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1.
Adv Exp Med Biol ; 1180: 85-98, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784958

RESUMO

Major depressive disorder (MDD) or depression is one of the most highly prevalent, chronic, and recurrent disorders, which is associated with a high burden of disease and substantial impairment in social functions. Both immune molecules and cells have been implicated in the pathophysiology and maintenance of MDD. Findings in animals and MDD patients have suggested that both pro- and anti-inflammatory cytokines are activated in the neuroinflammation which contribute to behavioral symptoms and changes in the course of depression. There is a growing body of evidence to support that neuroinflammation is a mediator for the communication among stress response, neuroendocrine, neurotransmission, neurogenesis, and gut microbiota. These communications have been known as risk factors in the pathogenesis of MDD. In the meantime, accumulating evidence has suggested that some interventions targeting the inflammatory processes may play an important role in the treatment of MDD.


Assuntos
Transtorno Depressivo Maior/imunologia , Animais , Citocinas/imunologia , Microbioma Gastrointestinal , Humanos , Inflamação , Neurogênese , Transmissão Sináptica
2.
J Clin Neurosci ; 70: 14-19, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629608

RESUMO

Cognitive dysfunction and pro-inflammatory effect has been associated with major depressive disorder (MDD), but sex differences have seldom been studied. The study was to determine the sex difference of cognitive dysfunction and pro-inflammatory biomarkers among patients with MDD in Chinese Han population. 104 MDD patients (male n = 37, female n = 67) were included in the study. Their sociodemographic and clinical features, including age, body mass index (BMI), education, smoking, alcohol use, illness characteristics and medicine use were recorded. Montreal Cognitive Assessment (MoCA) was used to assess cognition. And we detected pro-inflammatory biomarkers Interleakin-1ß (IL-1ß), Interleakin-6 (IL-6) and C-reaction protein (CRP) levels by enzyme linked immunosorbent assay. We found that male patients showed higher scores than female in MoCA, and performed better than female patients particularly in visuaspatial, naming, attention, orientation subscale. CRP and IL-1ß levels showed no significant difference between male and female patients in MDD. However, Male's IL-6 level was significantly declined than female, negative closed associated with cognition in MOCA score. These results suggested that the difference in IL-6 could reflect a cognitive difference between male and female in MDD, and IL-6 elevation could represent a state indicator for cognitive ability particular in female MDD patients. And it maybe a biological treatment target in cognition dysfunction of female patients in MDD.


Assuntos
Biomarcadores/sangue , Disfunção Cognitiva/imunologia , Transtorno Depressivo Maior/imunologia , Interleucina-6/sangue , Caracteres Sexuais , Adulto , Grupo com Ancestrais do Continente Asiático , Disfunção Cognitiva/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/complicações , Feminino , Humanos , Interleucina-6/imunologia , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade
3.
Psychiatr Danub ; 31(Suppl 3): 252-257, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488736

RESUMO

Major depression is one of the most frequent psychiatric conditions. Despite many available treatment methods, more than 30% of patients do not achieve remission, even after trying several antidepressants and augmentation strategies. S-enantiomer of ketamine, well-known anesthetic and analgesic, has been recently approved by Food and Drug Administration in the intranasal form as a new generation antidepressant. However, the mechanism in which ketamine reduces depressive symptoms in treatment-resistant depression patients is still not completely understood. There are several theories explaining how ketamine might reduce depressive symptoms, which have been described in detail; one of them is immunomodulatory effect of ketamine, according to the inflammatory theory of depression. In the review authors present and summarize studies showing ketamine effect on human immune system ex vivo and in vitro, including changes in cytokine levels, number, ratio and activity of various immune cell population and the correlation with clinical improvement in depressive symptoms. Most of the results confirm the anti-inflammatory effect of ketamine. There are only a few studies in the population of patients suffering from depression receiving ketamine, focused on correlation between immunological changes and clinical outcome of the therapy; further studies of that area are neccesary for understanding the immunomodulatory effect of ketamine in depression.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/imunologia , Ketamina/imunologia , Ketamina/uso terapêutico , Antidepressivos/imunologia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Depressão/imunologia , Humanos , Imunomodulação/imunologia
4.
Malays J Pathol ; 41(2): 169-176, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31427552

RESUMO

INTRODUCTION: Regulatory T cell (Treg) is a subtype of T lymphocyte that plays a crucial role in establishing immunologic self-tolerance and maintaining immune homeostasis. In this study, we set out to investigate the percentage and absolute count of Tregs in major depressive disorder (MDD) patients and their correlation with disease severity. MATERIALS & METHODS: This is a case-control study consisting of 47 MDD patients and 47 healthy controls. MDD patients were treated with antidepressant drugs according to their physician's choice. The severity of MDD was assessed using Beck Depression Inventory (BDI) and Montgomery-Asberg Depression Rating Scale (MADRS) at the time of recruitment. Healthy controls completed the Depression Anxiety Scoring System (DASS21) questionnaire to ensure they were in good mental health without history of MDD. The percentage and absolute count of CD4+ CD25+ Tregs and CD4+ CD25+ FOXP3+ Tregs were identified by multiparameter flow cytometry. RESULTS: The percentage and absolute count of CD4+ CD25+ Treg cells were significantly higher in MDD patients than in healthy controls (P<0.001, in both cases). Likewise, the percentage and absolute count of CD4+ CD25+ FOXP3+ Treg cells were also significantly higher in MDD patients compared to healthy controls (P=0.003 and P=0.002, respectively). However, there was no significant correlation between the percentage and absolute count of CD4+ CD25+ Treg and CD4+ CD25+ FOXP3+ Treg cells with BDI or MADRS score. CONCLUSIONS: Our results suggest that antidepressant treatments contributed to an upregulation of Tregs in MDD patients.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
Psychopharmacology (Berl) ; 236(10): 3063-3079, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31359117

RESUMO

Social Signal Transduction Theory of Depression is a biologically plausible, multi-level theory that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of social-environmental adversity with internal biological processes that drive depression pathogenesis, maintenance, and recurrence. Central to this theory is the hypothesis that interpersonal stressors involving social threat (e.g., social conflict, evaluation, rejection, isolation, and exclusion) upregulate inflammatory processes that can induce several depressive symptoms, including sad mood, anhedonia, fatigue, psychomotor retardation, and social-behavioral withdrawal. The original article describing this formulation (Psychol Bull 140:774-815, 2014) addressed critical questions involving depression onset and recurrence, as well as why depression is strongly predicted by early life stress and comorbid with anxiety disorders and certain physical disease conditions, such as asthma, rheumatoid arthritis, chronic pain, and cardiovascular disease. Here, we extend the theory to help explain sex differences in depression prevalence, which is a defining feature of this disorder. Central to this extension is research demonstrating that ovarian hormone fluctuations modulate women's susceptibility to stress, brain structure and function, and inflammatory activity and reactivity. These effects are evident at multiple levels and are highly context-dependent, varying as a function of several factors including sex, age, reproductive state, endogenous versus exogenous hormones, and hormone administration mode and dose. Together, these effects help explain why women are at greater risk for developing inflammation-related depressed mood and other neuropsychiatric, neurodevelopmental, and neurodegenerative disorders during the reproductive years, especially for those already at heightened risk for depression or in the midst of a hormonal transition period.


Assuntos
Transtorno Depressivo Maior/imunologia , Hormônios Esteroides Gonadais/imunologia , Transtornos do Humor/imunologia , Caracteres Sexuais , Transdução de Sinais/fisiologia , Estresse Psicológico/imunologia , Encéfalo/imunologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Inflamação/diagnóstico , Inflamação/imunologia , Inflamação/psicologia , Masculino , Transtornos do Humor/diagnóstico , Transtornos do Humor/psicologia , Estresse Psicológico/diagnóstico , Estresse Psicológico/psicologia
6.
Transl Psychiatry ; 9(1): 151, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31123247

RESUMO

Psychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) arise from complex interactions between genetic and environmental factors. Common genetic variants associated with multiple psychiatric disorders suggest that shared genetic architecture could contribute to divergent clinical syndromes. To evaluate shared transcriptional alterations across connected brain regions, Affymetrix microarrays were used to profile postmortem dorsolateral prefrontal cortex (DLPFC), hippocampus, and associative striatum from 19 well-matched tetrads of subjects with SCZ, BD, MDD, or unaffected controls. SCZ subjects showed a substantial burden of differentially expressed genes across all examined brain regions with the greatest effects in hippocampus, whereas BD and MDD showed less robust alterations. Pathway analysis of transcriptional profiles compared across diagnoses demonstrated commonly enriched pathways between all three disorders in hippocampus, significant overlap between SCZ and BD in DLPFC, but no significant overlap of enriched pathways between disorders in striatum. SCZ samples showed increased expression of transcripts associated with inflammation across all brain regions examined, which was not evident in BD or MDD, or in rat brain following chronic dosing with antipsychotic drugs. Several markers of inflammation were confirmed by RT-PCR in hippocampus, including S100A8/9, IL-6, MAFF, APOLD1, IFITM3, and BAG3. A cytokine ELISA panel showed significant increases in IL-2 and IL-12p70 protein content in hippocampal tissue collected from same SCZ subjects when compared to matched control subjects. These data suggest an overlapping subset of dysregulated pathways across psychiatric disorders; however, a widespread increase in inflammation appears to be a specific feature of the SCZ brain and is not likely to be attributable to chronic antipsychotic drug treatment.


Assuntos
Transtorno Bipolar , Corpo Estriado , Transtorno Depressivo Maior , Perfilação da Expressão Gênica , Hipocampo , Inflamação , Córtex Pré-Frontal , Esquizofrenia , Animais , Autopsia , Transtorno Bipolar/genética , Transtorno Bipolar/imunologia , Transtorno Bipolar/metabolismo , Corpo Estriado/imunologia , Corpo Estriado/metabolismo , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Maior/metabolismo , Hipocampo/imunologia , Hipocampo/metabolismo , Humanos , Inflamação/genética , Inflamação/imunologia , Inflamação/metabolismo , Masculino , Córtex Pré-Frontal/imunologia , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Sprague-Dawley , Esquizofrenia/genética , Esquizofrenia/imunologia , Esquizofrenia/metabolismo
7.
J Neuroinflammation ; 16(1): 90, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30995920

RESUMO

Major depressive disorder (MDD) is a leading cause of disability worldwide. After the first episode, patients with remitted MDD have a 60% chance of experiencing a second episode. Consideration of therapy continuation should be viewed in terms of the balance between the adverse effects of medication and the need to prevent a possible relapse. Relapse during the early stages of MDD could be prevented more efficiently by conducting individual risk assessments and providing justification for continuing therapy. Our previous work established the neuroimaging markers of relapse by comparing patients with recurrent major depressive disorder (rMDD) in depressive and remitted states. However, it is not known which of these markers are trait markers that present before initial relapse and, consequently, predict disease course. Here, we first describe how inflammation can be translated to subtype-specific clinical features and suggest how this could be used to facilitate clinical diagnosis and treatment. Next, we address the central and peripheral functional state of the immune system in patients with MDD. In addition, we emphasize the important link between the number of depressive episodes and rMDD and use neuroimaging to propose a model for the latter. Last, we address how inflammation can affect brain circuits, providing a possible mechanism for rMDD. Our review suggests a link between inflammatory processes and brain region/circuits in rMDD.


Assuntos
Encéfalo/imunologia , Transtorno Depressivo Maior/imunologia , Inflamação/complicações , Encéfalo/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Humanos , Inflamação/fisiopatologia , Recidiva
8.
Gen Hosp Psychiatry ; 58: 7-12, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30818102

RESUMO

OBJECTIVE: Neutrophil-lymphocyte, monocyte-lymphocyte and platelet-lymphocyte ratio are inexpensive and reproducible biomarkers of inflammation found to be elevated in mood disorders. This study aimed to compare inflammatory ratios between bipolar disorder and major depressive disorder and between bipolar disorder manic episodes and bipolar disorder depressive episodes. METHOD: We included 142 Caucasian patients (major depressive disorder: n = 36; bipolar disorder manic episode: n = 66; bipolar disorder depressive episode: n = 40). We measured white blood cells, neutrophils, lymphocytes, monocytes, platelets, glucose, and total cholesterol. Neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio, and platelet-lymphocyte ratio were calculated. RESULTS: Neutrophil-lymphocyte ratio and monocyte-lymphocyte ratio were significantly higher in bipolar disorder manic episodes when compared to bipolar disorder depressive episodes and major depressive disorder episodes after adjustment for age, sex, body mass index, and smoking. CONCLUSION: To our knowledge, our study is the first one to compare inflammatory ratios between different bipolar disorder phases and major depressive disorder episodes. In accord with previous studies on other inflammatory mediators, we found higher neutrophil-lymphocyte and monocyte-lymphocyte ratios in bipolar manic episodes, suggesting that inflammatory changes occur especially during acute episodes of mania.


Assuntos
Transtorno Bipolar/imunologia , Contagem de Células Sanguíneas , Transtorno Depressivo Maior/imunologia , Inflamação/imunologia , Monócitos/imunologia , Neutrófilos/imunologia , Doença Aguda , Adulto , Idoso , Biomarcadores/sangue , Transtorno Bipolar/diagnóstico , Estudos de Coortes , Estudos Transversais , Transtorno Depressivo Maior/diagnóstico , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Retrospectivos
9.
Physiology (Bethesda) ; 34(2): 123-133, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30724127

RESUMO

Metabolic syndrome and major depression are two of the most common and debilitating disorders worldwide, occurring with significant rates of comorbidity. Recent studies have uncovered that each of these conditions is associated with chronic, low-grade inflammation. This is characterized by increased circulating pro-inflammatory cytokines, altered leukocyte population frequencies in blood, accumulation of immune cells in tissues including the brain, and activation of these immune cells. Cytokines that become elevated during obesity can contribute to the progression of metabolic syndrome by directly causing insulin resistance. During chronic stress, there is evidence that these cytokines promote depression-like behavior by disrupting neurotransmitter synthesis and signal transduction. Animal models of obesity and depression have revealed a bi-directional relationship whereby high-fat feeding and chronic stress synergize and exacerbate metabolic dysregulation and behavioral abnormalities. Although far from conclusive, emerging evidence suggests that inflammation in the central and peripheral immune system may link metabolic syndrome to major depressive disorder. In this review, we will synthesize available data supporting this view and identify critical areas for future investigation.


Assuntos
Transtorno Depressivo Maior/imunologia , Encefalite/imunologia , Mediadores da Inflamação/imunologia , Inflamação/imunologia , Síndrome Metabólica/imunologia , Animais , Citocinas/metabolismo , Transtorno Depressivo Maior/complicações , Encefalite/complicações , Humanos , Inflamação/complicações , Leucócitos/imunologia , Síndrome Metabólica/complicações , Obesidade/complicações , Obesidade/imunologia , Estresse Psicológico/complicações , Estresse Psicológico/imunologia
10.
Mol Neurobiol ; 56(6): 4288-4305, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30306457

RESUMO

Major depressive disorder (MDD) is one of the leading causes of disability worldwide, and its incidence is expected to increase. Despite tremendous efforts to understand its underlying biological mechanisms, MDD pathophysiology remains elusive and pharmacotherapy outcomes are still far from ideal. Low-grade chronic inflammation seems to play a key role in mediating the interface between psychological stress, depressive symptomatology, altered intestinal microbiology, and MDD onset. We review the available pre-clinical and clinical evidence of an involvement of pro-inflammatory pathways in the pathogenesis, treatment, and remission of MDD. We focus on caspase 1, inducible nitric oxide synthase, and interferon gamma, three inflammatory systems dysregulated in MDD. Treatment strategies aiming at targeting such pathways alone or in combination with classical therapies could prove valuable in MDD. Further studies are needed to assess the safety and efficacy of immune modulation in MDD and other psychiatric disorders with neuroinflammatory components.


Assuntos
Caspase 1/metabolismo , Transtorno Depressivo Maior/enzimologia , Transtorno Depressivo Maior/imunologia , Interferon gama/metabolismo , Neuroimunomodulação , Óxido Nítrico Sintase Tipo II/metabolismo , Animais , Transtorno Depressivo Maior/microbiologia , Microbioma Gastrointestinal , Humanos
11.
Brain Behav Immun ; 76: 215-222, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30476563

RESUMO

Obesity is a major public health burden associated with neuropsychiatric comorbidities leading to social and occupational impairment. Given the growing prevalence of both obesity and mental disorders worldwide, understanding the risk factors of obesity-related neuropsychiatric comorbidities is crucial to develop preventive strategies and individualized treatments. Recent findings suggest that adiposity-driven inflammation contributes to neuropsychiatric comorbidities in obesity. However, not all obese subjects afflicted with chronic inflammation develop neuropsychiatric symptoms, suggesting additional risk factors. The aim of this study was to investigate the impact of personal history of major depressive disorder (MDD) on obesity-related inflammation and neuropsychiatric symptoms, and their relationship. A case-control study was conducted comparing 66 obese patients (body mass index > 35 kg/m2) and 22 healthy non-obese participants, free of any current neuropsychiatric diseases including MDD. Neuropsychiatric symptoms were assessed using the Neurotoxicity Rating Scale (NRS). Sociodemographic and clinical variables were gathered and blood was collected for the measurement of serum levels of high-sensitivity C-reactive protein (hs-CRP). Multiple regression analyses were performed to assess the contribution of obesity and personal history of MDD to clinical outcomes and inflammatory status in study participants. Hs-CRP levels as well as NRS scores were significantly increased in the obese group. Overall, personal history of depression accounted for increased NRS scores but no significant association was found with inflammatory status. In addition, history of depression did not significantly modulate the relationship of obesity-related inflammation with NRS scores. Interestingly, obese individuals with history of recurrent MDD (n = 13) exhibited higher scores in the cognitive and sickness symptoms dimensions of the NRS compared to obese subjects with history of one depressive episode only. Findings indicate that history of depression contributes to neuropsychiatric symptoms, but not to systemic inflammation, in obese subjects free of current depressive episode. These results provide relevant information on the risk factors that may help identify obese subjects with increased risk of neuropsychiatric comorbidity.


Assuntos
Transtorno Depressivo Maior/imunologia , Inflamação/psicologia , Obesidade/psicologia , Adulto , Índice de Massa Corporal , Proteína C-Reativa/análise , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Depressão/metabolismo , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/fisiopatologia , Feminino , França , Humanos , Inflamação/fisiopatologia , Masculino , Transtornos Mentais/imunologia , Transtornos Mentais/fisiopatologia , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Prevalência , Fatores de Risco
12.
Physiol Behav ; 198: 108-119, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30393143

RESUMO

The psycho-immune-neuroendocrine (PINE) network is a regulatory network of interrelated physiological pathways that have been implicated in major depressive disorder (MDD). A model of disease progression for MDD is presented where the stable, healthy state of the PINE network (PINE physiome) undergoes progressive pathophysiological changes to an unstable but reversible pre-disease state (PINE pre-diseasome) with chronic stress. The PINE network may then undergo critical transition to a stable, possibly irreversible disease state of MDD (PINE pathome). Critical transition to disease is heralded by early warning signs which are detectible by biomarkers specific to the PINE network and may be used as a screening test for MDD. Critical transition to MDD may be different for each individual, as it is reliant on diathesis, which comprises genetic predisposition, intrauterine and developmental factors. Finally, we propose the PINE pre-disease state may form a "universal pre-disease state" for several non-communicable diseases (NCDs), and critical transition of the PINE network may lead to one of several frequently associated disease states (influenced by diathesis), supporting the existence of a common Chronic Illness Risk Network (CIRN). This may provide insight into both the puzzle of multifinality and the growing clinical challenge of multimorbidity.


Assuntos
Encéfalo/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Sistemas Neurossecretores/fisiopatologia , Encéfalo/imunologia , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Maior/psicologia , Progressão da Doença , Humanos , Sistemas Neurossecretores/imunologia
13.
Pharmacol Biochem Behav ; 177: 34-60, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30590091

RESUMO

Alcohol use disorder (AUD) is a widespread disease with limited treatment options. Targeting the neuroimmune system is a new avenue for developing or repurposing effective pharmacotherapies. Alcohol modulates innate immune signaling in different cell types in the brain by altering gene expression and the molecular pathways that regulate neuroinflammation. Chronic alcohol abuse may cause an imbalance in neuroimmune function, resulting in prolonged perturbations in brain function. Likewise, manipulating the neuroimmune system may change alcohol-related behaviors. Psychiatric disorders that are comorbid with AUD, such as post-traumatic stress disorder, major depressive disorder, and other substance use disorders, may also have underlying neuroimmune mechanisms; current evidence suggests that convergent immune pathways may be involved in AUD and in these comorbid disorders. In this review, we provide an overview of major neuroimmune cell-types and pathways involved in mediating alcohol behaviors, discuss potential mechanisms of alcohol-induced neuroimmune activation, and present recent clinical evidence for candidate immune-related drugs to treat AUD.


Assuntos
Alcoolismo/epidemiologia , Alcoolismo/imunologia , Encéfalo/efeitos dos fármacos , Transtorno Depressivo Maior/epidemiologia , Imunidade Inata/efeitos dos fármacos , Neuroimunomodulação , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Alcoolismo/metabolismo , Alcoolismo/terapia , Animais , Encéfalo/imunologia , Encéfalo/metabolismo , Comorbidade , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/terapia , Humanos , Imunomodulação , Camundongos , Ratos , Transtornos de Estresse Pós-Traumáticos/imunologia , Transtornos de Estresse Pós-Traumáticos/metabolismo , Transtornos de Estresse Pós-Traumáticos/terapia
14.
Neuroscience ; 403: 93-110, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29604382

RESUMO

Major depressive disorder (MDD) is a very common disease that affects more than 350 million people worldwide, representing an enormous socioeconomic burden. From a clinical perspective, MDD can be divided into different subtypes, such as melancholic or atypical MDD. Interestingly, increasing evidence points toward an involvement of the immune system in MDD pathogenesis. However, inflammation does not seem to have the same impact on every MDD type. Here, we describe how inflammation can affect monoaminergic and glutamatergic neurotransmission, which provides a possible mechanism for MDD onset. Next, we examine the regional specificity of neuroinflammation, which shows striking overlaps with neural patterns activated in atypical MDD. Furthermore, we outline how inflammation may translate to subtype-specific clinical features and we suggest how this could be used for diagnostic and treatment purposes. By providing a link back to a dysregulated immune system as a contributing factor to MDD subtypes, we explain how brain regions particularly affected by certain subtypes may regulate the cortisol circuitry.


Assuntos
Transtorno Depressivo Maior/imunologia , Inflamação/imunologia , Inflamação/psicologia , Animais , Encéfalo/imunologia , Transtorno Depressivo Maior/classificação , Transtorno Depressivo Maior/psicologia , Humanos , Modelos Biológicos
15.
Front Immunol ; 9: 2693, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30532752

RESUMO

Several lines of evidence have strongly implicated inflammatory processes in the pathobiology of major depressive disorder (MDD). However, the cellular origin of inflammatory signals and their specificity remain unclear. We examined the phenotype and glucocorticoid signaling in key cell populations of the innate immune system (monocytes) vs. adaptive immunity (T cells) in a sample of 35 well-characterized, antidepressant-free patients with MDD and 35 healthy controls individually matched for age, sex, smoking status and body mass index. Monocyte and T cell phenotype was assessed by flow cytometry. Cell-specific steroid signaling was determined by mRNA expression of pre-receptor regulation (11ß-hydroxysteroid dehydrogenase type 1; 11ß -HSD1), steroid receptor expression [glucocorticoid receptor (GR) and mineralocorticoid receptor (MR)], and the downstream target glucocorticoid-induced leucine-zipper (GILZ). We also collected salivary cortisol samples (8:00 a.m. and 10:00 p.m.) on two consecutive days. Patients showed a shift toward a pro-inflammatory phenotype characterized by higher frequency and higher absolute numbers of non-classical monocytes. No group differences were observed in major T cell subset frequencies and phenotype. Correspondingly, gene expression indicative of steroid resistance (i.e., lower expression of GR and GILZ) in patients with MDD was specific to monocytes and not observed in T cells. Monocyte phenotype and steroid receptor expression was not related to cortisol levels or serum levels of IL-6, IL-1ß, or TNF-α. Our results thus suggest that in MDD, cells of the innate and adaptive immune system are differentially affected with shifts in monocyte subsets and lower expression of steroid signaling related genes.


Assuntos
Transtorno Depressivo Maior/imunologia , Monócitos/imunologia , Transdução de Sinais/imunologia , Esteroides/imunologia , 11-beta-Hidroxiesteroide Desidrogenases/imunologia , Adolescente , Adulto , Transtorno Depressivo Maior/patologia , Feminino , Regulação da Expressão Gênica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Receptores de Glucocorticoides/imunologia , Receptores de Mineralocorticoides/imunologia , Linfócitos T/imunologia , Fatores de Transcrição/imunologia
16.
Psychiatry Res ; 270: 775-779, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30551324

RESUMO

Several studies have established that Major depressive disorder is associated with excess inflammation with an elevation of both pro and anti-inflammatory cytokines in major depressive disorder. In addition, individuals with major depressive disorder are at higher risk of developing coronary artery disease. The role of innate immunity and NFκB-mediated inflammation in depression and its increased association with coronary artery disease is yet to be fully elucidated. Polymorphisms in the Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat and Pyrin Domain Containing 12 (NLRP12), are associated with depression and coronary artery disease in trauma exposed individuals. In a cohort of Vietnam War veterans (n = 299) NLRP12 polymorphisms were analysed for association with depression and coronary calcium scores. The NLRP12 polymorphism, rs34436714 was associated with a higher DASS21 Score for depression (p = 0.037). NLRP12 polymorphisms rs34971363 and rs6509825 (p = 0.022 and p = 0.020) were associated with raised coronary calcium score. To our knowledge, this is the first time rs34436714 has been investigated in Vietnam veterans identifying AC as a risk genotype for depression in Caucasian cohorts. It is also the first time the rs34971363 (CG) and rs6509825 (CT) genotype have been associated with raised coronary calcium score.


Assuntos
Distúrbios de Guerra/genética , Doença da Artéria Coronariana/genética , Transtorno Depressivo Maior/genética , Genótipo , Inflamassomos/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Veteranos , Estudos de Coortes , Distúrbios de Guerra/imunologia , Doença da Artéria Coronariana/imunologia , Transtorno Depressivo Maior/imunologia , Humanos , Imunidade Inata/genética , Imunidade Inata/imunologia , Inflamassomos/imunologia , Masculino , NF-kappa B/genética , Polimorfismo Genético , Fatores de Risco
17.
J Psychiatr Res ; 107: 57-67, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30326340

RESUMO

Major depressed patients show increased bacterial translocation with elevated plasma levels of lipopolysaccharide (LPS), which may trigger immune-inflammatory and neuro-oxidative responses. Recently, an animal model based on chronic LPS administration was developed which was associated with long-lasting depressive-like and neuro-oxidative alterations in female mice. The aim of the current study was to investigate behavioral, neuroimmune and neuroprogressive alterations in female mice 6 weeks after LPS chronic exposure. Female mice received increasing doses of LPS during 5 days at one-month intervals repeated for 4 consecutive months. Six weeks after the last LPS-exposure, we assessed behavioral despair and anhedonia, microglial activation, alterations in tryptophan, 5-HT, kynurenine, quinolinic acid (QUIN) levels and spermidine/spermine N1-acetyltransferase (SAT1) expression in the hippocampus, both with and without fluoxetine administration. Our results show that six weeks post-LPS, mice present behavioral despair and anhedonia in association with increased IBA1 expression (a microglia activation marker), NF-kB p65 and IL-1ß levels, indoleamine 2,3-dioxygenase (IDO1) mRNA expression, kynurenine, QUIN levels and QUIN/tryptophan ratio, and lowered tryptophan, 5-HT levels and SAT1 mRNA expression. Fluoxetine reversed the behavioral and neuroimmune alterations but had no effect in the reversal of IDO1 increased expression, QUIN levels and QUIN/tryptophan ratio. In conclusion, our results support the validity of the chronic LPS model of major depression and additionally shows its translational relevance with respect to neuroimmune and neuroprogressive pathways.


Assuntos
Comportamento Animal/efeitos dos fármacos , Transtorno Depressivo Maior/induzido quimicamente , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/imunologia , Fluoxetina/farmacologia , Lipopolissacarídeos/farmacologia , Inibidores de Captação de Serotonina/farmacologia , Serotonina/metabolismo , Triptofano/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Feminino , Fluoxetina/administração & dosagem , Lipopolissacarídeos/administração & dosagem , Camundongos , Inibidores de Captação de Serotonina/administração & dosagem
18.
J Psychiatr Res ; 107: 19-27, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30312913

RESUMO

The molecular factors involved in the pathophysiology of major depressive disorder (MDD) remain poorly understood. One approach to examine the molecular basis of MDD is co-expression network analysis, which facilitates the examination of complex interactions between expression levels of individual genes and how they influence biological pathways affected in MDD. Here, we applied an unsupervised gene-network based approach to a prospective experimental design using microarray genome-wide gene expression from the peripheral whole blood of older adults. We utilised the Sydney Memory and Ageing Study (sMAS, N = 521) and the Older Australian Twins Study (OATS, N = 186) as discovery and replication cohorts, respectively. We constructed networks using Weighted Gene Co-expression Network Analysis (WGCNA), and correlated identified modules with four subtypes of depression: single episode, current, recurrent, and lifetime MDD. Four modules of highly co-expressed genes were associated with recurrent MDD (N = 27) in our discovery cohort (FDR<0.2), with no significant findings for a single episode, current or lifetime MDD. Functional characterisation of these modules revealed a complex interplay between dysregulated protein processing in the endoplasmic reticulum (ER), and innate and adaptive immune response signalling, with possible involvement of pathogen-related pathways. We were underpowered to replicate findings at the network level in an independent cohort (OATS), however; we found a significant overlap for 9 individual genes with similar co-expression and dysregulation patterns associated with recurrent MDD in both cohorts. Overall, our findings support other reports on dysregulated immune response and protein processing in the ER in MDD and provide novel insights into the pathophysiology of depression.


Assuntos
Imunidade Adaptativa/imunologia , Transtorno Depressivo Maior , Retículo Endoplasmático/metabolismo , Perfilação da Expressão Gênica , Expressão Gênica , Redes Reguladoras de Genes , Imunidade Inata/imunologia , Idoso , Idoso de 80 Anos ou mais , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Maior/metabolismo , Regulação para Baixo , Retículo Endoplasmático/genética , Feminino , Humanos , Masculino , Recidiva
19.
BMC Psychiatry ; 18(1): 330, 2018 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-30314474

RESUMO

BACKGROUND: Major depressive disorder (MDD) is related to human's immune status, and immunological indicators such as mitogen stimulated cell proliferation and cytokines may become candidate biomarkers for disease diagnosis. METHODS: One hundred diagnosed major depressive disorder subjects and 100 health controls were enrolled in this study. Phytohaemagglutinin and lipopolysaccharide stimulated cell proliferations and cytokine concentrations were detected in peripheral blood mononuclear cells from both groups. The corresponding stimulated responses were conducted and confirmed in chronic unpredictable mild stress (CUMS) mice. RESULTS: Compared to the people in control group, there were lower cell proliferations and lower TNF-α produced in lipopolysaccharide stimulated peripheral blood mononuclear cells in depression patients, lower IL-2 and IL-10 produced in phytohaemagglutinin stimulated peripheral blood mononuclear cells in depression patients, higher IL-6, IL-10 and lower IL-2 secretions were detected in peripheral plasma in depression patients. In CUMS mice we found lower splenocyte proliferations, lower IL-1α productions and higher IL-6 secretions in lipopolysaccharide stimulated splenocytes. It seems lipopolysaccharide stimulated cell proliferation activities were inhibited in depressive states. CONCLUSIONS: Lower lipopolysaccharide stimulated cell proliferation and phytohaemagglutinin stimulated or plasma cytokine IL-2 decreases should be potential monitoring indices in the depressive state assessment for major depressive disorder patients.


Assuntos
Proliferação de Células/fisiologia , Citocinas/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/psicologia , Lipopolissacarídeos/toxicidade , Fito-Hemaglutininas/toxicidade , Adulto , Animais , Proliferação de Células/efeitos dos fármacos , Citocinas/efeitos dos fármacos , Citocinas/imunologia , Transtorno Depressivo Maior/imunologia , Feminino , Humanos , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-1alfa/sangue , Interleucina-1alfa/imunologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia
20.
Rev Colomb Psiquiatr ; 47(3): 177-186, 2018.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30017041

RESUMO

OBJECTIVE: To highlight the inflammatory and immunological mechanisms involved in depression and psoriasis. METHODS: A comprehensive literature search was performed in various databases, in total 145 studies were selected. RESULTS: Depression and psoriasis have an association. Immune mechanisms -the actions of tumor necrosis factor-α, interleukin 1 (IL-1), IL-2, IL-10, IL-22, IL-17, interferon-γ, IL-1ß, prostaglandin E2, C-reactive protein, IL-6, and IL-8 etc.-, and some genetic changes are involved. CONCLUSIONS: A possible bidirectional relationship of psoriasis and major depression exists; i.e. the depression leads to psoriasis, and psoriasis leads to depression. We recommend more studies in the future to get a deeper and better understanding about this relationship.


Assuntos
Citocinas/imunologia , Transtorno Depressivo Maior/psicologia , Psoríase/psicologia , Biomarcadores/metabolismo , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/imunologia , Humanos , Mediadores da Inflamação/imunologia , Psoríase/genética , Psoríase/imunologia
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