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1.
Biol Rev Camb Philos Soc ; 96(2): 642-672, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33314677

RESUMO

During a long-duration manned spaceflight mission, such as flying to Mars and beyond, all crew members will spend a long period in an independent spacecraft with closed-loop bioregenerative life-support systems. Saving resources and reducing medical risks, particularly in mental heath, are key technology gaps hampering human expedition into deep space. In the 1960s, several scientists proposed that an induced state of suppressed metabolism in humans, which mimics 'hibernation', could be an ideal solution to cope with many issues during spaceflight. In recent years, with the introduction of specific methods, it is becoming more feasible to induce an artificial hibernation-like state (synthetic torpor) in non-hibernating species. Natural torpor is a fascinating, yet enigmatic, physiological process in which metabolic rate (MR), body core temperature (Tb ) and behavioural activity are reduced to save energy during harsh seasonal conditions. It employs a complex central neural network to orchestrate a homeostatic state of hypometabolism, hypothermia and hypoactivity in response to environmental challenges. The anatomical and functional connections within the central nervous system (CNS) lie at the heart of controlling synthetic torpor. Although progress has been made, the precise mechanisms underlying the active regulation of the torpor-arousal transition, and their profound influence on neural function and behaviour, which are critical concerns for safe and reversible human torpor, remain poorly understood. In this review, we place particular emphasis on elaborating the central nervous mechanism orchestrating the torpor-arousal transition in both non-flying hibernating mammals and non-hibernating species, and aim to provide translational insights into long-duration manned spaceflight. In addition, identifying difficulties and challenges ahead will underscore important concerns in engineering synthetic torpor in humans. We believe that synthetic torpor may not be the only option for manned long-duration spaceflight, but it is the most achievable solution in the foreseeable future. Translating the available knowledge from natural torpor research will not only benefit manned spaceflight, but also many clinical settings attempting to manipulate energy metabolism and neurobehavioural functions.

3.
Front Pharmacol ; 11: 739, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528286

RESUMO

Weight gain and metabolic disturbances, potentially influenced by increased appetite, are common effects of olanzapine treatment in patients with schizophrenia. In this study, we explored the association between olanzapine-induced weight gain and metabolic effects with increased appetite. Drug-naïve, first-episode schizophrenia patients were treated with olanzapine for 12 weeks. Assessments included time to increased appetite, body weight, body mass index, biochemical indicators of blood glucose and lipids, proportion of patients who gained more than 7% or 10% of their baseline weight upon treatment conclusion, patients who developed dyslipidemia, and Positive and Negative Syndrome Scale scores. In total, 33 patients with schizophrenia receiving olanzapine were enrolled and 31 completed the study. During the 12-week olanzapine treatment, 77.4% (24/31) patients had increased appetite with 58.1% (18/31) patients having increased appetite within the first 4 weeks. The mean time for increased appetite was 20.3 days. More patients in the increased appetite group increased their initial body weight by more than 7% after 12 weeks when compared to patients with unchanged appetite (22/24 [91.7%] vs. 3/7 [42.9%], p = 0.004). Earlier increased appetite led to more weight gain during the following month. Overall, 50% of patients in the increased appetite group had dyslipidemia after 12 weeks. Our results demonstrated that olanzapine induced significantly appetite increase in first-episode patients with schizophrenia and appetite increase played a key role in olanzapine-induced weight gain and dyslipidemia. Clinical Trial Registration: NCT03451734. Registered March 2, 2018 (retrospectively registered).

4.
Front Psychiatry ; 10: 497, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379619

RESUMO

Bipolar disorder (BD) is a chronic and refractory disease with high probability of morbidity and mortality. Although epidemiological studies have established a strong association between BD and immune dysfunction, the precise etiology is still debatable, and the underpinning mechanism remains poorly investigated and understood. In the present study, manic-like symptoms of BD were induced in rats after intracerebroventricular administration of ouabain. Aspirin, a commonly used anti-inflammatory agent, was used to treat the induced manic-like symptoms and inflammation. Concentrations of a spectrum of inflammatory cytokines were examined by enzyme-linked immunosorbent assay in both plasma and brain tissues, and expression of Toll-like receptors 3 and 4 were determined in rat brains. Locomotor activity was monitored with open-field test to assess the effects of ouabain challenge and to evaluate the treatment efficacy of aspirin. Ouabain administration recapitulated many mania-like features such as increased stereotypic counts, traveling distance in open-field test, and decreased expression of brain-derived neurotrophic factor, interferon gamma, and Toll-like receptor 3, which were frequently found in patients with BD. These abnormalities could be partially reversed by aspirin. Our findings suggest that aspirin could be used as a promising adjunctive therapy for BD.

5.
Front Pharmacol ; 10: 761, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333472

RESUMO

Background: The relation between the ATP-binding cassette subfamily B member 1 (ABCB1) gene and major depressive disorder (MDD) has been studied in a local Chinese Han population. MDD is associated with the rs2032582 (G2677T) and rs1128503 (C1236T) single-nucleotide polymorphisms (SNPs) of ABCB1 but not with rs1045642, rs2032583, rs2235040, and rs2235015. This study aims to explore the potential correlations of therapeutic responses with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in a local Chinese Han population. Methods: The study population included 292 patients with MDD. All patients were assessed at baseline and at first, second, fourth, and sixth weeks according to the 17-item Hamilton Rating Scale for Depression (HAM-D17) to determine their therapeutic responses to SSRIs and SNRIs. Results: In the SSRI therapy group, the genotype or allele distribution of six SNPs was not significantly different between responders and nonresponders. In the SNRI therapy group, only rs2032583 was associated with a therapeutic response to SNRIs. The C allele of the ABCB1 rs2032583 polymorphism was negatively correlated with therapeutic responses according to logistic regression analysis. Conclusion: The ABCB1 gene polymorphisms may not be associated with therapeutic responses to SSRIs but not with SNRIs. The TT genotype of rs2032583 could be a predictive factor of improved treatment responses to SNRIs in the Chinese population. These findings should be replicated in future studies with larger patient groups.

6.
Pharmacopsychiatry ; 52(1): 24-31, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29486513

RESUMO

INTRODUCTION: Weight gain is a common antipsychotic (AP)-related adverse drug reaction (ADR) that can increase the risk of cardiovascular diseases and premature mortality. This meta-analysis examined the efficacy and tolerability of combining metformin and lifestyle intervention for AP-related weight gain in schizophrenia. METHODS: Randomized controlled trials (RCTs) with meta-analyzable data were searched and retrieved by 2 independent investigators. RevMan software (version 5.3) was used to synthesize data, and to calculate the standardized or weighted mean differences and risk ratio with their 95% confidence intervals. RESULTS: Six RCTs (n=732) were included and meta-analyzed. The metformin and lifestyle combination (MLC) group had significant reduction in weight and body mass index compared with the metformin group, lifestyle group, and placebo group. There was less frequent weight gain of≥7% in the MLC group over placebo. No other group differences in ADRs, total psychopathology, and all-cause discontinuation were found. In terms of study quality, 5 RCTs were open-labelled, 1 RCT had low risk allocation concealment, and 3 RCTs specifically described randomization methods. CONCLUSION: Combining metformin and lifestyle intervention shows significant effect in reducing AP-related weight gain. Higher quality and larger RCTs are needed to confirm these findings.Review registration: CRD42017059198.


Assuntos
Antipsicóticos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Estilo de Vida , Metformina/uso terapêutico , Ganho de Peso/efeitos dos fármacos , Adolescente , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/tratamento farmacológico , Adulto Jovem
7.
Medicine (Baltimore) ; 97(52): e13902, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30593205

RESUMO

The aim of this study was first to investigate associations between maternal dietary patterns and autism spectrum disorders (ASDs) and second to investigate association between maternal supplement intake and ASD.We used a case-control study design to enroll typically developing (TD) children and children with ASD, and data were derived from the Autism Clinical and Environmental Database (ACED).Three seventy four children with AUTISM and 354 age matched TD children were included. The multivariate logistic regression model revealed that maternal unbalanced dietary patterns before conception had a significant increased risk of ASD in offspring (mostly meat: adjusted OR, 4.010 [95% CI, 1.080, 14.887]; mostly vegetable: adjusted OR, 2.234 [95% CI, 1.009, 4.946]); maternal supplementation of calcium during pregnancy preparation was associated with decreased ASD risk (adjusted OR, 0.480 [95% CI, 0.276, 0.836]).This study provided preliminary evidence that maternal unbalanced dietary patterns may be a risk factor for ASD and supplementation of calcium during pregnancy preparation may be inversely associated with ASD in offspring.


Assuntos
Transtorno do Espectro Autista/epidemiologia , Dieta/estatística & dados numéricos , Suplementos Nutricionais/estatística & dados numéricos , Mães/estatística & dados numéricos , Adulto , Fatores Etários , Índice de Massa Corporal , Cálcio/administração & dosagem , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Feminino , Ácido Fólico/administração & dosagem , Humanos , Modelos Logísticos , Masculino , Fatores de Risco , Fatores Sexuais , Fatores Socioeconômicos
8.
Psychiatry Res ; 266: 168-174, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29864617

RESUMO

This study evaluated the life quality of Chinese parents of preschool children with autism spectrum disorder (ASD) and their association with child social impairment and childcare burden. The participants included 406 families of children with ASD and 513 families with typically developing (TD) children. The findings indicated that parents in the ASD group had a lower quality of life than parents in the TD group, whereas only mother of children with ASD experienced a greater childcare burden than mother with TD children. Lower parental quality of life were associated with higher social impairment of children. To further clarify the correlativity of child social impairment, parental quality of life and childcare burden, the mediation analyses were conducted. The results showed that childcare burden mediated the influence of child social impairment on maternal quality of life, while it has no mediating effect on fathers. It implies that social impairment of children affects parental quality of life in different ways.


Assuntos
Transtorno do Espectro Autista/psicologia , Desenvolvimento Infantil , Pais/psicologia , Qualidade de Vida/psicologia , Transtornos do Comportamento Social/psicologia , Adulto , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Pai/psicologia , Feminino , Humanos , Masculino , Mães/psicologia , Transtornos do Comportamento Social/diagnóstico , Transtornos do Comportamento Social/epidemiologia
9.
CNS Neurosci Ther ; 24(12): 1140-1148, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29691990

RESUMO

AIMS: Evidence of altered structural and functional connectivity in the frontal-occipital network is associated with cognitive deficits in patients with schizophrenia. However, the altered patterns of functional connectivity strength (FCS) in individuals with ultra-high risk (UHR) for psychosis remain unknown. In this study, whole-brain FCS was assessed to examine the altered patterns of FCS in UHR subjects. METHODS: A total of 34 UHR subjects and 37 age- and sex-matched healthy controls were enrolled to undergo resting-state functional magnetic resonance imaging. The imaging data were analyzed using the graph theory method. RESULTS: Compared with healthy controls, UHR subjects showed significantly decreased FCS in the left middle frontal gyrus and significantly increased FCS in the left calcarine cortex. The FCS values in the left middle frontal gyrus were positively correlated to the scores of the Brief Assessments of Cognitionin Schizophrenia Symbol Coding Test (r = 0.366, P = 0.033) in the UHR subjects. A negative correlation was found between the FCS values in the left calcarine cortex and the scores of the Stroop color-naming test (r = -0.475, P = 0.016) in the UHR subjects. A combination of the FCS values in the 2 brain areas showed an accuracy of 87.32%, a sensitivity of 73.53%, and a specificity of 100% for distinguishing UHR subjects from healthy controls. CONCLUSIONS: Significantly altered FCS in the frontal-occipital network is observed in the UHR subjects. Furthermore, decreased FCS in the left middle frontal gyrus and increased FCS in the left calcarine have significant correlations with the cognitive measures of the UHR subjects and thus improve our understanding of the underlying pathophysiological mechanisms of schizophrenia. Moreover, a combination of the FCS values in the 2 brain areas can serve as a potential image marker to distinguish UHR subjects from healthy controls.


Assuntos
Transtornos Cognitivos/etiologia , Lobo Frontal/fisiopatologia , Lobo Occipital/fisiopatologia , Transtornos Psicóticos/complicações , Descanso , Adolescente , Adulto , Mapeamento Encefálico , Estudos de Casos e Controles , Transtornos Cognitivos/diagnóstico por imagem , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Lobo Occipital/diagnóstico por imagem , Oxigênio/sangue , Transtornos Psicóticos/diagnóstico por imagem , Adulto Jovem
10.
Autism Res ; 10(6): 1155-1162, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28266803

RESUMO

Aggressive behaviors of children with autism spectrum disorder (ASD) are common. We conducted this study to describe the aggressive mode of preschool children with ASD and examine the associations between specific aggressive behaviors and two treatable factors: sleep problems and attention deficit hyperactivity disorder (ADHD) symptoms. In total, 577 typically developing (TD) children and 490 children with ASD were investigated in this study. The Institute for Basic Research - Modified Overt Aggression Scale (IBR-MOAS) was used to assess aggressive behaviors. Children's social impairments, sleep problems and ADHD symptoms were also measured with specific scales. The total IBR-MOAS score was significantly higher (worse) in the TD group [4.47 (5.36)] than in the ASD group [3.47 (5.63), P = 0.004]. The aggressive modes differed between groups: when compared with each other, the TD group received higher scores on Verbal and Physical Aggression Toward Others (all P < 0.01), while the ASD group had higher scores on Physical Aggression Against Self (P = 0.006). The linear regression model demonstrated that the aggressive behaviors of children with ASD were significantly associated with two treatable factors: sleep problems and ADHD symptoms. These findings have substantial clinical implications: treatment of these two risk factors may be helpful in managing aggressive behavior in children with ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1155-1162. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.


Assuntos
Agressão/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/psicologia , Transtornos do Sono-Vigília/complicações , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Fatores de Risco , Comportamento Social
11.
Schizophr Res ; 183: 56-63, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27876273

RESUMO

OBJECTIVE: This meta-analysis aimed to examine the decisional capacity measured by the MacArthur Competence Assessment Tools (MacCAT) in schizophrenia. METHOD: English (PubMed, PsycINFO, Embase, Cochrane Library databases and the Cochrane Controlled Trials Register) and Chinese (Wan Fang Database and Chinese National Knowledge Infrastructure) databases were systematically and independently searched from 1995 until August 1, 2016. Weighted and standardized mean differences were calculated. The random effects model was used in all cases. RESULTS: Altogether 10 studies were identified, with 7 studies using the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) and 3 studies using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T). The meta-analysis showed that there was significant impairment in decision-making capacity in schizophrenia patients compared to the healthy control group in terms of Understanding (SMD=-0.81, 95% CI: -1.06 to -0.56, P<0.001), Reasoning (SMD=-0.57, 95% CI: -0.80 to -0.34, P<0.001), Appreciation (SMD=-0.87, 95% CI: -1.20 to -0.53, P<0.001), and Expression a choice (SMD=-0.24, 95% CI: -0.43 to -0.05, P=0.01). CONCLUSION: Compared to the control group, schizophrenia patients are more likely to have impaired decision-making capacity in clinical research and treatment as measured by the MacCAT instruments. Researchers and clinicians need to consider the impaired decisional capacity in schizophrenia patients providing informed consent.


Assuntos
Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Tomada de Decisões/fisiologia , Testes Neuropsicológicos , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Bases de Dados Bibliográficas/estatística & dados numéricos
12.
Beijing Da Xue Xue Bao Yi Xue Ban ; 47(5): 846-52, 2015 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-26474629

RESUMO

OBJECTIVE: To estimate the pharmacokinetics for two solution types of propofol glycoside injections in rats. METHODS: A high performance liquid chromatography-high resolution mass spectrometry (HPLC-MS) was established for measuring propofol in rat plasma. Two kinds of propofol glycoside injections were developed and intravenously administered to rats via tail vein, respectively, and a commercially available propofol emulsion injection was intravenously administered as a control. Propofol plasma concentration-time curves were determined, and the pharmacokinetic parameters were estimated. RESULTS: HPLC-MS measurement was performed by using a quadrupole-orbit trap high-resolution mass spectrometer on a C18 chromatographic column. The mobile phase consisted of water and methanol (20:80, V/V). The ion source was an atmospheric pressure chemical ion source, and the negative ion was used for detection with a scanning mode of selective ion monitoring in which m/z 177.127 4 was used for propofol and m/z 149.096 1 used for thymol as an internal standard. A linear correlation between concentration and peak area ratio was constructed in the range of 50 µg/L-10.0 mg/L propofol. The limit of quantification was 50 µg/L propofol. The average recoveries of propofol from plasma were in the range of 93.6%-101.1%, and intra-day or inter-day relative standard deviation for measurement was <14%. The pharmacokinetic results showed that the two kinds of propofol glycoside injections exhibited the same pharmacokinetic behavior. However, the clearance and area under curve values of propofol for the two propofol glycoside injections were evidently increased as compared with those for propofol emulsion injection, respectively. Furthermore, their apparent distribution volumes were increased as well. Nevertheless, the propofol elimination half-life (t1/2) value of the newly developed propofol glycoside injections was the same as that of commercial propofol emulsion injection (approximately 1.5 h). CONCLUSION: The established HPLC-MS method can be used for measuring propofol concentration accurately in rat plasma. The clearance and distribution volumes of propofol glycoside injection are bigger than those of the propofol emulsion injection.


Assuntos
Glicosídeos/farmacocinética , Propofol/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão , Injeções Intravenosas , Ratos , Espectrometria de Massas em Tandem
13.
Neuropsychiatr Dis Treat ; 11: 1967-71, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26347319

RESUMO

BACKGROUND: Human P-glycoprotein encoded by the ATP-binding cassette sub-family B member 1 (ABCB1) gene is expressed in the blood-brain barrier. ABCB1 protects the brain from many drugs and toxins such as glucocorticoids through the efflux pump. Recent evidence suggests that a specific allele of the ABCB1 gene confers susceptibility to major depressive disorder (MDD) in the Japanese population. The aim of this study was to explore the association of ABCB1 gene polymorphisms with MDD in a local Chinese Han population. METHODS: Two hundred and ninety-two MDD patients and 208 unrelated individuals were matched by age and sex and examined using a case-control design. Six single nucleotide polymorphisms (SNPs) of the ABCB1 gene, including rs1045642, rs2032583, rs2032582, rs2235040, rs1128503, and rs2235015, were genotyped by ligase detection reaction and multiplex polymerase chain reaction. Linkage disequilibrium and haplotype analysis were investigated in the two study groups. RESULTS: Significant protection for MDD individuals carrying the TG haplotype of rs1045642-rs2032582 was observed (odds ratio 0.470, 95% confidence interval 0.251-0.897, P=0.01). The rs2032582 (G2677T) and rs1128503 (C1236T) SNPs of ABCB1 showed nominal associations with MDD; the other four SNPs of the ABCB1 gene were not associated with MDD. CONCLUSION: Chinese individuals carrying the TG haplotype of rs1045642-rs2032582 had a nearly 53% lower risk of developing MDD. To the best of our knowledge, this is the first report to analyze the effect of ABCB1 polymorphism on the risk of MDD in a Chinese population.

14.
BMC Psychiatry ; 15: 3, 2015 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-25608486

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) affects many aspects of family life, such as social and economic burden. Little investigation of this phenomenon has been carried out in China. We designed this study to evaluate the employment and financial burdens of families with ASD-diagnosed preschoolers. METHODS: Four hundred and fifty-nine nuclear families of children with ASD, 418 with some other disability (OD) and 424 with typically developing (TD) children were recruited for this study. Employment and financial burdens of families were evaluated using a structured questionnaire; logistic regression was used to examine differences in job change measures by group, and ordinal logistic regression was used to investigate the association between household income and group. RESULTS: Fifty-eight percent of families with ASD children and 19% of families with OD children reported that childcare problems had greatly affected their employment decisions, compared with 9% of families with TD children (p < 0.001). Age of child, parental education and parental age notwithstanding, having a child with ASD and having a child with OD were both associated with increased odds of reporting that childcare greatly interfered with employment (ASD, OR: 15.936; OD, OR: 2.502; all p < 0.001) and decreased the odds of living in a higher-income household (ASD, estimate = -1.271; OD, estimate = -0.569; all p < 0.001). The average loss of annual income associated with having a child with ASD was Chinese RenMinBi (RMB) 44,077 ($7,226), compared with RMB 20,788 ($3,408) for families of OD children. CONCLUSIONS: ASD is associated with severe employment and financial burdens, much more than for OD, in families with preschool children.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/economia , Efeitos Psicossociais da Doença , Emprego/estatística & dados numéricos , Renda/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adulto , Cuidado da Criança/economia , Pré-Escolar , China , Feminino , Humanos , Masculino , Inquéritos e Questionários
15.
Psychopharmacology (Berl) ; 225(3): 627-35, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22926006

RESUMO

OBJECTIVE: The objective of the study was to compare metabolic effects of ziprasidone versus olanzapine treatment in patients with first-episode schizophrenia. METHODS: In this 6-week, multicenter, open-label trial, 260 patients were randomly assigned to receive ziprasidone or olanzapine treatment (130 per group). Primary metabolic measures were changes in weight and body mass index (BMI). Secondary metabolic measures were changes in glucose, insulin, lipids, and blood pressure. Efficacy and safety were also measured additionally. RESULTS: A total number of 230 patients completed the study. The mean daily dosages were 138.2(28.6) mg for ziprasidone and 19.0(2.3) mg for olanzapine. After 6-week treatment, there were significant between-group differences in change scores on weight [4.22(3.49) kg versus -0.84(2.04) kg, p < 0.001] and BMI [1.59(1.37) versus -0.30(0.74), p < 0.001]. In addition, there were significant between-group differences in change scores on fasting plasma glucose, insulin, homeostasis model assessment 2-insulin resistance, low-density lipoprotein, total cholesterol, and triglycerides (p < 0.001); all the changes were clinically in favor of ziprasidone treatment. Both medications were effective in improving schizophrenia symptoms, but the decreases in Positive and Negative Syndrome Scale total scores of the olanzapine group were significantly greater than that of the ziprasidone group (p < 0.05). Compared with olanzapine, ziprasidone also induced more prolonging of corrected QT interval and extrapyramidal side effects (p < 0.05). Both medications were well tolerated, and no serious adverse events were observed in either group. CONCLUSIONS: Compared with olanzapine, ziprasidone treatment was associated with less adverse effects on glucose and lipid metabolism in patients with first-episode schizophrenia.


Assuntos
Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Piperazinas/efeitos adversos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Tiazóis/efeitos adversos , Adolescente , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/uso terapêutico , Benzodiazepinas/administração & dosagem , Benzodiazepinas/uso terapêutico , Peso Corporal/efeitos dos fármacos , Feminino , Glucose/metabolismo , Humanos , Insulina/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Olanzapina , Piperazinas/administração & dosagem , Piperazinas/uso terapêutico , Tiazóis/administração & dosagem , Tiazóis/uso terapêutico , Adulto Jovem
16.
J Psychiatr Res ; 46(10): 1366-73, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22835912

RESUMO

BACKGROUND: Patients with treatment-resistant depression (TRD) and those with treatment-sensitive depression (TSD) responded to antidepressants differently. Previous studies have commonly shown that patients with TRD or TSD had abnormal neural activity in different brain regions. In the present study, we used a coherence-based ReHo (Cohe-ReHo) approach to test the hypothesis that patients with TRD or TSD had abnormal neural activity in different brain regions. METHODS: Twenty-three patients with TRD, 22 with TSD, and 19 healthy subjects (HS) matched with gender, age, and education level participated in the study. RESULTS: ANOVA analysis revealed widespread differences in Cohe-ReHo values among the three groups in different brain regions which included bilateral superior frontal gyrus, bilateral cerebellum, left inferior temporal gyrus, left occipital cortex, and both sides of fusiform gyrus. Compared to HS, lower Cohe-ReHo values were observed in TRD group in bilateral superior frontal gyrus and left cerebellum; in contrast, in TSD group, lower Cohe-ReHo values were mainly found in bilateral superior frontal gyrus. Compared to TSD group, TRD group had lower Cohe-ReHo in bilateral cerebellum and higher Cohe-ReHo in left fusiform gyrus. There was a negative correlation between Cohe-ReHo values of the left fusiform gyrus and illness duration in the pooled patients (r = 0.480, p = 0.001). The sensitivity and specificity of cerebellar Cohe-ReHo values differentiating TRD from TSD were 83% and 86%, respectively. CONCLUSIONS: Compared to healthy controls, both TRD and TSD patients shared the majority of brain regions with abnormal neural activity. However, the lower Cohe-ReHo values in the cerebellum might be as a marker to differentiate TRD from TSD with high sensitivity and specificity.


Assuntos
Antidepressivos/farmacologia , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/patologia , Descanso , Adulto , Análise de Variância , Antidepressivos/uso terapêutico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Oxigênio/sangue , Escalas de Graduação Psiquiátrica , Estatística como Assunto , Adulto Jovem
17.
Neurosci Lett ; 522(2): 139-44, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22721700

RESUMO

Abnormalities of the white matter (WM) tracts integrity in brain areas involved in emotional regulation have been postulated in major depressive disorder (MDD). However, there is no diffusion tensor imaging (DTI) study in patients with treatment-responsive MDD at present. DTI scans were performed on 22 patients with treatment-responsive MDD and 19 well-matched healthy subjects. Tract-based spatial statistics (TBSS) approach was employed to analyze the scans. Voxel-wise statistics revealed four brain WM tracts with lower fractional anisotropy (FA) in patients compared to healthy subjects: the bilateral internal capsule, the genu of corpus callosum, the bilateral anterior corona radiata, and the right external capsule. FA values were nowhere higher in patients compared to healthy subjects. Our findings demonstrate that the abnormalities of the WM tracts, major in the projection fibers and corpus callosum, may contribute to the pathogenesis of treatment-responsive MDD.


Assuntos
Antidepressivos/uso terapêutico , Encéfalo/patologia , Transtorno Depressivo Maior/patologia , Adulto , Anisotropia , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Estudos de Coortes , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Imagem de Tensor de Difusão , Emoções , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Adulto Jovem
18.
Am J Psychiatry ; 169(8): 813-21, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22711171

RESUMO

OBJECTIVE: Data on the treatment of antipsychotic-induced amenorrhea, particularly when occurring with weight gain, are limited. The authors investigated the efficacy and safety of metformin in the treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia. METHOD: Eighty-four women (ages 18-40 years) with first-episode schizophrenia who suffered from amenorrhea during antipsychotic treatment were randomly assigned, in a double-blind study design, to receive 1000 mg/day of metformin or placebo in addition to their antipsychotic treatment for 6 months. The primary outcome measures were restoration of menstruation and change in body weight and body mass index (BMI). Secondary outcome measures were changes in levels of prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and testosterone; in fasting levels of insulin and glucose; in LH/FSH ratio; and in insulin resistance index. Repeated mixed models with repeated-measures regression analyses and binary logistic regression were used in the analysis. RESULTS: A total of 76 patients completed the 6-month trial. Significantly more patients in the metformin group (N=28, 66.7%) than in placebo group (N=2, 4.8%) resumed their menstruation. Among patients treated with metformin, BMI decreased by a mean of 0.93 and the insulin resistance index by 2.04. In contrast, patients who received placebo had a mean increase in BMI of 0.85. The prolactin, LH, and testosterone levels and LH/FSH ratio decreased significantly in the metformin group at months 2, 4, and 6, but these levels did not change in the placebo group. CONCLUSIONS: Metformin was effective in reversing antipsychotic-induced adverse events, including restoration of menstruation, promotion of weight loss, and improvement in insulin resistance in female patients with schizophrenia.


Assuntos
Amenorreia/induzido quimicamente , Antipsicóticos/efeitos adversos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Ganho de Peso/efeitos dos fármacos , Adolescente , Adulto , Amenorreia/tratamento farmacológico , Antipsicóticos/uso terapêutico , Glicemia/análise , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Método Duplo-Cego , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Resistência à Insulina , Hormônio Luteinizante/sangue , Prolactina/sangue , Testosterona/sangue , Adulto Jovem
19.
Prog Neuropsychopharmacol Biol Psychiatry ; 38(2): 201-6, 2012 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-22504778

RESUMO

BACKGROUND: The association between alterations of the white matter (WM) integrity in brain regions and mood dysregulation has been reported in major depressive disorder (MDD). However, there has never been a neuroimaging study in patients who have treatment-resistant depression (TRD) and are in a current treatment-resistant state. In the present study, we used diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) method to investigate the WM integrity of different brain regions in patients who had TRD and were in a current treatment-resistant state. METHODS: Twenty-three patients with TRD and Hamilton Rating Scale total score of ≥18 and 19 healthy controls matched with age, gender, and education level to patients were scanned with DTI. Thirty 4 mm thick, no gap, contiguous axial slices were acquired and fractional anisotropy (FA) images were generated for each participant. An automated TBSS approach was used to analyze the data. RESULTS: Voxel-wise statistics revealed that patients with TRD had lower FA values in the right anterior limb of internal capsule, the body of corpus callosum, and bilateral external capsule compared to healthy subjects. Patients with TRD did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain region and patients' demographics and the severity of illness. CONCLUSIONS: Our findings suggest the abnormalities of the WM integrity of neuronal tracts connecting cortical and subcortical nuclei and two brain hemispheres may play a key role in the pathogenesis of TRD.


Assuntos
Corpo Caloso/patologia , Transtorno Depressivo Resistente a Tratamento/patologia , Fibras Nervosas Mielinizadas/patologia , Prosencéfalo/patologia , Adulto , Axônios/patologia , Mapeamento Encefálico , Transtorno Depressivo Maior/patologia , Imagem de Tensor de Difusão , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Índice de Gravidade de Doença
20.
Prog Neuropsychopharmacol Biol Psychiatry ; 37(1): 153-60, 2012 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-22306865

RESUMO

BACKGROUND: Patients with treatment-resistant depression (TRD) and those with treatment-response depression (TSD) respond to antidepressants differently and previous studies have commonly reported different brain networks in resistant and nonresistant patients. Using the amplitude of low-frequency fluctuations (ALFF) approach, we explored ALFF values of the brain regions in TRD and TSD patients at resting state to test the hypothesis of the different brain networks in TRD and TSD patients. METHODS: Eighteen TRD patients, 17 TSD patients and 17 gender-, age-, and education-matched healthy subjects participated in the resting-state fMRI scans. RESULTS: There are widespread differences in ALFF values among TRD patients, TSD patients and healthy subjects throughout the cerebellum, the visual recognition circuit (middle temporal gyrus, middle/inferior occipital gyrus and fusiform), the hate circuit (putamen), the default circuit (ACC and medial frontal gyrus) and the risk/action circuit (inferior frontal gyrus). The differences in brain circuits between the TRD and TSD patients are mainly in the cerebellum, the visual recognition circuit and the default circuit. CONCLUSIONS: The affected brain circuits of TRD patients might be partly different from those of TSD patients.


Assuntos
Cerebelo/fisiologia , Depressão/fisiopatologia , Depressão/terapia , Imagem por Ressonância Magnética/métodos , Rede Nervosa/fisiologia , Descanso/fisiologia , Adulto , Depressão/psicologia , Feminino , Humanos , Masculino , Resultado do Tratamento , Adulto Jovem
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