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BACKGROUND: Individuals diagnosed with schizophrenia present diverse degrees and types of cognitive impairment, leading to variations in responses to antipsychotic treatments. Understanding the underlying cognitive structures is crucial for assessing this heterogeneity. Utilizing latent profile analysis (LPA) enables the delineation of latent categories of cognitive function. Integrating this approach with a dimensional perspective allows for the exploration of the relationship between cognitive function and treatment response. METHODS: This study examined 647 patients from two distinct cohorts. Utilizing LPA within the discovery cohort (n = 333) and the replication cohort (n = 314), latent subtypes were identified categorically. The stability of cognitive structures was evaluated employing Latent Transition Analysis (LTA). The relationship between cognitive function and treatment response were investigated by comparing Positive and Negative Syndrome Scale (PANSS) reduction rates across diverse cognitive subtypes. Furthermore, dimensional insights were gained through correlation analyses between cognitive tests and PANSS reduction rates. RESULTS: In terms of categorical, individuals diagnosed with schizophrenia can be categorized into three distinct subtypes: those 'without cognitive deficit', those 'with mild-moderate cognitive 'eficit', and those 'with moderate-severe cognitive deficit'. There are significant differences in PANSS reduction rates among patients belonging to these subtypes following antipsychotic treatment (p < 0.05). Furthermore, from a dimensional perspective, processing speed at baseline is positively correlated with PANSS score reduction rates at week 8/week 10 (p < 0.01). CONCLUSIONS: Our findings have unveiled the latent subtypes of cognitive function in schizophrenia, illuminating the association between cognitive function and responses to antipsychotic treatment from both categorical and dimensional perspectives.
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BACKGROUND: It remains a challenge to predict the long-term response to antipsychotics in patients with schizophrenia who do not respond at an early stage. This study aimed to investigate the optimal predictive cut-off value for early non-response that would better predict later non-response to antipsychotics in patients with schizophrenia. METHODS: This multicenter, 8-week, open-label, randomized trial was conducted at 19 psychiatric centers throughout China. All enrolled participants were assigned to olanzapine, risperidone, amisulpride, or aripiprazole monotherapy for 8 weeks. The positive and negative syndrome scale (PANSS) was evaluated at baseline, week 2, week 4, and week 8. The main outcome was the prediction of nonresponse. Nonresponse is defined as a < 20% reduction in the total scores of PANSS from baseline to endpoint. Severity ratings of mild, moderate, and severe illness corresponded to baseline PANSS total scores of 58, 75, and 95, respectively. RESULTS: At week 2, a reduction of < 5% in the PANSS total score showed the highest total accuracy in the severe and mild schizophrenia patients (total accuracy, 75.0% and 80.8%, respectively), and patients who were treated with the risperidone and amisulpride groups (total accuracy, 82.4%, and 78.2%, respectively). A 10% decrease exhibited the best overall accuracy in the moderate schizophrenia patients (total accuracy, 84.0%), olanzapine (total accuracy, 79.2%), and aripiprazole group (total accuracy, 77.4%). At week 4, the best predictive cut-off value was < 20%, regardless of the antipsychotic or severity of illness (total accuracy ranging from 89.8 to 92.1%). CONCLUSIONS: Symptom reduction at week 2 has acceptable discrimination in predicting later non-response to antipsychotics in schizophrenia, and a more accurate predictive cut-off value should be determined according to the medication regimen and baseline illness severity. The response to treatment during the next 2 weeks after week 2 could be further assessed to determine whether there is a need to change antipsychotic medication during the first four weeks. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov (NCT03451734).
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Antipsicóticos , Esquizofrenia , Humanos , Antipsicóticos/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Olanzapina/uso terapéutico , Risperidona/uso terapéutico , Aripiprazol/uso terapéutico , Amisulprida/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Impaired functional connectivity between the bilateral hemispheres may serve as the neural substrate for anxiety and depressive disorders, yet its role in comorbid generalized anxiety disorder (GAD) and depression, as well as the effect of treatment on this connectivity, remains unclear. We sought to examine functional connectivity between homotopic regions of the 2 hemispheres (voxel-mirrored homotopic connectivity [VMHC]) among people with GAD with and without comorbid depression at baseline and after a 4-week paroxetine treatment. METHODS: Drug-naïve patients with GAD, with or without comorbid depression and healthy controls underwent functional magnetic resonance imaging and clinical assessments at baseline and after treatment. We compared VMHC and seed-based functional connectivity across the 3 groups. We performed correlation analysis and support vector regression (SVR) to examine the intrinsic relationships between VMHC and symptoms. RESULTS: Both patient groups (n = 40 with GAD only, n = 58 with GAD and depression) showed decreased VMHC in the precuneus, posterior cingulate cortex and lingual gyrus compared with healthy controls (n = 54). Moreover, they showed decreased VMHC in different brain regions compared with healthy controls. However, we did not observe any significant differences between the 2 patient groups. Seeds from abnormal VMHC clusters in patient groups had decreased functional connectivity. Voxel-mirrored homotopic connectivity in the precuneus, posterior cingulate cortex and lingual gyrus was negatively correlated with cognitive impairment among patients with GAD only and among all patients. The SVR analysis based on abnormal VMHC showed significant positive correlations (p < 0.0001) between predicted and actual treatment responses. However, we did not observe significant differences in VMHC or functional connectivity after treatment. LIMITATIONS: A notable dropout rate and intergroup somatic symptom variations may have biased the results. CONCLUSION: Patients with GAD with or without comorbid depression exhibited shared and distinct abnormal VMHC patterns, which might be linked to their cognitive deficits. These patterns have the potential to serve as prognostic biomarkers for GAD.Clinical trial registration: ClinicalTrials.gov NCT03894085.
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Disfunción Cognitiva , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Depresión , Mapeo Encefálico/métodos , Estudios de Seguimiento , Trastornos de Ansiedad/diagnóstico por imagen , Ansiedad/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagenRESUMEN
This case-control study was designed to examine the association between different types of miscarriage history and autism spectrum disorder (ASD), and determine whether the number of miscarriage history affects the risk of ASD. All of 2274 children with ASD and 1086 healthy controls were recruited. Sociodemographic and prenatal, perinatal, and neonatal characteristics were compared between the two groups. Multivariable logistic regression analyses were applied to investigate association between miscarriage history and ASD. Stratified analyses based on sex and types of miscarriages were similarly performed. History of miscarriage was potential risk factors for ASD ([aOR] = 2.919; 95% [CI] = 2.327-3.517). Stratified analyses revealed that induced ([aOR] = 2.763, 95% [CI] = 2.259-3.379) and spontaneous miscarriage history ([aOR] = 3.341, 95% [CI] = 1.939-4.820) were associated with high risk of ASD, respectively. A sex-biased ratio in the risk of ASD was observed between females ([aOR] = 3.049, 95% [CI] = 2.153-4.137) and males ([aOR] = 2.538, 95% [CI] = 1.978-3.251). Stratified analysis of induced miscarriage history revealed that only iatrogenic miscarriage history was associated with an increased risk ASD ([aOR] = 2.843, 95% [CI] = 1.534-4.268). Also, multiple spontaneous miscarriage histories ([aOR] = 1.836, 95% [CI] = 1.252-2.693) were associated with higher autism risk than one spontaneous miscarriages history ([aOR] = 3.016, 95% [CI] = 1.894-4.174). In conclusion, miscarriage history is related to an increased risk for ASD in offspring, which is affected by the types of miscarriage and sex of the fetus.
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Aborto Espontáneo , Trastorno del Espectro Autista , Masculino , Embarazo , Femenino , Niño , Recién Nacido , Humanos , Trastorno del Espectro Autista/epidemiología , Aborto Espontáneo/epidemiología , Estudios de Casos y Controles , Factores de RiesgoRESUMEN
BACKGROUND: Abnormal activation of microglia is involved in the pathogenesis of schizophrenia. Minocycline and antipsychotics have been reported to be effective in inhibiting the activation of microglia and thus alleviating the negative symptoms of patients with schizophrenia. However, the specific molecular mechanism by which minocycline and antipsychotics inhibit microglial activation is not clear. In this study, we aimed to explore the molecular mechanism of treatment effect of minocycline and antipsychotics on schizophrenia. METHODS: Microglia cells were activated by lipopolysaccharide (LPS) and further treated with minocycline, haloperidol, and risperidone. Then cell morphology, specific marker, cytokines, and nitric oxide production process, and the proteins in related molecular signaling pathways in LPS-activated microglia were compared among groups. RESULTS: The study found that minocycline, risperidone, and haloperidol significantly inhibited morphological changes and reduced the expression of OX-42 protein induced by LPS. Minocycline significantly decreased the production of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1ß). Risperidone also showed significant decrease in the production of IL-6 and TNF-α, while haloperidol only showed significant decrease in the production of IL-6. Minocycline, risperidone, and haloperidol were found to significantly inhibit nitric oxide (NO) expression, but had no effect on inducible nitric oxide synthase (iNOS) expression. Both minocycline and risperidone were effective in decreasing the activity of cJun Nterminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in the mitogen-activated protein kinases (MAPKs) signal pathway. Additionally, minocycline and risperidone were found to increase the activity of phosphorylated-p38. In contrast, haloperidol only suppressed the activity of ERK. Minocycline also suppressed the activation of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), while risperidone and haloperidol only suppressed the activation of STAT3. CONCLUSIONS: The results demonstrated that minocycline and risperidone exert stronger anti-inflammatory and neuroprotective effects stronger than haloperidol, through MAPKs and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathways in BV2 cells stimulated with LPS, revealing the underlying mechanisms of minocycline and atypical antipsychotics in the treatment of negative schizophrenia symptoms.
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Antipsicóticos , Humanos , Antipsicóticos/farmacología , Microglía/metabolismo , Lipopolisacáridos/farmacología , Minociclina/farmacología , Haloperidol/farmacología , Risperidona/farmacología , Factor de Necrosis Tumoral alfa , Interleucina-6 , Óxido Nítrico/metabolismo , Transducción de Señal , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo II/farmacologíaRESUMEN
BACKGROUND: Anomalies in regional homogeneity (ReHo) have been documented in patients with major depressive disorder (MDD) and sleep disturbances (SDs). This investigation aimed to scrutinize changes in ReHo in MDD patients with comorbid SD, and to devise potential diagnostic biomarkers for detecting sleep-related conditions in patients with MDD. METHODS: Patients with MDD and healthy controls underwent resting-state functional magnetic resonance imaging scans. SD severity was quantified using the 17-item Hamilton Rating Scale for Depression. Subsequent to the acquisition of imaging data, ReHo analysis was performed, and a support vector machine (SVM) method was employed to assess the utility of ReHo in discriminating MDD patients with SD. RESULTS: Compared with MDD patients without SD, MDD patients with SD exhibited increased ReHo values in the right posterior cingulate cortex (PCC)/precuneus, right median cingulate cortex, left postcentral gyrus (postCG), and right inferior temporal gyrus (ITG). Furthermore, the ReHo values in the right PCC/precuneus and ITG displayed a positive correlation with clinical symptoms across all patients. SVM classification results showed that a combination of abnormal ReHo in the left postCG and right ITG achieved an overall accuracy of 84.21%, a sensitivity of 81.82%, and a specificity of 87.50% in identifying MDD patients with SD from those without SD. CONCLUSION: We identified disrupted ReHo patterns in MDD patients with SD, and presented a prospective neuroimaging-based diagnostic biomarker for these patients.
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Trastorno Depresivo Mayor , Trastornos del Sueño-Vigilia , Humanos , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Estudios Prospectivos , SueñoRESUMEN
Autism spectrum disorder is an early-onset neurodevelopmental condition. This study aimed to investigate the progressive structural alterations in the autistic brain during early childhood. Structural magnetic resonance imaging scans were examined in a cross-sectional sample of 67 autistic children and 63 demographically matched typically developing (TD) children, aged 2-7 years. Voxel-based morphometry and a general linear model were used to ascertain the effects of diagnosis, age, and a diagnosis-by-age interaction on the gray matter volume. Causal structural covariance network analysis was performed to map the interregional influences of brain structural alterations with increasing age. The autism group showed spatially distributed increases in gray matter volume when controlling for age-related effects, compared with TD children. A significant diagnosis-by-age interaction effect was observed in the fusiform face area (FFA, Fpeak = 13.57) and cerebellum/vermis (Fpeak = 12.73). Compared with TD children, the gray matter development of the FFA in autism displayed altered influences on that of the social brain network regions (false discovery rate corrected, P < 0.05). Our findings indicate the atypical neurodevelopment of the FFA in the autistic brain during early childhood and highlight altered developmental effects of this region on the social brain network.
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Trastorno del Espectro Autista/patología , Mapeo Encefálico/métodos , Encéfalo/patología , Sustancia Gris/patología , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética , MasculinoRESUMEN
BACKGROUND: Antipsychotic drugs are associated with adverse events, but serious side effects are not frequent. This study aimed to ascertain whether previous exposure to antipsychotic treatment was associated with metabolic disturbances induced by current antipsychotic medication. METHODS: A total of 115 antipsychotic-naïve patients, 65 patients with previous exposure to low-metabolic-risk antipsychotics, and 88 patients with previous exposure to high-metabolic-risk antipsychotics were enrolled in our case-control study. All patients were administered olanzapine. Body weight, body mass index (BMI), biochemical indicators of blood glucose and lipids, the proportion of patients who gained more than 7% of their body weight at baseline, and the percentage of dyslipidemia were evaluated. All assessments were conducted at baseline and at 4 and 6 weeks after treatment. RESULTS: Olanzapine treatment resulted in a significant increase in body weight and BMI in antipsychotic-naïve patients compared with the other two groups (both p < 0.05). However, increases in lipid levels in the high-metabolic-risk antipsychotics group were significantly higher than that in the other two groups (both p < 0.05). A history of antipsychotics use was not associated with weight gain (all p > 0.05). Higher low-density lipoprotein cholesterol ≥3.37 mmol/L-1 was observed in antipsychotics exposure group compared with no history of antipsychotics exposure (aOR, 1.75; 95% CI, 1.07-3.52). Particularly, a history of high-metabolic-risk antipsychotics use was associated with a higher risk of LDL-C ≥3.37 mmol/L-1(aOR, 2.18; 95% CI, 1.03-3.32) compare with other two groups. CONCLUSIONS: A history of exposure to antipsychotics, particularly high-metabolic-risk antipsychotics, is associated with current antipsychotic-induced metabolic disturbances.
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Antipsicóticos , Esquizofrenia , Antipsicóticos/efectos adversos , Benzodiazepinas/efectos adversos , Peso Corporal , Estudios de Casos y Controles , Humanos , Olanzapina/efectos adversos , Esquizofrenia/tratamiento farmacológicoRESUMEN
OBJECTIVES: Electroconvulsive therapy (ECT) has significant effects on improving psychotic symptoms in schizophrenia (SZ), but the changes of brain function induced by it are unclear. The purpose of the study was to explore progressive ECT-induced changes in regional homogeneity (ReHo) at multiple time points before, during, and after a course of ECT. METHODS: The 27 in-patients with SZ (SZ group) who met the recruitment criteria accepted clinical evaluations and resting-state functional magnetic resonance imaging scans before the first ECT (pre-ECT), after the first ECT (ECT1), and after the eighth ECT (ECT8), all conducted within 10 to 12 hours. Forty-three healthy controls (HCs; HC group) who matched well with the patients for age, sex, and years of education were recruited. For Positive and Negative Syndrome Scale (PANSS) and ReHo, progressive changes were examined. RESULTS: Pair-wise comparisons of patient pre-ECT, ECT1, and ECT8 ReHo values with HC ReHo values revealed that ECT normalized the ReHo values in bilateral superior occipital gyrus (SOG), right lingual gyrus (LG), left medial prefrontal cortex. Furthermore, improved ReHo in bilateral SOG and right LG appeared after the first ECT application. The ReHo values in right middle occipital gyrus, right middle temporal gyrus, and right inferior parietal lobule were not significantly altered by ECT. The total PANSS score was lower even after the first ECT application (mean ΔPANSSECT1, 11.7%; range, 2%-32.8%) and markedly reduced after the eighth application (mean ΔPANSSECT8, 86.3%; range, 72.5%-97.9%). CONCLUSIONS: The antipsychotic effects of ECT may be achieved through regulating synchronization of some regions such as bilateral SOG, right LG, and left medial prefrontal cortex. Furthermore, the enhanced synchronizations also take place in other regions.
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Terapia Electroconvulsiva , Esquizofrenia , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Terapia Electroconvulsiva/métodos , Humanos , Imagen por Resonancia Magnética/métodos , Esquizofrenia/terapiaRESUMEN
OBJECTIVES: Autism is a neurodevelopment disorder with unclear etiology. High heterogeneity is one of the main issues in the etiological studies. This study explores the relationship between RELN signaling pathway related genes (RELN, VLDLR, LRP8, DAB1, CDK5, FYN) and language development of autism patients based on a cluster analysis model which is established to reduce the heterogeneity. METHODS: Autism children were recruited from 5 different medical/autism training institutes from Hunan, Shandong, and Henan provinces, and were divided into 2 parts according to the recruitment time: The first part was the training sample, which was recruited from October 2006 to May 2011, and the second part was the validation sample, which was recruited from July 2011 to May 2012. A two-step cluster analysis was performed to cluster 374 Chinese Han autism patients into different subgroups based on 2 parameters: Onset age of the first word and interval from the first word to the first phase. A Bayes discriminatory equation was established followed the cluster results. Then we used this equation to divide another 310 autism children into prior defined subgroups. After the genotyping data was screened, a single marker case-control association study was conducted. RESULTS: The cluster analysis clustered 374 samples into 3 subgroups. Onset ages of the first word in the Group A were (11.83±4.37) months and intervals from the first word to the first phase were (24.55±8.67) months; onset ages of the first word in the Group B were (12.17±3.46) months, intervals from the first word to the first phase were (7.07±3.79) months; onset ages of the first word of Group C were (30.94±7.60) months, intervals from the first word to the first phase were (4.73±4.80) months. The established equations based on the cluster analysis were YA=-14.442+0.525X1+0.810X2, YB=-4.964+0.477X1+0.264X2, YC=-19.843+1.175X1+0.241X2. Cross validated analysis showed that the false rate of the equation was 3.8%. A total of 341 single nucleotide polymorphism (SNP) in 6 genes passed the quality control. Before divided subgroups, none of these SNPs reached the significant P value (P>2.44×10-5, Bonferroni adjustment). However the result showed that rs1288502 of LRP8 in Group B was significantly different from the control group (P=6.45×10-6). CONCLUSIONS: Based on the cluster analysis of language development, we could establish a discriminatory equation to reduce heterogeneity of autism sample. The association test indicates that LRP8 genein RELN signaling pathway is related to a particular type of language development of autism patients.
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Trastorno Autístico , Moléculas de Adhesión Celular Neuronal , Trastorno Autístico/genética , Teorema de Bayes , Moléculas de Adhesión Celular Neuronal/genética , Preescolar , Proteínas de la Matriz Extracelular/genética , Predisposición Genética a la Enfermedad , Humanos , Lactante , Desarrollo del Lenguaje , Proteínas del Tejido Nervioso , Polimorfismo de Nucleótido Simple , Proteína Reelina/metabolismo , Serina Endopeptidasas/genética , Transducción de Señal/genéticaRESUMEN
BACKGROUND: Affective temperaments have been considered antecedents of major depressive disorder (MDD). However, little is known about how the covariation between alterations in brain activity and distinct affective temperaments work collaboratively to contribute to MDD. Here, we focus on the insular cortex, a critical hub for the integration of subjective feelings, emotions, and motivations, to examine the neural correlates of affective temperaments and their relationship to depressive symptom dimensions. METHODS: Twenty-nine medication-free patients with MDD and 58 healthy controls underwent magnetic resonance imaging scanning and completed the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS). Patients also received assessments of the Hamilton Depression Rating Scale (HDRS). We used multivariate analyses of partial least squares regression and partial correlation analyses to explore the associations among the insular activity, affective temperaments, and depressive symptom dimensions. RESULTS: A profile (linear combination) of increased fractional amplitude of low-frequency fluctuations (fALFF) of the anterior insular subregions (left dorsal agranular-dysgranular insula and right ventral agranuar insula) was positively associated with an affective-temperament (depressive, irritable, anxious, and less hyperthymic) profile. The covariation between the insula-fALFF profile and the affective-temperament profile was significantly correlated with the sleep disturbance dimension (especially the middle and late insomnia scores) in the medication-free MDD patients. CONCLUSIONS: The resting-state spontaneous activity of the anterior insula and affective temperaments collaboratively contribute to sleep disturbances in medication-free MDD patients. The approach used in this study provides a practical way to explore the relationship of multivariate measures in investigating the etiology of mental disorders.
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Trastorno Depresivo Mayor/fisiopatología , Corteza Insular/fisiopatología , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatología , Adulto , Afecto , China , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/etiología , Femenino , Humanos , Corteza Insular/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , TemperamentoRESUMEN
PURPOSE/BACKGROUND: Hippocampal volume loss in early schizophrenia has been linked with markers of inflammation and oxidative stress, and with less response of negative symptoms. Aripiprazole has been reported to preserve hippocampal volume and to reduce inflammation. METHODS/PROCEDURES: Study 1 was a 12-month multicenter randomized placebo-controlled trial of citalopram added to clinician-determined second-generation antipsychotic medication in 95 patients with first-episode schizophrenia (FES), 19 of whom received aripiprazole. We compared participants taking aripiprazole with those on other antipsychotics to determine whether those on aripiprazole had less hippocampal volume loss. We also examined peripheral biomarker data from medication-naive patients with schizophrenia receiving 8 weeks of antipsychotic treatment (n = 24) to see whether markers of inflammation and oxidative stress that previously predicted hippocampal volume differed between aripiprazole (n = 9) and other antipsychotics (study 2). FINDINGS/RESULTS: Aripiprazole was associated with a mean increase in hippocampal volume of 0.35% (SD, 0.80%) compared with a 0.53% decrease (SD, 1.2%) with other antipsychotics during the first year of maintenance treatment in patients with FES. This difference was significant after adjusting for age, sex, citalopram treatment, and baseline Brief Psychiatric Rating Scale score (B = 0.0079, P = 0.03). Aripiprazole was also associated with reduced concentrations of the inflammatory cytokines interleukin-8 and tumor necrosis factor (P < 0.01) during the first 8 weeks of treatment in medication-naive patients with FES. IMPLICATIONS/CONCLUSIONS: These results suggest that aripiprazole may protect against hippocampal atrophy via an anti-inflammatory mechanism, but these results require replication in larger, randomized trials, and the clinical relevance of hippocampal volume loss is not established.
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Antipsicóticos/administración & dosificación , Aripiprazol/administración & dosificación , Hipocampo/efectos de los fármacos , Esquizofrenia/tratamiento farmacológico , Adolescente , Adulto , Antipsicóticos/farmacología , Aripiprazol/farmacología , Atrofia/prevención & control , Escalas de Valoración Psiquiátrica Breve , Femenino , Hipocampo/patología , Humanos , Inflamación/tratamiento farmacológico , Inflamación/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Esquizofrenia/fisiopatología , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unclear etiology and pathophysiology. Previous studies have indicated that the dysregulation of cytokines may be involved in the pathogenesis of ASD and that the levels of cytokines may serve as potential biomarkers of this disorder. METHODS: The current study employed a family triad-based case-control design to study the levels of plasma cytokines in families with ASD (n = 45 triads) and controls (n = 38 triads) with a Human Cytokine Twenty-Five-Plex Kit. The Social Responsiveness Scale (SRS) was used to measure social impairment of ASD children. RESULTS: After controlling for the levels of parental cytokines, we identified that interferon-α (IFN-α), interleukin-7 (IL-7), IL-8, IFN-γ-inducible protein-10, and macrophage inflammatory protein-1ß were associated with ASD, and IL-8 was the only cytokine also associated with the levels of both parental cytokines in the offspring-parents regression analysis and three subdomains of SRS (social awareness, cognition, and motivations) in the children with ASD. The receiver operating characteristic curve showed that the log-transformed IL-8 level discriminated children with autism from controls with an area under the curve of 0.858 (95% confidence interval: 0.777-0.939). CONCLUSIONS: Our study suggests that IL-8 is a potential biomarker for ASD and may be involved in the pathogenesis of ASD. IMPACT: The study suggests that IL-8 is a promising biomarker for ASD and may be involved in the pathogenesis of ASD. Only a very few studies have reported the parental cytokine levels. The significant strength of this article is that we applied the family triad-based approach to explore cytokine levels in families with autism and controls. There are no objective biomarkers, making the accurate diagnosis, prognostic prediction and effective treatment difficult, and our study provides promising results.
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Trastorno del Espectro Autista/fisiopatología , Trastorno del Espectro Autista/psicología , Interleucina-8/sangre , Trastorno de la Conducta Social/fisiopatología , Trastorno de la Conducta Social/psicología , Área Bajo la Curva , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Preescolar , China/epidemiología , Estudios Transversales , Salud de la Familia , Femenino , Humanos , Interferón-alfa/sangre , Interferón gamma/sangre , Interleucina-7/sangre , Masculino , Análisis de Regresión , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Electroconvulsive therapy (ECT) has been widely used to treat patients with schizophrenia. However, the underlying mechanisms of ECT remain unknown. In the present study, the treatment effects of ECT on brain structure in patients with schizophrenia were explored. Seventy patients with schizophrenia were scanned using structural magnetic resonance imaging. Patients in the drug group were scanned at baseline (time 1) and follow-up (time 2, 6 weeks of treatment). Patients in the ECT group were scanned before ECT treatment (baseline, time 1) and 10-12 h after the last ECT treatment (time 2). Voxel-based morphometry was applied to analyze the imaging data. Patients in the ECT group showed significantly increased gray matter volume (GMV) in the bilateral hippocampus/amygdala and left superior temporal gyrus (STG)/middle temporal gyrus (MTG) after ECT combined with antipsychotic therapy at time 2. In contrast, patients in the drug group showed decreased GMV in widespread brain regions. Correlation analysis results showed significantly negative correlations between the increased GMV in the bilateral hippocampus/amygdala and PANSS scores at baseline in the ECT group. ECT may modulate brain structure in patients with schizophrenia. The GMV in distinct subcortical regions was related to the individual therapeutic response in patients with schizophrenia.
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Terapia Electroconvulsiva , Sustancia Gris , Esquizofrenia , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Humanos , Imagen por Resonancia Magnética , Tamaño de los Órganos , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/patología , Esquizofrenia/terapiaRESUMEN
Previous studies have demonstrated the efficacy of metacognitive training (MCT) in schizophrenia. However, the underlying mechanisms related to therapeutic effect of MCT remain unknown. The present study explored the treatment effects of MCT on brain regional neural activity using regional homogeneity (ReHo) and whether these regions' activities could predict individual treatment response in schizophrenia. Forty-one patients with schizophrenia and 20 healthy controls were scanned using resting-state functional magnetic resonance imaging. Patients were randomly divided into drug therapy (DT) and drug plus psychotherapy (DPP) groups. The DT group received only olanzapine treatment, whereas the DPP group received olanzapine and MCT for 8 weeks. The results revealed that ReHo in the right precuneus, left superior medial prefrontal cortex (MPFC), right parahippocampal gyrus and left rectus was significantly increased in the DPP group after 8 weeks of treatment. Patients in the DT group showed significantly increased ReHo in the left ventral MPFC/anterior cingulate cortex (ACC), left superior MPFC/middle frontal gyrus (MFG), left precuneus, right rectus and left MFG, and significantly decreased ReHo in the bilateral cerebellum VIII and left inferior occipital gyrus (IOG) after treatment. Support vector regression analyses showed that high ReHo levels at baseline in the right precuneus and left superior MPFC could predict symptomatic improvement of Positive and Negative Syndrome Scale (PANSS) after 8 weeks of DPP treatment. Moreover, high ReHo levels at baseline and alterations of ReHo in the left ventral MPFC/ACC could predict symptomatic improvement of PANSS after 8 weeks of DT treatment. This study suggests that MCT is associated with the modulation of ReHo in schizophrenia. ReHo in the right precuneus and left superior MPFC may predict individual therapeutic response for MCT in patients with schizophrenia.
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Esquizofrenia , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Humanos , Imagen por Resonancia Magnética , Olanzapina , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/tratamiento farmacológicoRESUMEN
BACKGROUND: This study aimed to investigate the influence of CYP2D6 polymorphisms on risperidone plasma concentrations in patients with schizophrenia. Based on pharmacogenomics, we examined whether plasma concentration of risperidone is associated with clinical response and adverse side-effects. METHODS: We recruited patients with chronic schizophrenia who were then treated with risperidone. The CYP2D6 genotypes were determined using targeted sequencing. All high-frequency mutation sites of the nine exons of the gene were assayed in the present study. Plasma concentrations of risperidone and 9-hydroxyrisperidone (9-OH-RIS) were measured using high-performance liquid chromatography (HPLC). Psychiatric symptoms were monitored using The Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI). Adverse effects were evaluated using the Barnes Akathisia Scale (BAS) and Extrapyramidal Symptom Rating Scale (ESRS). Follow-up visits were scheduled at weeks 2,4, and 8 after treatment initiation. RESULTS: Among the 76 patients, 100 C > T (rs1065852), 1038 C > T (rs1081003), 1662 G > C (rs1058164), 2851 C > T (rs16947), and 4181G > C (rs1135840) variants were detected. The most common allele was CYP2D6*10 (81.6%), whereas CYP2D6*2 (9.2%) and CYP2D6*5 (17.1%) were relatively rare. Plasma levels of risperidone and the risperidone/9-OH risperidone ratio (R/9-OH) were significantly increased in individuals with CYP2D6*10 (P < 0.05). The change in PANSS score, weight, high-density lipoprotein (HDL) level, prolactin (PRL) level, and ESRS were significantly different from baseline, between the different genotypes (P < 0.01). Moreover, individuals with CYP2D6*10 homozygous (TT) mutations were associated with higher risperidone concentration and R/9-OH ratio than those with heterozygous mutations (CT) (P < 0.01). A change from baseline in BPRS scores was observed only during week 8 and was different between heterozygous and homozygous mutations. As for the C2851T polymorphism, the incidence of adverse metabolic effects was significantly different between the C/C and C/T genotypes (P < 0.01). Regarding the G4181C polymorphisms, the changes from baseline in GLU and TG, were different between the C/C and C/G genotypes (P < 0.01). CONCLUSIONS: The genotype of CYP2D6 significantly influences the plasma concentration of risperidone and may subsequently influence the adverse side-effects following risperidone treatment, while also exerting a slight influence on clinical outcomes.
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Antipsicóticos , Risperidona , Antipsicóticos/uso terapéutico , Citocromo P-450 CYP2D6/genética , Humanos , Isoxazoles , Palmitato de Paliperidona , Plasma , Pirimidinas , Risperidona/uso terapéuticoRESUMEN
BACKGROUND: To explore the association between cesarean section (CS) and risk of autism spectrum disorder (ASD), and evaluate the possible factors influencing this association. METHODS: In total, 950 patients diagnosed with ASD and 764 healthy controls were recruited in this study. Socio-demographic characteristics and prenatal, perinatal, and neonatal characteristics were compared between the two groups. Univariate and multivariable conditional logistic regression analyses were applied to adjust for confounders. Further stratified analyses based on sex and miscarriage history were similarly performed to explore the factors influencing the association between CS and ASD. RESULTS: CS was evidently associated with an elevated risk of ASD (adjusted odds ratio [aOR] = 1.606, 95% confidence interval (CI) = 1.311-1.969). Unlike regional anesthesia (RA), only CS performed under general anesthesia (GA) consistently elevated the risk of ASD (aOR = 1.887, 95% CI = 1.273-2.798) in females and males in further stratified analysis. The risk of children suffering from ASD following emergency CS was apparently increased in males (aOR = 2.390, 95% CI = 1.392-5.207), whereas a higher risk of ASD was observed among voluntary CS and indicated CS subgroups (aOR = 2.167, 95% CI = 1.094-4.291; aOR = 2.919, 95% CI = 1.789-4.765, respectively) in females. Moreover, the interaction term of CS and past miscarriage history (ß = - 0.68, Wald χ2 = 7.5, df = 1, p = 0.006)) was similarly defined as influencing ASD. CONCLUSIONS: The exposure of children to GA during CS may explain the possible/emerging association between CS and ASD. In addition, sex and miscarriage history could equally be factors influencing the association between CS and ASD.
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Aborto Espontáneo , Trastorno del Espectro Autista , Anestesia General , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/etiología , Estudios de Casos y Controles , Cesárea/efectos adversos , Niño , Femenino , Humanos , Recién Nacido , Masculino , Oportunidad Relativa , EmbarazoRESUMEN
Background: Melancholic depression has been assumed as a severe type of major depressive disorder (MDD). We aimed to explore if there were some distinctive alterations in melancholic MDD and whether the alterations could be used to discriminate the melancholic MDD and nonmelancholic MDD. Methods: Thirty-one outpatients with melancholic MDD, thirty-three outpatients with nonmelancholic MDD, and thirty-two age- and gender-matched healthy controls were recruited. All participants were scanned by resting-state functional magnetic resonance imaging (fMRI). Imaging data were analyzed with the network homogeneity (NH) and support vector machine (SVM) methods. Results: Both patient groups exhibited increased NH in the right PCC/precuneus and right angular gyrus and decreased NH in the right middle temporal gyrus compared with healthy controls. Compared with nonmelancholic patients and healthy controls, melancholic patients exhibited significantly increased NH in the bilateral superior medial frontal gyrus and decreased NH in the left inferior temporal gyrus. But merely for melancholic patients, the NH of the right middle temporal gyrus was negatively correlated with TEPS total and contextual anticipatory scores. SVM analysis showed that a combination of NH values in the left superior medial frontal gyrus and left inferior temporal gyrus could distinguish melancholic patients from nonmelancholic patients with accuracy, sensitivity, and specificity of 79.66% (47/59), 70.97% (22/31), and 89.29%(25/28), respectively. Conclusion: Our findings showed distinctive network homogeneity alterations in melancholic MDD which may be potential imaging markers to distinguish melancholic MDD and nonmelancholic MDD.
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Red en Modo Predeterminado , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo/fisiopatología , Adulto , Encéfalo/fisiopatología , Trastorno Depresivo/psicología , Trastorno Depresivo Mayor/psicología , Diagnóstico Diferencial , Femenino , Lóbulo Frontal/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Lóbulo Parietal/fisiopatología , Corteza Prefrontal , Escalas de Valoración Psiquiátrica , Reproducibilidad de los Resultados , Descanso , Sensibilidad y Especificidad , Máquina de Vectores de Soporte , Lóbulo Temporal/fisiopatología , Adulto JovenRESUMEN
Background: Previous studies have revealed the abnormalities in homotopic connectivity in schizophrenia. However, the relationship of these deficits to antipsychotic treatment in schizophrenia remains unclear. This study explored the effects of antipsychotic therapy on brain homotopic connectivity and whether the homotopic connectivity of these regions might predict individual treatment response in schizophrenic patients. Methods: A total of 21 schizophrenic patients and 20 healthy controls were scanned by the resting-state functional magnetic resonance imaging. The patients received olanzapine treatment and were scanned at two time points. Voxel-mirrored homotopic connectivity (VMHC) and pattern classification techniques were applied to analyze the imaging data. Results: Schizophrenic patients presented significantly decreased VMHC in the temporal and inferior frontal gyri, medial prefrontal cortex (MPFC), and motor and low-level sensory processing regions (including the fusiform gyrus and cerebellum lobule VI) relative to healthy controls. The VMHC in the superior/middle MPFC was significantly increased in the patients after eight weeks of treatment. Support vector regression (SVR) analyses revealed that VMHC in the superior/middle MPFC at baseline can predict the symptomatic improvement of the positive and negative syndrome scale after eight weeks of treatment. Conclusions: This study demonstrated that olanzapine treatment may normalize decreased homotopic connectivity in the superior/middle MPFC in schizophrenic patients. The VMHC in the superior/middle MPFC may predict individual response for antipsychotic therapy. The findings of this study conduce to the comprehension of the therapy effects of antipsychotic medications on homotopic connectivity in schizophrenia.
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Antipsicóticos/uso terapéutico , Imagen por Resonancia Magnética/métodos , Red Nerviosa/diagnóstico por imagen , Olanzapina/uso terapéutico , Corteza Prefrontal/diagnóstico por imagen , Esquizofrenia/diagnóstico por imagen , Adolescente , Adulto , Antipsicóticos/farmacología , Femenino , Humanos , Masculino , Red Nerviosa/efectos de los fármacos , Olanzapina/farmacología , Valor Predictivo de las Pruebas , Corteza Prefrontal/efectos de los fármacos , Esquizofrenia/tratamiento farmacológico , Resultado del Tratamiento , Adulto JovenRESUMEN
The current study explored how and to what extent sleep problems in children with autism spectrum disorder (ASD) impacted their parents' quality of life (QOL). A total of 440 ASD children and 344 age-matched typically developing (TD) children were included in the case-control designed study. In the TD group, a linear regression model showed that the Children's Sleep Habits Questionnaire (CSHQ) total scores were negatively associated with maternal mental health summary (MCS) scores in the SF-36v2 (ß = - 2.831), while in the ASD group, the CSHQ total scores were negatively associated with the parental physical health summary (PCS) scores (ß = - 3.030 for mothers, ß = - 3.651 for fathers). Path analysis showed that sleep problems in ASD children had both direct and indirect effects on maternal PCS scores. The results indicated that sleep problems in children with ASD might affect parental QOL differently from TD children, and act as independent impact factors on parental physical health.