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1.
Chin Med J (Engl) ; 132(14): 1689-1699, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31268909

RESUMO

BACKGROUND: Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods. In this study, we examined the effects of adolescent chronic social stress in aged mice on depressive behaviors and the excitatory-inhibitory (E/I) balance in stress-sensitive regions of the brain. METHODS: Sixty-four adolescent, male C57BL/6 mice were randomly assigned to either the 7-week (from post-natal days 29 to 77) social instability stress (stress group, n = 32) or normal housing conditions (control group, n = 32). At 15 months of age, 16 mice were randomly selected from each group for a series of behavioral tests, including two depression-related tasks (the sucrose preference test and the tail suspension test). Three days following the last behavioral test, eight mice were randomly selected from each group for immunohistochemical analyses to measure the cell density of parvalbumin (PV)- and calretinin (CR)-positive gamma-aminobutyric-acid (GABA)ergic inhibitory inter-neurons, and the expression levels of vesicular transporters of glutamate-1 (VGluT1) and vesicular GABA transporter (VGAT) in three stress-sensitive regions of the brain (the medial pre-frontal cortex [mPFC], hippocampus, and amygdala). RESULTS: Behaviorally, compared with the control group, adolescent chronic stress increased depression-like behaviors as shown in decreased sucrose preference (54.96 ±â€Š1.97% vs. 43.11 ±â€Š2.85%, t(22) = 3.417, P = 0.003) and reduced latency to immobility in the tail suspension test (92.77 ±â€Š25.08 s vs. 33.14 ±â€Š5.95 s, t(25) = 2.394, P = 0.025), but did not affect anxiety-like behaviors and pre-pulse inhibition. At the neurobiologic level, adolescent stress down-regulated PV, not CR, inter-neuron density in the mPFC (F(1, 39) = 19.30, P < 0.001), and hippocampus (F(1, 42) = 5.823, P = 0.020) and altered the CR, not PV, inter-neuron density in the amygdala (F(1, 28) = 23.16, P < 0.001). The VGluT1/VGAT ratio was decreased in all three regions (all F > 10.09, all P < 0.004), which suggests stress-induced hypoexcitability in these regions. CONCLUSIONS: Chronic stress during adolescence increased depression-like behaviors in aged mice, which may be associated with the E/I imbalance in stress-sensitive brain regions.

2.
Hippocampus ; 29(11): 1063-1074, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31066147

RESUMO

The early postnatal stage is a critical period of hippocampal neurodevelopment and also a period of high vulnerability to adverse life experiences. Recent evidence suggests that nectin-3, a cell adhesion molecule, mediates memory dysfunction and dendritic alterations in the adult hippocampus induced by postnatal stress. But it is unknown whether postnatal nectin-3 reduction alone is sufficient to alter hippocampal structure and function in adulthood. Here, we down regulated hippocampal expression of nectin-3 and its heterophilic adhesion partner nectin-1, respectively, from early postnatal stage by injecting adeno-associated virus (AAV) into the cerebral lateral ventricles of neonatal mice (postnatal day 2). We found that suppression of nectin-3, but not nectin-1, expression from the early postnatal stage impaired hippocampus-dependent novel object recognition and spatial object recognition in adult mice. Moreover, AAV-mediated nectin-3 knockdown significantly reduced dendritic complexity and spine density of pyramidal neurons throughout the hippocampus, whereas nectin-1 knockdown only induced the loss of stubby spines in CA3. Our data provide direct evidence that nectins, especially nectin-3, are necessary for postnatal hippocampal development of memory functions and structural integrity.

3.
Chin Med J (Engl) ; 132(13): 1582-1590, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31045908

RESUMO

BACKGROUND: Exposure to adverse experiences in early life may profoundly reshape the neurodevelopmental trajectories of the brain and lead to long-lasting behavioral and neural alterations. One deleterious effect of early-life stress that manifests in later life is sleep disturbance, but this has not been examined in aged mice and the underlying neural mechanisms remain unknown. Considering the important role of the nucleus accumbens (NAc) in the sleep-wake regulation, this study aimed to assess the effects of early-life stress on the sleep behaviors in aged mice and the potential involvement of the NAc in stress-induced sleep abnormalities. METHODS: Twenty aged male C57BL/6 mice (>16 months, n = 10 per group) were used in this study. During post-natal days 2 to 9, dams were provided with either sufficient (control) or a limited nesting and bedding materials (stressed). When the mice were 16 to 17 months old, their sleep-wake behaviors were recorded over 24 h using electroencephalogram and electromyelogram. The amount of each sleep-wake stage, mean duration, and stage transition was analyzed. Then, five animals were randomly chosen from each group and were used to measure the expression levels of vesicular glutamate transporter-1 (VGluT1) and vesicular transporters of γ-aminobutyric acid (VGAT) in the NAc using immunohistochemistry. Group comparisons were carried out using Student t test or analysis of variances when appropriate. RESULTS: Compared with the control mice, the early-life stressed aged mice spent less time awake over 24 h (697.97 ±â€Š77.47 min vs. 631.33 ±â€Š34.73 min, t17 = 2.376, P = 0.030), accordingly, non-rapid eye movement sleep time was increased (667.37 ±â€Š62.07 min vs. 723.54 ±â€Š39.21 min, t17 = 2.326, P = 0.033) and mean duration of rapid eye movement sleep was prolonged (73.00 ±â€Š8.98 min vs. 89.39 ±â€Š12.69 min, t17 = 3.277, P = 0.004). Meanwhile, we observed decreased VGluT1/VGAT ratios in the NAc in the stressed group (F(1, 16) = 81.04, P < 0.001). CONCLUSION: Early adverse experiences disrupt sleep behaviors in aged mice, which might be associated with the excitatory-inhibitory imbalance in the NAc.

4.
Artigo em Inglês | MEDLINE | ID: mdl-30392783

RESUMO

Adolescence is a critical period with ongoing maturational processes in stress-sensitive systems. It remains unknown how adolescent individuals would be affected by chronic exposure to corticosterone (the major stress hormone in rodents, CORT) at the doses that are usually not detrimental in adults. In this study, male Sprague-Dawley rats were injected with CORT (5 mg/kg) or vehicle for 21 days during adolescence (postnatal day (PND) 29-49) or adulthood (PND 71-91) and then subjected to behavioral testing or sacrifice for neurobiological analyses. Shortly after treatment cessation, different from CORT-treated adults showing increased anxiety-like behaviors, CORT-treated adolescents exhibited enhanced prepulse inhibition and spatial learning. They also showed increased expression of hippocampal neuroplasticity-related proteins, including BDNF, nectin3, and AMPA receptor subunits. These effects became undetectable after a four-week washout period when CORT-treated adolescents exhibited improved reversal learning. Together, these findings demonstrate that chronic CORT exposure at the dose of 5 mg/kg endows adolescent individuals with enhanced cognitive capacities, possibly supported by increased hippocampal neuroplasticity. This study also highlights mild elevation of CORT levels during adolescence as a potential approach of promoting adaptive behaviors.


Assuntos
Cognição/fisiologia , Corticosterona/metabolismo , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Plasticidade Neuronal/fisiologia , Animais , Ansiedade/metabolismo , Corticosterona/administração & dosagem , Masculino , Inibição Pré-Pulso/fisiologia , Distribuição Aleatória , Ratos Sprague-Dawley , Reversão de Aprendizagem/fisiologia , Maturidade Sexual , Aprendizagem Espacial/fisiologia , Regulação para Cima
5.
J Affect Disord ; 246: 285-289, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30594041

RESUMO

BACKGROUND: Little is known about the demographic and clinical features of the atypical subtype of major depressive disorder (MDD) patients in China. This study set out to investigate the prevalence of atypical depression in MDD patients in China, and identify its demographic and clinical features. METHODS: The study was conducted in 13 major psychiatric hospitals or in the psychiatric units of general hospitals in China, and recruited a sample of 1172 patients diagnosed with MDD. The patients' demographic and clinical features and prescriptions of psychotropic drugs were collected using a standardized questionnaire designed for the study. RESULTS: The prevalence of atypical depression was 15.3%. In multiple logistic regression analyses, compared to the non-atypical depression patients, the atypical depression patients were more likely to have depressive episodes with suicide ideation and attempts (OR = 1.49, 95% CI = 1.06, 2.10, P = 0.023), depressive episodes with psychotic features (OR = 2.15, 95% CI = 1.43, 3.22, P < 0.001), seasonal depressive episodes (OR = 1.77, 95% CI = 1.12, 2.78, P = 0.014), an earlier age of onset (OR = 0.98, 95% CI = 0.96, 0.99, P = 0.001), and lifetime depressive episodes (OR = 1.07, 95% CI = 1.01, 1.13, P = 0.020). LIMITATIONS: The assessment of atypical features was not based on a validated rating scale. CONCLUSION: Our results indicate that atypical depression is common in Chinese patients with MDD. MDD with atypical features may be more severe and debilitating than patients with non-atypical features.


Assuntos
Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Adulto , Idade de Início , China/epidemiologia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Feminino , Hospitais Psiquiátricos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Psicotrópicos/uso terapêutico , Ideação Suicida , Inquéritos e Questionários
6.
Artigo em Inglês | MEDLINE | ID: mdl-30426252

RESUMO

Genome-wide association study results have linked ADCK1 genetic variation with paliperidone efficacy in a European cohort. However, the generalizability of this locus to non-European populations is unknown. Han Chinese schizophrenia patients (n = 159) were treated with paliperidone palmitate and symptom severity was assessed over 3 months. Examination of 13 ADCK1 genetic variants revealed two single nucleotide polymorphisms (rs12590199, rs11159291) and one haplotype (rs2364747-rs12590199) associated with paliperidone palmitate response. Future work into ADCK1's function and its potential interaction with paliperidone is warranted.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30169628

RESUMO

Background: With the growing use of second-generation antipsychotics for the treatment of a spectrum of psychiatric illnesses in pregnancy, concerns have been raised about the long-term impact of these medications on offspring neurodevelopment. However, preclinical and clinical evidence on the lasting effects of prenatal antipsychotic exposure is still sparse. Methods: Risperidone, a widely used second-generation antipsychotic, and haloperidol, a representative first-generation antipsychotic, were administered to pregnant C57BL/6N mice from embryonic day 6 to 16. Behavioral tests, immunohistochemical staining, Golgi-Cox technique, and western blot were used to determine the effects of prenatal antipsychotic exposure on the plasticity of the dentate gyrus and related behavior in adult male mice. Results: Both prenatal haloperidol- and risperidone-exposed mice showed recognition memory deficits but had no anxiety-related behavior. In addition, both prenatal haloperidol and risperidone exposure impaired the proliferation and maturation of adult-born dentate granule cells. We found that haloperidol exposure decreased dendritic length of dentate granule cells, while risperidone had no effect. However, both drugs inhibited dendrite branching in granule cells. Haloperidol exposure also significantly reduced total spine density in the middle dendritic segment of dentate gyrus. Prenatally risperidone-exposed mice only displayed a loss in thin and mushroom spines of infrapyramidal blade of dentate gyrus. Collectively, prenatal haloperidol exposure exerted more robust negative effects than risperidone. Conclusion: These data provide evidence for the long-term programming effects of early-life exposure to antipsychotics on hippocampal plasticity and behavior.

8.
Front Psychiatry ; 9: 300, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30018575

RESUMO

Objective: To analyze the factors associated with recent suicide attempts including socio-demographic and clinical characteristics in major depressive disorder (MDD) patients in China. Methods: The data were from a nationwide sample from 13 major psychiatric hospitals or the psychiatric units of general hospitals in China, from September 1, 2010 to February 28, 2011. Melancholic features and suicide attempts in the past month were defined according to the melancholic feature module and the suicide module of the Mini International Neuropsychiatric Interview (MINI). Socio-demographic and clinical characteristics were compared between MDD patients with and without recent suicide attempts. Further analyses regarding the factors associated with recent suicide attempts in MDD patients were performed via multivariate logistic regression analysis. Results: Among 1,172 MDD patients, 57 (4.9%) were reported to have made a suicide attempt in the past month. Compared to the MDD patients without recent suicide attempt, significantly higher percentage of patients in the recent suicide attempters group had previous suicide attempts (χ2 = 171.861, p < 0.001) and depressive episodes with melancholic features (χ2 = 22.837, p < 0.001). Logistic regression analysis indicated that previous suicide attempts (OR = 20.81, 95% CI: 11.12-38.94, p < 0.001) and depressive episodes with melancholic features (OR = 4.43, 95% CI: 2.09-9.43, p < 0.001) were independently associated with recent suicide attempts in MDD patients. Limitations: Cross-sectional design, retrospective recall of suicide attempt data. Conclusion: Recent suicide attempts are associated with melancholic features and previous suicide attempts in MDD patients in China. These data may help clinicians to identify MDD patients at high risk of suicide attempt behavior.

9.
Chin Med J (Engl) ; 131(8): 912-919, 2018 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-29664050

RESUMO

Background: Patients with major depressive disorder (MDD) usually have high risk of suicidality. Few studies have investigated the effects of stressful life events (SLEs) on the risk of suicide in Chinese patients who have developed MDD. This study aimed to investigate the impact of SLEs on suicidal risk in Chinese patients with MDD. Methods: In total, 1029 patients with MDD were included from nine psychiatric hospitals to evaluate the impact of SLEs on suicidal risk. Patients fulfilling the Mini-International Neuropsychiatric Interview (MINI) criteria for MDD were included in the study. Patients were excluded if they had lifetime or current diagnoses of psychotic disorder, bipolar disorder, and alcohol or substance dependence. Depressive symptoms were assessed by the 17-item Hamilton Depression Scale (HAMD-17). The suicidal risk of MDD patients was determined by the suicide risk module of MINI. SLEs were assessed by the Life Events Scale. Results: No gender difference was found for suicidal risk in MDD patients. Patients with suicidal risk had younger ages, lower education levels, more drinking behavior, and lower marriage rate, and fewer people had child and more severe depressive symptoms than nonsuicidal risk group. High-level perceived stressfulness (HPS) and number of SLEs that patients were exposed to were significantly greater in patients with suicidal risk than patients without. In multivariate logistic analysis, HPS of SLEs (odds ratio [OR] = 1.54, 95% confidence interval [CI]: 1.16-2.05, P = 0.003) and depressive symptoms (OR = 1.08, 95% CI: 1.05-1.11, P < 0.001) were associated with suicidal risk even after adjustment of gender, age, marriage, drinking behavior, and childless. Conclusions: HPS of SLEs is associated with suicide risk in Chinese patients with MDD. Further suicide prevention programs targeting this risk factor are needed. Trial Registration: ClinicalTrials.gov: NCT02023567; https://clinicaltrials.gov/ct2/show/NCT02023567?term=NCT02023567&rank=1.


Assuntos
Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Suicídio/psicologia , Suicídio/estatística & dados numéricos , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/psicologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Escalas de Graduação Psiquiátrica , Fatores de Risco , Adulto Jovem
10.
CNS Neurosci Ther ; 24(11): 1063-1072, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29493113

RESUMO

OBJECTIVE: Growing evidence has implicated dysfunction of the thalamus and its projection cortical targets in depression. However, the anatomical specificity of thalamo-cortical connectivity in major depressive disorder (MDD) remains unknown due to the regional heterogeneity of the thalamus and limited methods to examine this. METHODS: Resting-state fMRI was collected on 70 MDD patients and 70 healthy controls. The thalamus was parcellated based on connectivity with six predefined cortical regions of interest (ROIs). The segmented thalamic nuclei were used as seeds to map connectivity with the rest of the whole brain. The cortical-to-thalamus connectivity values and thalamus-based connectivity maps were compared between groups. RESULTS: The cortical ROIs demonstrated correlations with spatially distinct zones within the thalamus. We found a trend toward reduced parietal ROI-to-thalamus connectivity in MDD. Importantly, MDD patients demonstrated reduced connectivity between prefrontal and parietal thalamus ROIs and bilateral middle frontal gyrus (MFG) and the right posterior default mode network (DMN) and between the prefrontal and motor thalamus ROIs and lateral temporal regions. Conversely, increased connectivity emerged between the motor thalamus ROI and right MFG and right medial frontal gyrus/anterior cingulate; between motor/somatosensory thalamus ROIs and right posterior DMN; between prefrontal/somatosensory thalamus ROIs and cerebellum; and between the parietal thalamus ROI and left insula. CONCLUSIONS: This study is the first to examine the anatomical specificity of thalamo-cortical connectivity disturbances in MDD. Subjects with MDD demonstrated altered thalamo-cortical connectivity characterized by a complex pattern of region-dependent hypo- or hyperconnectivity. We therefore speculate that selectively modulating the connectivity of thalamo-cortical circuitry may be a potential novel therapeutic mechanism for MDD.

11.
Front Cell Neurosci ; 12: 67, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29593501

RESUMO

In adulthood, chronic exposure to stressful experiences disrupts synaptic plasticity and cognitive function. Previous studies have shown that perirhinal cortex-dependent object recognition memory is impaired by chronic stress. However, the stress effects on molecular expression and structural plasticity in the perirhinal cortex remain unclear. In this study, we applied the chronic social defeat stress (CSDS) paradigm and measured the mRNA levels of nectin-1, nectin-3 and neurexin-1, three synaptic cell adhesion molecules (CAMs) implicated in the adverse stress effects, in the perirhinal cortex of wild-type (WT) and conditional forebrain corticotropin-releasing hormone receptor 1 conditional knockout (CRHR1-CKO) mice. Chronic stress reduced perirhinal nectin-1 mRNA levels in WT but not CRHR1-CKO mice. In conditional forebrain corticotropin-releasing hormone conditional overexpression (CRH-COE) mice, perirhinal nectin-1 mRNA levels were also reduced, indicating that chronic stress modulates nectin-1 expression through the CRH-CRHR1 system. Moreover, chronic stress altered dendritic spine morphology in the main apical dendrites and reduced spine density in the oblique apical dendrites of perirhinal layer V pyramidal neurons. Our data suggest that chronic stress disrupts cell adhesion and dendritic spine plasticity in perirhinal neurons, which may contribute to stress-induced impairments of perirhinal cortex-dependent memory.

12.
Cell Rep ; 21(4): 891-900, 2017 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-29069596

RESUMO

Calbindin modulates intracellular Ca2+ dynamics and synaptic plasticity. Reduction of hippocampal calbindin levels has been implicated in early-life stress-related cognitive disorders, but it remains unclear how calbindin in distinct populations of hippocampal neurons contributes to stress-induced memory loss. Here we report that early-life stress suppressed calbindin levels in CA1 and dentate gyrus (DG) neurons, and calbindin knockdown in adult CA1 or DG excitatory neurons mimicked early-life stress-induced memory loss. In contrast, calbindin knockdown in CA1 interneurons preserved long-term memory even after an acute stress challenge. These results indicate that the dysregulation of calbindin in hippocampal excitatory, but not inhibitory, neurons conveys susceptibility to stress-induced memory deficits. Moreover, calbindin levels were downregulated by early-life stress through the corticotropin-releasing hormone receptor 1-nectin3 pathway, which in turn reduced inositol monophosphatase levels. Our findings highlight calbindin as a molecular target of early-life stress and an essential substrate for memory.


Assuntos
Região CA1 Hipocampal/metabolismo , Calbindinas/metabolismo , Interneurônios/metabolismo , Transtornos da Memória/metabolismo , Estresse Psicológico/metabolismo , Animais , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/fisiologia , Calbindinas/genética , Giro Denteado/citologia , Giro Denteado/metabolismo , Giro Denteado/fisiologia , Interneurônios/fisiologia , Masculino , Transtornos da Memória/etiologia , Memória de Longo Prazo , Camundongos , Camundongos Endogâmicos C57BL , Nectinas/metabolismo , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Memória Espacial , Estresse Psicológico/complicações
13.
J Psychiatry Neurosci ; 42(6): 414-423, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28949286

RESUMO

BACKGROUND: Bulimia nervosa is a severe psychiatric syndrome with uncertain pathogenesis. Neural systems involved in sensorimotor and visual processing, reward and impulsive control may contribute to the binge eating and purging behaviours characterizing bulimia nervosa. However, little is known about the alterations of functional organization of whole brain networks in individuals with this disorder. METHODS: We used resting-state functional MRI and graph theory to characterize functional brain networks of unmedicated women with bulimia nervosa and healthy women. RESULTS: We included 44 unmedicated women with bulimia nervosa and 44 healthy women in our analyses. Women with bulimia nervosa showed increased clustering coefficient and path length compared with control women. The nodal strength in patients with the disorder was higher in the sensorimotor and visual regions as well as the precuneus, but lower in several subcortical regions, such as the hippocampus, parahippocampal gyrus and orbitofrontal cortex. Patients also showed hyperconnectivity primarily involving sensorimotor and unimodal visual association regions, but hypoconnectivity involving subcortical (striatum, thalamus), limbic (amygdala, hippocampus) and paralimbic (orbitofrontal cortex, parahippocampal gyrus) regions. The topological aberrations correlated significantly with scores of bulimia and drive for thinness and with body mass index. LIMITATIONS: We reruited patients with only acute bulimia nervosa, so it is unclear whether the topological abnormalities comprise vulnerability markers for the disorder developing or the changes associated with illness state. CONCLUSION: Our findings show altered intrinsic functional brain architecture, specifically abnormal global and local efficiency, as well as nodal- and network-level connectivity across sensorimotor, visual, subcortical and limbic systems in women with bulimia nervosa, suggesting that it is a disorder of dysfunctional integration among large-scale distributed brain regions. These abnormalities contribute to more comprehensive understanding of the neural mechanism underlying pathological eating and body perception in women with bulimia nervosa.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Bulimia Nervosa/diagnóstico por imagem , Bulimia Nervosa/fisiopatologia , Conectoma , Feminino , Humanos , Imagem por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes , Descanso , Adulto Jovem
14.
Psychiatry Res ; 257: 132-136, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28755603

RESUMO

Our previous study demonstrated that there have been changes in the patterns of prescription antipsychotic use in China over the period from 2002 to 2012. The aim of this study was to evaluate whether time trends were present for the prescription of anticholinergic medications (ACMs) during the observation period. A total of 14,013 patients with schizophrenia treated in 45 psychiatric hospitals/centers nationwide were surveyed in 2002, 2006 and 2012. Basic socio-demographic and clinical characteristics and the prescription of psychotropic drugs were recorded using a standardized protocol and data collection procedure. The frequency of ACM prescription was 25.9% in the whole sample (29.5%, 21.6%, and 27.4% in 2002, 2006 and 2012, respectively). In addition, different temporal trends were observed across age groups. Multiple logistic regression analysis of the entire sample showed that ACM prescriptions were predicted by females, outpatients, patients receiving high doses of antipsychotic medication, select study years, benzodiazepine users, patients displaying extrapyramidal side effects, as well as antipsychotic prescription patterns. Although there was more widespread use of second-generation antipsychotics over the past decade, the frequency of ACM use only slightly decreased. How to use ACM appropriately is still a therapeutic issue that needs to foster evidence-based prescription practice.


Assuntos
Antagonistas Colinérgicos/uso terapêutico , Uso de Medicamentos/tendências , Psicotrópicos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Doenças dos Gânglios da Base/induzido quimicamente , Doenças dos Gânglios da Base/epidemiologia , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , China/epidemiologia , Antagonistas Colinérgicos/efeitos adversos , Estudos Transversais , Prescrições de Medicamentos , Feminino , Hospitais Psiquiátricos/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Psicotrópicos/efeitos adversos
15.
Front Mol Neurosci ; 10: 25, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28210212

RESUMO

Adolescence is a critical period with ongoing maturational processes in stress-sensitive systems. While adolescent individuals show heightened stress-induced hormonal responses compared to adults, it is unclear whether and how the behavioral and neurobiological consequences of chronic stress would differ between the two age groups. Here we address this issue by examining the effects of chronic exposure to the stress hormone, corticosterone (CORT), in both adolescent and adult animals. Male Sprague-Dawley (SD) rats were injected intraperitoneally with CORT (40 mg/kg) or vehicle for 21 days during adolescence (post-natal day (PND) 29-49) or adulthood (PND 71-91) and then subjected to behavioral testing or sacrifice for western blot analyses. Despite of similar physical and neuroendocrine effects in both age groups, chronic CORT treatment produced a series of behavioral and neurobiological effects with striking age differences. While CORT-treated adult animals exhibited decreased sucrose preference, increased anxiety levels and cognitive impairment, CORT-treated adolescent animals demonstrated increased sucrose preference, decreased anxiety levels, and increased sensorimotor gating functions. These differential behavioral alterations were accompanied by opposite changes in the two age groups in the expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylation of the obligatory subunit of the NMDA receptor, GluN1, and PSD-95 in rat hippocampus. These results suggest that prolonged glucocorticoid exposure during adolescence produces different behavioral and neurobiological effects from those in adulthood, which may be due to the complex interaction between glucocorticoids and the ongoing neurodevelopmental processes during this period.

16.
Hum Psychopharmacol ; 32(1)2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28120487

RESUMO

OBJECTIVE: This study examined the pattern of adjunctive antidepressant use in schizophrenia patients and its demographic and clinical correlates in a nationwide survey in China. METHODS: Fourteen thousand and thirteen patients in 45 Chinese psychiatric hospitals or centers were interviewed (4,486 in 2002, 5,288 in 2006, and 4,239 in 2012). Patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Chi-square test, independent-samples t test, Mann-Whitney U test, and multiple logistic regression analysis were used in data analyses. RESULTS: Antidepressant use was found in 5.2% of the study population with 4.6% in 2002, 4.3% in 2006, and 6.9% in 2012, respectively. A significant increase in use from 2006 to 2012 was found (p < .001). Multiple logistic regression analyses in the whole population revealed that patients receiving adjunctive antidepressants were more likely to be outpatients in tertiary referral centers (level-III hospitals) and who had an earlier age of onset, less severe global illness, but more depressive symptoms. They were less likely to receive first-generation antipsychotics but more likely to receive benzodiazepines (R2  = 0.255, p < .001). CONCLUSIONS: Despite an increasing trend, the frequency of antidepressant use in schizophrenia in China was considerably lower than in Western countries. The benefits and risks associated with concomitant use of antidepressants in schizophrenia need to be studied further.


Assuntos
Antidepressivos/administração & dosagem , Antipsicóticos/administração & dosagem , Benzodiazepinas/administração & dosagem , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Inquéritos e Questionários , Adulto , China/epidemiologia , Estudos Transversais , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
J ECT ; 33(2): 138-142, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27753759

RESUMO

OBJECTIVE: Little is known about electroconvulsive therapy (ECT) use in the treatment of schizophrenia in China. This study examined the frequency of ECT use, its trend between 2006 and 2012, and its independent demographic and clinical correlates in a nationwide survey in China. METHODS: A total of 5162 inpatients in 45 Chinese psychiatric hospitals/centers were interviewed (2696 in 2006 and 2466 in 2012). Patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. RESULTS: Electroconvulsive therapy was used in 6.1% of the whole sample; 4.7% in 2006 and 7.7% in 2012 (P < 0.001) with wide interprovince variations. Multiple logistic regression analyses of the whole sample revealed that patients receiving ECT were more likely to be women, receive second-generation antipsychotics, treated in tertiary referral centers (level III hospitals), had a shorter illness duration, and more positive and depressive symptoms (R = 0.181; P < 0.001). CONCLUSIONS: Electroconvulsive therapy for schizophrenia has increased between 2006 and 2012 in China. Its percentage was higher than the figures reported in most other countries. Reasons for the substantial variations in the frequency of ECT across different provinces in China require further investigations.


Assuntos
Eletroconvulsoterapia/estatística & dados numéricos , Esquizofrenia/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos/uso terapêutico , Grupo com Ancestrais do Continente Asiático , China , Terapia Combinada , Estudos Transversais , Depressão/etiologia , Depressão/psicologia , Depressão/terapia , Feminino , Pesquisas sobre Serviços de Saúde , Hospitais Psiquiátricos/estatística & dados numéricos , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Psicologia do Esquizofrênico , Fatores Sexuais , Fatores Socioeconômicos , Adulto Jovem
18.
Front Behav Neurosci ; 11: 260, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29375333

RESUMO

Cognitive dysfunction constitutes an essential component in schizophrenia for its early presence in the pathophysiology of the disease and close relatedness to life quality of patients. To develop effective treatment of cognitive deficits, it is important to understand their neurobiological causes and to identify potential therapeutic targets. In this study, adopting repeated MK-801 treatment as an animal model of schizophrenia, we investigated whether antipsychotic drugs, olanzapine and haloperidol, can reverse MK-801-induced cognitive deficits and how the reversal processes recruited proteins involved in glutamate neurotransmission in rat medial prefrontal cortex (mPFC) and hippocampus. We found that low-dose chronic MK-801 treatment impaired object-in-context recognition memory and reversal learning in the Morris water maze, leaving reference memory relatively unaffected, and that these cognitive deficits can be partially reversed by olanzapine, not haloperidol, treatment. At the molecular level, chronic MK-801 treatment resulted in the reduction of multiple N-methyl-D-aspartate (NMDA) receptor subunits in rat mPFC and olanzapine, not haloperidol, treatment restored the levels of GluN1 and phosphorylated GluN2B in this region. Taken together, MK-801-induced cognitive deficits may be associated with region-specific changes in NMDA receptor subunits and the reversal of specific NMDA receptor subunits may underlie the cognition-enhancing effects of olanzapine.

19.
Psychiatry Res ; 246: 303-307, 2016 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-27744232

RESUMO

This study was designed to examine the validity and reliability of the Chinese version of the Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ-SALSEX) in patients with schizophrenia taking antipsychotics. It was conducted in a sample of 135 patients aged between 18 and 50 years old and diagnosed with schizophrenia. Demographic data and clinical features were assessed with PRSexDQ, the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI), and the Udvalg for Kliniske Undersøgelser (UKU) Side Effects Rating Scale. The internal consistency of the Chinese version of PRSexDQ using Cronbach's α was 0.902. The test-retest and inter rater reliability was both high with p<0.001. PRSexDQ was correlated with corresponding items in the UKU Side Effects Rating Scale (Items 4.12-4.16), and showed good sensitivity, specificity, positive and negative predictive value. It could also clearly detect differences in SD rates of three monotherapy groups: patients treated with risperidone had the highest scores, followed by patients treated with olanzapine, whereas patients treated with aripiprazole had the lowest scores. The Chinese version of PRSexDQ is a reliable and valid instrument to assess patients with schizophrenia. Assessed by PRSexDQ, 53.2% of total subjects in our study reported symptoms of SD.


Assuntos
Antipsicóticos/efeitos adversos , Esquizofrenia/tratamento farmacológico , Disfunções Sexuais Fisiológicas/induzido quimicamente , Disfunções Sexuais Fisiológicas/diagnóstico , Inquéritos e Questionários/normas , Adolescente , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
20.
Front Mol Neurosci ; 9: 17, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26973457

RESUMO

Adolescence is of particular significance to schizophrenia, since psychosis onset typically occurs in this critical period. Based on the N-methyl-D-aspartate (NMDA) receptor hypofunction hypothesis of schizophrenia, in this study, we investigated whether and how repeated NMDA receptor blockade during adolescence would affect GABAergic interneurons in rat medial prefrontal cortex (mPFC) and mPFC-mediated cognitive functions. Specifically, adolescent rats were subjected to intraperitoneal administration of MK-801 (0.1, 0.2, 0.4 mg/kg), a non-competitive NMDA receptor antagonist, for 14 days and then tested for reference memory and reversal learning in the water maze. The density of parvabumin (PV)-, calbindin (CB)- and calretinin (CR)-positive neurons in mPFC was analyzed at either 24 h or 7 days after drug cessation. We found that MK-801 treatment delayed reversal learning in the water maze without affecting initial acquisition. Strikingly, MK-801 treatment also significantly reduced the density of PV(+) and CB(+) neurons, and this effect persisted for 7 days after drug cessation at the dose of 0.2 mg/kg. We further demonstrated that the reduction in PV(+) and CB(+) neuron densities was ascribed to a downregulation of the expression levels of PV and CB, but not to neuronal death. These results parallel the behavioral and neuropathological changes of schizophrenia and provide evidence that adolescent NMDA receptors antagonism offers a useful tool for unraveling the etiology of the disease.

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