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1.
Artigo em Inglês | MEDLINE | ID: mdl-31364826

RESUMO

Objective: The evidence linking schizophrenia and total and unconjugated bilirubin is primarily from retrospective studies. To overcome this limitation, we conducted a prospective study of total and unconjugated bilirubin levels of patients diagnosed with schizophrenia or bipolar affective disorder. Methods: Serum total and unconjugated bilirubin levels were compared between patients diagnosed with schizophrenia (n = 50) and bipolar affective disorder (n = 43) (ICD-10 criteria) admitted to an inpatient psychiatric unit of a tertiary hospital in India. The study was conducted between October 2013 and July 2015. Results: The median serum levels (mg/dL) of total and unconjugated bilirubin were significantly higher (P = .027 and P = .004, respectively) among patients with schizophrenia compared to those with bipolar affective disorder. Analysis of covariance revealed that unconjugated bilirubin was significantly higher (P = .029) in patients with schizophrenia compared to those with bipolar affective disorder, even after controlling for the effects of age, sex, and medications. Conclusions: In this prospective study, serum levels of unconjugated bilirubin were significantly higher in patients with schizophrenia compared to patients with bipolar affective disorder. The findings suggest that serum unconjugated bilirubin could be a potential marker for schizophrenia. However, the results need to be replicated in a larger sample including patients living in the community.


Assuntos
Bilirrubina/sangue , Transtorno Bipolar/sangue , Esquizofrenia/sangue , Adulto , Biomarcadores/sangue , Transtorno Bipolar/terapia , Estudos Transversais , Feminino , Hospitalização , Humanos , Masculino , Serviços de Saúde Mental , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Esquizofrenia/terapia , Índice de Gravidade de Doença
2.
Nord J Psychiatry ; 73(6): 372-379, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31304832

RESUMO

Background: Currently, increasing evidence supports the hypothesis that alterations in the immune-inflammatory system are critical for the pathophysiology of bipolar disorder (BD). Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and mean platelet volume (MPV) have recently been investigated as inexpensive and simple inflammatory markers. Aims: The aim of this study is to compare NLR, PLR, MLR, and MPV in depressive, manic, and euthymic patients with BD and healthy controls, and to evaluate whether values of NLR, PLR, MLR, and MPV are possible state or trait biomarkers in BD. Methods: This retrospective study was conducted with 341 patients with BD (100 patients in a depressive state, 141 patients in a manic state, and 100 patients in a euthymic state) and 114 healthy controls. Results: We found that patients with BD in manic states had higher levels of MPV, NLR, and MLR, and patients with BD in depressive states had higher levels of MPV than the controls. Moreover, MPV predicted all states of BD, while NLR and MLR predicted the manic state of BD. Conclusions: NLR, MLR, and MPV obtained from simple and inexpensive blood tests were significantly higher in patients with BD than in healthy controls, which each imply low-grade inflammation. MPV may serve as a possible trait biomarker of BD, while NLR and MLR may both serve as possible state biomarkers of the manic state.


Assuntos
Transtorno Bipolar/sangue , Inflamação/sangue , Linfócitos/citologia , Volume Plaquetário Médio , Monócitos/citologia , Neutrófilos/citologia , Adulto , Biomarcadores/sangue , Plaquetas/citologia , Plaquetas/fisiologia , Feminino , Humanos , Masculino , Estudos Retrospectivos
3.
Acta Neuropsychiatr ; 31(4): 230-234, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31169098

RESUMO

BACKGROUND: Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear. METHODS: Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response. RESULTS: Compared to participants with WBC counts of 4.5-10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses. CONCLUSIONS: An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.


Assuntos
Antimaníacos/uso terapêutico , Transtorno Bipolar , Lítio/uso terapêutico , Fumarato de Quetiapina/uso terapêutico , Adulto , Afeto , Transtorno Bipolar/sangue , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/imunologia , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Adulto Jovem
4.
Psychiatry Res ; 273: 685-689, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31207853

RESUMO

OBJECTIVE: The aim of this study was to assess if cytokines levels (IL-6 and IL-10) are related to major depressive disorder (MDD) and bipolar disorder (BD), in a population-based study. METHODS: This was a cross-sectional study population-based, involving 1037 people aged 18-35. MDD, BD, anxiety and suicide risk were assessed using the Mini International Neuropsychiatric Interview. Serum IL-6 and IL-10 were measured by ELISA using a commercial kit. RESULTS: The total sample comprised 1034 young adults, being 14.4% with MDD and 13.7% with BD. MDD and BD groups showed significantly higher serum IL-6 levels (p ≤ 0.001) and IL-10 levels (p ≤ 0.001) when compared to healthy control group. No correlation was found between serum IL-6 and IL-10 levels in health control group (p = 0.830; r = -0.008), non-suicide risk (p = 0.337; r = 0.032) and non-anxiety disorder (p = 0.375; r = 0.031). Covariance analysis showed that mood disorders alone, increase both interleukin levels (IL-6, p = 0.019; and IL-10, p = 0.026), whilst the interaction of mood disorders and suicide risk or anxiety disorders did not. CONCLUSION: Our results suggest that inflammatory dysregulation may be involved in the physiopathology of mood disorders and serum IL-6 and IL-10 levels are putative biomarkers for these disorders.


Assuntos
Transtorno Bipolar/sangue , Transtorno Depressivo Maior/sangue , Interleucina-10/sangue , Interleucina-6/sangue , Transtornos do Humor/sangue , Adolescente , Adulto , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Adulto Jovem
5.
Psychiatry Res ; 273: 706-711, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31207856

RESUMO

Toxoplasmosis has been previously associated with an increased risk of having Schizophrenia or Bipolar disorder in several epidemiological studies. The aim of this observational, cross-sectional study was to examine the seroprevalence of Toxoplasma infection in a cohort of Italian psychiatric inpatients and to verify the presence of circulating Toxoplasma gondii DNA in the seropositive subjects. Sixty-three patients affected by bipolar or schizoaffective disorders according to DSM-5 criteria were enrolled. The presence of Toxoplasma infection was firstly examined using an indirect serological method (ELFA), and three different direct PCR-based methods were performed to detect circulating DNA in the seropositive patients. The seroprevalence of infection was 28.6%, with a significant association between higher age and the infection status. PCR, nested-PCR and Real-Time PCR revealed no positive samples for Toxoplasma gondii. This result is in contrast with recent data from case-control studies that detected parasite genome in patients with different neuropsychiatric diagnosis without clinical evidence of acute toxoplasmosis. Our findings are to be interpreted with caution, because of the small sample size, the heterogeneity of enrolled patients and the observational nature of the study. Further studies are needed to better define the clinical features correlated to the seropositive status in neuropsychiatric patients.


Assuntos
Transtorno Bipolar/sangue , DNA de Protozoário/sangue , Esquizofrenia/sangue , Toxoplasma/genética , Toxoplasmose/psicologia , Adulto , Transtorno Bipolar/parasitologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Esquizofrenia/parasitologia , Estudos Soroepidemiológicos , Toxoplasmose/sangue , Toxoplasmose/parasitologia
6.
Int J Psychiatry Clin Pract ; 23(2): 128-133, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31081413

RESUMO

Objectives: Agmatine is a cationic amine resulting from the decarboxylation of l-arginine. Agmatine has neuroprotective, anti-inflammatory, anti-stress, and anti-depressant properties. In this study, plasma agmatine, arginine decarboxylase, and agmatinase levels were measured during manic episode and remission period in patients with bipolar disorder. Methods: Thirty healthy volunteers and 30 patients who meet Bipolar Disorder Manic Episode diagnostic criteria were included in the study. Additionally, the changes in the patient group between manic episode and remission period were examined. We evaluated the relationship between levels of l-arginine and arginine decarboxylase in the agmatine synthesis pathway, and level of agmatinase that degrades agmatine. Results: Levels of agmatine and l-arginine were significantly increased than control group during manic episode (p < .01). All parameters were increased during manic episode compared to remission period (p < .05). Agmatinase was significantly decreased both during manic episode (p < .01) and remission period (p < .05) in comparison to the control group. Arginine decarboxylase levels did not show a significant difference between the groups (p > .05). Conclusions: This study indicate that there may be a relationship between bipolar disorder and agmatine and its metabolic pathway. Nonetheless, we believe more comprehensive studies are needed in order to reveal the role of agmatine in etiology of bipolar disorder. Key points Agmantine, agmatinase, l-arginine and arginine decarboxylase levels in BD have not been explored before. Various neuro-chemical mechanisms act to increase agmatine in BD; however, agmatine could have elevated to compensate agmatine deficit prior to the manifestation of the disease as in schizophrenia. Elevated agmatine degradation resulting from excess expression of agmatinase which is suggested to be effective in pathogenesis of mood disorders was compensated by this way. Elevated agmatine may be one of the causes which play a role in mania development. Elevated agmatine levels are also suggested to trigger psychosis and be related with the etiology of manic episode and lead to BD.


Assuntos
Agmatina/sangue , Transtorno Bipolar/sangue , Transtorno Bipolar/fisiopatologia , Carboxiliases/sangue , Redes e Vias Metabólicas , Ureo-Hidrolases/sangue , Adulto , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão
7.
Bipolar Disord ; 21(5): 394-409, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31112628

RESUMO

AIMS: To systematically review the existing trials on optimal serum levels for lithium for maintenance treatment of bipolar disorder and to develop clinical recommendations. METHODS: Systematic literature search. Discussion of major characteristics, limitations, methodological quality, and results of selected trials. Delphi survey consisting of clinical questions and corresponding statements. For statements endorsed by at least 80% of the members, consensus was considered as having been achieved. RESULTS: With strict inclusion criteria no studies could be selected, making it difficult to formulate evidence-based recommendations. After loosening the inclusion criteria 7 trials were selected addressing our aims at least to some extent. Four of these studies suggest better efficacy being associated with lithium serum levels in a range above a lower threshold around 0.45/0.60 and up to 0.80/1.00 mmol/L. These findings support the outcome of the Delphi survey. CONCLUSIONS: For adults with bipolar disorder there was consensus that the standard lithium serum level should be 0.60-0.80 mmol/L with the option to reduce it to 0.40-0.60 mmol/L in case of good response but poor tolerance or to increase it to 0.80-1.00 mmol/L in case of insufficient response and good tolerance. For children and adolescents there was no consensus, but the majority of the members endorsed the same recommendation. For the elderly there was also no consensus, but the majority of the members endorsed a more conservative approach: usually 0.40-0.60 mmol/L, with the option to go to maximally 0.70 or 0.80 mmol/L at ages 65-79 years, and to maximally 0.70 mmol/L over age 80 years.


Assuntos
Transtorno Bipolar/sangue , Transtorno Bipolar/tratamento farmacológico , Compostos de Lítio/administração & dosagem , Compostos de Lítio/sangue , Comitês Consultivos , Consenso , Tolerância a Medicamentos , Humanos , Guias de Prática Clínica como Assunto , Inquéritos e Questionários
8.
Bratisl Lek Listy ; 120(3): 195-199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31023037

RESUMO

OBJECTIVES: We aimed to compare altered inflammatory status between patients with bipolar manic and mixed episodes through neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) levels. BACKGROUND: NLR, PLR, and MLR are systemic inflammation biomarkers that have recently studied in bipolar disorder (BD) manic and depressive episodes. Immunological biomarker signature of mixed episodes and MLR levels in BD have less been studied. DESIGN AND SETTING: Our study included 48 bipolar patients in a mood episode (28 manic, 20 mixed) and 32 controls. Study-specific form including sociodemographic and clinical variables with laboratory findings were filled for all participants. METHODS: Red cell distribution width (RDW), mean platelet volume (MPV) neutrophil, lymphocyte and platelet count, NLR, PLR, and MLR were recorded. RESULTS: PLR and MLR were found significantly higher in bipolar patients compared to controls while NLR and MLR were significantly higher in manic patients than in mixed patients. RDW was found higher in mixed episode compared to controls. CONCLUSIONS: One can interpret these findings as MLR would be considered as a novel state biomarker for bipolar mood episodes and greater inflammatory activation may be involved in mania rather than mixed episode (Tab. 2, Fig. 1, Ref. 35).


Assuntos
Transtorno Bipolar , Inflamação , Contagem de Linfócitos , Volume Plaquetário Médio , Neutrófilos , Transtorno Bipolar/sangue , Transtorno Bipolar/imunologia , Humanos , Linfócitos , Contagem de Plaquetas
9.
Rev Assoc Med Bras (1992) ; 65(3): 361-369, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30994834

RESUMO

BACKGROUND: There is no strong evidence on the link between inflammatory profile and pattern of drug treatment response in depressive patients that could result in Coronary Artery Disease occurrence. OBJECTIVE: This study aimed to compare the subclinical atherosclerosis markers, inflammatory profile, and BDNF production in Resistant Depression (RD) or Bipolar Affective Disorder (BAD) patients under conventional treatment. METHODS: The population evaluated was comprised of 34 RD, 43 BAD, and 41 controls. Subclinical atherosclerosis markers were evaluated using ultrasonography, tomography, and exercise stress test. Plasma concentrations of TNFα, IL-1ß, IL-6, and BDNF were measured using Luminex100™. The usCRP concentration was measured using turbidimetric immunoassay. IL1B, IL6, and TNFA expression were determined using TaqMan®. For the statistical analysis, the significance level was established at p<0.05. RESULTS: Concerning subclinical atherosclerosis markers, only O2 consumption was reduced in the BAD group (p = 0.001). Although no differences were found in gene expression, BDNF and IL-1ß plasma concentration was increased in the RD group (p = 0.002 and p = 0.005, respectively) even with an antidepressant treatment, which suggests that these drugs have no effect in IL-1ß secretion and that the inflammasome may play a role in therapy response. CONCLUSION: Taken together, both BDNF and IL-1ß plasma concentrations could be used to the early identification of RD patients.


Assuntos
Transtorno Bipolar/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Transtorno Depressivo Resistente a Tratamento/sangue , Interleucina-1beta/sangue , Adulto , Anti-Inflamatórios/uso terapêutico , Antidepressivos/uso terapêutico , Aterosclerose/sangue , Biomarcadores/sangue , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Índice de Massa Corporal , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Feminino , Humanos , Interleucina-6/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Estatísticas não Paramétricas , Fator de Necrose Tumoral alfa/sangue
10.
Eur J Clin Pharmacol ; 75(8): 1109-1116, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30968172

RESUMO

PURPOSE: To assess in a large naturalistic sample, whether clinical response to a treatment with venlafaxine is associated with different patterns of plasma concentrations of active moiety, AM (sum of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODVEN)). METHODS: Applying a regression model, plasma concentrations and plasma concentrations corrected-by-dosage (C/D) for AM were included as independent variable with Clinical Global Impressions-Improvement (CGI-I) scale ratings as dependent variable. Moreover, AM, VEN, and ODVEN were compared between treatment responders and non-responders, defining response as much or very much improved on the CGI-I scale based on the non-parametric Mann-Whitney U (M-W-U) test with a significance level of 0.05. RESULTS: No correlations were found between AM and C/D AM plasma concentrations and CGI-I ratings (regression coefficient 0.0, CI 0.000, 0.001, p = 0.492 for AM and 0.047, CI - 0.065, 0.159, p = 0.408 for C/D AM). Venlafaxine daily dosage did not differ between responders and non-responders (217.7 ± 76.9 vs. 222.0 ± 72.7 mg/day, p = 0.45 for M-W-U). Responders displayed lower ODVEN (p = 0.033) and AM (p = 0.031) plasma concentrations than non-responders (p = 0.033 and 0.031, respectively for M-W-U). No other differences were detected. Using a cut-off level of 400 ng/mL for AM concentrations, a higher percentage of responders was reported in the group of patients with AM < 400 ng/mL (13.04%) compared to patients with AM > 400 ng/mL (8%) (p = 0.038). CONCLUSIONS: Higher ODVEN and AM concentrations in non-responders than in responders indicate that treatment escalation above upper thresholds of therapeutic reference ranges of venlafaxine is not promising. Hence, the therapeutic reference range for venlafaxine can help in improving outcomes in a measurement-based care model that takes advantage of therapeutic drug monitoring.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Inibidores da Recaptação de Serotonina e Norepinefrina/farmacocinética , Cloridrato de Venlafaxina/farmacocinética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtorno Bipolar/sangue , Transtorno Bipolar/diagnóstico , Bases de Dados Factuais/estatística & dados numéricos , Succinato de Desvenlafaxina/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Estudos Retrospectivos , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Inibidores da Recaptação de Serotonina e Norepinefrina/administração & dosagem , Resultado do Tratamento , Cloridrato de Venlafaxina/administração & dosagem , Adulto Jovem
11.
Psychiatry Res ; 274: 395-399, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30852433

RESUMO

Brain-derived neurotrophic factor (BDNF) is deemed to be associated with the psychopathology of bipolar I disorder (BD). However, studies focusing on accuracy of BDNF levels to differentiate these patients from healthy controls (HCs) are scarce. Over a discrete twelve-year period, we investigated serum BDNF levels in patients with BD and compared them to age-, sex- and body mass index (BMI)-matched HCs. There were lower serum BDNF levels in 83 samples with BD than in 222 HCs samples (5.7 ±â€¯4.2 ng/ml vs. 12.2 ±â€¯7.5 ng/ml, F = 46.784). Pearson's correlation test showed significant positive correlations between Young Mania Rating Scale scores and the BDNF levels among 61 manic patients (γ = 0.339). The receiver operating characteristic curve analysis showed BDNF levels demonstrated a moderate accuracy of being able to differentiate BD patients from HCs (AUC = 0.801). The most adequate cut-off points of the BDNF level were 6.74 ng/ml (sensitivity = 82.0%, specificity = 63.9%). Our results support that BDNF demonstrated moderate accuracy to distinguish BD patients from HCs. In the future, greater samples would be required to prove these results.


Assuntos
Transtorno Bipolar/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Adulto , Área Sob a Curva , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estatísticas não Paramétricas
12.
Medicine (Baltimore) ; 98(7): e14419, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30762747

RESUMO

Immune system dysregulation plays a key role in the physiopathology of bipolar disorder (BD) and major depressive disorder (MDD). However, whether interleukins might be biomarkers to distinguish these 2 affective disorders is unclear. Here, we assessed the differences in serum levels of interleukin 6 (IL-6) and interleukin 8 (IL-8) as well as C-reactive protein (CRP) in patients with MDD and BD. In total, we enrolled 21 MDD patients, 26 BD patients, and 20 healthy controls. We collected a total of 35 samples from BD patients in 3 different phases, depression phase, manic phase, and remission stage, and 27 samples from MDD patients in acute and remission phases. Serum IL-6 and IL-8 levels were assessed with solid phase sandwich ELISA-based quantitative arrays, and CRP levels were determined with an automatic analyzer. Both serum IL-6 and IL-8 levels were elevated in BD patients but not MDD patients. Subgroup analysis indicated elevated serum IL-6 in both the depression and manic phases in BD patients. The serum CRP levels did not change in either BD or MDD patients. However, sex differences in CRP concentrations were observed in healthy controls. Furthermore, there were linear correlations between the CRP levels and Bech-Rafaelsen Mania Rating Scale (BRMS) scores in BD patients. IL-6 and IL-8 levels may serve as biomarkers to differentiate between MDD and BD patients, even when the clinical manifestations are atypical. IL-6 may be used for the differential diagnosis of MDD and depressive episodes in BD.


Assuntos
Transtorno Bipolar/sangue , Transtorno Depressivo Maior/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Retrospectivos , Fatores Sexuais
13.
J Affect Disord ; 249: 169-174, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30772744

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) have established roles in the pathogenesis of diverse human disorders including neuropsychiatric disorders. METHODS: In the current study, we evaluated expression levels of six apoptosis-related lncRNAs (CCAT2, TUG1, PANDA, NEAT1, FAS-AS1 and OIP5-AS1) in the peripheral blood of bipolar disorder (BD) patients and healthy subjects to assess their contribution in the pathogenesis of BD. RESULTS: CCAT2, TUG1 and PANDA were up-regulated in total BD patients compared with total healthy subjects (P values = 0.006, <0.001 and 0.004 respectively) while OIP5-AS1 was down-regulated (P = 0.001). When expression levels of these genes were compared between patients and sex-matched healthy subjects, CCAT2 and TUG1 expression levels were only different in male subgroups; while PANDA expression was different in both male and female subgroups compared with the corresponding control subgroups. Transcript levels of lncRNAs were not correlated with any of demographic or clinical parameters of BD patients or controls after adjustment for gender. Pairwise correlations between expression levels of lncRNAs followed a disease-dependent manner. Based on receiver operating characteristic curves, among the assessed lncRNAs TUG1 had the highest diagnostic power in BD. Combination of transcript levels of CCAT2, TUG1, PANDA and OIP5-AS1 improved both sensitivity and specificity resulting in diagnostic power of 0.96. CONCLUSION: Our data demonstrated a possible role of certain lncRNAs in the pathogenesis of BD and potentiated them as diagnostic markers in this disorder.


Assuntos
Transtorno Bipolar/sangue , RNA Longo não Codificante/sangue , Apoptose , Biomarcadores/sangue , Transtorno Bipolar/genética , Estudos de Casos e Controles , Regulação para Baixo/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/metabolismo , Curva ROC , Regulação para Cima/fisiologia
14.
Clin Drug Investig ; 39(5): 485-489, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30805791

RESUMO

Lithium is a well established therapeutic agent in the treatment of uni- and bipolar affective disorders. Angiotensin-converting enzyme (ACE) inhibitors are the most frequently used class of drugs in the treatment of cardiovascular diseases. Combination therapy with both may be considered in clinical practice on occurrence of arterial hypertension after years of successful lithium therapy, yet an increased risk of lithium intoxication in combination with ACE inhibitors has been described and thus the combination has been warned against. We describe three cases in which enalapril, lisinopril or ramipril was combined with lithium. Either additional co-medication with hydrochlorothiazide or dehydration rather than co-medication with ACE inhibitors could be identified as necessary factors for lithium intoxication. These cases suggest that a combination of lithium with ACE inhibitors is possible when sufficient hydration is ensured and a combination with hydrochlorothiazide is avoided. Lithium concentration should be controlled on a regular level.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Transtorno Bipolar/tratamento farmacológico , Carbonato de Lítio/administração & dosagem , Transtornos Psicóticos/tratamento farmacológico , Idoso , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/sangue , Transtorno Bipolar/sangue , Transtorno Bipolar/complicações , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Carbonato de Lítio/efeitos adversos , Carbonato de Lítio/sangue , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/sangue , Transtornos Psicóticos/complicações
15.
Psychiatry Res ; 272: 643-648, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30616135

RESUMO

Bipolar disorder (BD), a psychiatric illness, results partly as a side effect of psychotropic medications and presents a high risk of metabolic disturbance. Fibroblast growth factor 21 (FGF21) is as an important regulator in carbohydrate and lipid metabolism. In this study, we investigated the serum levels of FGF21 and analyzed its association with metabolic parameters in bipolar mania patients at pre- and post-treatment with psychotropic medications. Bipolar mania inpatients (n = 99) and healthy controls (n = 99) were included at baseline; the patients were followed up after four-week treatment. Serum levels of FGF21 and several metabolic parameters were measured by appropriate detection methods. We found that baseline serum FGF21 levels were significantly higher in bipolar manic patients when compared to that in controls. After four-week medication, FGF21 levels were found to be decreased in patients when compared to the baseline suggesting that FGF21 may be associated with the psychopathology of bipolar mania. Moreover, FGF21 levels were found to be negatively correlated with the serum triglycerides (TG), cholesterol (CHO), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), glucose (Glu), and Body Mass Index (BMI). In addition, our data also indicates that FGF21 may monitor and/or prevent the metabolic abnormalities induced by psychotropic drugs.


Assuntos
Transtorno Bipolar/sangue , Transtorno Bipolar/tratamento farmacológico , Fatores de Crescimento de Fibroblastos/sangue , Doenças Metabólicas/sangue , Doenças Metabólicas/induzido quimicamente , Psicotrópicos/uso terapêutico , Adulto , Biomarcadores/sangue , Transtorno Bipolar/diagnóstico , Índice de Massa Corporal , Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Glucose/metabolismo , Humanos , Masculino , Doenças Metabólicas/diagnóstico , Pessoa de Meia-Idade , Psicotrópicos/efeitos adversos
16.
Neuroendocrinology ; 108(3): 232-243, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30673659

RESUMO

BACKGROUND/AIMS: Although abnormalities of amplitude of low-frequency fluctuations (ALFF) and hormone levels of hypothalamus-pituitary-thyroid axis have been reported in patients with bipolar disorder (BD), the association between abnormal ALFF and serum thyroid hormone levels remains unknown. METHOD: A total of 90 patients with unmedicated BD II depression and 100 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging, and then routine band (0.01-0.1 Hz), slow-5 band (0.01-0.027 Hz), and slow-4 band (0.027-0.073 Hz) ALFF analysis were performed. Additionally, serum thyroid hormone levels including free tri-iodothyronine (FT3), total tri-iodothyronine (TT3), free thyroxin (FT4), total thyroxin (TT4), and thyroid-stimulating hormone (TSH) were detected. The correlation between abnormal serum thyroid hormone levels and ALFF values in patients with BD II depression was calculated. RESULTS: Compared with the HCs, patients with BD II depression showed decreased ALFF in bilateral precuneus (PCu)/posterior cingulate cortex (PCC) in routine and slow-4 frequency bands, decreased ALFF in the right PCu, and increased ALFF in the right middle occipital gyrus (MOG) in the slow-5 frequency band. Additionally, patients with BD II depression showed lower TSH level than HCs, and TSH level was positively correlated with ALFF values in the bilateral PCu/PCC in the routine frequency band. CONCLUSIONS: These findings suggest that patients with BD II depression display intrinsic activity abnormalities, mainly in the PCu/PCC and MOG, which are associated with specific frequency bands. Moreover, altered intrinsic activity in the PCu/PCC may be related to TSH levels in bipolar II depression.


Assuntos
Transtorno Bipolar/fisiopatologia , Giro do Cíngulo/fisiopatologia , Lobo Occipital/fisiopatologia , Lobo Parietal/fisiopatologia , Tireotropina/sangue , Adolescente , Adulto , Transtorno Bipolar/sangue , Estudos de Casos e Controles , Feminino , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto Jovem
17.
Transl Psychiatry ; 9(1): 37, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30696814

RESUMO

Metabolites of the kynurenine pathway of tryptophan degradation, in particular, the N-Methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA), are increasingly recognized as primary pathophysiological promoters in several psychiatric diseases. Studies analyzing central KYNA levels from subjects with psychotic disorders have reported increased levels. However, sample sizes are limited and in contrast many larger studies examining this compound in blood from psychotic patients commonly report a decrease. A major question is to what extent peripheral KYNA levels reflect brain KYNA levels under physiological as well as pathophysiological conditions. Here we measured KYNA in plasma from a total of 277 subjects with detailed phenotypic data, including 163 BD subjects and 114 matched healthy controls (HCs), using an HPLC system. Among them, 94 BD subjects and 113 HCs also had CSF KYNA concentrations analyzed. We observe a selective increase of CSF KYNA in BD subjects with previous psychotic episodes although this group did not display altered plasma KYNA levels. In contrast, BD subjects with ongoing depressive symptoms displayed a tendency to decreased plasma KYNA concentrations but unchanged CSF KYNA levels. Sex and age displayed specific effects on KYNA concentrations depending on if measured centrally or in the periphery. These findings implicate brain-specific regulation of KYNA under physiological as well as under pathophysiological conditions and strengthen our previous observation of CSF KYNA as a biomarker in BD. In summary, biomarker and drug discovery studies should include central KYNA measurements for a more reliable estimation of brain KYNA levels.


Assuntos
Transtorno Bipolar/sangue , Transtorno Bipolar/líquido cefalorraquidiano , Ácido Cinurênico/sangue , Ácido Cinurênico/líquido cefalorraquidiano , Adulto , Transtorno Bipolar/complicações , Cromatografia Líquida de Alta Pressão , Depressão/complicações , Feminino , Humanos , Masculino , Transtornos Psicóticos/complicações , Comportamento Autodestrutivo/complicações , Tentativa de Suicídio/estatística & dados numéricos
18.
Psychiatry Res ; 273: 252-259, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30658210

RESUMO

Bipolar disorder (BD) is multifactorial mood disorder characterized by alternating episodes of hyperactive mania and severe depression. Lithium is one of the most preferred drug used as mood stabilizer in treating BD. In this study, we examined the changes in plasma metabolome in BD subjects in the context of lithium responsiveness. Plasma samples from clinically defined, age and gender matched unrelated healthy controls and BD subjects (lithium responders and non-responders) were obtained and processed in positive and negative mode using untargeted liquid chromatography/mass spectrometry analysis. We identified significant alterations in plasma levels of dopamine along with its precursors (tyrosine and phenylalanine), branched chain amino acid such as valine and excitatory neurotransmitter glutamate between healthy control and BD subjects. Lipid molecules such as, eicosenoic acid and retinyl ester also showed distinguished patterns between control and BD individuals. Lithium responsiveness was markedly associated with significant differences in proline, L-gamma-glutamyl-isoleucine, dopamine, palmitic acid methyl ester, cholesterol sulfate, androsterone sulfate and 9S,12S,13S-triHOME levels. Altered metabolites enriched with key biochemical pathways associated with neuropsychiatry disorders. We hypothesize that BD pathogenesis and lithium responsiveness is associated with impaired homeostasis of amino acid and lipid metabolism.


Assuntos
Transtorno Bipolar/sangue , Transtorno Bipolar/tratamento farmacológico , Compostos de Lítio/farmacologia , Metaboloma/efeitos dos fármacos , Psicotrópicos/farmacologia , Adulto , Aminoácidos de Cadeia Ramificada/sangue , Dopamina/sangue , Feminino , Ácido Glutâmico/sangue , Homeostase/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Fenilalanina/sangue , Resultado do Tratamento , Tirosina/sangue
20.
Bipolar Disord ; 21(1): 61-67, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29600584

RESUMO

OBJECTIVES: We previously demonstrated oxidative stress in bipolar patients and a relationship between the age of illness onset and total glutathione, a principal antioxidant. In this study, we sought to replicate these findings in a new cohort of patients. METHODS: We recruited bipolar patients from Warneford Hospital, Oxford, UK, of similar age and grouped them according to age of onset of illness. The early-onset group comprised patients with onset at <23 years, and the late group comprised patients with onset at >30 years. A third group, comprising age-matched healthy volunteers, was also included. Reduced and oxidized glutathione, cysteine, and cystine were determined in plasma, using high-performance liquid chromatography. Mitochondrial DNA copy number, measured in whole blood, was also compared between patients and healthy controls. RESULTS: Significant increases in oxidative stress were observed in the patient groups, compared with the control group; however, no differences in glutathione-related oxidative stress measures were detected between the early- and late-onset bipolar patient groups. No differences were observed in the amount of mitochondrial DNA, and there was no correlation with mood state. CONCLUSION: Using a more accurate method to quantify oxidative stress than in our previous study, we show that oxidative stress is a consistent feature of bipolar disorder. Although we did not reproduce our finding correlating age of onset of illness to oxidative stress, we have shown, once again, that oxidative stress is a consistent feature of bipolar disorder.


Assuntos
Transtorno Bipolar/sangue , Glutationa/sangue , Estresse Oxidativo/fisiologia , Adulto , Antioxidantes/metabolismo , Transtorno Bipolar/diagnóstico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo
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