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1.
Psychiatr Danub ; 31(Suppl 3): 520-523, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488784

RESUMO

Major depressive disorder is one of the most important psychiatric issues worldwide, with important prevalence of treatment-resistant depression (TRD). Non-monoaminergic agents are currently in the spotlight. Objective was to explore for information about mechanisms of action of ketamine, its connections with copper and possible importance for TRD treatment. There are at least few possible pathways for ketamine action in depression in which copper and other divalent ions may show a vital role. There is urgent need for more studies to gather information about correlation between ketamine, copper and antidepressive features of these agents.


Assuntos
Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Cobre/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Ketamina/farmacologia , Ketamina/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/metabolismo , Humanos
2.
J Immunoassay Immunochem ; 40(5): 502-514, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31339439

RESUMO

Both Behçet's disease (BD) and major depressive disorder (MDD) are diseases associated with nitric oxide (NO). We hypothesized that the comorbidity of MDD affects the levels of NO in BD. In this study, we investigate whether there was a difference in NO levels among BD patients with accompanying MDD, BD patients with no depressive symptoms and healthy control group. There was a significant difference in NO levels among BD and control group (P < 0.05). Also, there was a significant difference between the BD group with MDD and BD group without psychiatric comorbidity in terms of NO levels (P < 0.05). This study is interesting as it demonstrates that accompanying psychiatric comorbidity puts an additional NO burden on the shoulders of BD patients.


Assuntos
Síndrome de Behçet/metabolismo , Síndrome de Behçet/psicologia , Transtorno Depressivo Maior/metabolismo , Óxido Nítrico/análise , Adulto , Síndrome de Behçet/epidemiologia , Comorbidade , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Masculino
3.
Med Sci Monit ; 25: 4322-4332, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31180069

RESUMO

BACKGROUND We previously discovered that 3 long non-coding RNAs (lncRNAs) NONHSAT089447, NONHSAT021545, and NONHSAT041499 were differentially expressed in the peripheral blood of patients with schizophrenia, in comparison to those in normal healthy controls. In this study, we conducted bioinformatic analysis of these 3 lncRNAs and the regulatory role of lncRNA NONHSAT089447 in the dopamine signaling pathway in patients with schizophrenia. MATERIAL AND METHODS There lncRNAs in peripheral blood mononuclear cells (PBMCs) were screened using microarray analysis. Pearson's correlation analysis was performed to assess the levels of co-expressed mRNAs of respective lncRNAs. The Database for Annotation, Visualization and Integrated Discovery (DAVID) software was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes or Genomes (KEGG) enrichment analysis for these lncRNAs. Human neuroblastoma cell lines (SK-N-SH) were cultured and treated with dopamine or olanzapine (OLP), or transfected with siRNA targeting NONHSAT089447 or plasmid expressing NONHSAT089447. Levels of lncRNAs were detected by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Then, mRNA and protein expression of the dopamine receptors DRD1, DRD2, DRD3, DRD4, and DRD5 were measured by RT-PCR and western blot analysis, respectively. RESULTS OLP treatment significantly inhibited the expression of NONHSAT089447. Knockdown of NONHSAT089447 by siRNA decreased DRD3 and DRD5 expression, while overexpression of NONHSAT089447 significantly upregulated expression of DRD3 and DRD5. Western blot analysis confirmed that levels of NONHSAT089447 regulated downstream DRD signaling. CONCLUSIONS Our results revealed that the lncRNA NONHSAT089447 participated in the dopamine signaling pathway via upregulation of DRDs.


Assuntos
Dopamina/metabolismo , RNA Longo não Codificante/metabolismo , Esquizofrenia/metabolismo , Adulto , Transtornos de Ansiedade/metabolismo , Linhagem Celular Tumoral , Biologia Computacional/métodos , Transtorno Depressivo Maior/metabolismo , Dopamina/genética , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Esquizofrenia/genética , Transdução de Sinais/genética
5.
Cell Mol Neurobiol ; 39(6): 721-727, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31037515

RESUMO

Mental disorders, such as major depressive disorder and schizophrenia, are complex multigenetic conditions, but focused studies of single genes might reveal genes involved in the pathogenesis of mental disorders, including major depressive disorder and schizophrenia. Several candidate genes have been identified using transgenic mice. VGF nerve growth factor inducible (VGF) is a neuropeptide expression of which is induced by nerve growth factor (NGF). VGF is robustly and exclusively synthesized in neuronal and neuroendocrine cells. In central nervous system (CNS), VGF is extensively expressed especially in the cerebral cortex, hippocampus, and hypothalamus. VGF has many roles in the CNS, such as promotion of synaptic plasticity, neurogenesis, and neurite outgrowth. In clinical studies, altered expression and genetic mutations of VGF have been reported in patients with major depressive disorder and schizophrenia. On this basis, studies using transgenic mice to overexpress or knockout VGF have been performed to investigate the roles of upregulation or downregulation of VGF. In this review, we will discuss studies of the roles of VGF using transgenic mice and its relevance to pathologies in major depressive disorder and schizophrenia.


Assuntos
Transtorno Depressivo Maior/metabolismo , Neuropeptídeos/metabolismo , Esquizofrenia/metabolismo , Animais , Transtorno Depressivo Maior/genética , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Transgênicos , Neuropeptídeos/genética , Esquizofrenia/genética , Regulação para Cima/genética
6.
Cell Tissue Res ; 377(1): 73-79, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31076872

RESUMO

Most growth factors are synthesized as precursors and biologically active forms are generated by proteolytic cleavage of the pro-domain. However, the biological functions of pro-domains are ill-defined. New roles were recently reported for the pro-domain of brain-derived neurotrophic factor (BDNF), a well-known growth factor in the brain. Interestingly, the pro-domain of BDNF (BDNF pro-peptide) is localized at presynaptic termini, where it facilitates long-term depression (LTD) in hippocampal slices, implicating it as a novel synaptic modulator. BDNF binds its pro-peptide with high affinity in a pH-dependent manner and when bound to BDNF, the BDNF pro-peptide cannot facilitate hippocampal LTD, representing a new mechanism of regulation. The BDNF pro-peptide is present in human cerebrospinal fluid (CSF) and levels were significantly lower in patients with major depressive disorder (MDD) than in controls. Notably, male MDD patients exhibit significantly lower levels of CSF pro-peptide than females. These findings demonstrate that the BDNF pro-peptide is a biologically important synaptic modulator and is associated with MDD, particularly in males.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transtorno Depressivo Maior/metabolismo , Hipocampo/metabolismo , Depressão Sináptica de Longo Prazo/fisiologia , Neurotransmissores/metabolismo , Terminações Pré-Sinápticas/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Camundongos , Precursores de Proteínas/líquido cefalorraquidiano , Precursores de Proteínas/metabolismo , Ratos , Transmissão Sináptica
7.
Int J Mol Sci ; 20(9)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075818

RESUMO

Major depressive disorder (MDD) is a debilitating condition, whose high prevalence and multisymptomatic nature set its standing as a leading contributor to global disability. To better understand this psychiatric disease, various pathophysiological mechanisms have been proposed, including changes in monoaminergic neurotransmission, imbalance of excitatory and inhibitory signaling in the brain, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, and abnormalities in normal neurogenesis. While previous findings led to a deeper understanding of the disease, the pathogenesis of MDD has not yet been elucidated. Accumulating evidence has confirmed the association between chronic inflammation and MDD, which is manifested by increased levels of the C-reactive protein, as well as pro-inflammatory cytokines, such as Interleukin 1 beta, Interleukin 6, and the Tumor necrosis factor alpha. Furthermore, recent findings have implicated a related family of cytokines with chemotactic properties, known collectively as chemokines, in many neuroimmune processes relevant to psychiatric disorders. Chemokines are small (8-12 kDa) chemotactic cytokines, which are known to play roles in direct chemotaxis induction, leukocyte and macrophage migration, and inflammatory response propagation. The inflammatory chemokines possess the ability to induce migration of immune cells to the infection site, whereas their homeostatic chemokine counterparts are responsible for recruiting cells for their repair and maintenance. To further support the role of chemokines as central elements to healthy bodily function, recent studies suggest that these proteins demonstrate novel, brain-specific mechanisms including the modulation of neuroendocrine functions, chemotaxis, cell adhesion, and neuroinflammation. Elevated levels of chemokines in patient-derived serum have been detected in individuals diagnosed with major depressive disorder, bipolar disorder, and schizophrenia. Furthermore, despite the considerable heterogeneity of experimental samples and methodologies, existing biomarker studies have clearly demonstrated the important role of chemokines in the pathophysiology of psychiatric disorders. The purpose of this review is to summarize the data from contemporary experimental and clinical studies, and to evaluate available evidence for the role of chemokines in the central nervous system (CNS) under physiological and pathophysiological conditions. In light of recent results, chemokines could be considered as possible peripheral markers of psychiatric disorders, and/or targets for treating depressive disorders.


Assuntos
Quimiocinas/metabolismo , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/fisiopatologia , Humanos , Neurogênese , Plasticidade Neuronal , Receptores de Quimiocinas/metabolismo , Transmissão Sináptica
8.
Depress Anxiety ; 36(8): 766-779, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31111623

RESUMO

BACKGROUND: Brain mitochondrial dysfunction is implicated in the pathophysiology of mood disorders. Brain cytochrome-c-oxidase (COX) activity is associated with the mitochondrial function. Near-infrared spectroscopy (NIRS) noninvasively measures oxidized COX (oxCOX) and tissue oxygenation index (TOI) reflecting cerebral blood flow and oxygenation. METHODS: oxCOX and TOI were assessed in prefrontal cortex (Fp1/2, Brodmann area 10) in patients in a major depressive episode (N = 13) with major depressive disorder (MDD; N = 7) and bipolar disorder (BD; N = 6) compared with the controls (N = 10). One patient with MDD and all the patients with BD were taking medications. Computational modeling estimated oxCOX and TOI related indices of mitochondrial function and cerebral blood flow, respectively. RESULTS: oxCOX was lower in patients than controls (p = .014) correlating inversely with depression severity (r = -.72; p = .006), driven primarily by lower oxCOX in BD compared with the controls. Computationally modeled mitochondrial parameters of the electron transport chain, such as the nicotinamide adenine dinucleotide ratio (NAD+ /NADH; p = .001) and the proton leak rate across the inner mitochondrial membrane (klk2 ; p = .008), were also lower in patients and correlated inversely with depression severity. No such effects were found for TOI. CONCLUSIONS: In this pilot study, oxCOX and related mitochondrial parameters assessed by NIRS indicate an abnormal cerebral metabolic state in mood disorders proportional to depression severity, potentially providing a biomarker of antidepressant effect. Because the effect was driven by the medicated BD group, findings need to be evaluated in a larger, medication-free population.


Assuntos
Encéfalo/metabolismo , Encéfalo/fisiopatologia , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/fisiopatologia , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Mitocôndrias/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Mapeamento Encefálico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/fisiologia , Projetos Piloto , Espectroscopia de Luz Próxima ao Infravermelho , Adulto Jovem
9.
PLoS One ; 14(4): e0215085, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31026258

RESUMO

Childhood adversity is a potent risk factor for mental health conditions via disruptions to stress response systems. Dysregulations in oxidative stress systems have been associated with both childhood adversity and several psychological disorders (e.g., major depressive disorder) in adult populations. However, few studies have examined associations between childhood adversity, oxidative stress, and mental health in pediatric populations. Childhood adversity (Adverse Childhood Events [ACE]), oxidative stress [F2t-isoprostanes (IsoPs)], and mental health pathology were assessed in 50 adolescent females recruited primarily through the Department of Youth Services. Standard ordinary least squares regression models were run co-varying for age, race/ethnicity, adolescent nicotine use, study condition, and parent history of ACEs. Adolescents who reported experiencing four or more ACEs had significantly elevated IsoP levels. Further, internalizing symptom scores across diagnoses were significantly associated with elevated IsoPs, whereas no externalizing symptoms scores, except Attention Deficit Hyperactivity Disorder, were related to altered oxidative stress. Results indicate that IsoPs may be a global marker of childhood adversity and mental health symptomatology, particularly within internalizing symptom domains. A limitation is that body mass index was not collected for this sample. Future studies are needed to replicate and extend these findings in larger, more diverse samples.


Assuntos
Experiências Adversas da Infância/estatística & dados numéricos , Biomarcadores/análise , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Saúde Mental/estatística & dados numéricos , Estresse Oxidativo , Adolescente , Transtorno Depressivo Maior/metabolismo , Feminino , Humanos , Incidência , Projetos Piloto , Fatores de Risco , Estados Unidos/epidemiologia
10.
Int J Mol Sci ; 20(8)2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31018568

RESUMO

Despite numerous studies on major depressive disorder (MDD) susceptibility, the precise underlying molecular mechanism has not been elucidated which restricts the development of etiology-based disease-modifying drug. Major depressive disorder treatment is still symptomatic and is the leading cause of (~30%) failure of the current antidepressant therapy. Here we comprehended the probable genes and pathways commonly associated with antidepressant response and MDD. A systematic review was conducted, and candidate genes/pathways associated with antidepressant response and MDD were identified using an integrative genetics approach. Initially, single nucleotide polymorphisms (SNPs)/genes found to be significantly associated with antidepressant response were systematically reviewed and retrieved from the candidate studies and genome-wide association studies (GWAS). Also, significant variations concerning MDD susceptibility were extracted from GWAS only. We found 245 (Set A) and 800 (Set B) significantly associated genes with antidepressant response and MDD, respectively. Further, gene set enrichment analysis revealed the top five co-occurring molecular pathways (p ≤ 0.05) among the two sets of genes: Cushing syndrome, Axon guidance, cAMP signaling pathway, Insulin secretion, and Glutamatergic synapse, wherein all show a very close relation to synaptic plasticity. Integrative analyses of candidate gene and genome-wide association studies would enable us to investigate the putative targets for the development of disease etiology-based antidepressant that might be more promising than current ones.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Inibidores de Captação de Serotonina/uso terapêutico , Antidepressivos/farmacologia , AMP Cíclico/metabolismo , Transtorno Depressivo Maior/metabolismo , Estudo de Associação Genômica Ampla , Genômica/métodos , Humanos , Inibidores de Captação de Serotonina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fluxo de Trabalho
11.
Nutrients ; 11(4)2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995790

RESUMO

Major depressive disorder (MDD) is a chronic mental disorder characterized by mixed symptoms and complex pathogenesis. With long history of practical application, traditional Chinese medicine (TCM) offers many herbs for the treatment and rehabilitation of chronic disease. In this study, we developed a modified Chinese herbal formula using Panax ginseng, Angelica Sinensis, Polygala tenuifolia Willd, and Ziziphi spinosae Semen (PAPZ), based on an ancient TCM prescription. The antidepressant effects of PAPZ were investigated with a corticosterone (CORT) model of depression in mice. Our results showed that administration of PAPZ ameliorated depression-like phenotypes in the CORT model. An anatomic study showed that chronic PAPZ administration upregulated the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampal tissue. The enzyme activity of superoxide dismutase was enhanced in hippocampal tissue, in line with a decreased malondialdehyde level. Taken together, these findings suggested that PAPZ has therapeutic effects in a mice depression model through increasing protein expression of BDNF and improving the anti-oxidation ability of the brain.


Assuntos
Antioxidantes/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Hipocampo/efeitos dos fármacos , Magnoliopsida , Fitoterapia , Angelica sinensis , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corticosterona , Depressão/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Hipocampo/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos C57BL , Panax , Polygala , Superóxido Dismutase/metabolismo , Ziziphus
12.
Metabolism ; 95: 65-76, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30954559

RESUMO

Changes of sphingolipid metabolism were suggested to contribute to the patho-etiology of major depression (MD) and bipolar disorder (BD). In a pilot study we assessed if lipid allostasis manifested in pathological plasma concentrations of bioactive lipids i.e. endocannabinoids, sphingolipids, ceramides, and lysophosphatidic acids. METHODS: Targeted and untargeted lipidomic analyses were performed according to GLP guidelines in 67 patients with unipolar or bipolar disorders (20-67 years, 36 male, 31 female) and 405 healthy controls (18-79 years, 142 m, 263 f), who were matched according to gender, age and body mass index. Multivariate analyses were used to identify major components, which accounted for the variance between groups and were able to predict group membership. RESULTS: Differences between MD and BP patients versus controls mainly originated from ceramides and their hexosyl-metabolites (C16Cer, C18Cer, C20Cer, C22Cer, C24Cer and C24:1Cer; C24:1GluCer, C24LacCer), which were strongly increased, particularly in male patients. Ceramide levels were neither associated with the current episode, nor with the therapeutic improvement of the Montgomery Åsberg Depression Rating Scale (MARDS). However, long-chain ceramides were linearly associated with age, stronger in patients than controls, and with high plasma levels of diacyl- and triacylglycerols. Patients receiving antidepressants had higher ceramide levels than patients not taking these drugs. There was no such association with lithium or antipsychotics except for olanzapine. CONCLUSION: Our data suggest that high plasma ceramides in patients with major depression and bipolar disorder are indicative of a high metabolic burden, likely aggravated by certain medications.


Assuntos
Transtorno Bipolar/metabolismo , Ceramidas/metabolismo , Transtorno Depressivo Maior/metabolismo , Metabolismo dos Lipídeos/genética , Adolescente , Adulto , Fatores Etários , Idoso , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Antimaníacos/efeitos adversos , Antimaníacos/uso terapêutico , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Índice de Massa Corporal , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Diglicerídeos/metabolismo , Feminino , Humanos , Lítio/efeitos adversos , Lítio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Escalas de Graduação Psiquiátrica , Caracteres Sexuais , Triglicerídeos/metabolismo , Adulto Jovem
13.
Neuron ; 102(1): 13-16, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30946818

RESUMO

Perinatal depression (PND) is a heterogeneous disorder with differences in timing of onset of depression, which influences symptomology, severity, and treatment efficacy. Researchers must embrace the heterogeneity to bring fruition to a precision medicine approach for women in reproductive mental health care.


Assuntos
Depressão Pós-Parto/metabolismo , Transtorno Depressivo Maior/metabolismo , Complicações na Gravidez/metabolismo , Animais , Ansiedade/psicologia , Comportamento Compulsivo/psicologia , Depressão Pós-Parto/psicologia , Depressão Pós-Parto/terapia , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Maior/terapia , Modelos Animais de Doenças , Feminino , Humanos , Comportamento Obsessivo/psicologia , Medicina de Precisão , Gravidez , Complicações na Gravidez/psicologia , Complicações na Gravidez/terapia
14.
Behav Pharmacol ; 30(2 and 3-Spec Issue): 163-186, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30844963

RESUMO

The amino-acid tryptophan (TRY) is converted into kynurenine (KYN) and subsequent metabolites by the tryptophan/catabolites (TRY/CAT) pathway (kynurenine pathway). 'Excito-toxic' and 'neuro-protective' metabolites are produced, which modulate the glutamatergic neurotransmission. The TRY/CAT pathway is activated by hypothalamic-pituitary-adrenal endocrine induction during stress by corticoids hormones, and the excitotoxic branch of the TRY/CAT pathway is activated by proinflammatory cytokines. During stress and major depressive disorders, it is generally accepted that inflammation induces an imbalance toward the excitotoxic branch of the TRY/CAT pathway, causing changes in brain connectivity in corticolimbic structures and therefore psychocognitive abnormalities. In neurodegenerative diseases, the activation of the oxidative branch of the TRY/CAT pathway has been frequently reported. We propose a comprehensive survey of the TRY/CAT pathway (kynurenine pathway) abnormalities in stress and inflammation-induced MDD and neurodegenerative diseases. As TRY/CAT pathway is a common feature of stress, inflammation, affective disorders, and neurodegenerative diseases, we discuss the status of the TRY/CAT pathway as a possible link among chronic stress, inflammation, depressive disorders and neurodegenerative diseases. This review does not claim to be exhaustive, but in a pharmacological perspective, it will be proposed that modulation of the excitotoxicity/neuroprotection balance is a valuable strategy for new and more effective treatments of mood disorders.


Assuntos
Cinurenina/metabolismo , Triptofano/metabolismo , Animais , Encéfalo/metabolismo , Citocinas , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/fisiopatologia , Fármacos atuantes sobre Aminoácidos Excitatórios/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Inflamação/metabolismo , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/fisiopatologia , Neuroproteção , Sistema Hipófise-Suprarrenal/metabolismo
15.
J Affect Disord ; 250: 432-438, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30878656

RESUMO

BACKGROUND: Inflammation has been shown previously to predict antidepressant treatment response. This retrospective study was conducted to test if the baseline serum C-reactive protein (CRP) levels could predict antidepressant treatment responses in a Chinese sample. METHODS: 75 adult inpatients (26 male, 49 female) with major depressive disorder (MDD) diagnosed according to DSM-5 were included in this study. Sociodemographic and clinical features, baseline CRP levels, 17-item Hamilton Depression Rating Scale (HDRS-17) and Hamilton Anxiety Rating Scale (HARS) scores assessed at baseline and weeks 1, 2, 3 and 4 were then collected. Afterwards patients were divided into two groups: the low CRP group (baseline CRP < 1 mg/L, n = 47) and the high CRP group (baseline CRP ≥ 1 mg/L, n = 28). Depression severity and treatment response were compared between the two groups. RESULTS: Repeated-measures ANOVA showed a significant group * assessments interaction in HDRS-17 scores (F = 4.754; p = 0.005). Post-hoc test showed that the two groups differed in HDRS-17 scores at week 4 (F = 6.698; p = 0.012), with the low CRP group having lower HDRS-17 scores than the high CRP group. Moreover, the low CRP group exhibited higher percent reduction in HDRS-17 scores at week 3 (F = 5.016; p = 0.028) and week 4 (F = 9.865; p = 0.003) as compared to the high CRP group. Cox proportional hazard model showed that the remission rate was higher in the low CRP group (p = 0.010). LIMITATIONS: Patients received uncontrolled antidepressant therapy and the sample size was limited. CONCLUSIONS: Baseline serum CRP levels may predict antidepressant treatment responses in patients with MDD and patients with higher levels of CRP were less likely to get remission.


Assuntos
Antidepressivos/uso terapêutico , Proteína C-Reativa/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Índice de Gravidade de Doença , Adulto , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tamanho da Amostra , Resultado do Tratamento
16.
Biomed Pharmacother ; 111: 1057-1065, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30841419

RESUMO

Major depressive disorder (MDD) affects ˜16% of the world population. Chronic stressors contribute to reduced hippocampal volumes and increase the risk of developing MDD. Our previous work showed that XYS ameliorates social isolation and chronic unpredictable mild stress (CUMS) induced depressive-like behaviors in rats by regulating hypothalamic-pituitary-adrenal hyperactivation, locus coeruleus -norepinephrine activity and kynurenine/5-hydroxytryptamin balance. Here, we report that CUMS & isolation-treated mice exhibit depressive-like behaviors and show a phenotype of mixed apoptosis/autophagy characteristic in mice hippocampus in vivo. Modified Xiaoyao San (MXS) significantly ameliorates CUMS & social isolation-induced anhedonia, loss of interests, psychomotor retardation and behavioral despair. It suppresses the apoptosis by downregulaing condensation of heterochromatin and reducing hippocampal TdT-mediated dUTP Nick-End Labeling (TUNEL)-positive cells. MSX significantly inhibits mitochondrial outer membrane permeabilization (MOMP) reduces the release of cytochrome C and the shift of apoptosis inducing factor (AIF) from mitochondria to nucleus. Further, it stimulates the formation of autophagosomes and activates the expression of Atg5 and LC3II. Combined silencing of Atg5 and Atg7 dampens MOMP and impaired the anti-apoptotic effects of MXS. In conclusion, MXS ameliorates depressive-like behaviors by triggering autophagy to alleviate neuronal apoptosis. MXS is an effective supplement for MDD treatment, and can be harnessed to enhance autophagy and synergize with antidepressant action.


Assuntos
Antidepressivos/farmacologia , Apoptose/efeitos dos fármacos , Autofagossomos/efeitos dos fármacos , Depressão/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Neurônios/efeitos dos fármacos , Animais , Fator de Indução de Apoptose/metabolismo , Autofagossomos/metabolismo , Autofagia/efeitos dos fármacos , Depressão/metabolismo , Transtorno Depressivo Maior/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/metabolismo , Permeabilidade/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo
17.
Brain Connect ; 9(5): 388-398, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30848160

RESUMO

Children with familial risk for major depressive disorder (MDD) have elevated risk for developing depression as adolescents. Here, we investigated longitudinally whether resting-state functional connectivity (RSFC) could predict the onset of MDD. In this pilot study, we followed a group of never-depressed children with familial risk for MDD and a group of age-matched controls without familial risk who had undergone an MRI study at 8-14 years of age. Participants were reassessed 3-4 years later with diagnostic interviews. We first investigated group differences in RSFC from regions in the emotion regulation, cognitive control, and default mode networks in the children who later developed MDD (converted), the children who did not develop MDD (nonconverted), and the control group. We then built a prediction model based on baseline RSFC that was independent of the group differences to classify the individuals who later developed MDD. Compared with the nonconverted group, the converted group exhibited hypoconnectivity between subgenual anterior cingulate cortex (sgACC) and inferior parietal lobule (IPL) and between left and right dorsolateral prefrontal cortices. The nonconverted group exhibited higher sgACC-IPL connectivity than did both the converted and control groups, suggesting a possible resilience factor to MDD. Classification between converted and nonconverted individuals based on baseline RSFC yielded high predictive accuracy with high sensitivity and specificity that was superior to classification based on baseline clinical rating scales. Intrinsic brain connectivity measured in healthy children with familial risk for depression has the potential to predict MDD onset, and it can be a useful neuromarker in early identification of children for preventive treatment.


Assuntos
Mapeamento Encefálico/métodos , Transtorno Depressivo Maior/diagnóstico por imagem , Vias Neurais/fisiopatologia , Adolescente , Encéfalo/fisiopatologia , Criança , Simulação por Computador , Transtorno Depressivo Maior/metabolismo , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Sistema Límbico/fisiopatologia , Estudos Longitudinais , Imagem por Ressonância Magnética/métodos , Masculino , Vias Neurais/metabolismo , Lobo Parietal/fisiopatologia , Projetos Piloto , Córtex Pré-Frontal/fisiopatologia , Prognóstico , Descanso
19.
Int J Mol Sci ; 20(6)2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30871246

RESUMO

Numerous studies have demonstrated the antidepressant effects of group II metabotropic glutamate (mGlu2/3) receptor antagonists in various rodent models. Importantly, it has been shown that the antidepressant effects of mGlu2/3 receptor antagonists in rodent models are similar to those of ketamine, which exerts rapid and long-lasting antidepressant effects in patients with major depressive disorders, including patients with treatment-resistant depression. In addition, the synaptic mechanisms underlying the effects of mGlu2/3 receptor antagonists are reported to be similar to those underlying the effects of ketamine. The roles of the serotonergic system in the antidepressant effects of mGlu2/3 receptor antagonists have recently been demonstrated. Moreover, it was investigated how mGlu2/3 receptor antagonists interact with the serotonergic system to exert antidepressant effects. Notably, the same neural mechanisms as those underlying the effects of ketamine may be involved in the antidepressant actions of the mGlu2/3 receptor antagonists. In this review, we shall summarize the antidepressant potential of mGlu2/3 receptor antagonists and their mechanisms of action in comparison with those of ketamine. In particular, we shall focus on the roles of the serotonergic system in the antidepressant actions of mGlu2/3 receptor antagonists.


Assuntos
Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Ketamina/farmacologia , Ketamina/uso terapêutico , Receptores de Glutamato Metabotrópico/metabolismo , Neurônios Serotoninérgicos/efeitos dos fármacos , Animais , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Humanos , Neurônios Serotoninérgicos/metabolismo
20.
Adv Exp Med Biol ; 1118: 63-70, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30747417

RESUMO

Mental disorders, such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ), are generally characterized by a combination of abnormal thoughts, perceptions, emotions, behavior, and relationships with others. Multiple risk factors incorporating genetic and environmental susceptibility are associated with development of these disorders. Mitochondria have a central role in the energy metabolism, and the literature suggests energy metabolism abnormalities are widespread in the brains of subjects with MDD, BPD, and SZ. Numerous studies have shown altered expressions of mitochondria-related genes in these mental disorders. In addition, environmental factors for these disorders, such as stresses, have been suggested to induce mitochondrial abnormalities. Moreover, animal studies have suggested that interactions of altered expression of mitochondria-related genes and environmental factors might be involved in mental disorders. Further investigations into interactions of mitochondrial abnormalities with environmental factors are required to elucidate of the pathogenesis of these mental disorders.


Assuntos
Metabolismo Energético , Transtornos Mentais/metabolismo , Mitocôndrias/patologia , Animais , Transtorno Bipolar/metabolismo , Transtorno Bipolar/fisiopatologia , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/fisiopatologia , Humanos , Transtornos Mentais/fisiopatologia , Esquizofrenia/metabolismo , Esquizofrenia/fisiopatologia
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