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1.
BMC Med Genet ; 21(1): 194, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008326

RESUMO

BACKGROUND: Schizophrenia is a severe, heritable, and refractory psychiatric disorder. Several studies have shown that the disrupted in schizophrenia 1 (DISC1) gene is closely associated with schizophrenia by its role in neuronal morphology, synaptic function, brain development, and dopamine homeostasis etc. This study intended to investigate the expression levels of DISC1 gene in schizophrenia patients compared with healthy controls, and the expression variation of DISC1 gene before and after antipsychotic treatment in schizophrenia patients. METHODS: In this study, we compared DISC1 expression levels in blood of 48 healthy controls, and 32 schizophrenia patients before and after 12 weeks of antipsychotic treatment using real-time quantitative PCR (RT-qPCR) analysis. RESULTS: The expression levels of DISC1 gene in peripheral blood mononuclear cells of schizophrenia patients before antipsychotic treatment were higher than those in healthy controls (P < 0.01); whereas after antipsychotic treatment, the expression levels of DISC1 gene in peripheral blood mononuclear cells of schizophrenia patients still remained increased (P < 0.01). CONCLUSIONS: Our study provided further support for the involvement of DISC1 in the development of schizophrenia.


Assuntos
Expressão Gênica , Leucócitos Mononucleares/efeitos dos fármacos , Proteínas do Tecido Nervoso/genética , Esquizofrenia/genética , Adulto , Antipsicóticos/uso terapêutico , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/sangue , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Adulto Jovem
2.
BMC Psychiatry ; 20(1): 241, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414343

RESUMO

BACKGROUND: Recent studies show that oxidative stress is associated with the pathogenesis of schizophrenia. There are two major types of antioxidant systems in vivo, namely enzymatic antioxidants and non-enzymatic antioxidants. This study investigated differences of non-enzymatic antioxidants between schizophrenia patients and healthy controls. METHODS: Peripheral UA, ALB, and TBIL of 107 schizophrenic patients in the acute stage and 101 in the remission stage were measured respectively, so were 273 healthy controls. RESULTS: The levels of UA (P = 0.020) and TBIL (P < 0.001) of schizophrenic patients in the acute stage were higher than those of healthy controls, while the level of ALB (P < 0.001) was lower. Similar results were detected form schizophrenic patients in the remission stage. Schizophrenic patients in the acute stage were divided into antipsychotics-use subgroup (n = 56) and antipsychotics-naïve/free subgroup (n = 51). The level of UA (P = 0.001) in the antipsychotics-use subgroup was higher than that in the antipsychotics-naïve/free subgroup, while the level of TBIL (P = 0.002) was lower than that in the antipsychotics-naïve/free subgroup. Seventy-seven schizophrenic patients in the acute stage were followed up, and there was no significant difference in the level of UA before and after treatment, but levels of ALB (P < 0.001) and TBIL (P < 0.001) decreased significantly after the treatment. CONCLUSION: This study demonstrated that the dysfunction of the peripheral non-enzymatic anti-oxidation system might be involved in the pathogenesis of schizophrenia.


Assuntos
Antioxidantes/metabolismo , Esquizofrenia/sangue , Adulto , Albuminas/análise , Bilirrubina/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Ácido Úrico/sangue
3.
Compr Psychiatry ; 100: 152176, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32430144

RESUMO

OBJECTIVE: Early-onset schizophrenia is a severe and rare form of schizophrenia that is clinically and neurobiologically continuous with the adult form of schizophrenia. Neuregulin1 (NRG1)-mediated signaling is crucial for early neurodevelopment, which exerts its function by limited ß-secretase 1 (BACE1) proteolysis processing. However, circulating neuregulin1-ß1 (NRG1-ß1), an isoform of NRG1, and its cleavage enzyme BACE1 have not been studied in early-onset patients with schizophrenia. METHODS: In this study, we collected plasma and clinical information from 71 young patients (7 ≤ age years ≤20) with schizophrenia and 53 age- and sex-matched healthy controls. Immunoassay was used to test levels of circulating NRG1-ß1 and BACE1 expression. We further analyzed the relationship of disease-onset age and gender with NRG1-ß1 and BACE1 levels. RESULTS: We found that circulating plasma levels of NRG1-ß1 were significantly decreased in young patients with early-onset schizophrenia. In males with childhood onset schizophrenia (COS), NRG1-ß1 was reduced and was inversely correlated with positive symptom of PANSS; moreover, these male patients with higher plasma BACE1 levels showed more severe general symptoms of PANSS and defective social functioning; whereas, no aforementioned results were found in adolescent-onset schizophrenia (AOS). Notably, young female patients with COS and AOS had no significant change in NRG1-ß1 and BACE1, which demonstrated a sex-dependent effect in early-onset schizophrenia. CONCLUSION: Our results suggest that decreased levels of NRG1-ß1 and its cleavage enzyme BACE1 contribute to increased risk of etiology of schizophrenia. Synthetic biomarkers may have clinical applications for the early diagnosis of male COS.


Assuntos
Secretases da Proteína Precursora do Amiloide/sangue , Ácido Aspártico Endopeptidases/sangue , Neuregulina-1/sangue , Esquizofrenia/sangue , Adolescente , Idade de Início , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Esquizofrenia/etiologia , Esquizofrenia/metabolismo , Fatores Sexuais , Transdução de Sinais , Adulto Jovem
4.
Psychiatry Res ; 288: 112959, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32335466

RESUMO

Schizophrenia is a heterogeneous disorder in which there is an interaction between genetic and environmental factors. Accumulating data show that there may be an association between vitamin D deficiency and schizophrenia. We conducted an updated meta-analysis to investigate the relationship between schizophrenia and blood vitamin D level. All published observational articles have been searched from five databases until September 2019. In total, 36 articles with a total of 12528 participants were included in this study. Patients with schizophrenia have significantly lower levels of vitamin D than controls. The subgroup analyses based on study design, hospitalization status, quality score, type of biomarker [25-hydroxyvitamin D or 25-hydroxyvitamin D3], and the country did not explain between-study heterogeneity; however, meta-regression on match factors indicted that match of BMI could account for some degree of heterogeneity. No significant differences in publication bias were observed. Also, subjects with schizophrenia were more likely to have vitamin D deficiency or insufficiency compared to controls. In conclusion, our analyses are consistent with the hypothesis that vitamin D deficiency is associated with schizophrenia. More well-designed randomized control trials are needed to determine whether this association is causal.


Assuntos
Estudos Observacionais como Assunto/métodos , Esquizofrenia/sangue , Esquizofrenia/epidemiologia , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Biomarcadores/sangue , Humanos , Vitamina D/sangue
6.
Psychiatr Danub ; 32(1): 46-54, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32303029

RESUMO

BACKGROUND: Patients with schizophrenia exhibit a higher mortality rate compared with the general population. This mortality has been attributed predominantly by the high risk of type 2 diabetes mellitus in the patients. We aimed to assess the inherent risk of glucose metabolism abnormalities in first-episode drug-naive schizophrenia. SUBJECTS AND METHODS: We searched English database (PubMed, EMBASE, MEDLINE, Cochrane Library databases) and Chinese database (Wan Fang Data, CBM disc, VIP, and CNKI) from their inception until Jul 2018 for case-control studies examining glucose metabolism abnormalities. Measurements, such as fasting plasma glucose levels, fasting plasma insulin levels, insulin resistance and HbA1c levels in first-episode antipsychotic-naive patients were used to test for prediabetes. Standardized/weighted mean differences and 95% confidence intervals were calculated and analyzed. RESULTS: 19 studies (13 in English and 6 in Chinese) consisting of 1065 patients and 873 controls were included. Fasting plasma glucose levels (95% CI; 0.02 to 0.29; P=0.03), 2 h plasma glucose levels after an OGTT (95% CI; 0.63 to 1.2; P<0.00001), fasting plasma insulin levels (95% CI; 0.33 to 0.73; P<0.00001), insulin resistance (95% CI; 0.29 to 0.6; P<0.00001) in patients with first-episode schizophrenia were significant elevated. There was no significant difference in HbA1c level (95% CI; -0.34 to 0.18; P=0.54) in patients with first-episode schizophrenia compared with controls. CONCLUSIONS: This meta-analysis showed that glucose metabolism was impaired in patients with first-episode schizophrenia. Higher quality studies with larger samples are warranted to confirm these findings.


Assuntos
Glucose/metabolismo , Esquizofrenia/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Insulina/sangue , Insulina/metabolismo , Esquizofrenia/sangue , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico
7.
Braz J Psychiatry ; 42(4): 398-402, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32159713

RESUMO

OBJECTIVE: To determine whether changes in serum galectin-3 (gal-3) concentrations in schizophrenia patients have etiopathogenetic importance. Since very little research has assessed the connection between galectins and schizophrenia, we wanted to examine alterations in the inflammatory marker gal-3 in schizophrenia and investigate possible correlations between clinical symptomatology and serum concentrations. METHODS: Forty-eight schizophrenia patients and 44 healthy controls were included in this study. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) were administered to determine symptom severity. Venous blood samples were collected, and serum gal-3 levels were measured. RESULTS: Mean serum gal-3 levels were significantly lower in schizophrenia patients, and there were no significant differences in age or sex with the control group. There was also a significant positive correlation between serum gal-3 concentrations and negative schizophrenia symptoms according to the SANS. CONCLUSION: The results indicate that gal-3 is decreased in schizophrenia patients, which could contribute to inflammation in the pathogenesis of schizophrenia.


Assuntos
Galectina 3/sangue , Esquizofrenia/sangue , Biomarcadores/sangue , Feminino , Humanos , Inflamação , Masculino , Esquizofrenia/fisiopatologia
8.
Lancet Psychiatry ; 7(10): 911-914, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32213327

RESUMO

The naturalisation of mental disorders-ie, their translation into measurable and preferably molecular variables-has not progressed despite breath-taking discoveries in the neurosciences. We ask whether self-inflicted limits exist among psychiatrists that would prevent them from supporting an imaginary perfect blood test with diagnostic specificity, sensitivity, and validity, which was able to replace clinical diagnosis completely. Although relevant for many mental disorders, we use the clinical disease category schizophrenia here as an example to discuss factors that oppose the naturalisation of clinical disease categories. We defend the provocative position that a complete substitution of the clinical diagnosis by a blood test is generally not desired among clinicians because various factors perpetuate the current diagnostic culture. These are (1) methodological problems, such as a falsely presumed homogeneity of biological causes under the umbrella of one clinical diagnosis that prevents efficient subset identification, (2) professional fears, such as loss of importance of interview-diagnostic expert skills, and (3) conceptual problems, such as a dualistic mindset. We posit that doubts regarding the possibility of a blood test for diagnosing schizophrenia can subtly result in a negative self-fulfilling prophecy, discouraging serious scientific efforts to develop one. We give historical examples of how some of these problems have been solved in other medical disciplines. We predict that only blood tests that improve diagnostic accuracy but do not displace the primacy of clinical diagnosis will be successful. In the future, novel professional expertise for orchestrating various biological variables together with clinical criteria will be needed.


Assuntos
Testes Hematológicos , Esquizofrenia/diagnóstico , Biomarcadores/sangue , Humanos , Psiquiatria/tendências , Esquizofrenia/sangue
9.
Psychopharmacology (Berl) ; 237(6): 1861-1871, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32221694

RESUMO

AIM: To investigate whether circulating T cells including regulatory T cells (Treg) and derived cytokines contribute to the immune imbalance observed in schizophrenia. METHODS: Forty patients with schizophrenia and 40 age, sex, body mass index, education, and smoking status-matched healthy controls (HC) are included in the study. We stained cells with anti-CD14, anti-CD3, anti-CD4, anti-CD8, anti-CD19, anti-CD20, and anti-CD16/56. Peripheral blood mononuclear cells (PBMCs) were isolated and stained with the human FoxP3 kit containing anti-CD4/anti-CD25 and intracellular anti-Foxp3. PBMCs were cultured for 72 h and stimulated with anti-CD3/anti-CD28. Cytokines (IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17A) were measured from the culture supernatant and plasma using the Th1/Th2/Th17 cytokine bead array kit. RESULTS: In comparison with HC, Treg percentages in schizophrenia were higher (1.17 ± 0.63 vs 0.81 ± 0.53, P = 0.005) in unstimulated but lower in the stimulated condition (0.73 ± 0.69 vs 0.97 ± 0.55, P = 0.011). Activated T cell percentages were higher in schizophrenia than HC in unstimulated (2.22 ± 0.78 vs 1.64 ± 0.89, P = 0.001) and stimulated (2.25 ± 1.01 vs 1.72 ± 1.00, P = 0.010) conditions. The culture supernatant levels of IL-6 (7505.17 ± 5170.07 vs 1787.81 ± 1363.32, P < 0.001), IL-17A (191.73 ± 212.49 vs 46.43 ± 23.99, P < 0.001), TNF-α (1557 ± 1059.69 vs 426.57 ± 174.62, P = 0.023), and IFN-γ (3204.13 ± 1397.06 vs 447.79 ± 270.13, P < 0.001); and plasma levels of IL-6 (3.83 ± 3.41vs 1.89 ± 1.14, P = 0.003) and IL-17A (1.20 ± 0.84 vs 0.83 ± 0.53, P = 0.033) were higher in patients with schizophrenia than HC. CONCLUSION: Our explorative study shows reduced level of Foxp3 expressing Treg in a stimulated condition with induced levels of proinflammatory cytokines in patients with schizophrenia.


Assuntos
Mediadores da Inflamação/sangue , Mediadores da Inflamação/imunologia , Esquizofrenia/sangue , Esquizofrenia/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Adulto , Estudos Transversais , Feminino , Humanos , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-17/sangue , Interleucina-17/imunologia , Subunidade alfa de Receptor de Interleucina-2/sangue , Subunidade alfa de Receptor de Interleucina-2/imunologia , Masculino , Pessoa de Meia-Idade , Esquizofrenia/diagnóstico , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia
10.
Rev. psiquiatr. salud ment. (Barc., Ed. impr.) ; 13(1): 31-35, ene.-mar. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-194432

RESUMO

INTRODUCCIÓN: Los niveles plasmáticos de clozapina son útiles para monitorizar el cumplimento farmacológico, pero también para evaluar y prevenir los efectos secundarios. Recientemente, se ha propuesto realizar controles plasmáticos a todos los pacientes para prevenir recaídas. A pesar de ello, también se ha documentado una alta variabilidad intraindividual, aunque los estudios tienen algunas limitaciones. MÉTODOS: Aquí analizamos las diferencias entre 2determinaciones de niveles plasmáticos con al menos un año de diferencias en un subgrupo de 28 pacientes (82% hombres, media de edad=47,9 años) con diagnósticos de psicosis no afectiva y en remisión clínica con dosis de clozapina y niveles de tabaquismo estable. RESULTADOS: Encontramos un incremento no significativo de los niveles de clozapina (0,30mg/l [DE=0,14] vs. 0,32 [DE=0,17]; t=-0,858, p = 0,40) y un descenso significativo de la norclozapina (0,27 [DE=0,11] vs. 0,22 [DE=0,10]; t=3,27; p = 0,003]. Calculamos el coeficiente de variación absoluto (CV) entre la primera y segunda determinación. El CV del 20% en los niveles de clozapina y norclozapina se encontró en el 46 y el 57% de los casos, respectivamente, mientras que el CV 50% se obtuvo en el 20,7 y el 13,8%. Discutimos las causas potenciales de CV tan altos. CONCLUSIONES: Nuestro estudio encontró una alta variación intraindividual incluso en un subgrupo de pacientes especialmente estables, lo que sugiere que la monitorización rutinaria sería adecuada para detectar cambios significativos de los niveles. Creemos que los clínicos deberían ser cautos a la hora de asumir pobre cumplimiento terapéutico a la hora de explicar cambios de los niveles plasmáticos no acompañados de cambios clínicos


INTRODUCTION: Clozapine plasma levels are useful to monitor drug compliance, and also to assess and to prevent some side effects. Recently, routine monitoring to all clozapine-treated patients has been proposed to prevent relapses. However, high intra-individual variability in plasma levels has been reported too, although these studies have some limitations. METHODS: We analysed differences between 2clozapine plasma levels separated by at least one year in a subgroup of 28 outpatients (82% male, mean age 47.9 years-old) with diagnosis of non-affective psychosis in clinical remission whose clozapine doses and smoking habits remained unchanged. RESULTS: We found a non-significant increase in clozapine plasma levels [.30mg/L (SD=.14) vs. .32 (SD=.17); t=-.858, p=.40] and a significant decrease in norclozapine plasma levels [.27 (SD=.11) vs. .22 (SD=.10); t=3.27; p=.003]. Absolute coefficient of variation (CV) between first and second assessment were calculated. Forty-six and fifty-seven percent of cases had CV 20% in clozapine and norclozapine, respectively. CV of 50% was seen in 20.7% and 13.8% of clozapine and norclozapine test respectively. We discussed potential causes of such high CV. CONCLUSIONS: Our study suggest high intra-individual variation even in a subgroup of very stable patients, which suggest that routine monitoring of these levels may be indicated in order to detect significant plasma variations. We think that clinicians should act with caution in case of a sudden decrease in plasma level. In the absence of obvious symptom severity variation, sources of intra-individual fluctuations might be considered first, before assuming poor compliance


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Antipsicóticos/sangue , Clozapina/análogos & derivados , Clozapina/sangue , Esquizofrenia/sangue , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Monitoramento de Medicamentos , Adesão à Medicação , Estudos Retrospectivos , Esquizofrenia/tratamento farmacológico , Fumar , Fatores de Tempo
11.
PLoS One ; 15(3): e0226688, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32191705

RESUMO

BACKGROUND: Schizophrenia is linked with abnormal brain neurodevelopment, on which IGF-2 (insulin-like growth factor-2) has a great impact. The purpose of this study was to assess the levels of serum IGF-2 and its binding proteins IGFBP-3 and IGFBP-7 in schizophrenia patients and the associations of these proteins with schizophrenia psychopathology and cognitive deficits. METHODS: Thirty-two schizophrenia patients and 30 healthy controls were recruited. The PANSS and a neurocognitive test battery were used to assess schizophrenic symptomatology and cognition, respectively. Serum IGF-2, IGFBP-3 and IGFBP-7 levels were determined using ELISA. RESULTS: The schizophrenia patients had a much lower content of serum IGF-2, IGFBP-3 and IGFBP-7 than controls. For the patients, IGF-2 levels were negatively correlated with the PANSS negative scores and positively associated with working memory, attention, and executive function. The correlations between IGF-2 and the PANSS negative scores, working memory or executive function were still significant after controlling for age, sex, education level, BMI, illness history and age of onset. No significant associations of IGFBP-3 or IGFBP-7 with the PANSS scores and cognitive function were observed in the patients. CONCLUSIONS: Our study demonstrates that serum IGF-2 was significantly correlated with negative and cognitive symptoms in patients with schizophrenia, suggesting that altered IGF-2 signaling may be implicated in the psychopathology and cognitive deficits in schizophrenia.


Assuntos
Encéfalo/fisiopatologia , Disfunção Cognitiva/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Esquizofrenia/metabolismo , Adulto , Encéfalo/crescimento & desenvolvimento , Estudos de Casos e Controles , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Função Executiva/fisiologia , Feminino , Humanos , Fator de Crescimento Insulin-Like II/análise , Masculino , Memória de Curto Prazo/fisiologia , Testes Neuropsicológicos , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Transdução de Sinais/fisiologia , Adulto Jovem
12.
J Neuroimmunol ; 341: 577165, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32007786

RESUMO

Neuroinflammation has been considered to be involved in the development of schizophrenia. This study aimed to study circulating autoantibodies for inflammatory cytokines in first-episode schizophrenia. A total of 181 patients and 197 controls were recruited for detection of plasma IgG antibodies against peptide antigens derived from interleukin 1α (IL1α), IL1ß, IL6, IL8 and tumour necrosis factor alpha (TNFα). The major finding was that patients with schizophrenia had significantly higher levels of anti-IL1ß IgG, anti-IL6 IgG and anti-IL8 IgG, and a significantly lower level of anti-IL1α IgG. This study suggests that inflammatory response may contribute to the development of schizophrenia.


Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Citocinas/imunologia , Imunoglobulina G/sangue , Esquizofrenia/imunologia , Adulto , Especificidade de Anticorpos , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Autoanticorpos/imunologia , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Esquizofrenia/sangue , Esquizofrenia/etnologia , Adulto Jovem
13.
Nord J Psychiatry ; 74(5): 374-379, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32105154

RESUMO

Background: Certain antipsychotics are known to cause QTc interval prolongation, which has been associated with increased risk of arrhythmia and sudden death. Previous studies have investigated whether there is an association between oral antipsychotic dose and QTc interval prolongation, however only few have examined the association between antipsychotic plasma concentrations and QTc interval.Material and methods: We performed a cross-sectional study with 22 forensic psychiatric in-patients. We measured the plasma concentration of the prescribed antipsychotics and performed an ECG simultaneously. We used Bazett's formula to calculate QTc and defined QTc as prolonged when: >460 ms for women and >450 ms for men.Results: Seventy-seven percent (n = 17) of the subjects were men (mean age = 40 years) and 91% (n = 20) were diagnosed with schizophrenia. QTc's ranged from 369 to 437 ms. Patients receiving QTc prolonging drugs had significantly greater QTc interval compared to patients receiving non-prolonging drugs. Weak to moderate negative correlations were found between QTc interval and both defined daily dose (DDD) and antipsychotic plasma concentration. There was no statistical difference between the correlations for DDD and plasma concentration versus QTc interval.Conclusion: We did not find a stronger association between antipsychotic plasma concentration and QTc than between antipsychotic dose and QTc. We suggest close monitoring with regular electroencephalogram's until the development of a better marker for predicting the risk of cardiac arrhythmia.


Assuntos
Antipsicóticos/efeitos adversos , Antipsicóticos/sangue , Síndrome do QT Longo/sangue , Síndrome do QT Longo/induzido quimicamente , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/uso terapêutico , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Risco , Adulto Jovem
14.
Int J Med Sci ; 17(2): 255-262, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32038109

RESUMO

Several studies have been suggested that immunity plays a part in neurodevelopment and schizophrenia pathogenesis. Early age of onset in schizophrenia is associated with genetic factors which affect neurodevelopment. This study aims to identify immune abnormalities associated with neurodevelopmental impairments in early-onset schizophrenia (EOS) and adult-onset schizophrenia (AOS) patients. We determined the plasma levels of six cytokines (IL-1ß, IL-4, IL-6, IL-10, IL-12 and TNF-α) in schizophrenia patients and healthy controls. Measurements included neurological soft signs (NSS) to distinguish and subgroup those with neurodevelopmental impairments. The study included 210 schizophrenia patients, which were divided into 84 EOS and 126 AOS patients, as well as 122 healthy controls. We observed significant differences in levels of IL-4, IL-6 and IL-10 between EOS and AOS patients. The results demonstrated the area under ROC curve (AUC) of the IL-4 in EOS and healthy controls was 0.81. Moreover, these results indicated that AUC of the IL-4 and the combination of IL-4, IL-6 and IL-12 in EOS with NSS and healthy controls were 0.91 and 0.95. These cytokines are altered in EOS and schizophrenia patients with neurodevelopmental impairments and demonstrated good classification abilities. These findings manifested that both pro- and anti-inflammatory cytokines are contributed to the clinical and pathophysiological features of schizophrenia. Future works are expected to explore potential genetic effectors and predictors as well as therapeutic directions in personalized medicine for early-onset schizophrenia.


Assuntos
Biomarcadores/sangue , Citocinas/sangue , Esquizofrenia/sangue , Adulto , Idade de Início , Feminino , Humanos , Interleucina-10/sangue , Interleucina-4/sangue , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade
15.
Psychiatry Res ; 284: 112757, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31955055

RESUMO

Increasing evidence indicates that oxidative damage and inflammation is present in patients with schizophrenia. In this study, we investigated the association between the serum concentrations of four typical oxidative stress and inflammatory biomarkers (monocyte chemotactic protein-1, heme oxygenase-1, interleukin-8, and 8-Hydroxydeoxyguanine) and schizophrenia using a case-control study design. In total, 44 patients with schizophrenia and 45 normal controls from Shandong Province, China were recruited. Fasting blood samples were collected from all participants and the serum concentration of the four biomarkers were analyzed by Enzyme-linked immunosorbent assay. The concentrations of monocyte chemotactic protein-1 and interleukin-8 were significantly higher in the patients than in the controls, while there was no significant difference in the serum concentrations of heme oxygenase-1 and 8-Hydroxydeoxyguanine. Moreover, the serum concentrations of monocyte chemotactic protein-1 and interleukin-8 in patients were positively correlated with severity of clinical symptoms. Dose-response relationships between serum biomarker concentrations and schizophrenia were observed. This study suggests that levels of monocyte chemotactic protein-1 and interleukin-8 are increased in patients with schizophrenia and correlated with positive symptom severity.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/análogos & derivados , Quimiocina CCL2/sangue , Heme Oxigenase-1/sangue , Interleucina-8/sangue , Esquizofrenia/sangue , 8-Hidroxi-2'-Desoxiguanosina/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , China , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Projetos Piloto
16.
J Pharm Biomed Anal ; 180: 113056, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31887669

RESUMO

OBJECTIVE: Clozapine is one of the most effective drugs for resistant schizophrenia, but its severe metabolic and hematological side effects limit the use of clozapine. It has been reported that clozapine blood concentrations should be maintained between 350-600 ng/mL. Our aim was to develop a determination method for clozapine and its main metabolites norclozapine and clozapine-N-oxide, to perform validation studies and to investigate the change of various biochemical parameters in patients using clozapine. METHODS: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for clozapine measurement. Thus, blood samples were collected from 38 patients with schizophrenia and 32 healthy volunteers. Biochemical and hematological parameters were measured by Beckman-Coulter AU 5800 (Beckman Coulter, Brea, USA) and Beckman Coulter LH 780 analyzer (Beckman Coulter, Miami, FL, USA), respectively. Hormone levels were analyzed using Cobas 6000 analyzer (Roche Diagnostics, Germany). RESULTS: The LCMS/MS method was linear between 1.22-2500 ng/mL (r2 = 0.9971) for clozapine. The retention times of clozapine, norclozapine and clozapine-N-oxide were 0.92, 0.89 and 0.95, respectively. Blood glucose (GLU) (p = 0.025), low density lipoprotein (LDL-cholesterol) (p = 0.015), triglyseride (TG) (p = 0.042) and total cholesterol (TC) (p = 0.024) levels were higher; hemoglobin (HGB) (0.015), mean corpuscular hemoglobin (MCH) (0.036), red blood cell count (RBC) (0.020), neutrophil (NEU) (0.034), and platelet (PLT) (P = 0.005) levels were lower in the clozapine group. CONCLUSIONS: This LC-MS/MS method was rapid, simple, cost-effective and suitable for the routine clozapine monitoring. Furthermore, norclozapine and clozapine-N-oxide were also determined. Monitoring of metabolic and hematological parameters with clozapine levels is very important. However, the limitations of the study were that the method was not validated for norclozapine and clozapine-N-oxide, so the validation parameters were not evaluated for these two metabolites.


Assuntos
Antipsicóticos/sangue , Clozapina/análogos & derivados , Monitoramento de Medicamentos/métodos , Esquizofrenia/sangue , Adulto , Antipsicóticos/efeitos adversos , Contagem de Células Sanguíneas , Glicemia/análise , Estudos de Casos e Controles , Colesterol/sangue , Cromatografia Líquida , Clozapina/efeitos adversos , Clozapina/sangue , Hemoglobinas/análise , Humanos , Limite de Detecção , Reprodutibilidade dos Testes , Esquizofrenia/tratamento farmacológico , Espectrometria de Massas em Tandem , Triglicerídeos/sangue
17.
BMC Res Notes ; 12(1): 802, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831048

RESUMO

OBJECTIVE: The association between unbalanced iron indices and the conditions of schizophrenia are not well understood. Liver dysfunction which has been linked to iron metabolism might be a contributing factor. This case-control study evaluated serum iron indices and liver function in treatment-naïve schizophrenia patients and those already on treatment at the Psychiatric Department of the Komfo Anokye Teaching Hospital (KATH), Kumasi-Ghana. RESULTS: The mean age of the respondents was 39.6 ± 0.8 years. Increased levels of serum iron, TS, AST, ALT and AST:ALT ratio and lower levels of UIBC, TIBC, Transferrin, and log Ferritin:AST ratio levels were observed among the treatment-naïve group compared to the control. The treatment-naïve and treatment groups showed significantly higher serum AST:ALT ratio, and lower log10ferrtin:AST ratio than the healthy controls. There was a significant correlation between log10ferritin and AST, and log10ferritin and GGT in both treatments (r = 0.343; p = 0.003, and r = 0.502; p = 0.001 respectively) and treatment-naïve groups (r = 0.348; p = 0.002, and r = 0.614; p < 0.001 respectively). Percentage transferrin saturation correlated significantly with GGT only, in the treatment-naïve group (r = 0.667; p < 0.001), and ALT and GGT in the treatment group (r = 0.252; p = 0.030 and r = 0.646; p = 0.014 respectively).


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Ferritinas/sangue , Sobrecarga de Ferro/sangue , Ferro/sangue , Esquizofrenia/complicações , Adulto , Alanina Transaminase/análise , Aspartato Aminotransferases/análise , Estudos de Casos e Controles , Feminino , Ferritinas/análise , Gana , Humanos , Sobrecarga de Ferro/complicações , Fígado/metabolismo , Testes de Função Hepática , Masculino , Esquizofrenia/sangue , Transferrina/química , Transferrina/metabolismo
18.
BMC Psychiatry ; 19(1): 403, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842818

RESUMO

BACKGROUND: Accumulating evidence suggests that serum vascular endothelial growth factor (VEGF) in many neurobiological processes potentially contributes to the pathophysiology of psychiatric disorders, particularly cognitive decline. The purpose of this study was to explore the differences in neurocognition, social cognition and VEGF among remitted first-episode schizophrenic patients, non-remitters and normal control subjects. Moreover, we investigated the association between serum VEGF levels and cognitive functions. METHOD: 65 remission (RS) and 45 nonremission patients (NRS) after first-episode schizophrenia, as well as 58 healthy controls (HC) were enrolled in this study. Social cognition was assessed using the Chinese Facial Emotion Test (CFET); neurocognition was measured with a test battery consisting of Hopkins Verbal Learning Test-Revised, Verbal Fluency Test, Trail Making Tests, Digit Span Tests (DST) and Stroop Tests. Blood samples were collected for VEGF measurements. Data was analyzed with SPSS 22.0 (Chicago, IL, USA). RESULTS: On nearly all neurocognitive tests (except for DST), RS performed significantly worse than HC but better than NRS (P < 0.05). NRS, but not RS, exhibited markedly poorer social cognition than HC (except for Happiness and Surprise subscales of the CFET) (P < 0.05). VEGF levels showed a gradient change among three groups (HC > RS > NRS). CONCLUSION: Compared to HC, RS demonstrated poorer neurocognitive but intact social cognition functioning. These results indicate that VEGF levels decreased gradually with the severity of cognitive impairment in schizophrenia. VEGF may be involved in the pathological mechanism of cognitive performance in RS.


Assuntos
Cognição/fisiologia , Esquizofrenia/sangue , Psicologia do Esquizofrênico , Comportamento Social , Percepção Social , Fator A de Crescimento do Endotélio Vascular/sangue , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Adulto Jovem
19.
Biomol Concepts ; 10(1): 209-225, 2019 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-31734647

RESUMO

In schizophrenia, a single latent trait underlies psychosis, hostility, excitation, mannerism, negative (PHEMN) symptoms, formal thought disorders (FTD) and psychomotor retardation (PMR). Schizophrenia is accompanied by a breakdown of gut and blood-brain-barrier (BBB) pathways, increased tryptophan catabolite (TRYCAT) levels, bacterial translocation, and lowered natural IgM and paraoxonase (PON)1 activity. The aim of this study was to examine the factor structure of schizophrenia symptom domains and the biomarker correlates of these factors. We recruited 80 patients with schizophrenia and 40 healthy subjects and assessed the IgA/IgM responses to paracellular/transcellular (PARA/TRANS) ratios, IgA responses to TRYCATs, natural IgM to malondialdehyde and Gram-negative bacteria, and PON1 enzymatic activity. Direct Hierarchical Exploratory Factor Analysis showed a bifactorial oblique model with a) a general factor which loaded highly on all symptom domains, named overall severity of schizophrenia ("OSOS"); and b) a single-group factor (SGF) loading on negative symptoms and PMR. We found that 40% of the variance in OSOS score was explained by IgA/IgM to PARA/TRANS ratio, male sex and education while 36.9% of the variance in SGF score was explained by IgA to PARA/TRANS, IgM to Gram-negative bacteria, female sex (positively associated) and IgM to MDA, and PON1 activity (negatively associated). Schizophrenia phenomenology comprises two biologically-validated dimensions, namely a general OSOS dimension and a single-group negative symptom dimension, which are associated with a breakdown of gut/BBB barriers, increased bacterial translocation and lowered protection against oxidation, inflammation and bacterial infections through lowered PON1 and natural IgM.


Assuntos
Neurotoxinas/imunologia , Esquizofrenia/genética , Esquizofrenia/imunologia , Adulto , Biomarcadores/sangue , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Neurotoxinas/sangue , Esquizofrenia/sangue , Índice de Gravidade de Doença , Triptofano/sangue , Triptofano/imunologia , Triptofano/metabolismo
20.
J Clin Psychopharmacol ; 39(6): 639-643, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31688384

RESUMO

BACKGROUND: Biomarkers identified for psychosis might allow for early diagnosis, more accurate prognosis, and tailored individualized interventions. Brain-derived neurotrophic factor (BDNF) is suggested to be a likely candidate biomarker for the diagnosis and treatment evaluation in psychosis. The aims of present study were to examine the levels of serum BDNF in both patients with first-episode psychosis (FEP) and in healthy controls for a year, and to investigate the association between BDNF with symptom severity and remission status. METHODS: A sample of 31 healthy controls and 29 patients with FEP were included in this study. Diagnoses were ascertained on the Structured Clinical Interview for DSM-IV-TR. Symptom severity was assessed on the Positive and Negative Syndrome Scale. Serum levels of BDNF were measured using enzyme-linked immunosorbent assay method at recruitment and at 3-, 6-, and 12-month time points. RESULTS: Serum BDNF levels in both groups did not differ significantly over time. Baseline BDNF levels in patients with FEP did not correlate with symptom severity and neither baseline BDNF level nor its relative change at 3-month predicted remission status at 6- and 12-month follow-up visits. Of note, we observe similar fluctuations in serum BDNF levels in both patients and healthy controls over the 12-month period. CONCLUSIONS: Findings from our study did not support a role for serum BDNF as a biomarker for patients with FEP. Because of the polygenic nature of psychosis, we recommend a comprehensive multimarker profile consisting of markers from representative components of mediated neuronal nutrition, neuroimmunology, and neurologic functional deficit to allow for better predictive power.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Esquizofrenia/sangue , Esquizofrenia/fisiopatologia , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Estudos Longitudinais , Masculino , Índice de Gravidade de Doença , Adulto Jovem
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