Maior/sangue , Adulto , Biomarcadores/sangue , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/metabolismo , Cromatografia Líquida , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/metabolismo , Feminino , Humanos , Masculino , Espectrometria de Massas em Tandem
7.
J Psychosom Res ; 133: 110105, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32272297

RESUMO

BACKGROUND: The complement system is involved in multiple biological processes including inflammation, synaptic pruning, and apoptosis. However, it is not well understood whether peripheral complement C1q levels are altered in major depressive disorder (MDD) patients. OBJECTIVE: This study aimed at assessing serum levels of complement C1q in MDD patients using a cross-sectional, case-control design. Also, the correlations between complement C1q and inflammation and lipid profile in patients with MDD were also assessed. METHODS: Serum complement C1q levels were measured by ADVIA 2400 biochemical analyzer in 160 patients with MDD diagnosed using International Classification of Diseases-10 criteria (ICD-10) and were compared with those of 159 healthy controls between January 2017 to May 2019. Then correlation analysis was carried out between the level of serum complement C1q among MDD patients with inflammation and lipid profile. RESULTS: Serum complement C1q levels were higher in MDD patients than in controls (P < .0001) and the difference between the two groups was small (r = 0.239 [0.128 to 0.350]). We found that serum complement C1q concentrations was positively correlated with HAMD-24 score (r = 0.234, P = .003) and log hs-CRP (r = 0.334, P < .001). CONCLUSION: We found serum complement C1q levels were significantly higher in MDD patients than in controls. The current results suggest that the dysfunction of complement C1q may be involved in the pathophysiology of MDD.


Assuntos
Complemento C1q/metabolismo , Transtorno Depressivo Maior/sangue , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
PLoS One ; 15(3): e0229626, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130258

RESUMO

OBJECTIVE: We aimed to investigate the difference in serum uric acid(SUA)levels between subtypes of depression and normal population, and whether SUA can be used to identify bipolar disorder depressive episode and major depressive disorder and predict the length of hospital stay. METHODS: 1543 depression patients and 1515 healthy controls were obtained according to the entry and exclusion criteria from one mental health center of a tertiary hospital in southwestern China. The diagnosis and classification of depression was in accordance with ICD-10. The SUA value was derived from fasting plasma samples analysis. The level of SUA of all the participants was quantified using Roche cobas8000-c702-MSB automatic biochemical analyzer. Data were analyzed by SPSS18.0 statistical software package. RESULTS: Overall, the level of SUA in patients with depression was lower than that in normal control. Specifically, males' SUA levels were in the interval of [240, 323.3) and [323.3, 406.6), and women were in the [160, 233.3] levels. The SUA level of bipolar disorder depressive episode was higher compared to major depressive disorder level. Interestingly, male patients who were hospitalized for two weeks had higher SUA than those who were hospitalized for three weeks or four weeks. CONCLUSIONS: Our results suggest that the length of hospital stay may be associated with SUA, and when it is difficult to make a differential diagnosis of bipolar disorder depressive episode and major depressive disorder, the level of SUA may be considered. The adjustment of SUA as a method for treating depression needs to be carefully assessed.


Assuntos
Depressão/sangue , Ácido Úrico/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Transtorno Bipolar/sangue , Estudos de Casos e Controles , China , Depressão/classificação , Transtorno Depressivo Maior/sangue , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Adulto Jovem
9.
BMC Res Notes ; 13(1): 83, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32085720

RESUMO

OBJECTIVE: We do not have any consistent markers for major depressive disorder (MDD) though various biological factors are involved in the pathophysiology. We aimed to evaluate the serum brain-derived neurotrophic factor (BDNF) levels in MDD patients with or without antidepressant therapy compared to healthy controls (HCs). RESULTS: We assessed serum BDNF levels among three groups: drug-naïve MDD patients (n = 41), drug-treated MDD patients (n = 44), and age-and sex-matched HCs (n = 82). Serum BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA) kit. Serum levels of BDNF were detected significantly lower in drug-naïve MDD patients compared to HCs. No significant alterations of serum BDNF levels between drug-treated patients and HCs were identified. Significant negative correlations between serum BDNF levels and Hamilton depression rating (Ham-D) scores were observed in both drug-naïve and drug-treated MDD patients. Receiver operating characteristic (ROC) analysis showed good diagnostic value for serum BDNF levels in drug-naïve MDD patients with the area under the curve at 0.821. The present study suggests that low serum BDNF levels may be involved in the pathophysiology of MDD. The reduced serum BDNF levels might be used as an early risk assessment marker for major depression.


Assuntos
Antidepressivos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Adulto , Estudos de Casos e Controles , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Masculino , Curva ROC , Fatores de Risco
10.
Sci Rep ; 10(1): 1961, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029791

RESUMO

Previous reports have shown that during chronic inflammation, the tryptophan (TRP)-kynurenine (KYN) pathway plays a pivotal role in the onset of depression. The aim of this study was to investigate the characteristics of the serum TRP-KYN pathway metabolite profile in high-risk subjects of major depressive disorder (HRMDD) defined by depression scores. The concentrations of TRP-KYN pathway metabolites {TRP, KYN, 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), kynurenic acid (KYNA) and anthranilic acid (AA)} were assessed in serum from HRMDD, chronic pain disorder patients and healthy controls. In serum from HRMDD, elevated levels of AA and decreased levels of TRP were observed, but the levels of other metabolites were not changed. Furthermore, the change in the AA2nd/AA1st ratio in subjects who progressed from a health. y state to a depressive state was correlated with an increase in the CES-D score. The level of IL-1 receptor antagonist (IL-1RA) was negatively correlated with that of AA. Interestingly, we confirmed AA as a possible biomarker for depression-related symptoms, since the metabolite profiles in the chronic pain disorder group and chronic unpredictable mild stress model mice were similar to those in the HRMDD. These results suggest that AA may be an effective marker for HRMDD.


Assuntos
Dor Crônica/diagnóstico , Transtorno Depressivo Maior/diagnóstico , Estresse Psicológico/diagnóstico , ortoaminobenzoatos/sangue , Ácido 3-Hidroxiantranílico/análise , Ácido 3-Hidroxiantranílico/metabolismo , Adulto , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Casos e Controles , Dor Crônica/sangue , Dor Crônica/metabolismo , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/metabolismo , Modelos Animais de Doenças , Feminino , Voluntários Saudáveis , Humanos , Proteína Antagonista do Receptor de Interleucina 1/sangue , Ácido Cinurênico/sangue , Ácido Cinurênico/metabolismo , Cinurenina/análogos & derivados , Cinurenina/sangue , Cinurenina/metabolismo , Masculino , Metaboloma , Camundongos , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estresse Psicológico/sangue , Estresse Psicológico/metabolismo , Triptofano/metabolismo , ortoaminobenzoatos/metabolismo
11.
Psychiatry Res ; 284: 112690, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31757642

RESUMO

OBJECTIVE: We aimed to study the association among venlafaxine antidepressive outcome, NR3C2 gene polymorphisms and the change of two neuroendocrine hormones during treatment. METHODS: 195 Chinese Han major depressive disorder (MDD) patients were recruited and received a 6-week venlafaxine treatment in this study. Adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH) levels were measured at the beginning and at the end of treatment. Six single-nucleotide polymorphisms (SNPs) (NR3C2: rs1512325, rs1512342, rs2070951; NR3C1: rs6191, rs6196, rs10482614) were selected for high-throughput SNP genotyping. Allele and genotype frequencies of them were compared between remission and non-remission groups. RESULTS: We found that genotype frequency of the rs1512325 located in the NR3C2 gene was significantly different between remission and non-remission groups respectively (p < 0.05). Meanwhile, the frequency of the rs1512325 C-allele was significantly lower (p < 0.05) in remission group. The TSH concentration significantly increased after venlafaxine treatment in remission group (p < 0.05). CONCLUSION: The rs1512325 in NR3C2 gene and TSH concentration may be related to venlafaxine treatment outcome in Chinese Han MDD patients.


Assuntos
Antidepressivos/farmacologia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Receptores de Mineralocorticoides/efeitos dos fármacos , Cloridrato de Venlafaxina/farmacologia , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Transtorno Depressivo Maior/sangue , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Receptores de Mineralocorticoides/genética , Tireotropina/sangue , Resultado do Tratamento
12.
Biochem Biophys Res Commun ; 523(2): 405-410, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-31866009

RESUMO

Although the current evidences may suggest that the 25(OH)D associated with depression, still there exists conflicting results. In addition, little known is concerning the relationship between the 25(OH)D and the chronic stress-induced depressive-like behaviors. We detected the 25(OH)D levels in serum and the VDR protein expression in different brain regions aiming to explore the relationship between 25(OH)D/VDR signaling and major depression. The chemiluminescent microparticle immunoassay (CMIA) was used to detect the serum concentration of 25(OH)D in patients, the enzyme-linked immunosorbent assay (ELISA) was applied to measure the serum 25(OH)D levels in both CRS-treated and CSDS-treated mice models of MDD. Meanwhile, the VDR protein expression levels were validated among three MDD related brain regions from CRS-treated mice by western blotting. In this study, we mainly observed that the concentration of the 25(OH)D was decreased in the serum of MDD patients comparing to healthy controls. Consistent with the clinical findings, the CRS-treated mice also displayed down-regulated 25(OH)D level comparing with control mice. While in the CSDS model, the serum 25(OH)D status of depressive mice remained unchanged. Moreover, we found the protein level of VDR was significantly decreased in the hippocampus while increased in the hypothalamus of CRS-treated mice. Nevertheless, the prefrontal cortex exhibited no change regarding VDR protein expression compared with control mice. Taken together, these findings further confirmed that the 25(OH)D together with VDR may involve in the pathophysiological mechanism of depression-like behaviors induced by chronic stress.


Assuntos
Encéfalo/metabolismo , Transtorno Depressivo Maior/metabolismo , Receptores de Calcitriol/metabolismo , Vitamina D/análogos & derivados , Adulto , Animais , Estudos de Casos e Controles , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/etiologia , Modelos Animais de Doenças , Feminino , Hipocampo/metabolismo , Humanos , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Restrição Física , Transdução de Sinais , Estresse Fisiológico , Estresse Psicológico , Distribuição Tecidual , Vitamina D/sangue , Vitamina D/metabolismo
13.
Depress Anxiety ; 37(2): 146-155, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31730745

RESUMO

BACKGROUND: Sex differences in psychiatric disorders are common and could involve sex steroids. Aromatase, the product of the CYP19A1 gene, is the key enzyme in the conversion of androgen to estrogen. Whether CYP19A1 variants could be associated with depression differently in men and women has not been examined. METHODS: This population-based study included 405 men and 602 women aged ≥65 years. A clinical level of depression (DEP) was defined as having a score ≥16 on the Center for Epidemiology Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to DSM-IV criteria. Seven single-nucleotide polymorphisms (SNPs) spanning the CYP19A1 gene were genotyped and circulating levels of estradiol and testosterone were determined. Multivariable analyses were adjusted for age, body mass index, ischemic pathologies, cognitive impairment, and anxiety. RESULTS: Five SNPs were associated with DEP in women specifically and this varied according to a history of major depression (p-values .01 to .0005). Three SNPs were associated with an increased risk of late-life DEP in women without a history of major depression, while two SNPs were associated with a decreased DEP risk in women with a history of major depression and were also associated with higher estradiol levels. CONCLUSIONS: Variants of the CYP19A1 gene appear to be susceptibility factors for late-life depression in a sex-specific manner. The polymorphisms decreasing the risk of recurrent depression in postmenopausal women also influence estradiol levels.


Assuntos
Aromatase/genética , Depressão/sangue , Depressão/genética , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/genética , Estradiol/sangue , Polimorfismo de Nucleotídeo Único , Testosterona/sangue , Idade de Início , Idoso , Índice de Massa Corporal , Feminino , Genótipo , Humanos , Masculino
14.
Int J Neuropsychopharmacol ; 23(2): 88-95, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31819986

RESUMO

INTRODUCTION: Antidepressant drugs are effective therapies for major depressive disorder; however, they are frequently associated with side effects. Although there is some evidence for a relationship between genetic variation and side effects, little is known regarding the role of dynamic molecular factors as moderators of side effects. The aim of this study was to assess microRNA (miRNA) changes associated with side effects during escitalopram treatment and their downstream effects on target gene expression. METHODS: A total 160 patients with major depressive disorder from the CAN-BIND-1 cohort were included. Side effects were assessed with the Toronto Side Effect Scale after 2 weeks of treatment with escitalopram. We assessed the relationship between side effects and changes in peripheral expression of miRNAs between baseline and week 2. For miRNA whose expression changed, we used target prediction algorithms to identify putative messenger RNA (mRNA) targets and assessed their expression. RESULTS: Nausea was experienced by 42.5% of patients. We identified 45 miRNAs whose expression changed on initiation of escitalopram treatment, of which 10 displayed a negative association with intensity of nausea (miR15b-5p, miR17-5p, miR20a-5p, miR20b-5p, miR103a-3p, miR103b, miR106a-5p, miR182-5p, miR185-5p, and miR660-5p). Additionally, we found negative associations between 4 microRNAs (miR20a-5p, miR106a-5p, miR185-5p, miR660-5p) and mRNA targets. The expression of the miR185-5p target, CAMK2δ was significantly decreased [log 2 mean = -0.048 (0.233)] between weeks 0 and 2 (P = .01)]. CONCLUSIONS: We identified an overexpression of miR185-5p during escitalopram treatment of major depressive disorder, which was negatively associated with intensity of nausea, and identified a potential mRNA target that may mediate this effect.


Assuntos
Citalopram/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Expressão Gênica/efeitos dos fármacos , MicroRNAs/efeitos dos fármacos , Náusea/induzido quimicamente , Inibidores de Captação de Serotonina/efeitos adversos , Adolescente , Adulto , Estudos de Coortes , Transtorno Depressivo Maior/sangue , Feminino , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Adulto Jovem
15.
Stress Health ; 36(1): 11-18, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31693291

RESUMO

Adults with type 2 diabetes (T2DM) and depression are associated with higher hemoglobin A1C (HbA1C ) compared to their nondepressed counterparts. Little is known about related clinical and demographic components contributing to these differences. We examined differences in HbA1C between adults who have T2DM with and without major depression. T tests and chi-square analyses measured differences in HbA1C and clinical/demographic variables. HbA1C was statistically higher in depressed participants compared to nondepressed participants. The difference was no longer statistically significant after controlling for age. Age and HbA1C were negatively correlated across the sample and were still correlated in each group independently. The interaction of age and HbA1C was moderated by depression status. Additionally, mechanisms for diabetes severity differences were assessed using moderation analyses and Blinder-Oaxaca decomposition technique. Seventy-four percent of the mean outcome HbA1C difference between depressed and nondepressed diabetic participants was explained by age. Furthermore, age was negatively correlated with clinical variables, such as diastolic blood pressure and cholesterol. Comparing age to smoking and nonsmoking participants, smokers were statistically younger. Younger adults with T2DM may require more attention regarding self-management, particularly in the context of depression. Depression should be screened and treated among individuals with diabetes since this exacerbates diabetes severity.


Assuntos
Fatores Etários , Transtorno Depressivo Maior/sangue , Diabetes Mellitus Tipo 2/sangue , Hemoglobina A Glicada/análise , Adulto , Idoso , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco
16.
Eur Arch Psychiatry Clin Neurosci ; 270(2): 183-193, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30929060

RESUMO

One important symptom of patients with major depressive disorder (MDD) is memory dysfunction. However, little is known about the relationship between memory performance and depression severity, about the course of memory performance during antidepressant treatment as well as about the relationship between memory performance and brain-derived neurotrophic factor (BDNF). Memory function [learning and delayed recall) was assessed in 173 MDD patients (mean age 39.7 ± 11.3 years] treated by a pre-defined treatment algorithm within the early medication change (EMC) study at baseline, days 28 and 56. Depression severity was assessed in weekly intervals, BDNF plasma levels were measured at baseline, days 14 and 56, BDNF exon IV and p11 methylation status at baseline. Linear mixed regression models revealed that the course of depression severity was not associated with the course of learning or delayed recall in the total group. 63 (36%) of the investigated patients showed memory deficits (percent range ≤ 16) at baseline. Of those, 26(41%) patients experienced a normalization of their memory deficits during treatment. Patients with a normalization of their delayed recall performance had significantly higher plasma BDNF levels (p = 0.040) from baseline to day 56 than patients with persistent deficits. Baseline BDNF exon IV promoter and p11 gene methylation status were not associated with memory performance. Our results corroborate a concomitant amelioration of learning and delayed recall dysfunctions with successful antidepressant therapy in a subgroup of patients and support a role of BDNF in the neural mechanisms underlying the normalization of memory dysfunctions in MDD. ClinicalTrials.gov number: NCT00974155; EudraCT: 2008-008280-96.


Assuntos
Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Transtornos da Memória/sangue , Transtornos da Memória/tratamento farmacológico , Rememoração Mental/efeitos dos fármacos , Avaliação de Resultados em Cuidados de Saúde , Adulto , Transtorno Depressivo Maior/complicações , Feminino , Humanos , Masculino , Transtornos da Memória/etiologia , Pessoa de Meia-Idade
17.
Eur Arch Psychiatry Clin Neurosci ; 270(2): 169-181, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30929061

RESUMO

Preliminary evidence suggests that BDNF (brain derived neurotrophic factor) rs6265 genetic polymorphism, BDNF gene promotor methylation and BDNF serum levels might play an important role in the pathogenesis of affective disorders. As studies testing the BDNF system across molecular levels are sparse, this study aimed at investigating the BDNF val66met genotype, BDNF DNA methylation changes and peripheral BDNF serum levels in acute and remitted phases of MDD (major depressive disorder) and BD (bipolar disorder) and healthy controls. We found a significant difference of methylation levels at CpG site 1-1-1 and 3-1-1 between MDD and healthy controls (p < 0.003) with MDD patients showing significantly higher methylation levels. CpG 5-2-1 revealed a statistically significant difference between MDD and healthy controls and MDD and BD (p = 0.00003). Similar to the results of the methylation analysis a significant difference between MDD and healthy controls was found in BDNF serum levels (p = 0.002) with significantly lower BDNF serum levels in MDD compared to healthy controls. A difference between the samples from admission and discharge from hospital of both BDNF gene methylation and serum levels could not be detected in the present study and no influence of the BDNF val66met genotype on neither methylation nor BDNF serum level.


Assuntos
Transtorno Bipolar/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Metilação de DNA , Transtorno Depressivo Maior/sangue , Adulto , Biomarcadores/sangue , Transtorno Bipolar/genética , Transtorno Bipolar/terapia , Fator Neurotrófico Derivado do Encéfalo/genética , Ilhas de CpG , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/terapia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Alta do Paciente , Regiões Promotoras Genéticas , Indução de Remissão
18.
Biol Res Nurs ; 22(2): 256-262, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31858822

RESUMO

BACKGROUND: The postpartum period can be a vulnerable time during which many women are prone to mood disturbances. Since telomere length (TL) is known to be associated with dysphoric moods, inflammation, and stress in many populations, this study's objective was to assess the relationships among TL, dysphoric moods, stress, and inflammation during the postpartum period. METHOD: This cross-sectional pilot study is a secondary analysis of data collected in a larger parent study of anti-thyroid peroxidase (TPO) enzyme antibody positive versus negative women. The parent study followed selected mothers every month for 6 postpartum months. From this parent study, a random sample of preserved peripheral blood mononuclear cells from 97 participants collected at 2-4 months postpartum were measured for TL. Data were available on the production of interleukin-6 (IL-6), an inflammatory cytokine, in stimulated ex vivo cultures for 59 of these women. Dysphoric moods and stress were measured. Pearson correlations and linear regressions were performed, controlling for postpartum thyroiditis status and age. RESULTS: There were no statistically significant relationships between TL and demographic factors, stress, depression, or TPO status. There were significant negative correlations between TL and anxiety and a trend for a relationship between TL and IL-6 levels. IL-6 levels were significantly, positively associated with negative moods. CONCLUSIONS: Higher anxiety scores and inflammation were associated with shorter TL. Inflammation was related to anxiety and other dysphoric moods and was marginally associated with shorter TLs.


Assuntos
Transtornos de Ansiedade/sangue , Citocinas/sangue , Transtorno Depressivo Maior/sangue , Inflamação/sangue , Iodeto Peroxidase/sangue , Leucócitos Mononucleares/fisiologia , Período Pós-Parto/psicologia , Telômero , Adulto , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Adulto Jovem
19.
Neurotox Res ; 37(2): 338-348, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31802379

RESUMO

Major depressive disorder (MDD) is accompanied by higher serum IgM/IgA responses to LPS of Gram-negative bacteria, suggesting increased bacterial translocation and gut dysbiosis while the latter may occur in bipolar disorder (BD). There are differences between MDD and BD type 1 (BP1) and 2 (BP2) in nitro-oxidative stress biomarkers associated with leaky gut. This study examines serum IgM/IgA responses directed to LPS of 6 Gram-negative bacteria as well as IgG responses to oxidized LDL (oxLDL) in 29 BP1, 37 BP2, 44 MDD, and 30 healthy individuals. Increased IgM/IgA responses to Pseudomonas aeruginosa significantly discriminated patients with affective disorders (MDD plus BD) from controls. BP1 patients showed higher IgM responses to Morganella morganii as compared with MDD and BP2 patients. Patients with melancholia showed higher IgA responses to Citrobacter koseri as compared to controls and non-melancholic depression. The total score on the Hamilton Depression Rating Scale was significantly associated with IgA responses to C. koseri. IgG to oxLDL was significantly associated with increased bacterial translocation. In conclusion, MDD, BP1, and BP2 are accompanied by an immune response due to the increased load of LPS while these aberrations in the gut-brain axis are most pronounced in BP1 and melancholia. Activated oxidative stress pathways and autoimmune responses to oxidative specific epitopes in mood disorders may be driven by a breakdown in gut paracellular, transcellular, and/or vascular pathways. If replicated, drugs that protect the integrity of the gut barrier may offer novel therapeutic opportunities for BP1 and MDD.


Assuntos
Translocação Bacteriana/fisiologia , Transtorno Bipolar/sangue , Transtorno Depressivo Maior/sangue , Microbioma Gastrointestinal/fisiologia , Bactérias Gram-Negativas/metabolismo , Imunoglobulina G/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Transtorno Bipolar/psicologia , Estudos de Casos e Controles , Transtorno Depressivo/sangue , Transtorno Depressivo/psicologia , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Acta Neuropsychiatr ; 32(2): 99-108, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31753054

RESUMO

OBJECTIVE: This study was carried out to delineate differences between major depressive disorder (MDD) and healthy controls in dynorphin and kappa opioid receptor (KOR) levels in association with changes in the ß-endorphin - mu opioid receptor (MOR) and immune-inflammatory system. METHODS: The present study examines dynorphin, KOR, ß-endorphin, MOR, interleukin (IL)-6 and IL-10 in 60 drug-free male participants with MDD and 30 age-matched healthy males. RESULTS: Serum dynorphin, KOR, ß-endorphin and MOR are significantly higher in MDD as compared to controls. The increases in the dynorphin/KOR system and ß-endorphin/MOR system are significantly intercorrelated and are both strongly associated with increased IL-6 and IL-10 levels. Dynorphin, ß-endorphin, KOR and both cytokines showed a good diagnostic performance for MDD versus controls with a bootstrapped (n = 2000) area under the receiver operating curve of 0.972. The dynorphin/KOR system is significantly decreased in depression with comorbid nicotine dependence. CONCLUSION: Our findings suggest that, in MDD, immune activation is associated with a simultaneous activation of dynorphin/KOR and ß-endorphin/MOR signaling and that these opioid systems may participate in the pathophysiology of depression by (a) exerting immune-regulatory activities attenuating the primary immune response and (b) modulating reward responses and mood as well as emotional and behavioural responses to stress.


Assuntos
Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/imunologia , Interleucina-10/sangue , Interleucina-6/sangue , Receptores Opioides kappa/sangue , Receptores Opioides mu/sangue , Receptores Opioides/sangue , Adulto , Humanos , Masculino , Transdução de Sinais/fisiologia
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