Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.914
Filtrar
1.
PLoS One ; 15(8): e0237235, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785256

RESUMO

Mitochondrial DNA copy number (mtDNAcn) is a putative biomarker of oxidative stress and biological aging. Modifiable factors, including physical activity (PA), avoidance of heavy alcohol use and smoking, and maintaining good mental health, may reduce oxidative stress and promote healthy aging. Yet, limited data exist regarding how these factors are associated with mtDNAcn or whether age, sex or race/ethnicity moderate associations. In this cross-sectional study, we selected 391 adults (183 non-Hispanic White, 110 Black and 98 Hispanic; mean = 67 years) from the VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention) ancillary to the VITAL trial. We estimated associations between lifestyle and behavioral factors (PA, alcohol consumption, cigarette smoking and depression) and log-transformed mtDNAcn using multivariable linear regression models. MtDNAcn was not correlated with chronological age; women had ~17% higher mtDNAcn compared to men. There were no significant associations between PA measures (frequency, amount or intensity) or alcohol consumption with mtDNAcn. Cigarette smoking (per 5 pack-years) was significantly associated with mtDNAcn (percent difference = -2.9% (95% confidence interval (CI) = -5.4%, -0.4%)); a large contrast was observed among heavy vs. non-smokers (≥30 vs. 0 pack-years): percent difference = -28.5% (95% CI = -44.2%, -8.3%). The estimate of mtDNAcn was suggestively different for past vs. no depression history (percent difference = -15.1% 95% CI = -30.8%, 4.1%), but this difference was not statistically significant. The association between smoking and log-mtDNAcn varied by sex and race/ethnicity; it was stronger in men and Black participants. While chance findings cannot be excluded, results from this study support associations of smoking, but not chronological age, with mtDNAcn and suggest nuanced considerations of mtDNAcn as indicative of varying oxidative stress states vs. biological aging itself.


Assuntos
Variações do Número de Cópias de DNA , DNA Mitocondrial/genética , Estilo de Vida , Idoso , Envelhecimento , Consumo de Bebidas Alcoólicas/genética , Fumar Cigarros/genética , Estudos Transversais , Depressão/genética , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
2.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(7): 922-929, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32701232

RESUMO

OBJECTIVE: To investigate the differential expression of miR-30a-5p in patients with poststroke depression and explore the possible mechanism. METHODS: We obtained the target microRNAs through searching PubMed using the online software VENNY2.1. We collected the baseline demographic, clinical and radiographic data from consecutive patients with first-ever acute ischemic stroke on admission in our department from October, 2018 to March, 2019. From each patient, 5 mL peripheral venous blood was collected upon admission. Hamilton Depression Scale (HAMD-17) was used to evaluate the degree of depression at the end of the 3-month follow-up. The patients with a HAMD-17 score≥7 were diagnosed to have depression according to the diagnostic criteria of the Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association (DSM-IV). The patients were divided into post-stroke depression group (PSD group, n=11) and non-post-stroke depression group (non-PSD group, n=25), and their plasma levels of miR-30a-5p were detected using qPCR. The STARBASE Database ENCORI miRNA-mRNA module and Comparative Toxicogenomics Database were used to predict and screen the possible target genes related to miR-30a-5p, and the possible mechanism of the target genes was further analyzed through bioinformatics. RESULTS: miR-30a-5p was identified by cross-screening as the target miRNA associated with stroke and depression and showed obvious differential expression between PSD and non-PSD patients (2.462±0.326 vs 1±0.126, P < 0.0001). ROC curve analysis showed that the AUC of miR-30a-5p for predicting PSD was 0.869 (95%CI: 0.745-0.993, P=0.0005) at the cutoff value of 1.597, with a sensitivity and specificity of 0.727 and 0.840, respectively. The target proteins of miR-30a-5p involved a wide range of biological processes, including signal transduction, intercellular communication, regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism. KEGG pathway enrichment analysis showed that the target proteins affected mainly the neural nutrient signaling pathway, axon guidance signaling pathway and insulin signaling system. We also identified the top 20 HUB genes that might be associated with post-stroke depression. CONCLUSIONS: Plasma miR-30a-5p is differentially expressed in PSD and can serve as a new blood marker for diagnosis and also a therapeutic target of PSD.


Assuntos
Isquemia Encefálica , Biologia Computacional , Depressão , MicroRNAs/genética , Acidente Vascular Cerebral , Depressão/etiologia , Depressão/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Acidente Vascular Cerebral/complicações
3.
Proc Natl Acad Sci U S A ; 117(24): 13771-13782, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32487727

RESUMO

The nucleus accumbens (NAc), a central component of the midbrain dopamine reward circuit, exhibits disturbed circadian rhythms in the postmortem brains of depressed patients. We hypothesized that normal mood regulation requires proper circadian timing in the NAc, and that mood disorders are associated with dysfunctions of the NAc cellular circadian clock. In mice exhibiting stress-induced depression-like behavior (helplessness), we found altered circadian clock function and high nighttime expression of the core circadian clock component CRYPTOCHROME (CRY) in the NAc. In the NAc of helpless mice, we found that higher expression of CRY is associated with decreased activation of dopamine 1 receptor-expressing medium spiny neurons (D1R-MSNs). Furthermore, D1R-MSN-specific CRY-knockdown in the NAc reduced susceptibility to stress-induced helplessness and increased NAc neuronal activation at night. Finally, we show that CRY inhibits D1R-induced G protein activation, likely by interacting with the Gs protein. Altered circadian rhythms and CRY expression were also observed in human fibroblasts from major depressive disorder patients. Our data reveal a causal role for CRY in regulating the midbrain dopamine reward system, and provide a mechanistic link between the NAc circadian clock and vulnerability to depression.


Assuntos
Relógios Circadianos , Criptocromos/metabolismo , Depressão/metabolismo , Núcleo Accumbens/metabolismo , Animais , Comportamento Animal , Depressão/genética , Depressão/fisiopatologia , Depressão/psicologia , Dopamina/metabolismo , Feminino , Desamparo Aprendido , Humanos , Masculino , Camundongos , Neurônios/metabolismo , Receptores Dopaminérgicos/genética , Receptores Dopaminérgicos/metabolismo
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(1): 56-60, 2020 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-32376566

RESUMO

OBJECTIVE: To study the behavioral changes of inositol 1, 4, 5-trisphosphate receptor type 2 knockout (Itpr2-/- mice) and investigate the blood perfusion changes in the hippocampus using three-dimensional arterial spin labeling (3D-ASL). METHODS: 28 Itpr2-/- mice and 20 wild-type mice were assessed for depressive phenotype using behavioral tests (including sucrose consumption test, tail suspension test, forced swimming test and open field test). 15 Itpr2-/- mice and 14 wild-type mice were randomly selected for 3D-T2WI imaging of the whole brain and 3D-ASL imaging of the middle hippocampal layer, and cerebral blood flow (CBF) of the middle hippocampal layer was calculated. ITK-SNAP was used to delineate the bilateral hippocampal area and measure the average CBF value. RESULTS: Compared with the wild-type mice, Itpr2-/- mice exhibited a distinct depressive phenotype with significantly decreased sucrose preference (P < 0.05) and increased immobile time in tail suspension test (P < 0.05) and forced swimming test (P < 0.01), without obvious changes in the performance in open field test (P > 0.05). Significantly decreased mean CBF values were found in the left and right hippocampus of Itpr2-/- mice as compared with the wild-type mice (left: 73.30 ±5.609 vs 95.77±5.095; right: 73.53±5.700 vs 100.5±4.696; bilateral means: 73.42±5.607 vs98.12±4.754; P < 0.01). CONCLUSIONS: Itpr2 deficiency can cause depressive phenotype and affect the cerebral blood flow in the hippocampus of mice.


Assuntos
Circulação Cerebrovascular , Depressão/genética , Hipocampo/diagnóstico por imagem , Imageamento Tridimensional , Animais , Hipocampo/irrigação sanguínea , Receptores de Inositol 1,4,5-Trifosfato/genética , Camundongos , Camundongos Knockout , Imagem de Perfusão , Marcadores de Spin
6.
N Z Med J ; 133(1515): 70-78, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32438378

RESUMO

AIMS: To describe health conditions in New Zealand nuclear veterans and their offspring, and examine the utility of tests to assess their heritability. METHOD: An online survey, open to all veterans and offspring, with questions on health conditions, the GHQ12 to measure psychological distress, the Euroquol-5D visual analogue scale (EQ5D VAS) to measure health state, and free text items on veteran support. RESULTS: Eighty-three responses (56%) were from veterans, 65 (44%) from offspring. Anxiety and depression were prevalent in both groups, with cancers (n=31, 37%) and joint conditions common in veterans (n=26, 31%). Few offspring reported cancer, rather problems with fertility (n=18, 40%). The free text themes fell into four domains, official commitment, health, emotional and information support; however, little support had been sought. CONCLUSION: Cancers have utility in assessing heritability, but a low prevalence and lack of diagnostic data rules this out. Psychological conditions may be heritable, but the techniques to assess this are still developing. Chromosomal damage in veterans and offspring can be detected, but with present knowledge cannot explain health outcomes. Future work should assemble a veteran and family register with linkage to routine data-sets. Veterans and offspring should be encouraged to seek support.


Assuntos
Ansiedade/epidemiologia , Depressão/epidemiologia , Neoplasias/epidemiologia , Armas Nucleares , Exposição Ocupacional , Veteranos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Ansiedade/genética , Depressão/genética , Família , Testes Genéticos , Inquéritos Epidemiológicos , Humanos , Infertilidade/epidemiologia , Infertilidade/genética , Artropatias/epidemiologia , Artropatias/genética , Pessoa de Meia-Idade , Neoplasias/genética , Nova Zelândia/epidemiologia , Exposição Ocupacional/efeitos adversos , Prevalência , Radiação Ionizante , Apoio Social , Adulto Jovem
7.
Nat Commun ; 11(1): 2301, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385265

RESUMO

Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (ß: 0.125 to 0.868, pFDR < 0.043). Several behavioural traits are also associated with depression-PRS (ß: 0.014 to 0.180, pFDR: 0.049 to 1.28 × 10-14) and we find a significant and positive interaction between depression-PRS and adverse environmental exposures on mental health outcomes. This study reveals replicable associations between depression-PRS and white matter microstructure. Our results indicate that white matter microstructure differences may be a causal consequence of liability to depression.


Assuntos
Depressão/genética , Córtex Pré-Frontal/metabolismo , Idoso , Bancos de Espécimes Biológicos , Depressão/metabolismo , Depressão/patologia , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Neuroimagem/métodos , Polimorfismo de Nucleotídeo Único/genética , Córtex Pré-Frontal/patologia , Fatores de Risco
8.
Am J Hum Genet ; 106(6): 885-892, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32413284

RESUMO

Leveraging high-dimensional molecular datasets can help us develop mechanistic insight into associations between genetic variants and complex traits. In this study, we integrated human proteome data derived from brain tissue to evaluate whether targeted proteins putatively mediate the effects of genetic variants on seven neurological phenotypes (Alzheimer disease, amyotrophic lateral sclerosis, depression, insomnia, intelligence, neuroticism, and schizophrenia). Applying the principles of Mendelian randomization (MR) systematically across the genome highlighted 43 effects between genetically predicted proteins derived from the dorsolateral prefrontal cortex and these outcomes. Furthermore, genetic colocalization provided evidence that the same causal variant at 12 of these loci was responsible for variation in both protein and neurological phenotype. This included genes such as DCC, which encodes the netrin-1 receptor and has an important role in the development of the nervous system (p = 4.29 × 10-11 with neuroticism), as well as SARM1, which has been previously implicated in axonal degeneration (p = 1.76 × 10-08 with amyotrophic lateral sclerosis). We additionally conducted a phenome-wide MR study for each of these 12 genes to assess potential pleiotropic effects on 700 complex traits and diseases. Our findings suggest that genes such as SNX32, which was initially associated with increased risk of Alzheimer disease, may potentially influence other complex traits in the opposite direction. In contrast, genes such as CTSH (which was also associated with Alzheimer disease) and SARM1 may make worthwhile therapeutic targets because they did not have genetically predicted effects on any of the other phenotypes after correcting for multiple testing.


Assuntos
Encéfalo/metabolismo , Variação Genética/genética , Doenças do Sistema Nervoso/genética , Fenômica , Proteoma/genética , Proteômica , Doença de Alzheimer/genética , Esclerose Amiotrófica Lateral/genética , Proteínas do Domínio Armadillo/genética , Proteínas de Transporte/genética , Catepsina H/genética , Proteínas do Citoesqueleto/genética , Depressão/genética , Estudo de Associação Genômica Ampla , Humanos , Inteligência/genética , Doenças do Sistema Nervoso/metabolismo , Neuroticismo , Proteínas Nucleares/genética , Fenótipo , Proteoma/metabolismo , Esquizofrenia/genética , Distúrbios do Início e da Manutenção do Sono/genética , Nexinas de Classificação/genética
9.
N Z Med J ; 133(1513): 116-118, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32325477

RESUMO

Perry syndrome is a rare neurological condition characterised clinically by depression, sleep disturbance, central hypoventilation and parkinsonism. Perry syndrome is a TAR DNA-binding protein 43 (TDP-43) proteinopathy associated with mutated dynactin-1 protein, inherited in an autosomal dominant manner. Several pathogenic mutations in exon 2 in the dynactin 1 gene have been identified; p. F521, p. G67d, p. G71R, p. G71E, p. G71A, p. T72p, p. Q74p and p. Y78C. We present the second known case Perry syndrome with confirmed DCTN1 mutation (p. Y78C) in New Zealand, who initially was thought to have a depressive illness. Perry syndrome should be considered in the differential diagnosis of young parkinsonism, especially if there is family history of sleep disorders, weight loss and/or marked depression.


Assuntos
Complexo Dinactina/genética , Hipoventilação , Mutação/genética , Transtornos Parkinsonianos , Depressão/diagnóstico , Depressão/genética , Depressão/fisiopatologia , Feminino , Humanos , Hipoventilação/diagnóstico , Hipoventilação/genética , Hipoventilação/fisiopatologia , Pessoa de Meia-Idade , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/genética , Transtornos Parkinsonianos/fisiopatologia , Linhagem
10.
J Acupunct Meridian Stud ; 13(3): 94-103, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32278077

RESUMO

BACKGROUND AND OBJECTIVE: Perimenopausal depression is caused by the impaired function of the ovarium before menopause and with a series of symptoms. Electroacupuncture (EA) therapy has been demonstrated to improve clinically depression. However, the mechanism underlying its therapeutic activity remains unknown. This study aimed to investigat the effects of EA treatment on the hippocampal neural proliferation through Wnt signaling pathway. METHODS: Chronic unpredictable mild stress (CUMS) combined with bilateral ovariectomy (OVX) were used to establish a rat model of perimenopausal depression. The open field test (OFT) and sucrose preference test (SPT) were used to assess depression-like behaviors in rats. ELISAs were used to measure estrogen (E2), luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) levels in the serum. RT-PCR and Western blot assay were utilized for measuring the mRNA expressions and protein expressions of GSK-3ß/ß-catenin. RESULTS: Four-week EA treatment at three points including "Shenshu" (BL23), "Baihui" (GV20) and "Sanyinjiao" (SP6) simultaneously ameliorated depression-like behaviors in rats with CUMS and OVX, whereas rescued the decreased serum level of E2 and prevented the increased serum levels of GnRH and LH. EA treatment ameliorated CUMS and OVX-induced alterations of glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin mRNA levels, ß-catenin and phosphorylated ß-catenin (p-ß-catenin) protein levels. CONCLUSIONS: The results showed that EA treatment promoted hippocampal neural proliferation in perimenopausal depression rats via activating the Wnt/ß-catenin signaling pathway, indicating that EA may represent an efficacious therapy for perimenopausal depression.


Assuntos
Depressão/terapia , Hipocampo/metabolismo , Neurônios/citologia , Perimenopausa/psicologia , Via de Sinalização Wnt , beta Catenina/metabolismo , Animais , Proliferação de Células , Depressão/etiologia , Depressão/genética , Depressão/metabolismo , Modelos Animais de Doenças , Eletroacupuntura , Feminino , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo/fisiopatologia , Humanos , Masculino , Neurônios/metabolismo , Perimenopausa/metabolismo , Ratos , Ratos Sprague-Dawley , beta Catenina/genética
11.
BMC Neurol ; 20(1): 142, 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32305063

RESUMO

BACKGROUND: Emotional health disturbances are common after aneurysmal subarachnoid hemorrhage (aSAH) and their causes are largely unexplored. Corticotropin-releasing hormone receptor 1 (CRHR1) is a key factor in stress reactivity and development of mental health disturbances after adverse life-events. METHODS: We explore the effect of CRHR1 genotype on mental health after aSAH in a retrospective cohort study. One hundred twenty-five patients have been assessed using EST-Q mental health questionnaire. Genotyping of CRHR1 single nucleotide polymorphisms (SNP-s) was performed (Rs7209436, Rs110402, Rs242924). RESULTS: Fatigue was present in almost half of aSAH patients, depression and anxiety in one-third. There was a high prevalence of insomnia and panic complaints. Rs110402 minor allele decreased the risk of depression (OR = 0.25, p = 0.027 for homozygotes). Depression was present in 14% vs 41% in minor and major allele homozygotes, respectively. Rs110402, Rs242924 and Rs7209436 minor alleles and TAT-haplotype, formed by them, were protective against fatigue. After Bonferroni correction only the association of Rs110402 with fatigue remained statistically significant (OR = 0.21, p = 0.006 for minor allele homozygotes). Results remained statistically significant when adjusted for gender, admission state, age and time from aSAH. In multiple regression analysis occurrence of fatigue was dependent on anxiety, modified Rankin score and Rs110402 genotype (R2 = 0.34, p <  0.001). CONCLUSIONS: CRHR1 minor genotype was associated with a lower risk of fatigue and depression after aSAH. Genetic predisposition to mental health disturbances associated with negative life-events could be a risk factor for fatigue and depression after aSAH and selected patients might benefit from advanced counselling in the recovery phase.


Assuntos
Depressão , Fadiga , Receptores de Hormônio Liberador da Corticotropina/genética , Hemorragia Subaracnóidea , Depressão/epidemiologia , Depressão/etiologia , Depressão/genética , Fadiga/epidemiologia , Fadiga/etiologia , Fadiga/genética , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/genética
12.
Neuron ; 106(6): 912-926.e5, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32304628

RESUMO

Depression is a common disorder that affects women at twice the rate of men. Here, we report that long non-coding RNAs (lncRNAs), a recently discovered class of regulatory transcripts, represent about one-third of the differentially expressed genes in the brains of depressed humans and display complex region- and sex-specific patterns of regulation. We identified the primate-specific, neuronal-enriched gene LINC00473 as downregulated in prefrontal cortex (PFC) of depressed females but not males. Using viral-mediated gene transfer to express LINC00473 in adult mouse PFC neurons, we mirrored the human sex-specific phenotype by inducing stress resilience solely in female mice. This sex-specific phenotype was accompanied by changes in synaptic function and gene expression selectively in female mice and, along with studies of human neuron-like cells in culture, implicates LINC00473 as a CREB effector. Together, our studies identify LINC00473 as a female-specific driver of stress resilience that is aberrant in female depression.


Assuntos
Transtorno Depressivo Maior/genética , Córtex Pré-Frontal/metabolismo , RNA Longo não Codificante/genética , Resiliência Psicológica , Estresse Psicológico/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Comportamento Animal , Depressão/genética , Depressão/metabolismo , Transtorno Depressivo Maior/metabolismo , Regulação para Baixo , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Neurônios/metabolismo , RNA Longo não Codificante/metabolismo , RNA-Seq , Fatores Sexuais , Estresse Psicológico/metabolismo , Adulto Jovem
13.
BMC Med Genet ; 21(1): 53, 2020 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171272

RESUMO

BACKGROUND: Adolescence is a distinctive stage of various changes and is noted as peak age for onset of many psychiatric disorders, especially linked to stress and depression. Several genetic variations are being increasingly known to be linked with stress and depression. The polymorphisms in two such genes, the BDNF and SLC1A3, have been reported to be linked with either depression/stress or with suicidal behaviour. These genes have not been validated in Indian population, and therefore there is a need to investigate these genes in Indian population. The present study was undertaken to test whether the known polymorphisms SLC1A3 C3590T, SLC1A3 C869G and BDNF G196A are associated or not with stress or depression in an eastern Indian population. METHODS: A case-control association study was performed with 108 cases having variable levels of stress and depression and 205 matched controls. Detection of stress and depression was done by using standard instruments as PSS and CES-D, respectively and demographic profile was obtained for each individual on the basis of personal data sheet. Genotyping for the selected polymorphisms was performed by PCR followed by restriction digestion. RESULTS: The SNP SLC1A3 C3590T was found to be associated with stress and depression (p = 0.0042, OR = 2.072). Therefore, the T allele increases the risk by more than two folds for stress and depression in the present population. The other allele of SLC1A3, G869C, as well as BDNF G196A were not associated with stress or depression in the population studied. CONCLUSION: SLC1A3 C3590T is a predisposition factor for stress and depression in an eastern Indian population, whereas SLC1A3 G869C and BDNF G196A were not found to be a risk factor. Therefore, presence of T allele of SLC1A3 C3590T, may predict the development of stress and depression in an individual. This may also help in the understanding of pathophysiology of the disease. However, these findings warrant a wider study in Indian populations and would be of significance in understanding the predisposition of stress and depression in this population.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Depressão/genética , Transportador 1 de Aminoácido Excitatório/genética , Polimorfismo de Nucleotídeo Único , Estresse Psicológico/genética , Adolescente , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Estudos de Casos e Controles , Depressão/epidemiologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Índia/epidemiologia , Masculino , Psicologia do Adolescente , Fatores de Risco , Estresse Psicológico/epidemiologia , Adulto Jovem
14.
Gynecol Oncol ; 157(1): 280-286, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32057464

RESUMO

BACKGROUND: Timely genetic testing at ovarian cancer diagnosis is essential as results impact front line treatment decisions. Our objective was to determine rates of genetic counseling and testing with an expedited genetics referral pathway wherein women with newly-diagnosed ovarian cancer are contacted by a genetics navigator to facilitate genetic counseling. METHODS: Patients were referred for genetic counseling by their gynecologic oncologist, contacted by a genetics navigator and offered appointments for genetic counseling. Patients completed quality of life (QoL) surveys immediately pre- and post-genetic assessment and 6 months later. The primary outcome was feasibility of this pathway defined by presentation for genetic counseling. RESULTS: From 2015 to 2018, 100 patients were enrolled. Seventy-eight had genetic counseling and 73 testing. Median time from diagnosis to genetic counseling was 34 days (range 10-189). Among patients who underwent testing, 12 (16%) had pathogenic germline mutations (BRCA1-7, BRCA2-4, MSH2-1). Sixty-five patients completed QoL assessments demonstrating stress and anxiety at time of testing, however, scores improved at 6 months. Despite the pathway leveling financial and logistical barriers, patients receiving care at a public hospital were less likely to present for genetic counseling compared to private hospital patients (56% versus 84%, P = 0.021). CONCLUSIONS: Facilitated referral to genetic counselors at time of ovarian cancer diagnosis is effective, resulting in high uptake of genetic counseling and testing, and does not demonstrate a long term psychologic toll. Concern about causing additional emotional distress should not deter clinicians from early genetics referral as genetic testing can yield important prognostic and therapeutic information.


Assuntos
Ansiedade/genética , Carcinoma Epitelial do Ovário/genética , Depressão/genética , Aconselhamento Genético/organização & administração , Testes Genéticos , Neoplasias Ovarianas/genética , Estresse Psicológico/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/etiologia , Carcinoma Epitelial do Ovário/psicologia , Depressão/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/psicologia , Estudos Prospectivos , Encaminhamento e Consulta/organização & administração , Estresse Psicológico/etiologia , Adulto Jovem
15.
Proc Natl Acad Sci U S A ; 117(5): 2656-2662, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31941713

RESUMO

Slow response to the standard treatment for depression increases suffering and risk of suicide. Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, can rapidly alleviate depressive symptoms and reduce suicidality, possibly by decreasing hyperactivity in the lateral habenula (LHb) brain nucleus. Here we find that in a rat model of human depression, opioid antagonists abolish the ability of ketamine to reduce the depression-like behavioral and LHb hyperactive cellular phenotypes. However, activation of opiate receptors alone is not sufficient to produce ketamine-like effects, nor does ketamine mimic the hedonic effects of an opiate, indicating that the opioid system does not mediate the actions of ketamine but rather is permissive. Thus, ketamine does not act as an opiate but its effects require both NMDA and opiate receptor signaling, suggesting that interactions between these two neurotransmitter systems are necessary to achieve an antidepressant effect.


Assuntos
Antidepressivos/administração & dosagem , Depressão/tratamento farmacológico , Ketamina/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Animais , Depressão/genética , Depressão/metabolismo , Modelos Animais de Doenças , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores Opioides/genética , Receptores Opioides/metabolismo
16.
Lipids Health Dis ; 19(1): 4, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915015

RESUMO

BACKGROUND: Menopause predisposes individuals to affective disorders, such as depression, which is tightly related to neuroinflammation. While the neuroinflammatory condition has been demonstrated in ovariectomized (OVX) rodents, there is limited evidence concerning microglial polarization, a key process in brain immune activation, in menopause-related brain. METHODS: Therefore, the present study aims to evaluate the polarized microglia in long-term OVX rats and we further explored whether supplementation of ω-3 polyunsaturated fatty acids (PUFA), the pleiotropic bioactive nutrient, is effective in the neurobehavioral changes caused by OVX. RESULTS: Our data showed that OVX-induced anxiety and depression-like behaviors in rats, accompanied with increased neural apoptosis and microglial activation in the hippocampus. Additionally, OVX enhanced proinflammatory cytokines expression and suppressed the expression of anti-inflammatory cytokine, IL-10. Correspondingly, OVX reinforced NFκB signaling and shifted the microglia from immunoregulatory M2 phenotype to proinflammatory M1 phenotype. Meanwhile, daily supplementation with PUFA suppressed microglial M1 polarization and potentiated M2 polarization in OVX rats. In parallel, PUFA also exerted antidepressant and neuroprotective activities, accompanied with neuroimmune-modulating actions. CONCLUSION: Collectively, the present study firstly demonstrated the disturbed microglial polarization in the OVX brain and provide novel evidence showing the association between the antidepressant actions of PUFA and the restraint neuroinflammatory progression.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Ácidos Graxos Ômega-3/farmacologia , Interleucina-10/genética , Animais , Depressão/genética , Depressão/patologia , Modelos Animais de Doenças , Ácidos Graxos Insaturados/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/patologia , Masculino , Microglia/efeitos dos fármacos , Microglia/patologia , NF-kappa B/genética , Ratos , Transdução de Sinais/efeitos dos fármacos
17.
Compr Psychiatry ; 97: 152159, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31931428

RESUMO

BACKGROUND: Depression is associated with inflammation and Alzheimer's disease (AD). However, detailed molecular mechanisms linking mood, neuroinflammation and AD remain unclear. Although changes in peripheral inflammatory factors such as Interleukin 18 (IL18), and AD-associated amyloid-ß (Aß) peptides have been linked to depression, a solid relationship between these factors in depressive disorder has yet to be established. This study aims to further determine whether plasma IL18, Aß40, Aß42, and the AD-associated tangle component Tau, as well as IL18 single nucleotide polymorphisms (SNPs) may be biomarkers for depression. METHODS: We measured plasma IL18, Aß40, Aß42, and Tau in 64 depressive patients and 75 healthy controls, and characterized genotypes of three IL18 SNPs (rs187238, rs1946518 and rs1946519) in these subjects. Comparisons between depressive patients and controls were carried out in males, in females or in combination. Regression analyses were conducted to examine the correlation between these parameters. RESULTS: We found that none of the plasma levels of IL18, Aß40, Aß42, and Tau, the ratio of Aß42/Aß40, and the genotypes of IL18 SNPs were significantly different between combined depressive patients and combined healthy controls, or between male depressive patients and male controls. However, IL18 levels were less in females than in males in healthy people and were significantly increased in female depressive patients compared to female controls. Moreover, IL18 and standardized IL18 were correlated with standardized Aß42/Aß40 ratio and standardized Tau in depressive patients. CONCLUSIONS: Plasma IL18 may be a potential biomarker for depression in women.


Assuntos
Peptídeos beta-Amiloides/sangue , Depressão/sangue , Interleucina-18/sangue , Proteínas tau/sangue , Idoso , Apolipoproteínas E , Biomarcadores/sangue , Estudos de Casos e Controles , Depressão/diagnóstico , Depressão/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Polimorfismo de Nucleotídeo Único
18.
Gene ; 735: 144276, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31816363

RESUMO

Depression is increasingly threatening human health as a serious psychological problem. However, it is remarkable that the precise mechanism underlying depression remains unelucidated. Recent studies have clarified that non-coding RNA, including but not limited to microRNA, long non-coding RNA, and circular RNA, plays an important role in the pathogenesis of depression. The research results cited in this paper reveal the origin, expression, distribution, function, and mechanism of microRNA in the nervous system. MicroRNA is involved in regulation of life activities, including growth, immune reaction, haematopoiesis, and metabolism, which are significant for maintaining normal physiological functions. Moreover, microRNA plays an important role in cell death and proliferation, development of cancer, and disease prognosis. Here, we also introduce the general research status of long non-coding RNA and circular RNA. Next, descriptive study methods, including fluorescence quantitative polymerase chain reaction, northern blot, microarray technology, RNA-seq, and fluorescent in situ hybridization are discussed. Functional study methods are also summarized and divided into gain- and loss-of-function studies. Moreover, the roles of non-coding RNA in the pathogenesis of depression, including neurogenesis, synaptic plasticity, brain-derived neurotrophic factor expression, HPA axis regulation, neurotransmission, neuropeptide expression, neuro-inflammation, and polyamine synthesis are discussed. Nevertheless, many unknown associations between non-coding RNA and depression remain to be clarified.


Assuntos
Depressão/genética , RNA não Traduzido/genética , Depressão/etiologia , Humanos , RNA não Traduzido/metabolismo
19.
Psychoneuroendocrinology ; 111: 104480, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31707294

RESUMO

The highly conserved transcription factor LIM-only 3 (Lmo3) is involved in important neurodevelopmental processes in several brain areas including the amygdala, a central hub for the generation and regulation of emotions. Accordingly, a role for Lmo3 in the behavioral responses to ethanol and in the display of anxiety-like behavior in mice has been demonstrated while the potential involvement of Lmo3 in the control of mood-related behavior has not yet been explored. Using a mouse model of Lmo3 depletion (Lmo3z), we here report that genetic Lmo3 deficiency is associated with altered performance in behavioral paradigms assessing anxiety-like and depression-like traits and additionally accompanied by impairments in learned fear. Importantly, long-term potentiation (LTP) in the basolateral amygdala (BLA), a proposed cellular correlate of fear learning, is impaired in Lmo3z mice. RNA-Seq analysis of BLA tissue and gene set enrichment analysis (GSEA) of differentially expressed genes in Lmo3z mice reveals a significant overlap between genes overexpressed in Lmo3z mice and those enriched in the amygdala of a cohort of patients suffering from major depressive disorder. Consequently, we propose that Lmo3 may play a role in the regulation of gene networks that are relevant to the regulation of emotions. Future work may aid to further explore the role of Lmo3 in the pathophysiology of affective disorders and its genetic foundations.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Tonsila do Cerebelo/metabolismo , Proteínas com Domínio LIM/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Afeto , Tonsila do Cerebelo/fisiologia , Animais , Ansiedade/genética , Transtornos de Ansiedade/genética , Comportamento Animal/fisiologia , Encéfalo/metabolismo , Depressão/genética , Transtorno Depressivo Maior/genética , Medo/fisiologia , Feminino , Proteínas com Domínio LIM/metabolismo , Potenciação de Longa Duração/fisiologia , Masculino , Camundongos , Camundongos Knockout , Fatores de Transcrição/genética
20.
BMC Pregnancy Childbirth ; 19(1): 479, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805950

RESUMO

BACKGROUND: Antenatal depression affects 10-20% of pregnant women. Around 2-4% of European pregnant women use antidepressant treatment, most commonly selective serotonin reuptake inhibitors (SSRIs). Poor pregnancy outcomes, such as preterm birth and low birth weight, have been described in women with antenatal depression and in pregnant women on SSRI treatment. However, the effects of antenatal depression and antidepressant treatment on the placenta are largely unknown. The aim of this work was to compare placental gene and protein expression in healthy women, women with untreated antenatal depression and women on antidepressant treatment during pregnancy. METHODS: Placental samples from 47 controls, 25 depressed and 45 SSRI-treated women were analysed by means of qPCR using custom-designed TaqMan low-density arrays (TLDAs) for 44 genes previously known to be involved in the pathophysiology of depression, and expressed in the placenta. Moreover, placental protein expression was determined by means of immunohistochemistry in 37 healthy controls, 13 women with untreated depression and 21 women on antidepressant treatment. Statistical comparisons between groups were performed by one-way ANOVA or the Kruskal-Wallis test. RESULTS: Nominally significant findings were noted for HTR1A and NPY2R, where women with untreated depression displayed higher gene expression than healthy controls (p < 0.05), whereas women on antidepressant treatment had similar expression as healthy controls. The protein expression analyses revealed higher expression of HTR1A in placentas from women on antidepressant treatment, than in placentas from healthy controls (p < 0.05). CONCLUSION: The differentially expressed HTR1A, both at the gene and the protein level that was revealed in this study, suggests the involvement of HTR1A in the effect of antenatal depression on biological mechanisms in the placenta. More research is needed to elucidate the role of depression and antidepressant treatment on the placenta, and, further, the effect on the fetus.


Assuntos
Antidepressivos/efeitos adversos , Depressão/tratamento farmacológico , Placenta/metabolismo , Complicações na Gravidez/tratamento farmacológico , Proteínas da Gravidez/metabolismo , Adulto , Antidepressivos/uso terapêutico , Depressão/genética , Depressão/metabolismo , Feminino , Expressão Gênica , Voluntários Saudáveis , Humanos , Imuno-Histoquímica , Placenta/patologia , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/metabolismo , Proteínas da Gravidez/genética , Efeitos Tardios da Exposição Pré-Natal , Reação em Cadeia da Polimerase em Tempo Real , Receptor 5-HT1A de Serotonina/metabolismo , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores de Captação de Serotonina/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA