RESUMO
IntroductionOxidative stress has been documented in chronic schizophrenia and in the first episode of psychosis, but there are very little data on oxidative stress prior to the disease onset. OBJECTIVE: This work aimed to compare serum levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in young individuals at ultra-high risk (UHR) of developing psychosis with a comparison healthy control group (HC). METHODS: Thirteen UHR subjects and 29 age- and sex-matched healthy controls (HC) were enrolled in this study. Clinical assessment included the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I) or the Kiddie-SADS-Present and Lifetime Version (K-SADS-PL), and the Global Assessment of Functioning (GAF) scale. Activities of SOD and GPx were measured in serum by the spectrophotometric method using enzyme-linked immunosorbent assay kits. RESULTS: After adjusting for age and years of education, there was a significant lower activity of SOD and lower GPX activity in the UHR group compared to the healthy control group (rate ratio [RR]=0.330, 95% CI 0.187; 0.584, p<0.001 and RR=0.509, 95% CI 0.323; 0.803, p=0.004, respectively). There were also positive correlations between GAF functioning scores and GPx and SOD activities. CONCLUSION: Our results suggest that oxidative imbalances could be present prior to the onset of full-blown psychosis, including in at-risk stages. Future studies should replicate and expand these results.
Assuntos
Glutationa Peroxidase/sangue , Transtornos Psicóticos/sangue , Superóxido Dismutase/sangue , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologiaRESUMO
Preliminary evidence suggests that premature immunosenescence is involved in bipolar disorder (BD) pathophysiology. The cellular marker CD69 is expressed in T lymphocyte surface during their activation and its expression is negatively correlated with age. The objective of this study was to assess the moderating effects of obesity on the reduction of expression of CD69, a marker of immunosenescence. Forty euthymic patients with BD type I, aged 18-65 years, were included in this study. The healthy comparison group consisted of 39 volunteers who had no current or lifetime history of mental disorders, no use of psychotropic medications, and no known family history of mood disorders or psychosis. Peripheral blood mononuclear cells from BD patients and healthy controls were collected and isolated. The cells were allowed to grow in culture and stimulated for 3 days. CD69 was marked and read in flow cytometry. We found that the lower expression of CD69 in BD patients was moderated by body mass index (BMI) in both CD4+ (RR = 0.977, 95% CI 0.960-0.995, p = 0.013) and CD8+ cells (RR = 0.972, 95% CI 0.954-0.990, p = 0.003). Our findings indicate that BMI could potentially influence the process of premature aging in BD.
RESUMO
OBJECTIVES: The study aims to generate an immunological age (IA) trait on the basis of immune cell differentiation parameters, and to test whether the IA is related to age and disease characteristics. METHODS: Forty-four euthymic type I bipolar disorder patients were included in this study. Five immunosenescence-related parameters were assessed: proportions of late-differentiated cells (e.g., CD3+CD8+CD28-CD27- and CD3-CD19+IgD-CD27-), and the expression of CD69, CD71, and CD152 after stimulation. Confirmatory factor analysis was applied to generate an IA trait underling the 5 measures. RESULTS: The best-fit model was constituted by 4 parameters that were each related to an underlying IA trait, with 1 cell population positively correlated (CD3+CD8+CD28-CD27- [λ = 0.544, where λ represents the loading of the parameter onto the IA trait] and 3 markers negatively correlated (CD69 [λ = -0.488], CD71 [λ = -0.833], and CD152 [λ = -0.674]). The IA trait was associated with chronological age (ß = 0.360, p = .013) and the number of previous mood episodes (ß = 0.426, p = .006). In a mediation model, 84% of the effect between manic episodes, and IA was mediated by body mass index. CONCLUSION: In bipolar disorder type I, premature aging of the immune system could be reliably measured using an index that validated against chronological age, which was related to adverse metabolic effects of the disease course.
Assuntos
Senilidade Prematura/imunologia , Transtorno Bipolar/imunologia , Transtorno Bipolar/fisiopatologia , Imunossenescência , Adolescente , Adulto , Senilidade Prematura/sangue , Biomarcadores/sangue , Transtorno Bipolar/sangue , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The present study aimed at investigating possible alterations in the serum lipid profile of euthymic patients with bipolar disorder type I (BD) compared to healthy controls (HC). Thirty-five individuals from both genders were recruited, with 14 diagnosed and treated as BD patients (BD group) and 21 healthy subjects (HC group). Clinical assessment was based on the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Young Mania Rating Scale (YMRS), and 17-items of Hamilton Depression Rating Scale (HDRS-17) data, which were used to confirm diagnosis, to verify psychiatric comorbidities, and to estimate the severity of manic and depressive symptoms. Ultra-high performance liquid chromatography (UHPLC) coupled to high resolution mass spectrometry (HRMS) was applied to analyze the lipids extracted from all serum samples from both studied groups. In this pioneer and exploratory study, we observed different serum lipid profiles for BD and HC groups, especially regarding glycerophospholipid, glycerolipid, and sphingolipid distribution. Multivariate statistical analyses indicated that 121 lipids were significantly different between BD and HC. Phosphatidylinositols were identified as the most altered lipids in BD patient sera. The results of this preliminary study reinforce the role of lipid abnormalities in BD and offer additional methodological possibilities for investigation in the field.
Assuntos
Transtorno Bipolar/sangue , Lipídeos/sangue , Espectrometria de Massas , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Estudos de Casos e Controles , Comorbidade , Depressão/sangue , Depressão/diagnóstico , Depressão/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilinositóis/sangueRESUMO
AIM: This study aimed to compare plasma copeptin levels, the c-terminal of provasopressin, between individuals with bipolar disorder (BD) and healthy controls and to assess the relation between copeptin and metabolic parameters. METHODS: We measured plasma levels of copeptin in individuals with BD (n = 55) and healthy controls (n = 21). Information related to psychiatric/medical history, as well as to metabolic comorbidities and laboratorial parameters was also captured. Insulin resistance and ß-cell function in basal state were calculated from fasting plasma glucose and C-peptide using the HOMA2 calculator. Impaired glucose metabolism was defined as pre-diabetes or type 2 diabetes mellitus. Copeptin, adiponectin, and leptin plasma levels were determined by enzyme-linked immunosorbent assay. RESULTS: Plasma copeptin levels were lower in individuals with BD, relative to healthy controls (P < 0.001). There were significant interactions between BD and plasma copeptin on ß-cell function (rate ratio [RR] = 1.048; P = 0.030) and on leptin levels (RR = 1.087; P = 0.012), indicating that there was a positive correlation between these markers in the BD group, but a negative one in healthy controls. Finally, in individuals with BD only, the association between ß-cell function, body mass index (RR = 1.007; P < 0.001), and insulin resistance (RR = 1.001; P = 0.037) was moderated by copeptin levels. CONCLUSION: Copeptin levels were lower in individuals with BD than in healthy controls. There were differential associations between copeptin and metabolic parameters within the BD and healthy control subgroups, suggesting an association between abnormal copeptin and metabolic dysregulation only in the BD population.
Assuntos
Transtorno Bipolar/sangue , Diabetes Mellitus Tipo 2/sangue , Dislipidemias/sangue , Glicopeptídeos/sangue , Estado Pré-Diabético/sangue , Adulto , Transtorno Bipolar/epidemiologia , Comorbidade , Diabetes Mellitus Tipo 2/epidemiologia , Dislipidemias/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/epidemiologiaRESUMO
BACKGROUND: The objective of this study was to identify molecular alterations in the human blood serum related to bipolar disorder, using nuclear magnetic resonance (NMR) spectroscopy and chemometrics. METHODS: Metabolomic profiling, employing 1H-NMR, 1H-NMR T2-edited, and 2D-NMR spectroscopy and chemometrics of human blood serum samples from patients with bipolar disorder (n = 26) compared with healthy volunteers (n = 50) was performed. RESULTS: The investigated groups presented distinct metabolic profiles, in which the main differential metabolites found in the serum sample of bipolar disorder patients compared with those from controls were lipids, lipid metabolism-related molecules (choline, myo-inositol), and some amino acids (N-acetyl-L-phenyl alanine, N-acetyl-L-aspartyl-L-glutamic acid, L-glutamine). In addition, amygdalin, α-ketoglutaric acid, and lipoamide, among other compounds, were also present or were significantly altered in the serum of bipolar disorder patients. The data presented herein suggest that some of these metabolites differentially distributed between the groups studied may be directly related to the bipolar disorder pathophysiology. CONCLUSIONS: The strategy employed here showed significant potential for exploring pathophysiological features and molecular pathways involved in bipolar disorder. Thus, our findings may contribute to pave the way for future studies aiming at identifying important potential biomarkers for bipolar disorder diagnosis or progression follow-up.
RESUMO
OBJECTIVES: Accumulating evidence indicates that oxidative stress and neurotrophins have a bidirectional relationship. In this post hoc, exploratory analysis, we investigated the association between plasma brain-derived neurotrophic factor (BDNF) levels and activities of the antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD) in individuals with bipolar disorder (BD) and healthy controls. METHODS: We measured plasma levels of BDNF and activities of GPx and SOD in individuals with BD (n=59) and healthy controls (n=26). Information related to current and past psychiatric/medical history, as well as to metabolic comorbidities, was also reported. RESULTS: There were negative correlations between BDNF, GPx (r=-.449, P≤.001) and GPx/SOD ratio (r=-.503, P<.001), and a positive correlation between BDNF and SOD (r=.254, P=.020). There was a moderating effect of body mass index (BMI) on the association between BDNF and GPx/SOD rate ratio [(RR)=1.002, P=.034]; interactions between impaired glucose metabolism (IGM), GPx (RR=1.016, P=.033), and GPx/SOD ratio (RR=1.026, P=.002) were also observed. These results were significant in models that included age, gender, alcohol, tobacco and medication use. CONCLUSIONS: There was a robust and independent correlation between peripheral BDNF and antioxidant enzyme activities in individuals with BD, which was moderated by metabolic comorbidities. These results reinforce the concept that these systems are associated and further extend knowledge of the putative effect of metabolic comorbidities in the pathophysiological substrates of BD.
Assuntos
Transtorno Bipolar , Fator Neurotrófico Derivado do Encéfalo/sangue , Glutationa Peroxidase/metabolismo , Estresse Oxidativo/fisiologia , Superóxido Dismutase/metabolismo , Adulto , Antioxidantes/metabolismo , Transtorno Bipolar/sangue , Transtorno Bipolar/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Estatística como AssuntoRESUMO
BACKGROUND: Early life stress (ELS) and addiction are related to age-related diseases and telomere shortening. However, the role of telomere length (TL) in crack cocaine addiction remains unknown. The purpose of this study was to investigate the TL in a sample of crack cocaine dependent-women who reported an ELS history and in a community-based sample of elderly women as a reference group for senescence. METHODS: This study included treatment seeking crack cocaine dependents women (n=127) and elderly women without a psychiatric diagnosis (ELD, n=49). The crack cocaine sample was divided in two groups according to their Childhood Trauma Questionnaire (CTQ) scores: presence of history of childhood abuse and neglect (CRACK-ELS) and absence of ELS history (CRACK). TL was assessed by T/S ratio obtained from peripheral blood DNA using quantitative PCR assay. RESULTS: CRACK and CRACK-ELS subjects exhibited shortened TL in comparison to the ELD group, despite their younger age. Among crack cocaine sample, CRACK-ELS group had significantly shorter telomeres than the CRACK group. Correlation analysis within crack cocaine group indicated that TL was negatively correlated with emotional abuse scores. CONCLUSIONS: These results support previous findings associating telomere shortening with both ELS and drug addiction. This study suggests new evidence of a distinct biological phenotype for drug-dependent women with ELS. The results support the biological senescence hypothesis underpinning ELS experience.
Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis , Envelhecimento , Transtornos Relacionados ao Uso de Cocaína , Cocaína Crack/efeitos adversos , Estresse Psicológico/genética , Adulto , Análise de Variância , Transtornos Relacionados ao Uso de Cocaína/complicações , Transtornos Relacionados ao Uso de Cocaína/etiologia , Transtornos Relacionados ao Uso de Cocaína/genética , Feminino , Humanos , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários , Telômero/genética , Encurtamento do Telômero/fisiologia , Adulto JovemRESUMO
OBJECTIVES: The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism (IGM) on plasma levels of BDNF in individuals with BD, and on the relationship between BDNF and variables of illness course. METHODS: We measured and compared the plasma levels of BDNF in individuals with BD (n=57) and healthy controls (n=26). IGM was operationalized as pre-diabetes or type 2 diabetes mellitus. Information related to current and past psychiatric/medical history, as well as prescription of pharmacological treatments was also captured. RESULTS: Individuals with BD had lower levels of BDNF, relative to healthy controls, after adjustment for age, gender, current medications, smoking, alcohol use, and IGM (P=.046). There was no effect of IGM (P=.860) and no interaction between BD diagnosis and IGM (P=.893). Peripheral BDNF levels were positively correlated with lifetime depressive episodes (P<.001), psychiatric hospitalizations (P=.001) and suicide attempts (P=.021). IGM moderated the association between BDNF and the number of previous mood episodes (P<.001), wherein there was a positive correlation in euglycemic participants and a negative correlation in individuals with IGM. CONCLUSIONS: BD is independently associated with lower levels of BDNF; IGM may modify the relationship between BDNF and BD course, suggesting an interactive effect of BDNF with metabolic status on illness progression.
Assuntos
Transtorno Bipolar , Fator Neurotrófico Derivado do Encéfalo/sangue , Diabetes Mellitus Tipo 2 , Glucose/metabolismo , Estado Pré-Diabético , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Biomarcadores/sangue , Transtorno Bipolar/sangue , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/fisiopatologia , Brasil , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/metabolismo , Estado Pré-Diabético/psicologia , Fatores de Risco , Fumar/epidemiologia , Estatística como AssuntoRESUMO
AIM: Childhood maltreatment (CM) has been related to a persistent reprograming of stress-response. Copeptin is a marker of hypothalamic-pituitary-adrenal axis activation; however, few studies have examined copeptin levels in children exposed to CM. The aim of this study was to compare serum copeptin levels in children reporting child abuse and/or neglect and children with no history of CM. METHODS: This study included 65 children with a positive history of moderate to severe CM, as reported by themselves and their parent(s) during a clinical interview, and 71 children with no history of CM as a comparison group. CM was considered moderate to severe based on the child-reported frequency of being exposed to events related to sexual abuse, physical abuse, emotional abuse, emotional neglect, and/or physical neglect. Child psychopathology symptoms were assessed using the Child Behavior Checklist (CBCL). We measured serum copeptin concentration using enzyme-linked immunosorbent assay. RESULTS: Children exposed to CM exhibited higher levels of serum copeptin compared to children without CM when controlling for sex, age, and psychiatric morbidity. The CBCL total score, including internalizing and externalizing symptoms, was higher in children with CM. We found no correlation between copeptin and CBCL scores for internalizing symptoms and externalizing symptoms. CONCLUSION: CM is associated with copeptin serum levels independently of age, sex, and symptom severity. Copeptin is a promising new biomarker for children with a history of abuse and/or neglect.
Assuntos
Maus-Tratos Infantis , Glicopeptídeos/sangue , Transtornos Mentais/sangue , Adolescente , Brasil , Criança , Feminino , Humanos , MasculinoRESUMO
Objectives: To compare hair cortisol concentrations (HCC) in drug-naïve first-episode psychosis (FEP) patients and healthy controls and to investigate the correlations between HCC and psychopathology. Methods: Twenty-four drug-naïve FEP patients and 27 gender- and age-matched healthy control subjects were recruited. The Structured Clinical Interview for DSM-IV (SCID-1) was used to confirm/rule out diagnoses, and the Positive and Negative Symptoms Scale (PANSS) was used to assess symptom severity. Hair samples (2-3 cm long) obtained from the posterior vertex region of the scalp were processed in 1-cm segments considering a hair growth rate of 1 cm per month. The 1-cm segments were classified according to their proximity to the scalp: segment A was the closest to the scalp and referred to the month prior to inclusion in the study. Segments B and C referred to the 2nd and 3rd months prior to the time of evaluation respectively. Hair steroid extraction was performed using a known protocol. Results: Two-way analysis of covariance (ANCOVA) with gender and age as covariates revealed a group effect (F1.106 = 4.899, p = 0.029) on HCC. Between-segment differences correlated with total PANSS score and with PANSS General Psychopathology subscale and total score. Conclusions: Our findings suggest that hypothalamic-pituitary-adrenal (HPA) axis, as assessed by long-term (3-month) cortisol concentration, is abnormal in the early stages of psychosis. The magnitude of changes in HCC over time prior to the FEP correlates to psychopathology. HPA axis abnormalities might begin prior to full-blown clinical presentation requiring hospital admission.
Assuntos
Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Transtornos Psicóticos/metabolismo , Hidrocortisona/metabolismo , Cabelo/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Fatores de Tempo , Índice de Gravidade de Doença , Estudos Transversais , Sistema Hipotálamo-Hipofisário/fisiopatologiaRESUMO
OBJECTIVES: To compare hair cortisol concentrations (HCC) in drug-naïve first-episode psychosis (FEP) patients and healthy controls and to investigate the correlations between HCC and psychopathology. METHODS: Twenty-four drug-naïve FEP patients and 27 gender- and age-matched healthy control subjects were recruited. The Structured Clinical Interview for DSM-IV (SCID-1) was used to confirm/rule out diagnoses, and the Positive and Negative Symptoms Scale (PANSS) was used to assess symptom severity. Hair samples (2-3 cm long) obtained from the posterior vertex region of the scalp were processed in 1-cm segments considering a hair growth rate of 1 cm per month. The 1-cm segments were classified according to their proximity to the scalp: segment A was the closest to the scalp and referred to the month prior to inclusion in the study. Segments B and C referred to the 2nd and 3rd months prior to the time of evaluation respectively. Hair steroid extraction was performed using a known protocol. RESULTS: Two-way analysis of covariance (ANCOVA) with gender and age as covariates revealed a group effect (F1.106 = 4.899, p = 0.029) on HCC. Between-segment differences correlated with total PANSS score and with PANSS General Psychopathology subscale and total score. CONCLUSIONS: Our findings suggest that hypothalamic-pituitary-adrenal (HPA) axis, as assessed by long-term (3-month) cortisol concentration, is abnormal in the early stages of psychosis. The magnitude of changes in HCC over time prior to the FEP correlates to psychopathology. HPA axis abnormalities might begin prior to full-blown clinical presentation requiring hospital admission.
Assuntos
Cabelo/metabolismo , Hidrocortisona/metabolismo , Transtornos Psicóticos/metabolismo , Adulto , Estudos Transversais , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Sistema Hipófise-Suprarrenal/fisiopatologia , Índice de Gravidade de Doença , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: To characterize the early stages of bipolar disorder (BD), defined as the clinical prodrome/subsyndromal stage and first-episode phase, and strategies for their respective treatment. METHODS: A selective literature search of the PubMed, Embase, PsycINFO, and ISI databases from inception until March 2014 was performed. Included in this review were articles that a) characterized prodromal and first-episode stages of BD or b) detailed efficacy and safety/tolerability of interventions in patients considered prodromal for BD or those with only one episode of mania/hypomania. RESULTS: As research has only recently focused on characterization of the early phase of BD, there is little evidence for the effectiveness of any treatment option in the early phase of BD. Case management; individual, group, and family therapy; supportive therapy; and group psychoeducation programs have been proposed. Most evidence-based treatment guidelines for BD do not address treatment specifically in the context of the early stages of illness. Evidence for pharmacotherapy is usually presented in relation to illness polarity (i.e., manic/mixed or depressed) or treatment phase. CONCLUSIONS: Although early recognition and treatment are critical to preventing unfavorable outcomes, there is currently little evidence for interventions in these stages of BD.
Assuntos
Transtorno Bipolar/patologia , Transtorno Bipolar/terapia , Intervenção Médica Precoce/métodos , Progressão da Doença , Feminino , Humanos , Masculino , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Objective: To characterize the early stages of bipolar disorder (BD), defined as the clinical prodrome/subsyndromal stage and first-episode phase, and strategies for their respective treatment. Methods: A selective literature search of the PubMed, Embase, PsycINFO, and ISI databases from inception until March 2014 was performed. Included in this review were articles that a) characterized prodromal and first-episode stages of BD or b) detailed efficacy and safety/tolerability of interventions in patients considered prodromal for BD or those with only one episode of mania/hypomania. Results: As research has only recently focused on characterization of the early phase of BD, there is little evidence for the effectiveness of any treatment option in the early phase of BD. Case management; individual, group, and family therapy; supportive therapy; and group psychoeducation programs have been proposed. Most evidence-based treatment guidelines for BD do not address treatment specifically in the context of the early stages of illness. Evidence for pharmacotherapy is usually presented in relation to illness polarity (i.e., manic/mixed or depressed) or treatment phase. Conclusions: Although early recognition and treatment are critical to preventing unfavorable outcomes, there is currently little evidence for interventions in these stages of BD.
Assuntos
Feminino , Humanos , Masculino , Transtorno Bipolar/patologia , Transtorno Bipolar/terapia , Intervenção Médica Precoce/métodos , Progressão da Doença , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Schizophrenia is accompanied by alterations in immuno-inflammatory pathways, including abnormalities in cytokine profile. The immune assessment of patients in a first episode of psychosis (FEP) and particularly in drug naïve patients is very important to further elucidate this association. The objectives of this study are to delineate the cytokine profile (IL-2, IL-10, IL-4, IL-6, IFNγ, TNFα and IL-17) in FEP patients (n=55) versus healthy controls (n=57) and to examine whether the presence of depressive symptoms in FEP is accompanied by a specific cytokine profile. We found increased levels of IL-6, IL-10 and TNFα in FEP patients when compared to healthy controls. FEP patients with depression showed higher IL-4 and TNFα levels versus those without depression. Cytokine levels were not correlated to the total PANSS and the positive or negative subscale scores. Our results suggest that FEP is accompanied by a cytokine profile indicative of monocytic and T regulatory cell (Treg) activation. Depression in FEP is accompanied by monocytic and Th-2 activation, whereas FEP without depression is characterized by Treg activation only. In conclusion, depression emerged as a key component explaining the cytokines imbalance in FEP that is responsible for a large part of the immune-inflammatory abnormalities described.
Assuntos
Citocinas/sangue , Depressão/sangue , Depressão/etiologia , Transtornos Psicóticos/complicações , Adolescente , Adulto , Análise de Variância , Distribuição de Qui-Quadrado , Estudos de Coortes , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Adulto JovemRESUMO
In the last decades convergent findings from several lines of evidence has revealed a robust association between major depressive disorder (MDD) and inflammatory pathways. Despite this, the translation of these findings into new and better treatments for MDD has not occurred. The objective of this study is to comprehensively review what is already known with reasonable certainty on inflammatory pathways in MDD, to clarify some points that have been insufficiently studied and to discuss the implications of these findings for future studies targeting inflammatory pathways as a therapeutic tool for individuals with MDD.