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1.
Mol Med Rep ; 24(6)2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34633054

RESUMO

The present study aimed to review major depression, including its types, epidemiology, association with different diseases status and treatments, as well as its correlation with the current COVID-19 pandemic. Mental depression is a common disorder that affects most individuals at one time or another. During depression, there are changes in mood and behavior, accompanied by feelings of defeat, hopelessness, or even suicidal thoughts. Depression has a direct or indirect relation with a number of other diseases including Alzheimer's disease, stroke, epilepsy, diabetes, cardiovascular disease and cancer. In addition, antidepressant drugs have several side effects including sedation, increased weight, indigestion, sexual dysfunction, or a decrease in blood pressure. Stopping medication may cause a relapse of the symptoms of depression and pose a risk of attempted suicide. The pandemic of COVID-19 has affected the mental health of individuals, including patients, individuals contacting patients and medical staff with a number of mental disorders that may adversely affect the immune ability of their bodies. Some of the drugs currently included in the protocols for treating COVID-19 may negatively affect the mental health of patients. Evidence accumulated over the years indicates that serotonin (5HT) deficiencies and norepinephrine (NE) in the brain can lead to mental depression. Drugs that increase levels of NE and 5HT are commonly used in the treatment of depression. The common reason for mood disorders, including mania and bipolar disease are not clearly understood. It is assumed that hyperactivity in specific parts of the brain and excessive activity of neurotransmitters may be involved. Early diagnosis and developing new treatment strategies are essential for the prevention of the severe consequences of depression. In addition, extensive research should be directed towards the investigation of the mental health disturbances occurring during and/or after COVID-19 infection. This may lead to the incorporation of a suitable antidepressant into the current treatment protocols.


Assuntos
COVID-19/epidemiologia , COVID-19/psicologia , Transtorno Depressivo Maior/epidemiologia , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , COVID-19/complicações , Síndrome da Liberação de Citocina/etiologia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/metabolismo , Ácido Glutâmico/metabolismo , Humanos , Estresse Oxidativo
2.
AAPS PharmSciTech ; 22(8): 261, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34705130

RESUMO

The first melatonergic antidepressant drug, agomelatine (AGM), is commonly used for controlling major depressive disorders. AGM suffers low (< 5%) oral bioavailability owing to the hepatic metabolism. The current work investigated the potential of low-frequency sonophoresis on enhancing transdermal delivery of AGM-loaded novasomes and, hence, bioavailability of AGM. Drug-loaded novasomes were developed using free fatty acid (stearic acid or oleic acid), surfactant (span 60 or span 80), and cholesterol via thin-film hydration technique. The systems (N1-N16) were assessed for zeta potential (ZP), particle size (PS), encapsulation efficiency (EE%), and drug percent released after 0.5 h (Q0.5 h) and 8 h (Q8h), drug-crystallinity, morphology, and ex vivo drug permeation. Skin pre-treatment with low-frequency ultrasound (LFU) waves, via N13-novasomal gel systems, was optimized to enhance ex vivo drug permeation. Influences of LFU mode (continuous or pulsed), duty cycle (50% or 100%), and application period (10 or 15 min) were optimized. The pharmacokinetics of the optimized system (N13-LFU-C4) was assessed in rabbits. N13 was the best achieved novasomal system with respect to PS (471.6 nm), ZP (- 63.6 mv), EE% (60.5%), Q0.5 h (27.8%), Q8h (83.9%), flux (15.5 µg/cm2/h), and enhancement ratio (6.9). N13-LFU-C4 was the optimized novasomal gel system (desirability; 0.997) which involves skin pre-treatment with LFU in a continuous mode, at 100% duty cycle, for 15 min. Compared to AGM dispersion, the significantly (P < 0.05) higher flux (26.7 µg/cm2/h), enhancement ratio (11.9), Cmax (118.23 ng/mL), and relative bioavailability (≈ 8.6 folds) could elucidate the potential of N13-LFU-C4 system in improving transdermal drug permeability and bioavailability.


Assuntos
Transtorno Depressivo Maior , Absorção Cutânea , Acetamidas , Administração Cutânea , Animais , Disponibilidade Biológica , Transtorno Depressivo Maior/metabolismo , Sistemas de Liberação de Medicamentos , Tamanho da Partícula , Coelhos , Pele/metabolismo
3.
Int J Mol Sci ; 22(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34502154

RESUMO

To an exceptional degree, and through multiple mechanisms, the PPARg system rapidly senses cellular stress, and functions in the CNS in glial cells, neurons, and cerebrovascular endothelial cell in multiple anti-inflammatory and neuroprotective ways. We now know that depression is associated with neurodegeneration in the subgenual prefrontal cortex and hippocampus, decreased neuroplasticity, and defective neurogenesis. Brain-derived neurotrophic factor (BDNF) is markedly depleted in these areas, and is thought to contribute to the neurodegeneration of the subgenual prefrontal cortex and the hippocampus. The PPARg system strongly increases BDNF levels and activity in these brain areas. The PPARg system promotes both neuroplasticity and neurogenesis, both via effects on BDNF, and through other mechanisms. Ample evidence exists that these brain areas transduce many of the cardinal features of depression, directly or through their projections to sites such as the amygdala and nucleus accumbens. Behaviorally, these include feelings of worthlessness, anxiety, dread of the future, and significant reductions in the capacity to anticipate and experience pleasure. Physiologically, these include activation of the CRH and noradrenergic system in brain and the sympathetic nervous system and hypothalamic-pituitary-adrenal axis in the periphery. Patients with depression are also insulin-resistant. The PPARg system influences each of these behavioral and physiological in ways that would ameliorate the manifestations of depressive illness. In addition to the cognitive and behavioral manifestations of depression, depressive illness is associated with the premature onsets of coronary artery disease, stroke, diabetes, and osteoporosis. As a consequence, patients with depressive illness lose approximately seven years of life. Inflammation and insulin resistance are two of the predominant processes that set into motion these somatic manifestations. PPARg agonists significantly ameliorate both pathological processes. In summary, PPARg augmentation can impact positively on multiple significant pathological processes in depression. These include loss of brain tissue, defective neuroplasticity and neurogenesis, widespread inflammation in the central nervous system and periphery, and insulin resistance. Thus, PPARg agonists could potentially have significant antidepressant effects.


Assuntos
Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/metabolismo , Suscetibilidade a Doenças , PPAR gama/genética , PPAR gama/metabolismo , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/parasitologia , Animais , Biomarcadores , Estudos de Casos e Controles , Cognição , Hormônio Liberador da Corticotropina/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Gerenciamento Clínico , Humanos , Inflamação/complicações , Inflamação/etiologia , Inflamação/metabolismo , Norepinefrina/metabolismo , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Estresse Fisiológico , Avaliação de Sintomas
4.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360865

RESUMO

Traumatic brain injury (TBI) affects over 69 million people annually worldwide, and those with pre-existing depression have worse recovery. The molecular mechanisms that may contribute to poor recovery after TBI with co-morbid depression have not been established. TBI and depression have many commonalities including volume changes, myelin disruption, changes in proliferation, and changes in glutamatergic signaling. We used a well-established animal model of depression, the Wistar Kyoto (WKY) rat, to elucidate changes after TBI that may influence the recovery trajectory. We compared the histological and molecular outcomes in the hippocampal dentate gyrus after experimental TBI using the lateral fluid percussion injury (LFPI) in the WKY and the parent Wistar (WIS) strain. We showed that WKY had exaggerated myelin loss after LFPI and baseline deficits in proliferation. In addition, we showed that while after LFPI WIS rats exhibited glutamate receptor subunit changes, namely increased GluN2B, the WKY rats failed to show such injury-related changes. These differential responses to LFPI helped to elucidate the molecular characteristics that influence poor recovery after TBI in those with pre-existing depression and may lead to targets for future therapeutic interventions.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Hipocampo , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Proliferação de Células , Transtorno Depressivo Maior/metabolismo , Hipocampo/patologia , Ratos , Ratos Endogâmicos WKY , Ratos Wistar
5.
Comput Math Methods Med ; 2021: 3036741, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394704

RESUMO

Aiming at a more comprehensive understanding of the molecular biomarkers and potential mechanisms of major depressive disorder (MDD), from the Gene Expression Omnibus (GEO) database, we first obtained mRNA expression profiles and identified 585 differentially expressed genes (DEGs) through the R software, including 263 upregulated genes and 322 downregulated genes. Then, through the Kyoto Encyclopedia of Genome and Genome (KEGG) pathway and biological process (BP) analysis, we found that the upregulated and downregulated DEGs were abundant in different pathways, respectively. It was noteworthy that upregulated DEGs were the most significantly enriched in the mTOR signaling pathway. Subsequently, through the protein-protein interaction (PPI) network, we identified seven hub genes, namely, EXOSC2, CAMK2A, PRIM1, SMC4, TYMS, CDK6, and RPA2. Finally, through gene set enrichment analysis (GSEA), we obtained that hypoxia, epithelial-mesenchymal transition, hedgehog signaling, and reactive oxygen species pathway were the enriched pathways for MDD patients. The above data results would provide a new direction for the treatment of MDD patients.


Assuntos
Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/metabolismo , Biomarcadores/metabolismo , Biologia Computacional , Bases de Dados Genéticas , Regulação para Baixo , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Marcadores Genéticos , Humanos , Redes e Vias Metabólicas/genética , Mapas de Interação de Proteínas/genética , Transdução de Sinais/genética , Regulação para Cima
6.
Biochemistry (Mosc) ; 86(6): 729-736, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34225595

RESUMO

Comparative analysis of available literature data on the pathogenetic neuroendocrine mechanisms of depression and post-traumatic stress disorder (PTSD) is provided in this review to identify their common features and differences. We discuss the multidirectional modifications of the activity of cortical and subcortical structures of the brain, levels of neurotransmitters and their receptors, and functions of the hypothalamic-pituitary-adrenocortical axis in depression and PTSD. The analysis shows that these disorders are examples of opposite failures in the system of adaptive stress response of the body to stressful psychotraumatic events. On this basis, it is concluded that the currently widespread use of similar approaches to treat these disorders is not justified, despite the significant similarity of their anxiety-depressive symptoms; development of differential therapeutic strategies is required.


Assuntos
Encéfalo/metabolismo , Transtorno Depressivo Maior/metabolismo , Glucocorticoides/metabolismo , Neurotransmissores/metabolismo , Transtornos de Estresse Pós-Traumáticos/metabolismo , Transtorno Depressivo Maior/etiologia , Humanos , Transtornos de Estresse Pós-Traumáticos/etiologia , Estresse Psicológico
7.
Psychopharmacology (Berl) ; 238(7): 2043-2044, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34115156

RESUMO

With respect to Guo's inspiring article (Guo et al. 2021), we would like to suggest several corrections about some of the figures. We felt obliged to write this erratum letter as these incompatibilities may cause confusion for the readers.


Assuntos
Transtorno Depressivo Maior/metabolismo , Receptores sigma/metabolismo , Analgésicos Opioides/metabolismo , Analgésicos Opioides/farmacologia , Animais , Ligantes , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos
8.
Int J Mol Sci ; 22(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071826

RESUMO

Major depressive disorder (MDD) is a severe psychiatric condition with key symptoms of low mood and lack of motivation, joy, and pleasure. Recently, the acid sphingomyelinase (ASM)/ceramide system has been implicated in the pathogenesis of MDD. ASM is a lysosomal glycoprotein that catalyzes the hydrolysis of sphingomyelin, an abundant component of membranes, into the bioactive sphingolipid ceramide, which impacts signaling pathways. ASM activity is inhibited by several common antidepressant drugs. Human and murine studies have confirmed that increased ASM activity and ceramide levels are correlated with MDD. To define a molecular marker for treatment monitoring, we investigated the mRNA expression of SMPD1, which encodes ASM, in primary cell culture models, a mouse study, and a human study with untreated MDD patients before and after antidepressive treatment. Our cell culture study showed that a common antidepressant inhibited ASM activity at the enzymatic level and also at the transcriptional level. In a genetically modified mouse line with depressive-like behavior, Smpd1 mRNA expression in dorsal hippocampal tissue was significantly decreased after treatment with a common antidepressant. The large human study showed that SMPD1 mRNA expression in untreated MDD patients decreased significantly after antidepressive treatment. This translational study shows that SMPD1 mRNA expression could serve as a molecular marker for treatment and adherence monitoring of MDD.


Assuntos
Antidepressivos/farmacologia , Biomarcadores , Regulação da Expressão Gênica/efeitos dos fármacos , Expressão Gênica , RNA Mensageiro , Esfingomielina Fosfodiesterase/genética , Animais , Antidepressivos/uso terapêutico , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Camundongos , Camundongos Transgênicos
9.
Sci Rep ; 11(1): 13365, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34183728

RESUMO

There is a large amount of evidence that selective serotonin reuptake inhibitors (SSRIs) are related to cardiovascular toxicity, which has aroused concern regarding their safety. However, few studies have evaluated the effects of SSRIs on cardiac injury biomarkers, such as creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The purpose of our study was to determine whether SSRIs elevated CK and CK-MB levels of prior medicated depressive patients (PMDP) compared to first-episode drug-naïve depressive patients (FDDPs). We performed an observational and retrospective study involving 128 patients with major depressive disorder. Patients who had never used any type of antidepressant were designated FDDP; patients who had used only one type of SSRI but were not treated after a recent relapse were designated PMDP. Serum CK and CK-MB levels were measured before and after using SSRIs for a period of time. The duration of current treatment in the FDDP and PMDP groups was 16.200 ± 16.726 weeks and 15.618 ± 16.902 weeks, respectively. After SSRI treatment, levels of serum CK in the PMDP group were significantly higher than in the FDDP group. Univariate ANCOVA results revealed that PMDP was 22.313 times more likely to elevate CK (OR 22.313, 95% CI 9.605-35.022) and 2.615 times more likely to elevate CK-MB (OR 2.615, 95% CI 1.287-3.943) than FDDP. Multivariate ANCOVA revealed an interaction between the group and sex of CK and CK-MB. Further pairwise analysis of the interaction results showed that in female patients, the mean difference (MD) of CK and CK-MB in PMDP was significantly greater than that in FDDP (MD = 33.410, P = 0.000, 95% CI 15.935-50.886; MD = 4.613, P = 0.000, 95% CI 2.846-6.381). Our findings suggest that patients, especially females, who had previously used SSRI antidepressants were more likely to have elevated CK and CK-MB, indicators of myocardial muscle injury. Use of SSRIs should not be assumed to be completely safe and without any cardiovascular risks.


Assuntos
Antidepressivos/uso terapêutico , Creatina Quinase Forma MB/sangue , Creatina Quinase/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Inibidores de Captação de Serotonina/uso terapêutico , Adulto , Biomarcadores/metabolismo , Depressão/sangue , Depressão/tratamento farmacológico , Depressão/metabolismo , Feminino , Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/tratamento farmacológico , Traumatismos Cardíacos/metabolismo , Humanos , Masculino , Miocárdio/metabolismo , Estudos Retrospectivos
10.
Am J Psychiatry ; 178(6): 522-529, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33985349

RESUMO

OBJECTIVE: The authors investigated the pathways (genetic, environmental, lifestyle, medical) leading to inflammation in major depressive disorder using C-reactive protein (CRP), genetic, and phenotypic data from the UK Biobank. METHODS: This was a case-control study of 26,894 participants with a lifetime diagnosis of major depressive disorder from the Composite International Diagnostic Interview and 59,001 control subjects who reported no mental disorder and had not reported taking any antidepressant medication. Linear regression models of log CRP level were fitted to regress out the effects of age, sex, body mass index (BMI), and smoking and to test whether the polygenic risk score (PRS) for major depression was associated with log CRP level and whether the association between log CRP level and major depression remained after adjusting for early-life trauma, socioeconomic status, and self-reported health status. RESULTS: CRP levels were significantly higher in patients with depression relative to control subjects (2.4 mg/L compared with 2.1 mg/L, respectively), and more case than control subjects had CRP levels >3 mg/L (21.2% compared with 16.8%, respectively), indicating low-grade inflammation. The PRS for depression was positively and significantly associated with log CRP levels, but this association was no longer significant after adjustment for BMI and smoking. The association between depression and increased log CRP level was substantially reduced, but still remained significant, after adjustment for the aforementioned clinical and sociodemographic factors. CONCLUSIONS: The data indicate that the "genetic" contribution to increased inflammation in depression is due to regulation of eating and smoking habits rather than an "autoimmune" genetic predisposition. Moreover, the association between depression and increased inflammation even after full adjustment indicates either the presence of yet unknown or unmeasured psychosocial and clinical confounding factors or that a core biological association between depression and increased inflammation exists independently from confounders.


Assuntos
Experiências Adversas da Infância , Proteína C-Reativa/metabolismo , Transtorno Depressivo Maior/metabolismo , Nível de Saúde , Inflamação/metabolismo , Classe Social , Bancos de Espécimes Biológicos , Estudos de Casos e Controles , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/psicologia , Feminino , Predisposição Genética para Doença , Humanos , Inflamação/genética , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Psicologia , Fumar/metabolismo , Reino Unido
11.
Int J Biol Macromol ; 183: 2001-2008, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34052271

RESUMO

Major depressive disorder (MDD) is the most common mood disorder, and causes various mental, physical and cognitive symptoms. Clinicians diagnose MDD using multiple interviews and overall impression during the interviews, which makes MDD diagnosis highly subjective. To overcome this, we investigated novel protein biomarker for MDD. Serum from each subject were analyzed using nano liquid chromatography-triple time-of-flight mass spectrometry. We identified two proteins, zinc-alpha-2-glycoprotein (ZA2G) and keratin type II cytoskeletal 1 (K2C1), as final biomarkers. These biomarkers were downregulated during depression (p < 0.05, AUC of ROC >0.7). ZA2G is related to tryptophan metabolism, which is a main serotonin synthesis pathway. K2C1 is involved in the kinin-kallikrein system, which produces bradykinin, an anti-inflammatory mediator in the brain. Our results suggest that the two protein candidates are related to inflammation and that MDD is highly associated with inflammation. Finally, since all subjects in the two groups were taking antidepressants, our results suggest that the identified biomarkers could determine the presence or absence of illness and could be used to monitor therapeutic effects.


Assuntos
Adipocinas/sangue , Biomarcadores/sangue , Transtorno Depressivo Maior/diagnóstico , Queratina-1/sangue , Proteômica/métodos , Regulação para Cima , Adulto , Idoso , Estudos de Casos e Controles , Cromatografia Líquida , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/metabolismo , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem , Triptofano/metabolismo
12.
Nat Commun ; 12(1): 3166, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039978

RESUMO

Stress is a significant risk factor for the development of major depressive disorder (MDD), yet the underlying mechanisms remain unclear. Preclinically, adaptive and maladaptive stress-induced changes in glutamatergic function have been observed in the medial prefrontal cortex (mPFC). Here, we examine stress-induced changes in human mPFC glutamate using magnetic resonance spectroscopy (MRS) in two healthy control samples and a third sample of unmedicated participants with MDD who completed the Maastricht acute stress task, and one sample of healthy control participants who completed a no-stress control manipulation. In healthy controls, we find that the magnitude of mPFC glutamate response to the acute stressor decreases as individual levels of perceived stress increase. This adaptative glutamate response is absent in individuals with MDD and is associated with pessimistic expectations during a 1-month follow-up period. Together, this work shows evidence for glutamatergic adaptation to stress that is significantly disrupted in MDD.


Assuntos
Transtorno Depressivo Maior/psicologia , Ácido Glutâmico/metabolismo , Pessimismo/psicologia , Córtex Pré-Frontal/fisiopatologia , Estresse Psicológico/metabolismo , Adaptação Fisiológica , Adolescente , Adulto , Anedonia , Estudos de Casos e Controles , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/fisiopatologia , Feminino , Seguimentos , Ácido Glutâmico/análise , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/metabolismo , Estresse Fisiológico , Estresse Psicológico/fisiopatologia , Adulto Jovem
13.
Sci Rep ; 11(1): 9645, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33958659

RESUMO

In addition to the psychological depressive phenotype, major depressive disorder (MDD) patients are also associated with underlying immune dysregulation that correlates with metabolic syndrome prevalent in depressive patients. A robust integrative analysis of biological pathways underlying the dysregulated neural connectivity and systemic inflammatory response will provide implications in the development of effective strategies for the diagnosis, management and the alleviation of associated comorbidities. In the current study, focusing on MDD, we explored an integrative network analysis methodology to analyze transcriptomic data combined with the meta-analysis of biomarker data available throughout public databases and published scientific peer-reviewed articles. Detailed gene set enrichment analysis and complex protein-protein, gene regulatory and biochemical pathway analysis has been undertaken to identify the functional significance and potential biomarker utility of differentially regulated genes, proteins and metabolite markers. This integrative analysis method provides insights into the molecular mechanisms along with key glycosylation dysregulation underlying altered neutrophil-platelet activation and dysregulated neuronal survival maintenance and synaptic functioning. Highlighting the significant gap that exists in the current literature, the network analysis framework proposed reduces the impact of data gaps and permits the identification of key molecular signatures underlying complex disorders with multiple etiologies such as within MDD and presents multiple treatment options to address their molecular dysfunction.


Assuntos
Transtorno Depressivo Maior/metabolismo , Biomarcadores , Encéfalo/metabolismo , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/genética , Doença/etiologia , Perfilação da Expressão Gênica , Glicosilação , Humanos , Metabolômica
14.
PLoS One ; 16(5): e0251026, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33956824

RESUMO

BACKGROUND: Major depression is a common comorbidity in cancer patients. Oncology clinics lack practical, objective tools for simultaneous evaluation of cancer and major depression. Fludeoxyglucose F-18 positron emission tomography-computed tomography (FDG PET/CT) is universally applied in modern medicine. METHODS: We used a retrospective analysis of whole-body FDG PET/CT images to identify brain regional metabolic patterns of major depression in multiple myeloma patients. The study included 134 multiple myeloma (MM) patients, 38 with major depression (group 1) and 96 without major depression (group 2). RESULTS: In the current study, Statistic Parameter Mapping (SPM) demonstrated that the major depression patient group (n = 38) had significant regional metabolic differences (clusters of continuous voxels) as compared to the non-major depression group (n = 96) with the criteria of height threshold T = 4.38 and extent threshold > 100 voxels. The five significant hypo- and three hyper-metabolic clusters from the computed T contrast maps were localized on the glass-brain view, consistent with published brain metabolic changes in major depression patients. Subsequently, using these clusters as features for classification learner, the fine tree and medium tree algorithms from 25 classification algorithms best fitted our data (accuracy 0.85%; AUC 0.88; sensitivity 79%; and specificity 88%). CONCLUSION: This study demonstrated that whole-body FDG PET/CT scans could provide added value for screening for major depression in cancer patients in addition to staging and evaluating response to chemoradiation therapies.


Assuntos
Encéfalo/metabolismo , Transtorno Depressivo Maior/etiologia , Mieloma Múltiplo/psicologia , Biomarcadores , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Estudos de Casos e Controles , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/metabolismo , Feminino , Fluordesoxiglucose F18 , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Neuroimagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Valor Preditivo dos Testes , Estudos Retrospectivos
15.
J Adv Res ; 30: 27-38, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34026284

RESUMO

Introduction: Major depressive disorder is caused by gene-environment interactions, and the host microbiome has been recognized as an important environmental factor. However, the underlying mechanisms of the host-microbiota interactions that lead to depression are complex and remain poorly understood. Objectives: The present study aimed to explore the possible mechanisms underlying gut microbiota dysbiosis-induced depressive-like behaviors. Methods: We used high-performance liquid chromatography-tandem mass spectrometry to analyze alterations in the hippocampal lysine acetylome and succinylome in male mice that had received gut microbiota from fecal samples of either patients with major depressive disorder or healthy controls. This was followed by bioinformatic analyses. Results: A total of 315 acetylation sites on 223 proteins and 624 succinylation sites on 494 proteins were differentially expressed in the gut microbiota-dysbiosis mice. The significantly acetylated proteins were primarily associated with carbon metabolism disruption and gene transcription suppression, while the synaptic vesicle cycle and protein translation were the most significantly altered functions for succinylated proteins. Additionally, our findings suggest that gut microbiota dysbiosis disturbs mitochondria-mediated biological processes and the MAPK signaling pathway through crosstalk between acetylation and succinylation on relevant proteins. Conclusions: This is the first study to demonstrate modifications in acetylation and succinylation in gut microbiota-dysbiosis mice. Our findings provide new avenues for exploring the pathogenesis of gut microbiota dysbiosis-related depression, and highlight potential targets for depression treatment.


Assuntos
Transtorno Depressivo Maior/metabolismo , Disbiose/metabolismo , Microbioma Gastrointestinal , Hipocampo/metabolismo , Lisina/metabolismo , Proteoma/metabolismo , Acetilação , Animais , Cromatografia Líquida de Alta Pressão/métodos , Depressão/metabolismo , Depressão/microbiologia , Transtorno Depressivo Maior/microbiologia , Disbiose/microbiologia , Transplante de Microbiota Fecal/métodos , Interação Gene-Ambiente , Humanos , Masculino , Camundongos , Processamento de Proteína Pós-Traducional , Ácido Succínico/metabolismo , Espectrometria de Massas em Tandem/métodos
16.
J Tradit Chin Med ; 41(2): 338-348, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33825416

RESUMO

OBJECTIVE: To investigate the mechanism underpinning the effect of Chaihu Shugan San ( CHSGS) on major depressive disorder (MDD). METHODS: We searched the compound components of from seven herbal ingredients of CHSGS from TCMSP, SymMap, ETCM, NPASS databases, and the chemical structure of the compound from PubChem, and collected the compound targets from TCMSP and TargetNet databases, and MDD-related targets from DiseaseGene Network. We established protein-protein interaction in the STRING database. Through gene mapping, topology analysis and enrichment analysis, the core targets and pathways of CHSGS for MDD, and the involved biological processes (BP), cell components (CC), and molecular functions (MF) were predicted. RESULTS: We collected a total of 1135 CHSGS compounds. After screening by ADME standards and the five rules of Ribinski, we obtained 99 different chemical components with different chemical structures, and related targets of 183 different CHSGS compounds. In the DiseaseGene Network, a total of 740 relevant targets for MDD were collected. Through gene mapping and topological analysis, 62 related targets of CHSGS for MDD, 24 targets with topological Chinese herbal medicine were obtained. Through enrichment analysis, 10 relevant pathways and 3 core pathways were obtained with the involvement of 127 BP, 27 CC, and 43 MF. CONCLUSION: There are multiple targets and signaling pathways are involved in the action of CHSGS in the treatment of MDD.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Transtorno Depressivo Maior/metabolismo , Medicamentos de Ervas Chinesas/química , Humanos , Proteínas/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Biochem Biophys Res Commun ; 553: 114-118, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33765555

RESUMO

Major depressive disorder (MDD) is a debilitating mental illness that can cause significant emotional disturbances and severe socioeconomic burdens. Rodent and nonhuman primate-based depression models have been studied, such as brain-derived neurotrophic factor (BDNF) and monoamine acid disorder hypotheses, as well as peripheral microbiota disturbances causing MDD; however, the pathogenesis is still largely unknown. This study aims to explore the relationship between ferritin and MDD. First, alterations in ferritin, including ferritin light chain (FTL) and ferritin heavy chain (FTH), in MDD patient plasma compared with healthy control (HC) plasma were detected using ELISA. Then, serum ferritin expression in cLPS-depressed mice was measured by ELISA. The existence of FTH in the hippocampus was validated by immunofluorescence, and the change in FTH levels in the hippocampus of mice injected with cLPS was detected by western blotting. FTL levels in MDD patients were decreased compared with those in HCs. In cLPS-depressed mice, serum ferritin was not different from that in the control group, while the expression of FTH in the hippocampus was significantly reduced in depressed mice. Our findings demonstrate the alteration of ferritin expression in MDD and provide new insight into the pathogenesis of MDD.


Assuntos
Apoferritinas/sangue , Apoferritinas/metabolismo , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/metabolismo , Hipocampo/metabolismo , Animais , Apoferritinas/deficiência , Apoferritinas/genética , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Casos e Controles , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/patologia , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Humanos , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Adulto Jovem
18.
Int J Mol Sci ; 22(4)2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33668515

RESUMO

Depression, the most prevalent psychiatric disorder in the Western world, is characterized by increased negative affect (i.e., depressed mood, cost value increase) and reduced positive affect (i.e., anhedonia, reward value decrease), fatigue, loss of appetite, and reduced psychomotor activity except for cases of agitative depression. Some forms, such as post-partum depression, have a high risk for suicidal attempts. Recent studies in humans and in animal models relate major depression occurrence and reoccurrence to alterations in dopaminergic activity, in addition to other neurotransmitter systems. Imaging studies detected decreased activity in the brain reward circuits in major depression. Therefore, the location of dopamine receptors in these circuits is relevant for understanding major depression. Interestingly, in cortico-striatal-dopaminergic pathways within the reward and cost circuits, the expression of dopamine and its contribution to reward are modulated by endocannabinoid receptors. These receptors are enriched in the striosomal compartment of striatum that selectively projects to dopaminergic neurons of substantia nigra compacta and is vulnerable to stress. This review aims to show the crosstalk between endocannabinoid and dopamine receptors and their vulnerability to stress in the reward circuits, especially in corticostriatal regions. The implications for novel treatments of major depression are discussed.


Assuntos
Corpo Estriado/metabolismo , Transtorno Depressivo Maior/metabolismo , Neurônios Dopaminérgicos/metabolismo , Endocanabinoides/metabolismo , Parte Compacta da Substância Negra/metabolismo , Corpo Estriado/patologia , Transtorno Depressivo Maior/patologia , Dopamina/metabolismo , Neurônios Dopaminérgicos/patologia , Humanos , Parte Compacta da Substância Negra/patologia
19.
Int J Mol Sci ; 22(4)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33672070

RESUMO

Serotonin communication operates mainly in the extracellular space and cerebrospinal fluid (CSF), using volume transmission with serotonin moving from source to target cells (neurons and astroglia) via energy gradients, leading to the diffusion and convection (flow) of serotonin. One emerging concept in depression is that disturbances in the integrative allosteric receptor-receptor interactions in highly vulnerable 5-HT1A heteroreceptor complexes can contribute to causing major depression and become novel targets for the treatment of major depression (MD) and anxiety. For instance, a disruption and/or dysfunction in the 5-HT1A-FGFR1 heteroreceptor complexes in the raphe-hippocampal serotonin neuron systems can contribute to the development of MD. It leads inter alia to reduced neuroplasticity and potential atrophy in the raphe-cortical and raphe-striatal 5-HT pathways and in all its forebrain networks. Reduced 5-HT1A auto-receptor function, increased plasticity and trophic activity in the midbrain raphe 5-HT neurons can develop via agonist activation of allosteric receptor-receptor interactions in the 5-HT1A-FGFR1 heterocomplex. Additionally, the inhibitory allosteric receptor-receptor interactions in the 5-HT1AR-5-HT2AR isoreceptor complex therefore likely have a significant role in modulating mood, involving a reduction of postjunctional 5-HT1AR protomer signaling in the forebrain upon activation of the 5-HT2AR protomer. In addition, oxytocin receptors (OXTRs) play a significant and impressive role in modulating social and cognitive related behaviors like bonding and attachment, reward and motivation. Pathological blunting of the OXTR protomers in 5-HT2AR and especially in 5-HT2CR heteroreceptor complexes can contribute to the development of depression and other types of psychiatric diseases involving disturbances in social behaviors. The 5-HTR heterocomplexes are novel targets for the treatment of MD.


Assuntos
Depressão/metabolismo , Transtorno Depressivo Maior/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Serotonina/metabolismo , Transdução de Sinais , Animais , Humanos , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Receptor 5-HT2A de Serotonina/metabolismo , Receptor 5-HT2C de Serotonina/metabolismo , Receptores de Ocitocina/metabolismo
20.
Nat Commun ; 12(1): 1647, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712584

RESUMO

Major depressive disorder (MDD) has been shown to be associated with structural abnormalities in a variety of spatially diverse brain regions. However, the correlation between brain structural changes in MDD and gene expression is unclear. Here, we examine the link between brain-wide gene expression and morphometric changes in individuals with MDD, using neuroimaging data from two independent cohorts and a publicly available transcriptomic dataset. Morphometric similarity network (MSN) analysis shows replicable cortical structural differences in individuals with MDD compared to control subjects. Using human brain gene expression data, we observe that the expression of MDD-associated genes spatially correlates with MSN differences. Analysis of cell type-specific signature genes suggests that microglia and neuronal specific transcriptional changes account for most of the observed correlation with MDD-specific MSN differences. Collectively, our findings link molecular and structural changes relevant for MDD.


Assuntos
Encéfalo/metabolismo , Encéfalo/patologia , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/metabolismo , Transcriptoma , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Neuroimagem/métodos , Neurônios
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