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1.
Mol Genet Genomic Med ; : e983, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578828

RESUMO

BACKGROUND: Evidence suggests that liability for suicide behavior is heritable; additionally, suicide has been partly related to other psychiatric disorders. Nevertheless, most of the information reported so far address Caucasian and Asian individuals. Hence, our aim was to conduct a gene-level association study in Mexican psychiatric individuals diagnosed with suicide attempt. METHODS: We recruited 192 individuals from two clinical centers in Mexico. All participants were born in Mexico and had Mexican parents and grandparents. Direct genotyping was performed using the commercial platform Infinium PsychArray BeadChip. A p-value lower than 1e-05 was considered as gene-level significant and a p-value lower than 1e-04 was considered as gene-level nominal significant. RESULTS: Our analyses showed that SCARA5 was associated to suicide intent at a gene-level with statistical significance (p-value = 1.12e-6). Other genes were nominally associated with suicide attempt: GHSR (p-value = 0.0004), RGS10 (p-value = 5.13e-5), and STK33 (p-value = 3.62e-5). Regarding gene variant analyses, the SNPs with a statistical association (p > .05) were rs561361616, rs1537577, rs11198999 for RGS10, and rs11041981, rs11041993, rs11041994, rs11041995, rs11041997, rs10840083, rs10769918 for STK33. For these genes, previous studies have associated SCARA5 with depression, GHSR with alcohol dependence and depression, and RGS10 with schizophrenia and depression. To date, STK33 has not been associated with any psychiatric disorder. CONCLUSION: Our outcomes revealed that SCARA5, GHSR, RGS10 and STK33 could be considered as risk biomarkers for suicide attempt behavior in our Mexican psychiatric sample. We recommend to perform larger scale analyses to have conclusive results.

2.
J Health Psychol ; : 1359105319876326, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31532262

RESUMO

The aim of this study was to determine the risk of having significant depressive symptoms in subjects with obesity and type 2 diabetes mellitus through a meta-analysis. Our results showed that individuals with obesity and diabetes have an increased risk of having significant symptoms of depression. In subgroup analyses, we observed that Caucasian populations have an increased risk of having these symptoms. Our meta-analysis suggests that obesity is associated with an increased risk of having significant depressive symptoms in patients with type 2 diabetes, and they could be even higher in Caucasian populations.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31349552

RESUMO

Background: individuals with type 2 diabetes show emotional distress as they learn how to cope with the disease. The emotional distress increases the possibility of complications in these patients. The aims of the present study were to evaluate the impact of the emotional distress in the quality of life of individuals with diabetes, and to investigate the demographic and clinical characteristics associated with the emotional distress of living with diabetes in a Mexican population. Methods: a total of 422 Mexican individuals with type 2 diabetes were recruited from the outpatient Diabetes Clinic of the Hospital Regional de Alta Especialidad Dr. Gustavo A. Rovirosa of Villahermosa, Tabasco. Demographic and clinical characteristics along with quality of life (SF-36) were assessed in these individuals. The emotional distress of living with diabetes was measured using the 5-item Problem Areas in Diabetes. Patients were divided according to the presence of high or low distress. Results: we identified that 31.8% (n = 134) of patients presented high diabetes-related emotional distress. We observed that hepatic diseases as comorbidities (p = 0.008) and diagnosis of major depression (p = 0.04) are factors associated with the emotional distress of living with diabetes. These patients showed a reduced quality of life in all dimensions (p < 0.001); the most affected dimensions were physical role (d = 0.37) and general health (d = 0.89) showing lower scores in comparison with patients with low emotional distress. Conclusions: our results suggest that Mexican individuals with type 2 diabetes mellitus show high emotional distress living with the disease and have a decreased quality of life. Therefore, it is necessary to decrease factors associated with the high emotional distress of living with diabetes in patients with type 2 diabetes.

4.
Brain Behav ; 9(7): e01286, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31199591

RESUMO

INTRODUCTION: The 5-HTR2A gene has been implicated as candidate gene for eating disorders. The aim of the present study was to analyze the association of rs6311 and rs6313 polymorphisms of 5-HTR2A gene with eating disorders in Mexican population, and to evaluate if the polymorphisms of 5-HTR2A gene were associated with comorbidities in eating behavior. METHODS: We conducted a case-control analysis with 460 subjects. We included 168 patients with eating disorders and 292 controls; two polymorphisms of 5-HTR2A gene were genotyped. We assessed the association by allele, genotype, and inheritance models. Psychiatric comorbidities were analyzed by genotype in patients with eating disorders. RESULTS: We found an association between rs6311 and eating disorders in a Mexican population by allele (OR = 8.09; 95% CI = 5.99-11.03; p = 2.2e-16) and genotype (OR = 76.14; 95% CI = 35.61-177.18; p = 2.2e-16). Individuals who carried GG genotype showed increased risk for suicide attempted (OR = 2.14; CI = 1.10-4.26; p = 0.035) as comorbidity associated with eating disorders. No positive associations were observed for rs6313 polymorphism. CONCLUSION: Our results showed an association of rs6311 (A1438G) polymorphism of 5-HTR2A gene with eating disorders, and these polymorphic variants could increase the risk of psychiatric comorbidities. However, more studies are required to replicate the results and to reach to a conclusive association between eating disorders and rs6311.

5.
Brain Behav ; 9(6): e01249, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31033179

RESUMO

INTRODUCTION: Several studies indicate that polygenic obesity is linked to fat-mass and obesity-associated (FTO) genetic variants. Nevertheless, the link between variants in FTO and mental disorders has been barely explored. The present work aims to determine whether FTO genetic variants are associated with bipolar disorder and obesity, and to perform an in silico prediction of variant-dependent functional impact on the developing brain transcriptome. METHODS: Four hundred and forty-six Mexican mestizos were included in a genetic association analysis. SNP-sequence kernel association test and linear mixed models were implemented for genetic association assessment. For functional impact prediction, we analyzed the mapping of regulatory elements, the modification of binding sites of transcription factors and the expression of transcription factors in the brain developing transcriptome, searching on different databases. RESULTS: In the set-based analysis, we found different associated regions to BD (bipolar disorder) and obesity. The promoter flanking region of FTO intron 1 was associated with differential effects on BMI, while intron 2 of RPGRIP1L and FTO upstream regions were associated with BD. The prediction analysis showed that FTO BD-associated variants disturb binding sites of SP1 and SP2; obesity-associated variants, on the other hand, disturb binding sites of FOXP1, which are transcription factors highly expressed during prenatal development stages of the brain. CONCLUSION: Our results suggest a possible effect of FTO variants on neurodevelopment in obesity and bipolar disorder, which gives new insights into the molecular mechanism underlying this association.

6.
BMJ Open ; 9(4): e025335, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975676

RESUMO

INTRODUCTION: Suicidality is a complex behaviour and a major health problem; the specific features that could predispose to suicidal behaviour have been extensively investigated, most frequently in European and Asian populations. Therefore, our aim is to present a protocol that will explore suicide attempt in Mexican individuals diagnosed with psychiatric disorders, through a genome-wide association study (GWAS). METHOD AND ANALYSIS: We will perform a GWAS by comparing 700 individuals who have suicide attempt history, with control subjects without suicide attempt history (n=500). The genotyping will be conducted using the Infinium PsychArray BeadChip and quality controls will be applied to single nucleotides (SNPs) genotyped. After that, we will perform the imputation using reference panels provided by the Haplotype Reference Consortium. We will perform two different workflows: (A) the classic GWAS analysis applying the same weight to all the variants and (B) an algorithm with prediction of deleteriousness of variants. ETHICS AND DISSEMINATION: This study was approved by the ethics and investigation committees of the National Institute of Genomic Medicine on 22 July 2015, No CEI 215/13. We plan to disseminate research findings in scientific conferences and as a manuscript in peer-reviewed journals. TRIAL REGISTRATION NUMBER: CEI 215/13.

7.
Medicine (Baltimore) ; 98(11): e14838, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30882674

RESUMO

The aim of the present case-control study was to explore the association between BDNF Val66Met (rs6265) polymorphism and generalized anxiety disorder in Mexican individuals, and whether this polymorphism plays a role in the symptomatology of anxiety.A total of 212 subjects were included in the study. Around 75 patients with generalized anxiety disorder were diagnosed by psychiatrists based on the DSM-IV instrument and 137 unrelated subjects psychiatrically healthy were used as comparison group. The subclinical symptomatology in patients was assessed with the State-Trait Anxiety Inventory. BDNF rs6265 genotypes were analyzed using the polymerase chain reaction end-point method.The association between BDNF Val66Met with the risk for generalized anxiety disorder was evaluated using 4 inheritance models. The present study showed that carrying the Met allele confers increased risk for the presence of generalized anxiety disorder (χ = 4.7, P = .03; OR (95%) 1.96 (1.05-3.56)) when patients with generalized anxiety disorder were compared with the comparison group.Our results provide evidence of an association between the Val66Met polymorphism of the BDNF gene and generalized anxiety disorder in a Mexican population. However, no association was observed between this polymorphism and the symptomatology of anxiety.


Assuntos
Transtornos de Ansiedade , Fator Neurotrófico Derivado do Encéfalo/genética , Adulto , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/genética , Transtornos de Ansiedade/psicologia , Sintomas Comportamentais/diagnóstico , Correlação de Dados , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Predisposição Genética para Doença , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Escalas de Graduação Psiquiátrica
8.
Metab Brain Dis ; 34(4): 967-977, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30900130

RESUMO

The enzyme nitric oxide synthase has been associated with suicide behavior. NOS1, NOS2 and NOS3 genes are implicated in the production of nitric oxide. However, the association between NOS genes and suicide behavior has not yet been established. To assess the association of Nitric Oxide Synthase (NOS) genes and suicide behavior we performed a systematic review a meta-analysis. We searched articles published in three electronic databases, PubMed, Scopus and Web of Sciences, up to February 2019. We used keywords and combinations "NOS", "NOS1", "NOS2", "NOS3" and "suicide". Only articles that met the inclusion criteria were included. To assess the association between NOS genes and suicide behavior we used allelic, dominant and recessive models, as well as homozygous and heterozygous comparisons. The pooled results showed that rs2682826 of Nitric Oxide Synthase 1 gene (NOS1) increased the risk for suicide attempt in the allelic (OR: 1.34; 95 CI: 1.00-1.78), recessive (OR: 1.45; 95 CI:1.06-1.98) and heterozygous (OR: 1.41; 95 CI: 1.09-1.81) models. We found that the rs2682826 of NOS1 could increase the risk for suicide attempt. However, these results should only be taken as exploratory; more studies are necessary to determine the association between NOS genes and suicide behavior.

9.
Psychiatry Res ; 271: 658-668, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30791339

RESUMO

Psychiatric disorders are complex polygenic diseases that show common genetic vulnerability. Several studies have investigated the association of polymorphisms of FK506 binding protein 51 (FKBP5) gene and depressive disorders or suicidal behavior, however, the results have been controversial and ambiguous. The aim of our study was to explore the role of the FKBP5 gene variants (rs1360780, rs3800373 and rs4713916), in depressive disorders or suicidal behavior through a systematic review and a meta-analysis. The protocol number of the study is PROSPERO CRD42018089295. The meta-analysis included 12 studies. Odds ratios with 95% confidence intervals were used to evaluate the association and the publication bias was tested by Egger's test and funnel plot; heterogeneity was assessed by the Cochran's chi-square-based Q statistic test and the inconsistency index. Our results showed that the rs3800373 and rs4713916 were associated with an increased risk of depressive disorders when using the heterozygous and dominant models. In the stratified analysis by ethnicity, a significantly increased risk of depressive disorders was also observed for rs3800373 and rs4713916 in Caucasians. When we analyzed suicidal behavior, we found a significant association with the rs1360780 of FKBP5 and suicidal behavior risk in the overall population and rs3800373 in completed suicide subgroup. Existing evidence indicates that the polymorphisms of FKBP5 gene are associated with risk of depressive disorders and suicidal behavior. Future studies with larger sample sizes will be necessary to confirm the present results.


Assuntos
Transtorno Depressivo/genética , Estudos de Associação Genética/métodos , Polimorfismo de Nucleotídeo Único/genética , Ideação Suicida , Suicídio , Proteínas de Ligação a Tacrolimo/genética , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Feminino , Predisposição Genética para Doença/genética , Predisposição Genética para Doença/psicologia , Humanos , Masculino , Suicídio/psicologia
10.
Biochem Genet ; 57(4): 583-605, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30778791

RESUMO

A genetic component is accepted in the etiology of the glioma. Evidence from candidate genes studies and GWAS reveal that CCDC26 gene could increase the risk of glioma. We performed a systematic review and up-to-date meta-analysis to explore if polymorphisms of CCDC26 gene (rs891835, rs6470745, and rs55705857) may be a susceptibility factor in developing glioma. An online search in PubMed, Web of Science, and SCOPUS up to September 2018 was performed. The pooled odds ratios were evaluated by fixed effects model and random effects model. Analyses of the overall sample and ethnic sub-groups were performed. In all the analyses, the allelic, additive, dominant, and recessive models were used. We found an association between all polymorphisms evaluated and an increased risk for glioma in the overall population in all the models studied. In sub-group analysis, we found that rs891835 and rs6470745 increased the risk of glioma in Europeans and Caucasians. On the other hand, the rs891835 polymorphism did not reveal any statistical association in Chinese population. Taken into consideration the limitations of this study, the present findings suggest a possible participation of rs891835, rs6470745, and rs55705857 as risk factors to develop glioma. Furthermore, it is possible that the involvement of CCDC26 variants depends on ethnicity. However, we recommend to perform further studies to have conclusive outcomes.


Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único , Fatores de Risco
11.
Gac Med Mex ; 154(5): 555-560, 2018.
Artigo em Espanhol | MEDLINE | ID: mdl-30464349

RESUMO

Introduction: In Mexico, the prevalence of neurocognitive disorders (NCDs) has increased in parallel with the increase in life expectancy. The E4 allele of the gene that encodes apolipoprotein E (APOE) is the main genetic risk factor for cognitive impairment. Objective: To replicate the association of APOE-E4 allele with neurocognitive impairment in a Mexican population, as well as to implement a genetic risk-detection program with the APOE-E4 allele. Method: A program was structured for the detection of APOE-E4 allele risk in different recruiting centers from the central zone of the Mexican Republic, with three stages: recruitment and selection of candidates for the detection of the risk-allele, genetic risk analysis and delivery of results. Results: In the genetic-association study to replicate the association with neurocognitive disorders by means of multivariate logistic models, the APOE-E4 allele increased the risk for cognitive impairment in the Mexican populations by approximately 6 % (OR: 5.83, p = 0.0025). In addition, 367 genetic risk results were delivered. Conclusions: The present program is the first one to be implemented in Mexico with the purpose to inform on a genetic risk factor for neurocognitive disorders in several centers of the country.

12.
Neuropsychiatr Dis Treat ; 14: 2485-2496, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319259

RESUMO

Background: It is accepted that there is a genetic factor that influences the risk of suicidal behavior. The catechol-O-methyltransferase (COMT) gene, especially the Val108/158Met polymorphism, has been associated with suicide; however, no conclusive outcome has been attained. Therefore, the aim of the present study was to assess the role of COMT Val108/158Met in suicidal behavior throughout an updated meta-analysis. Methods: We performed an online search using PubMed and Web of Science (up to March 2017). Our systematic review included case-control studies of individuals who attempted suicide and completed suicide. We tested allelic, homozygous, heterozygous, dominant, and recessive inheritance models. The meta-analysis was performed in accordance with the statement of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Results: The meta-analysis comprised 17 studies, which included 3,282 cases and 3,774 controls, and showed that when evaluating the overall population, the Val108/158Met polymorphism of COMT was not associated with suicidal behavior in any of the inheritance models; however, the subanalyses showed that this polymorphism exhibits a risk factor in males and a protective effect in females. Additionally, it conveyed a risk factor in Asian populations when using the allelic (OR 1.25; CI: 1.04-1.51) and recessive models (OR 1.32; CI: 1.03-1.68). Conclusion: Our updated meta-analysis suggests a possible association between COMT Val108/158Met and suicidal behavior in Asian populations. However, in view of the small number of studies, these results should be considered exploratory. We recommend that more studies be performed with larger samples.

13.
Metab Brain Dis ; 33(6): 2031-2038, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30264280

RESUMO

Artificial sweeteners are mainly used as substitutes for sucrose derivates. In this study, we analyzed if the chronic consumption of aspartame or acesulfame potassium at an early age, produces histological alterations, astrogliosis and decreased neuronal viability, in hippocampus, prefrontal cortex, amygdala and hypothalamus of male Wistar rats. A histological analysis was performed on male Wistar rats that consumed aspartame or acesulfame potassium during 90 days, initiating the consumption of sweeteners immediately after weaning. The evaluation of neuronal morphology in different areas of the brain was performed with hematoxylin - eosin staining. To measure astrogliosis and neuronal viability, we used the immunohistochemical technique, with the glial fibrillary acidic protein immunomodulators (GFAP) and with neuronal-specific enolase (NSE). The consumption of aspartame or acesulfame potassium promoted morphological changes of neurons including increased pyknotic nuclei and vacuolization in all the brain areas studied. In hippocampus, prefrontal cortex, amygdala and hypothalamus, astrogliosis and reduction of neural viability were observed in sweeteners consumers in comparison with the control group. Chronic consumption of ASP and ACK from early stages of development and during long periods, may promote neural modifications, astrogliosis and decrease neuronal viability in prefrontal cortex, amygdala, hippocampus, and hypothalamus.

14.
Neuropsychobiology ; 76(4): 193-198, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29966133

RESUMO

BACKGROUND: The aim of this study was to analyze the possible association of polymorphic variants of the DRD2 and ANKK1 genes with suicide attempt in a Mexican population. METHODS: We conducted a case-control study in 289 subjects (166 suicide attempters and 123 healthy controls). We genotyped 2 polymorphisms of DRD2 (rs6275 and rs1799978) and 1 polymorphism of ANKK1 (rs1800497); then we analyzed the association between suicide attempt and these polymorphisms through genotypes, alleles, and inheritance models. RESULTS: Individuals who carried the TT genotype of the rs1800497 showed a 3-fold risk of attempting suicide (OR = 3.01; 95% CI 1.56-5.81, p = 0.001) when evaluated through the recessive model. In an analysis stratified by gender, this risk factor remained present among females (OR = 2.81; 95% CI 1.37-5.75) as well as males (OR = 3.3; 95% CI 1.01-10.77). CONCLUSION: Our results suggest that the rs1800497 variant of the ANKK1 gene could increase the risk of suicide attempt in a Mexican population. However, further studies using larger samples are necessary to obtain more conclusive results.

15.
Neuropsychiatr Dis Treat ; 12: 1843-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27524902

RESUMO

BACKGROUND: The brain-derived neurotrophic factor (BDNF) has been considered as an important candidate gene in bipolar disorder (BD); this association has been derived from several genetic and genome-wide studies. A polymorphic variant of the BDNF (Val66Met) confers some differences in the clinical presentation of affective disorders. In this study, we evaluated a sample population from Mexico City to determine whether the BDNF (rs6265) Val66Met polymorphism is associated with the body mass index (BMI) of patients with BD. METHODS: This association study included a sample population of 357 individuals recruited in Mexico City. A total of 139 participants were diagnosed with BD and 137 were classified as psychiatrically healthy controls (all individuals were interviewed and evaluated by the Diagnostic Interview for Genetic Studies). Genomic DNA was extracted from peripheral blood leukocytes. The quantitative polymerase chain reaction (qPCR) assay was performed in 96-well plates using the TaqMan Universal Thermal Cycling Protocol. After the PCR end point was reached, fluorescence intensity was measured in a 7,500 real-time PCR system and evaluated using the SDS v2.1 software, results were analyzed with Finetti and SPSS software. Concerning BMI stratification, random groups were defined as follows: normal <25 kg/m(2), overweight (Ow) =25.1-29.9 kg/m(2), and obesity (Ob) >30 kg/m(2). RESULTS: In the present work, we report the association of a particular BMI phenotype with the presence of the Val66Met allele in patients with BD (P=0.0033 and odds ratio [95% confidence interval] =0.332 [157-0.703]), and correlated the risk for valine allele carriers with Ow and Ob in patients with BD. CONCLUSION: We found that the methionine allele confers a lower risk of developing Ow and Ob in patients with BD. We also confirmed that the G polymorphism represents a risk of developing Ow and Ob in patients with BD. In future studies, the haplotype analysis should provide additional evidence that BDNF may be associated with BD and BMI within the Mexican population.

16.
Hereditas ; 153: 13, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28096775

RESUMO

BACKGROUND: Neonatal lesion in the ventral hippocampus (NLVH) is a validated animal model to study schizophrenia from a neurodevelopmental perspective. This animal model is also used to investigate how neonatal lesions may alter the genetic expression of dopaminergic receptors. The present study compares mRNA expression levels of dopamine receptors (drd2 and drd3) in lymphocytes and brain of NLVH animals at two different age stages: young and adult. METHODS: The NLVH procedure was performed on 20 male Wistar rats at postnatal days 5-7. The mRNA expression levels of drd2 and drd3 genes in lymphocytes, nucleus accumbens, hippocampus and prefrontal cortex were measured and analyzed at postnatal days 45 and 90. The results were compared and contrasted with respective sham groups. RESULTS: In lymphocytes, only in NLVH-adult group we observed drd2 mRNA expression, while drd2 mRNA expression was not observed in the NLVH-juvenile rats; on the other hand, the drd3 mRNA expression did not show significant statistical differences. In hippocampus no differences were observed between drd2 mRNA or drd3 mRNA expression when comparing juvenile/adult shams with NLVH groups. In the prefrontal area, a decrease in drd2 mRNA expression levels were observed in the NLVH-adult group (F(1,3) = 52.83, p = 0,005) in comparison to the sham-adult group. Finally, in the nucleus accumbens, a strong decrease of drd3 mRNA expression was observed in the NLVH-adult group in comparison to the sham-adult group (F(1,3) = 123,2, p < 0.001). CONCLUSIONS: Our results show that differences in drd2 and drd3 mRNA levels in NLVH-adults are patent when compared to the sham-adult group or with the NLVH-juvenile group. These findings suggest that the expression levels may be regulated during adulthood, leading to behavioral and neurochemical changes related to schizophrenia. Therefore, more studies are necessary to determine the role of dopamine receptors as possible molecular markers for neurodevelopmental changes associated with schizophrenia.


Assuntos
Hipocampo/metabolismo , Núcleo Accumbens/metabolismo , Córtex Pré-Frontal/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo , Esquizofrenia/genética , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Hipocampo/patologia , Linfócitos/metabolismo , Masculino , Núcleo Accumbens/patologia , Córtex Pré-Frontal/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Receptores de Dopamina D2/genética , Receptores de Dopamina D3/genética
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