Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.758
Filtrar
1.
J Alzheimers Dis ; 79(3): 1015-1021, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33386809

RESUMO

We explored the impact of the Spanish COVID-19 strict home confinement on mental health and cognition in non-infected subjects (N = 16, 60-80 years) diagnosed with subjective cognitive decline and APOEɛ3/ɛ4 carriers. Mental health was monitored for 2 months on a daily, weekly, or monthly basis, and compared to pre-confinement values. Emotional distress, anxiety, and depression scores increased to pathological threshold values during and after confinement. Those with lower mood during confinement experienced a decline in their mood after confinement. Cognition did not change. These preliminary results suggest that mental health consequences of corona measures in preclinical stages of Alzheimer's disease should be further evaluated.


Assuntos
Doença de Alzheimer/psicologia , Transtornos Cognitivos/psicologia , Saúde Mental , Quarentena/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/genética , Transtornos de Ansiedade/psicologia , Apolipoproteína E3/genética , Apolipoproteína E4/genética , /terapia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/genética , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/genética , Disfunção Cognitiva/psicologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/genética , Transtorno Depressivo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Angústia Psicológica , Risco , Espanha
2.
Am J Psychiatry ; 177(10): 936-943, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32660297

RESUMO

OBJECTIVE: The authors investigated the associations between polygenic liability and progression to bipolar disorder or psychotic disorders among individuals diagnosed with unipolar depression in early life. METHODS: A cohort comprising 16,949 individuals (69% female, 10-35 years old at the first depression diagnosis) from the iPSYCH Danish case-cohort study (iPSYCH2012) who were diagnosed with depression in Danish psychiatric hospitals from 1994 to 2016 was examined. Polygenic risk scores (PRSs) for major depression, bipolar disorder, and schizophrenia were generated using the most recent results from the Psychiatric Genomics Consortium. Hazard ratios for each disorder-specific PRS were estimated using Cox regressions with adjustment for the other two PRSs. Absolute risk of progression was estimated using the cumulative hazard. RESULTS: Patients were followed for up to 21 years (median=7 years, interquartile range, 5-10 years). The absolute risks of progression to bipolar disorder and psychotic disorders were 7.3% and 13.8%, respectively. After mutual adjustment for the other PRSs, only the PRS for bipolar disorder predicted progression to bipolar disorder (adjusted hazard ratio for a one-standard-deviation increase in PRS=1.11, 95% CI=1.03, 1.21), and only the PRS for schizophrenia predicted progression to psychotic disorders (adjusted hazard ratio=1.10, 95% CI=1.04, 1.16). After adjusting for PRSs, parental history still strongly predicted progression to bipolar disorder (adjusted hazard ratio=5.02, 95% CI=3.53, 7.14) and psychotic disorders (adjusted hazard ratio=1.63, 95% CI=1.30, 2.06). CONCLUSIONS: PRSs for bipolar disorder and schizophrenia are associated with risk for progression to bipolar disorder or psychotic disorders, respectively, among individuals diagnosed with depression; however, the effects are small compared with parental history, particularly for bipolar disorder.


Assuntos
Transtorno Bipolar/genética , Transtorno Depressivo/genética , Herança Multifatorial/genética , Transtornos Psicóticos/genética , Adolescente , Adulto , Criança , Dinamarca , Progressão da Doença , Feminino , Técnicas de Genotipagem , Humanos , Masculino , Fatores de Risco , Esquizofrenia/genética , Adulto Jovem
3.
Psychopharmacology (Berl) ; 237(7): 1909-1915, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32529266

RESUMO

RATIONALE: Depression is a major mental disorder affecting millions of people worldwide. Serotonin and norepinephrine reuptake inhibitors (SNRIs) are one of the antidepressant drugs prescribed for depression treatment. OBJECTIVE AND METHOD: There are many contradiction studies about the adverse effect and genotoxicity of SNRIs. So here, based on the guidelines proposed at the PRISMA statement, we performed a quantitative systematic review by searching international electronic databases (PubMed, Scopus, Embase, and Web of Science) for published documents on SSNRIs and their genotoxicity effects. RESULTS: The database searches retrieved 336 records, 18 of which met the inclusion criteria. Evaluation of the selected articles showed that a total of 9 articles were appropriate for final review. Most of these studies (78%) reported positive results for the genotoxicity of SNRIs CONCLUSION: Finally, we can conclude that these drugs have the potential to damage DNA.


Assuntos
Antidepressivos/efeitos adversos , Dano ao DNA/efeitos dos fármacos , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/genética , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos , Antidepressivos/farmacologia , Dano ao DNA/fisiologia , Transtorno Depressivo/metabolismo , Humanos , Norepinefrina/antagonistas & inibidores , Norepinefrina/genética , Norepinefrina/metabolismo , Serotonina/genética , Serotonina/metabolismo , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores de Captação de Serotonina/farmacologia , Inibidores da Recaptação de Serotonina e Norepinefrina/farmacologia
4.
J Clin Psychiatry ; 81(3)2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32459403

RESUMO

In observational studies, significant associations have often been identified between antidepressant drug prescription during pregnancy, on the one hand, and autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), on the other. Interpreting these associations is problematic because they are based on analyses that could not adjust for inadequately measured, unmeasured, and unknown confounds. Recent clinical data suggest that a genetic relationship exists between depression and neurodevelopmental disorders. A very recent study identified many genetic loci that were common to depression, ASD, and ADHD. These findings suggest the possibility that depression in a pregnant woman may predispose to neurodevelopmental disorders in offspring through shared genes and not through antidepressant use during pregnancy. Previous studies that significantly associated gestational exposure to antidepressants with adverse pregnancy outcomes could not adjust for genetic factors because they were unknown confounds at the time. Now that common risk loci have been identified, at least some of the unknown (genetic) confounds are no longer unknown; however, unless specifically examined in prospective studies, they will remain as unmeasured confounds that will continue to compromise the interpretation of study results. The possibility of confounding by inadequately measured, unmeasured, and unknown risk factors must therefore be considered before indicting antidepressant use during pregnancy in neurodevelopmental risks. In this context, the importance of genetic factors as unmeasured and unknown confounds must be acknowledged.


Assuntos
Antidepressivos/efeitos adversos , Transtorno Depressivo/complicações , Transtornos do Neurodesenvolvimento/genética , Complicações na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/genética , Antidepressivos/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/genética , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/genética , Feminino , Loci Gênicos , Predisposição Genética para Doença/genética , Humanos , Transtornos do Neurodesenvolvimento/induzido quimicamente , Gravidez , Complicações na Gravidez/psicologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
8.
J Pharmacol Sci ; 143(1): 52-55, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32115365

RESUMO

Recently, we has reported that AMPK activator has antidepressant effect. Previous our study suggested that liver hydrolysate (LH) activated adenosine monophosphate-activated protein kinase (AMPK) in periphery. However, the effect of LH on depression is unclear. Therefore, we examines whether LH has antidepressant effect on olfactory bulbectomized (OBX) mice. OBX mice showed depressive-like behavior in tail-suspension test and reduction of hippocampal neurogenesis, while these changes were reversed by LH. LH enhanced hippocampal phosphate-AMPK, brain-derived neurotrophic factor (BDNF) and phosphate-cyclic adenosine monophosphate response element-binding protein (CREB) in OBX mice. These data indicate that LH may produce antidepressant effects via hippocampal AMPK/BDNF/CREB signaling.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/etiologia , Hipocampo/fisiologia , Neurogênese , Bulbo Olfatório/fisiologia , Bulbo Olfatório/cirurgia , Hidrolisados de Proteína/farmacologia , Hidrolisados de Proteína/uso terapêutico , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Animais , Transtorno Depressivo/genética , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos
10.
Biol Res Nurs ; 22(2): 277-286, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31908177

RESUMO

This study aimed to (1) identify subgroups of women with breast cancer with the psychological symptom cluster (fatigue, depressive symptoms, and anxiety) during the first 18 months of adjuvant therapy and (2) explore associations between demographic and clinical characteristics and variations in genetic polymorphisms related to hypothalamic-pituitary-adrenal (HPA) axis function and predicted symptom trajectory subgroup membership. We obtained symptom data at 4 time points from baseline to 18 months of adjuvant therapy among 292 postmenopausal women with breast cancer. Genetic data were collected in a subgroup at baseline (N = 184). Group-based multitrajectory modeling was used to classify women into subgroups with similar psychological symptom cluster trajectories. Binary logistic regression was used to explore the associations between each genotypic and phenotypic predictor and predicted subgroup membership. Two distinct symptom subgroups (low and high) were identified based on the trajectories of the symptom cluster of fatigue, depressive symptoms, and anxiety over the first 18 months of adjuvant therapy. Women who were younger, less educated, and who received chemotherapy had greater likelihood of being in the high-symptom subgroup. Variation in genes regulating the HPA axis (FKBP5 rs9394309 [odds ratio (OR) = 3.98, p = .015], NR3C2 rs5525 [OR = 2.54, p = .036], and CRHR1 rs12944712 [OR = 3.99, p = .021]) was associated with membership in the high-symptom subgroup. These results may help to identify women with breast cancer who are at increased risk for psychological symptoms, facilitating the development of individualized and preemptive interventions to better manage these symptoms during adjuvant therapy.


Assuntos
Transtornos de Ansiedade/induzido quimicamente , Transtornos de Ansiedade/genética , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/efeitos adversos , Transtorno Depressivo/induzido quimicamente , Transtorno Depressivo/genética , Fadiga/induzido quimicamente , Fadiga/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Humanos , Modelos Logísticos , Pessoa de Meia-Idade
11.
Behav Genet ; 50(2): 105-118, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31811520

RESUMO

This study documented the etiology contributions between anxiety symptoms (AS) and depressive symptoms (DS) from ages 6-12 years. Teachers assessed AS and DS in 1112 twins at 5 time points. A genetic cross-lagged model was used to estimate genetic/environmental contributions to cross-sectional, cross-age and cross-lag associations. The variance in AS and DS was largely time-specific and more genetic in nature for DS than for AS. Previous DS predicted subsequent DS better than cross-lag or previous common effects, and AS up to age 9 better than previous AS or previous common effects. Thereafter, previous AS predicted subsequent AS. All predictions involved both genetic and unique environment. Suppression effects were found and, when controlled, AS marginally predicted DS from age 7 onward through genetic influences. AS and DS are associated throughout childhood. DS are more stable than AS, and more central to both subsequent AS and DS. AS marginally contribute to subsequent DS.


Assuntos
Ansiedade/genética , Depressão/genética , Gêmeos/psicologia , Ansiedade/etiologia , Transtornos de Ansiedade/etiologia , Transtornos de Ansiedade/genética , Criança , Estudos Transversais , Depressão/etiologia , Transtorno Depressivo/etiologia , Transtorno Depressivo/genética , Feminino , Humanos , Estudos Longitudinais , Masculino , Modelos Genéticos , Gêmeos/genética , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
12.
Nicotine Tob Res ; 22(2): 293-296, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-30329132

RESUMO

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) is a growth factor in the central nervous system. There is evidence for the involvement of BDNF in addictions and mental disorders. We aimed to replicate the earlier reported association of a functional genetic variant of BDNF with smoking initiation (SI) using a large population-based sample and to test whether the association is independent of depression. METHODS: Our sample was drawn from the Finnish population-based FINRISK surveys conducted in 1992, 1997, 2002, and 2007. We had nonmissing data on the genotype BDNF  Val66Met (G/A) variant (rs6265) and self-reported never (n = 10 619) versus ever (n = 16 028) smoking among 26 647 adults aged 25-74 years. The association between BDNF  Val66Met and SI was modeled using logistic regression adjusted for age and sex, and in secondary analyses also for depression. Depression was defined as self-reported depression diagnosed or treated by physician during the past year. RESULTS: The sex- and age-adjusted analysis confirmed that the major (Val) allele increased the risk of being a lifetime ever smoker (per allele odds ratio [OR] = 1.07; 95% CI = 1.01 to 1.12; p = .01). When depression, which itself was significantly associated with SI (OR = 1.58; 95% CI = 1.37 to 1.82; p < .001), was added to the model, the association of the gene with SI remained significant (per allele OR = 1.06; 95% CI = 1.01 to 1.12; p = .01). Exclusion of depressed individuals did not change the results (OR = 1.06; 95% CI = 1.01 to 1.12; p = .02). CONCLUSIONS: In a Finnish population sample, we replicated the earlier reported association of BDNF Val66Met with SI. Our data further suggest that this association is independent of depression. IMPLICATIONS: Earlier finding about the association between the BDNF gene and smoking initiation is replicated and shown to be independent of depression within Finnish adult population.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/genética , Vigilância da População , Fumar Tabaco/epidemiologia , Fumar Tabaco/genética , Adulto , Idoso , Comportamento Aditivo/epidemiologia , Comportamento Aditivo/genética , Feminino , Finlândia/epidemiologia , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Masculino , Metionina/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Vigilância da População/métodos , Valina/genética , Adulto Jovem
13.
Transl Psychiatry ; 9(1): 343, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852885

RESUMO

Therapeutic sleep deprivation (SD) rapidly induces robust, transient antidepressant effects in a large proportion of major mood disorder patients suffering from a depressive episode, but underlying biological factors remain poorly understood. Research suggests that these patients may have altered circadian molecular genetic 'clocks' and that SD functions through 'resetting' dysregulated genes; additional factors may be involved, warranting further investigation. Leveraging advances in microarray technology enabling the transcriptome-wide assessment of gene expression, this study aimed to examine gene expression changes accompanying SD and recovery sleep in patients suffering from an episode of depression. Patients (N = 78) and controls (N = 15) underwent SD, with blood taken at the same time of day before SD, after one night of SD and after recovery sleep. A transcriptome-wide gene-by-gene approach was used, with a targeted look also taken at circadian genes. Furthermore, gene set enrichment, and longitudinal gene set analyses including the time point after recovery sleep, were conducted. Circadian genes were significantly affected by SD, with patterns suggesting that molecular clocks of responders and non-responders, as well as patients and controls respond differently to chronobiologic stimuli. Notably, gene set analyses revealed a strong widespread effect of SD on pathways involved in immune function and inflammatory response, such as those involved in cytokine and especially in interleukin signalling. Longitudinal gene set analyses showed that in responders these pathways were upregulated after SD; in non-responders, little response was observed. Our findings emphasize the close relationship between circadian, immune and sleep systems and their link to etiology of depression at the transcriptomic level.


Assuntos
Relógios Circadianos/genética , Transtorno Depressivo , Perfilação da Expressão Gênica , Imunidade , Inflamação , Privação do Sono/genética , Transcriptoma , Adulto , Transtorno Depressivo/genética , Transtorno Depressivo/imunologia , Transtorno Depressivo/terapia , Feminino , Humanos , Imunidade/genética , Imunidade/imunologia , Inflamação/genética , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade
14.
Genes (Basel) ; 10(12)2019 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-31801286

RESUMO

The association of candidate genes and psychological symptoms of depression, anxiety, and stress among women with gestational diabetes mellitus (GDM) in Malaysia was determined in this study, followed by the determination of their odds of getting psychological symptoms, adjusted for socio-demographical background, maternal, and clinical characteristics. Single nucleotide polymorphisms (SNPs) recorded a significant association between SNP of EPHX2 (rs17466684) and depression symptoms (AOR = 7.854, 95% CI = 1.330-46.360) and stress symptoms (AOR = 7.664, 95% CI = 1.579-37.197). Associations were also observed between stress symptoms and SNP of OXTR (rs53576) and (AOR = 2.981, 95% CI = 1.058-8.402) and SNP of NRG1 (rs2919375) (AOR = 9.894, 95% CI = 1.159-84.427). The SNP of EPHX2 (rs17466684) gene polymorphism is associated with depression symptoms among Malaysian women with GDM. SNP of EPHX2 (rs17466684), OXTR (rs53576) and NRG1 (rs2919375) are also associated with stress symptoms.


Assuntos
Transtorno Depressivo/genética , Diabetes Gestacional/genética , Polimorfismo de Nucleotídeo Único , Adulto , Ansiedade/genética , Ansiedade/fisiopatologia , Ansiedade/psicologia , Estudos Transversais , Transtorno Depressivo/fisiopatologia , Transtorno Depressivo/psicologia , Diabetes Gestacional/fisiopatologia , Diabetes Gestacional/psicologia , Feminino , Humanos , Malásia , Gravidez
15.
Adv Exp Med Biol ; 1180: 147-178, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784962

RESUMO

Stress is an adaptive response to environment aversive stimuli and a common life experience of one's daily life. Chronic or excessive stress especially that happened in early life is found to be deleterious to individual's physical and mental health, which is highly related to depressive disorders onset. Stressful life events are consistently considered to be the high-risk factors of environment for predisposing depressive disorders. In linking stressful life events with depressive disorder onset, dysregulated HPA axis activity is supposed to play an important role in mediating aversive impacts of life stress on brain structure and function. Increasing evidence have indicated the strong association of stress, especially the chronic stress and early life stress, with depressive disorders development, while the association of stress with depression is moderated by genetic risk factors, including polymorphism of SERT, BDNF, GR, FKBP5, MR, and CRHR1. Meanwhile, stressful life experience particularly early life stress will exert epigenetic modification in these risk genes via DNA methylation and miRNA regulation to generate long-lasting effects on these genes expression, which in turn cause brain structural and functional alteration, and finally increase the vulnerability to depressive disorders. Therefore, the interaction of environment with gene, in which stressful life exposure interplay with genetic risk factors and epigenetic modification, is essential in predicting depressive disorders development. As the mediator of environmental risk factors, stress will function together with genetic and epigenetic mechanism to influence brain structure and function, physiology and psychology, and finally the vulnerability to depressive disorders.


Assuntos
Transtorno Depressivo/genética , Epigênese Genética , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Estresse Psicológico , Transtorno Depressivo/fisiopatologia , Humanos , Fatores de Risco
16.
Twin Res Hum Genet ; 22(6): 460-466, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31708010

RESUMO

Meta-analyses suggest that clinical psychopathology is preceded by dimensional behavioral and cognitive phenotypes such as psychotic experiences, executive functioning, working memory and affective dysregulation that are determined by the interplay between genetic and nongenetic factors contributing to the severity of psychopathology. The liability to mental ill health can be psychometrically measured using experimental paradigms that assess neurocognitive processes such as salience attribution, sensitivity to social defeat and reward sensitivity. Here, we describe the TwinssCan, a longitudinal general population twin cohort, which comprises 1202 individuals (796 adolescent/young adult twins, 43 siblings and 363 parents) at baseline. The TwinssCan is part of the European Network of National Networks studying Gene-Environment Interactions in Schizophrenia project and recruited from the East Flanders Prospective Twin Survey. The main objective of this project is to understand psychopathology by evaluating the contribution of genetic and nongenetic factors on subclinical expressions of dimensional phenotypes at a young age before the onset of disorder and their association with neurocognitive processes, such as salience attribution, sensitivity to social defeat and reward sensitivity.


Assuntos
Transtorno Depressivo/epidemiologia , Doenças em Gêmeos/epidemiologia , Interação Gene-Ambiente , Transtornos Neurocognitivos/epidemiologia , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adolescente , Adulto , Bélgica/epidemiologia , Transtorno Depressivo/genética , Transtorno Depressivo/patologia , Doenças em Gêmeos/genética , Doenças em Gêmeos/patologia , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Transtornos Neurocognitivos/genética , Transtornos Neurocognitivos/patologia , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco , Meio Social , Adulto Jovem
17.
Transl Psychiatry ; 9(1): 299, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727881

RESUMO

Social processes are associated with depression, particularly understanding and responding to others, deficits in which can manifest as callousness/unemotionality (CU). Thus, CU may reflect some of the genetic risk to depression. Further, this vulnerability likely reflects the neurological substrates of depression, presenting biomarkers to capture genetic vulnerability of depression severity. However, heritability varies within brain regions, so a high-resolution genetic perspective is needed. We developed a toolbox that maps genetic and environmental associations between brain and behavior at high resolution. We used this toolbox to estimate brain areas that are genetically associated with both depressive symptoms and CU in a sample of 258 same-sex twin pairs from the Colorado Longitudinal Twin Study (LTS). We then overlapped the two maps to generate coordinates that allow for tests of downstream effects of genes influencing our clusters. Genetic variance influencing cortical thickness in the right dorsal lateral prefrontal cortex (DLFPC) sulci and gyri, ventral posterior cingulate cortex (PCC), pre-somatic motor cortex (PreSMA), medial precuneus, left occipital-temporal junction (OTJ), parietal-temporal junction (PTJ), ventral somatosensory cortex (vSMA), and medial and lateral precuneus were genetically associated with both depression and CU. Split-half replication found support for both DLPFC clusters. Meta-analytic term search identified "theory of mind", "inhibit", and "pain" as likely functions. Gene and transcript mapping/enrichment analyses implicated calcium channels. CU reflects genetic vulnerability to depression that likely involves executive and social functioning in a distributed process across the cortex. This approach works to unify neuroimaging, neuroinformatics, and genetics to discover pathways to psychiatric vulnerability.


Assuntos
Córtex Cerebral/fisiopatologia , Transtorno Depressivo/genética , Transtorno Depressivo/fisiopatologia , Adulto , Mapeamento Encefálico/métodos , Colorado , Depressão/genética , Depressão/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Rede Nervosa/fisiopatologia
18.
Eur Respir J ; 54(6)2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31619474

RESUMO

Epidemiological studies demonstrate an association between asthma and mental health disorders, although little is known about the shared genetics and causality of this association. Thus, we aimed to investigate shared genetics and the causal link between asthma and mental health disorders.We conducted a large-scale genome-wide cross-trait association study to investigate genetic overlap between asthma from the UK Biobank and eight mental health disorders from the Psychiatric Genomics Consortium: attention deficit hyperactivity disorder (ADHD), anxiety disorder (ANX), autism spectrum disorder, bipolar disorder, eating disorder, major depressive disorder (MDD), post-traumatic stress disorder and schizophrenia (sample size 9537-394 283).In the single-trait genome-wide association analysis, we replicated 130 previously reported loci and discovered 31 novel independent loci that are associated with asthma. We identified that ADHD, ANX and MDD have a strong genetic correlation with asthma at the genome-wide level. Cross-trait meta-analysis identified seven loci jointly associated with asthma and ADHD, one locus with asthma and ANX, and 10 loci with asthma and MDD. Functional analysis revealed that the identified variants regulated gene expression in major tissues belonging to the exocrine/endocrine, digestive, respiratory and haemic/immune systems. Mendelian randomisation analyses suggested that ADHD and MDD (including 6.7% sample overlap with asthma) might increase the risk of asthma.This large-scale genome-wide cross-trait analysis identified shared genetics and potential causal links between asthma and three mental health disorders (ADHD, ANX and MDD). Such shared genetics implicate potential new biological functions that are in common among them.


Assuntos
Transtornos de Ansiedade/genética , Asma/genética , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno Depressivo/genética , Adulto , Criança , Estudo de Associação Genômica Ampla , Humanos , Reino Unido
19.
Biomed Res Int ; 2019: 5705232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612144

RESUMO

Postmenopausal depression is closely associated with depletion of estrogen which modulates transmission of 5-HT, a key neurotransmitter that regulates stress-managing circuits in the brain. In this study, antidepressive efficacy of white ginseng (Panax gingseng Meyer, WG) was evaluated in stressed ovariectomized rats. Female Sprague Dawley rats were ovariectomized and repeatedly restraint stressed for 2 weeks (2h/day). Thirty minutes before restraint stress, rats were administered saline (control), WG 200 mg/kg (p.o.), WG 400 mg/kg (p.o.), or fluoxetine (PC, 10 mg/kg, i.p.). Tail suspension test (TST) and forced swimming test (FST) were performed to assess antidepressant effect of WG. After behavioral tests, levels of serum corticosterone (CORT) and hippocampal 5-HT were measured. Significant decrease of immobility time in TST and FST was shown in rats administered with PC or WG 400 compared to the control. WG200-treated rats showed remarkable reduction in immobility time of TST. PC, WG 200, or WG 400-administred group exhibited significant reduction of CORT compared to the control. PC or WG-treated rats exhibited remarkable increase in hippocampal 5-HT concentration compared to the control. Hippocampal 5-HT levels in WG groups were higher than those in the PC group. The present study demonstrated that WG had antidepressant efficacy in an animal model of menopausal depression. Treatment with WG enhanced hippocampal 5-HT level while suppressing depressive symptom and serum CORT level. These results provide evidence that WG plays an important role in activating serotonergic neurons in stressful situation, suggesting that WG might be a reliable natural alternative of antidepressant drugs to treat menopausal depression.


Assuntos
Depressão/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Panax/química , Serotonina/metabolismo , Animais , Antidepressivos/química , Antidepressivos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Depressão/genética , Depressão/fisiopatologia , Transtorno Depressivo/genética , Transtorno Depressivo/fisiopatologia , Modelos Animais de Doenças , Elevação dos Membros Posteriores/métodos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Ratos , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia , Natação
20.
PLoS One ; 14(10): e0222818, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31647818

RESUMO

Depression is a common psychiatric disorder that has been poorly understood. Consequently, current antidepressant agents have clinical limitations. Until today, most have exhibited the slow onset of therapeutic action and, more importantly, their effect on remission has been minimal. Thus, the need to find new forms of therapeutic intervention is urgent. The inflammation hypothesis of depression is widely acknowledged and is one that theories the relationship between the function of the immune system and its contribution to the neurobiology of depression. In this research, we utilized an environmental isolation (EI) approach as a valid animal model of depression, employing biochemical, molecular, and behavioral studies. The aim was to investigate the anti-inflammatory effect of etanercept, a tumor necrosis factor-α inhibitor on a toll-like receptor 7 (TLR 7) signaling pathway in a depressive rat model, and compare these actions to fluoxetine, a standard antidepressant agent. The behavioral analysis indicates that depression-related symptoms are reduced after acute administration of fluoxetine and, to a lesser extent, etanercept, and are prevented by enriched environment (EE) housing conditions. Experimental studies were conducted by evaluating immobility time in the force swim test and pleasant feeling in the sucrose preference test. The mRNA expression of the TLR 7 pathway in the hippocampus showed that TLR 7, MYD88, and TRAF6 were elevated in isolated rats compared to the standard group, and that acute treatment with an antidepressant and anti-inflammatory drugs reversed these effects. This research indicates that stressful events have an impact on behavioral well-being, TLR7 gene expression, and the TLR7 pathway. We also found that peripheral administration of etanercept reduces depressive-like behaviour in isolated rats: this could be due to the indirect modulation of the TLR7 pathway and other TLRs in the brain. Furthermore, fluoxetine treatment reversed depressive-like behaviour and molecularly modulated the expression of TLR7, suggesting that fluoxetine exerts antidepressant effects partially by modulating the TLR7 signaling pathway.


Assuntos
Comportamento Animal/efeitos dos fármacos , Transtorno Depressivo/tratamento farmacológico , Receptor 7 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Animais , Antidepressivos/farmacologia , Transtorno Depressivo/genética , Transtorno Depressivo/patologia , Modelos Animais de Doenças , Fluoxetina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Fator 88 de Diferenciação Mieloide/genética , Ratos , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/genética , Fator 6 Associado a Receptor de TNF/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...