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BACKGROUND: A better understanding of the mechanisms underlying cognitive impairment in schizophrenia is imperative, as it causes poor functional outcomes and a lack of effective treatments. AIMS: This study aimed to investigate the relationships of two proposed main pathophysiology of schizophrenia, altered prefrontal-striatal connectivity and the dopamine system, with cognitive impairment and their interactions. METHODS: Thirty-three patients with schizophrenia and 27 healthy controls (HCs) who are right-handed and matched for age and sex were recruited. We evaluated their cognition, functional connectivity (FC) between the dorsolateral prefrontal cortex (DLPFC)/middle frontal gyrus (MiFG) and striatum, and the availability of striatal dopamine transporter (DAT) using a cognitive battery investigating attention, memory, and executive function, resting-state functional magnetic resonance imaging with group independent component analysis and single-photon emission computed tomography with 99mTc-TRODAT. RESULTS: Patients with schizophrenia exhibited poorer cognitive performance, reduced FC between DLPFC/MiFG and the caudate nucleus (CN) or putamen, decreased DAT availability in the left CN, and decreased right-left DAT asymmetry in the CN compared to HCs. In patients with schizophrenia, altered imaging markers are associated with cognitive impairments, especially the relationship between DLPFC/MiFG-putamen FC and attention and between DAT asymmetry in the CN and executive function. CONCLUSIONS: This study is the first to demonstrate how prefrontal-striatal hypoconnectivity and altered striatal DAT markers are associated with different domains of cognitive impairment in schizophrenia. More research is needed to evaluate their complex relationships and potential therapeutic implications.
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Disfunción Cognitiva , Cuerpo Estriado , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Imagen por Resonancia Magnética , Esquizofrenia , Tomografía Computarizada de Emisión de Fotón Único , Humanos , Masculino , Femenino , Esquizofrenia/fisiopatología , Esquizofrenia/metabolismo , Esquizofrenia/diagnóstico por imagen , Adulto , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/etiología , Disfunción Cognitiva/diagnóstico por imagen , Cuerpo Estriado/metabolismo , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/fisiopatología , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Dopamina/metabolismo , Corteza Prefrontal/metabolismo , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Corteza Prefontal Dorsolateral/metabolismo , Estudios de Casos y Controles , Persona de Mediana Edad , Función Ejecutiva/fisiología , Pruebas Neuropsicológicas , Adulto JovenRESUMEN
BACKGROUND: Current evidence of volume changes in hippocampal subdivisions in schizophrenia remains inconsistent, and few studies have investigated the relationship between regional hippocampal volumes and symptom remission. METHODS: In this cross-sectional study, we recruited 31 patients with schizophrenia and 31 healthy controls (HCs). Symptomatic remission in schizophrenia was determined according to Remission in Schizophrenia Working Group criteria. The volumes of hippocampal longitudinal subregions and transverse subfields were measured using manual and automatic techniques, respectively. Between-group regional hippocampal volume differences were analyzed using multivariate analysis of covariance followed by univariate analysis of covariance. RESULTS: Compared with the HCs, the patients with schizophrenia had smaller bilateral heads and tails along the longitudinal axis; they also had reduced volumes of the bilateral CA1, CA3, CA4, GC-ML-DG, molecular layer, tail, left subiculum, left HATA, and right parasubiculum along the transverse axis in the hippocampus (all corrected p < 0.05). Furthermore, compared with the HCs and patients with remitted schizophrenia, the patients with nonremitted schizophrenia had smaller bilateral hippocampal tail subfields (corrected p < 0.05). CONCLUSION: Our results indicated that the pathophysiology and symptomatic remission of schizophrenia are related to changes in the volumes of hippocampal subdivisions. These volume changes might be clinically relevant as biomarkers for schizophrenia identification and treatment.
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Hipocampo , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/patología , Hipocampo/patología , Hipocampo/diagnóstico por imagen , Adulto , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Imagen por Resonancia MagnéticaRESUMEN
(1) Background: The hippocampus (HP) and amygdala are essential structures in obsessive-compulsive behavior (OCB); however, the specific role of the HP in patients with behavioral variant frontotemporal dementia (bvFTD) and OCB remains unclear. (2) Objective: We investigated the alterations of hippocampal and amygdalar volumes in patients with bvFTD and OCB and assessed the correlations of clinical severity with hippocampal subfield and amygdalar nuclei volumes in bvFTD patients with OCB. (3) Materials and methods: Eight bvFTD patients with OCB were recruited and compared with eight age- and sex-matched healthy controls (HCs). Hippocampal subfield and amygdalar nuclei volumes were analyzed automatically using a 3T magnetic resonance image and FreeSurfer v7.1.1. All participants completed the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Neuropsychiatric Inventory (NPI), and Frontal Behavioral Inventory (FBI). (4) Results: We observed remarkable reductions in bilateral total hippocampal volumes. Compared with the HCs, reductions in the left hippocampal subfield volume over the cornu ammonis (CA)1 body, CA2/3 body, CA4 body, granule cell layer, and molecular layer of the dentate gyrus (GC-ML-DG) body, molecular layer of the HP body, and hippocampal tail were more obvious in patients with bvFTD and OCB. Right subfield volumes over the CA1 body and molecular layer of the HP body were more significantly reduced in bvFTD patients with OCB than in those in HCs. We observed no significant difference in amygdalar nuclei volume between the groups. Among patients with bvFTD and OCB, Y-BOCS score was negatively correlated with left CA2/3 body volume (τb = -0.729, p < 0.001); total NPI score was negatively correlated with left GC-ML-DG body (τb = -0.648, p = 0.001) and total bilateral hippocampal volumes (left, τb = -0.629, p = 0.002; right, τb = -0.455, p = 0.023); and FBI score was negatively correlated with the left molecular layer of the HP body (τb = -0.668, p = 0.001), CA4 body (τb = -0.610, p = 0.002), and hippocampal tail volumes (τb = -0.552, p < 0.006). Mediation analysis confirmed these subfield volumes as direct biomarkers for clinical severity, independent of medial and lateral orbitofrontal volumes. (5) Conclusions: Alterations in hippocampal subfield volumes appear to be crucial in the pathophysiology of OCB development in patients with bvFTD.
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Approximately 40% of patients with major depressive disorder (MDD) had limited response to conventional antidepressant treatments, resulting in treatment-resistant depression (TRD), a debilitating subtype that yielded a significant disease burden worldwide. Molecular imaging techniques, such as positron emission tomography (PET) and single photon emission tomography (SPECT), can measure targeted macromolecules or biological processes in vivo. These imaging tools provide a unique possibility to explore the pathophysiology and treatment mechanisms underlying TRD. This work reviewed and summarized prior PET and SPECT studies to examine the neurobiology and treatment-induced changes of TRD. A total of 51 articles were included with supplementary information from studies for MDD and healthy controls (HC). We found that there were altered regional blood flow or metabolic activity in several brain regions, such as the anterior cingulate cortex, prefrontal cortex, insula, hippocampus, amygdala, parahippocampus, and striatum. These regions have been suggested to engage in the pathophysiology or treatment resistance of depression. There was also limited data to demonstrate the changes in the markers of serotonin, dopamine, amyloid, and microglia over some regions in TRD. Moreover, several observed abnormal imaging indices were linked to treatment outcomes, supporting their specificity and clinical relevance. To address the limitations of the included studies, we proposed that future studies needed longitudinal designs, multimodal approaches, and radioligands targeting specific neural substrates for TRD to evaluate their baseline and treatment-related alterations in TRD. Adequate data sharing and reproducible data analysis can facilitate advances in this field.
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Trastorno Depresivo Mayor , Trastorno Depresivo Resistente al Tratamiento , Humanos , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/diagnóstico por imagen , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Encéfalo/metabolismo , Corteza Prefrontal , Antidepresivos/farmacología , Antidepresivos/uso terapéuticoRESUMEN
INTRODUCTION: Amygdala and serotonergic system abnormalities have been documented in major depressive disorder (MDD). However, most studies have been conducted on recurrent MDD, and only a few have assessed their interaction. This study aimed to concurrently examine both the amygdala and serotonergic systems and their clinical relevance in first-episode, drug-naïve MDD. METHODS: This study included 27 patients with first-episode, drug-naïve MDD and 27 age- and gender-matched healthy controls (HCs). The amygdala substructure volumes were performed with Freesurfer from a 1.5 T magnetic resonance image. Serotonin transporter (SERT) availability was detected by single-photon emission computed tomography with 123I-ADAM. The Benjamini-Hochberg method was applied to adjust for multiple comparisons. RESULTS: No significant difference was found in the amygdala substructure volume and SERT availability between the two groups, respectively. Within MDD patients, the right medial, cortical nucleus, and centromedial volumes were positively associated with caudate SERT availability, respectively. Moreover, the right lateral nucleus volume in the amygdala was positively correlated with depression severity. However, these significances did not survive correction for multiple testing. CONCLUSIONS: There were no significant abnormalities in the amygdala substructure volumes and SERT availability in patients with first-episode, drug-naïve MDD. We did not observe an association between amygdala substructure volume and serotonergic dysregulation and their correlations with depression severity in patients with MDD. A larger sample size is warranted to elucidate the actual correlation.
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Trastorno Depresivo Mayor , Humanos , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Proyectos Piloto , Tomografía Computarizada de Emisión de Fotón Único , Amígdala del Cerebelo/metabolismo , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Cognitive impairments, the main determinants of functional outcomes in schizophrenia, had limited treatment responses and need a better understanding of the mechanisms. Dysfunctions of the dopamine system and N-methyl-d-aspartate receptor (NMDAR), the primary pathophysiologies of schizophrenia, may impair cognition. This study explored the effects and interactions of striatal dopamine transporter (DAT) and plasma NMDAR-related amino acids on cognitive impairments in schizophrenia. METHODS: We recruited 36 schizophrenia patients and 36 age- and sex-matched healthy controls (HC). All participants underwent cognitive assessments of attention, memory, and executive function. Single-photon emission computed tomography with 99mTc-TRODAT and ultra-performance liquid chromatography were applied to determine DAT availability and plasma concentrations of eight amino acids, respectively. RESULTS: Compared with HC, schizophrenia patients had lower cognitive performance, higher methionine concentrations, decreased concentrations of glutamic acid, cysteine, aspartic acid, arginine, the ratio of glutamic acid to gamma-aminobutyric acid (Glu/GABA), and DAT availability in the left caudate nucleus (CN) and putamen. Regarding memory scores, Glu/GABA and the DAT availability in left CN and putamen exhibited positive relationships, while methionine concentrations showed negative associations in all participants. The DAT availability in left CN mediated the methionine-memory relationship. An exploratory backward stepwise regression analysis for the four biological markers associated with memory indicated that DAT availability in left CN and Glu/GABA remained in the final model. CONCLUSIONS: This study demonstrated the interactions of striatal DAT and NMDAR-related amino acids on cognitive impairments in schizophrenia. Future studies to comprehensively evaluate their complex interactions and treatment implications are warranted.
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Disfunción Cognitiva , Esquizofrenia , Humanos , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Esquizofrenia/complicaciones , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Dopamina/metabolismo , Aminoácidos/metabolismo , Ácido Aspártico/metabolismo , Cisteína , Tomografía Computarizada de Emisión de Fotón Único/métodos , Cuerpo Estriado/metabolismo , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Metionina , Arginina/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Glutamatos/metabolismo , TropanosRESUMEN
Cognitive impairments are crucial in functional outcomes of major depressive disorder (MDD). The effectiveness of currently available treatment methods for cognitive deficits is suboptimal. A cognitive test battery is often applied to evaluate cognition with multiple interrelated and difficult-to-interpret outcomes. Generating cognitive factor scores after the confirmation of a common cognitive structure and measurement invariance between healthy controls (HCs) and patients may aid in understanding cognition further. This methodology has been applied for several neuropsychiatric disorders, but not for MDD. Therefore, we conducted a series of exploratory factor analyses (EFA), confirmatory factor analyses (CFA), and multiple groups CFA (MGCFA) for a cognitive test battery in HCs and patients with MDD. The initial EFA of 106 HCs yielded a three-factor model-comprising attention, memory, and executive function. The CFA confirmed the initial model in other 94 HCs with revisions, which reasonably fit the cognitive data of 54 patients with MDD. MGCFA supported the measurement invariance of the determined model between HCs and patients with MDD. The associations of cognitive factor scores with age or education and the effect sizes of group differences in cognitive factor scores externally validated the determined model. In conclusion, this is the first study to demonstrate the measurement invariance of a cognitive model between HCs and patients with MDD using MGCFA. The measurement invariance substantiated valid group comparisons of factor scores and their relationships with other markers. The current results may be applicable for the development of improved treatment strategies for cognitive impairments in MDD.
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Disfunción Cognitiva , Trastorno Depresivo Mayor , Atención , Cognición , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/psicología , Función Ejecutiva , Humanos , Pruebas NeuropsicológicasRESUMEN
OBJECTIVE: Cortisol is associated with cognition in both healthy individuals and patients with neuropsychiatric disorders. Regarding the effects of cortisol on the dopamine system and the association between dopamine transporter (DAT) and cognition, DAT might be a central target linking cortisol and cognition. This study explored the role of striatal DAT in the cortisol-cognition relationship. METHODS: We recruited 33 patients with carbon monoxide poisoning and 33 age- and sex-matched healthy controls. All participants underwent cognitive assessments of attention, memory, and executive function. Single-photon emission computed tomography with 99mTc-TRODAT was used to determine striatal DAT availability. Plasma cortisol, tumor necrosis factor α, and interleukin-10 levels were measured using enzyme-linked immunosorbent assays. RESULTS: Compared with healthy controls, patients with carbon monoxide poisoning had lower cognitive performance, bilateral striatal DAT availability, and plasma tumor necrosis factor-α levels and higher cortisol and interleukin-10 levels. In all participants, plasma cortisol level and bilateral striatal DAT availability were negatively and positively related to cognition, respectively, including memory and executive function with ß from -0.361 (95% confidence interval [CI] = -0.633 to -0.090) to 0.588 (95% CI = 0.319 to 0.858). Moreover, bilateral striatal DAT mediated the cortisol-cognition relationship with indirect effects from -0.067 (95% CI = -0.179 to -0.001) to -0.135 (95% CI = -0.295 to -0.024). The cytokine levels did not influence the mediation effects. CONCLUSIONS: This is the first study to demonstrate that striatal DAT mediates the cortisol-cognition relationship. Future studies are needed to comprehensively evaluate the role of the dopamine system in cortisol-cognition associations and treatment implications.
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Intoxicación por Monóxido de Carbono , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Cognición , Dopamina , Humanos , Hidrocortisona , Interleucina-10 , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
Hippocampal volume reduction was reported to underlie depressive symptomatology, however, the evidence to date remains inconsistent. For the complex intrinsic organization of hippocampus, the hippocampal volumes can be further divided into subfields or axial parts. The current study aimed to explore the alterations of hippocampal sub-regional volumes in first episode drug-naïve major depressive disorder (MDD) by two segmentation methods. Thirty-five first-episode drug-naïve MDD and 35 age- and gender-matched healthy controls (HC) were recruited. Volumes of three sub-regions of hippocampus along the longitudinal axis (head, body and tail) were analyzed manually and eight transverse subfields were automatically determined using FreeSurfer. An asymmetric index (AI) of volumes was defined as (â£Left - Rightâ£/â£Left + Rightâ£) * 100. There were significant reductions in the volumes of bilateral hippocampal head in MDD compared to HC. The volumes of eight subfields were not different between groups. MDD patients had higher AI values in the subfield of cornu ammonis 4/dentate gyrus than HC. The change in hippocampal sub-regional volumes might be an imaging biomarker in the first-episode, drug-naïve patients with MDD. Current findings may contribute to developing new diagnostic and therapeutic strategies for major depression.
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Trastorno Depresivo Mayor/diagnóstico , Hipocampo/patología , Adulto , Trastorno Depresivo Mayor/patología , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Índice de Severidad de la EnfermedadRESUMEN
Major depressive disorder (MDD) is associated with the disharmonic functioning of the serotonin system. The serotonin system is mainly modulated by the serotonin transporter (SERT) which regulates serotonin uptake and the metabolism of its precursor, tryptophan and following kynurenine pathway. Currently, there is a lack of research examining both markers concurrently in MDD. This study evaluated the alterations and inter-relationships of both markers in first-episode drug-naïve MDD patients. Thirty-three MDD patients and 33 age- and sex-matched healthy controls (HC) were recruited. The SERT availability were comparable between two groups in the midbrain, thalamus, caudate, and putamen. The kynurenine/tryptophan ratio which indicates tryptophan metabolism was lower in MDD than HC with no group difference in the tryptophan or kynurenine concentration. A negative correlation between the midbrain SERT availability and kynurenine concentration in HC was found. For the subgroup of HC with high kynurenine/tryptophan ratio, the SERT availability was positively associated with the kynurenine/tryptophan ratio and negatively correlated with tryptophan or kynurenine concentration. This study demonstrated the altered tryptophan metabolism and the relationship between tryptophan metabolism and the SERT availability in first-episode drug-naïve MDD patients, which gave a new insight towards the future investigation of the pathophysiology of MDD.
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Trastorno Depresivo Mayor , Preparaciones Farmacéuticas , Humanos , Quinurenina , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , TriptófanoRESUMEN
Abnormalities of neuroinflammatory process and serotonergic system have been reported in major depressive disorder (MDD). However, most previous studies were performed in recurrent MDD and only a few studies explored the interaction of the two systems. This study examined both systems concurrently and their clinical relevance in first-episode drug-naive MDD. Thirty-four MDD patients and 34 age and gender matched healthy controls (HC) were recruited. Plasma concentrations of the cytokines of interleukin-1 (IL-1) family, including IL-1α, IL-1ß, IL-1 receptor antagonist (IL-1Ra) and IL-1 receptor type 2 (IL-1R2) were measured using enzyme-linked immune-sorbent assays. The serotonin transporter (SERT) availability in midbrain, thalamus, caudate, and putamen was examined by single-photon emission computed tomography with 123I-ADAM. There were significantly lower concentrations of pro-inflammatory IL-1ß and its inhibitor, IL-1R2 in MDD than HC. The SERT availability was at the same level between groups. A negative association between IL-1Ra concentration and the SERT availability in midbrain was observed in MDD but not in HC. Both IL-1ß concentration and the SERT availability in caudate negatively correlated with depression severity and the effect of IL-1ß was not moderated or mediated by the SERT. In conclusion, this study demonstrated the involvement of IL-1 family in the early stage of MDD, especially for IL-1ß. SERT was not the main central target of altered IL-1ß and these two systems might contribute to MDD by different mechanisms. The pathophysiology might be varied between early and recurrent MDD and tuning treatment strategies at different clinical stages might be needed.
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Trastorno Depresivo Mayor , Preparaciones Farmacéuticas , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/tratamiento farmacológico , Humanos , Interleucina-1 , Proyectos Piloto , Proteínas de Transporte de Serotonina en la Membrana PlasmáticaRESUMEN
Cognitive dysfunction has been reported in patients with carbon monoxide (CO) poisoning. However, the underpinning mechanism remained unclear. This study examined dopamine transporter (DAT) and metabolite ratios concurrently and their relationships with cognitive dysfunction in CO poisoning. Eighteen suicide attempters with charcoal burning which results in CO poisoning and 18 age- and gender- matched normal controls were recruited. A battery of cognitive assessments including attention, memory, and executive function was administered. Each participant received one single photon emission computed tomography with 99mTc-TRODAT for measuring striatal DAT availability and proton magnetic resonance spectroscopy to determine N-acetyl aspartate/creatine (NAA/Cr), choline-containing compounds/creatine (Cho/Cr) and myo-inositol/creatine (mI/Cr) in the left parietal white matter and mid-occipital gray matter (OGM). CO poisoning patients had significant impairments in memory and executive function. Compared to normal, CO poisoning patients had lower striatal DAT availability, lower NAA/Cr levels in both regions and higher Cho/Cr levels in both regions. In CO poisoning patients, the altered left striatal DAT availability and Cho/Cr level in OGM were significantly associated with executive dysfunction in the expected directions. Moreover, there was a significant interaction between these two imaging indices on their relationships with executive dysfunction and combination of them could adequately predict executive dysfunction in more CO poisoning cases than either alone. The current results suggested that both alterations in DAT availability and metabolite ratios might play crucial roles in executive dysfunction in CO poisoning. This research also highlights the importance of multimodal imaging approaches for studying neurotoxicity effects.
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Intoxicación por Monóxido de Carbono/complicaciones , Disfunción Cognitiva/inducido químicamente , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Intoxicación por Monóxido de Carbono/diagnóstico por imagen , Intoxicación por Monóxido de Carbono/metabolismo , Estudios de Casos y Controles , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/metabolismo , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Neuroimagen , Pruebas Neuropsicológicas , Estudios Prospectivos , Espectroscopía de Protones por Resonancia Magnética , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
INTRODUCTION: Depression is the most commonly seen psychiatric co-morbidity of epilepsy. Depression in patients with epilepsy (PWE) is underrecognized. The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a useful tool to screen for major depressive episodes (MDEs) in PWE. This study validated the Taiwanese version of the NDDI-E using data from adult PWE in our hospital. METHOD: PWE were recruited from the Taipei Veterans General Hospital from April 2017 to December 2019. The Chinese version of the NDDI-E for the Taiwanese population and the Beck Depression Inventory-II (BDI-II) were completed as part of the self-rated psychiatric assessments. The mood disorder module of the Mini International Neuropsychiatric Interview (MINI) was completed as part of the psychiatric assessment before the self-rated assessment. Internal consistency, external validation, and receiver operator characteristic (ROC) curve analysis were used to assess the utility of the Taiwanese version of the NDDI-E. RESULTS: We recruited 109 patients during the 33-month study period. The mean age was 33.1 ± 8.94 years old. The mean NDDI-E score was 12.32 ± 4.96. The mean BDI-II score was 13.26 ± 12.77. All NDDI-E items were significantly positively associated with the corrected overall NDDI-E score (Cronbach's alpha = 0.902, r = 0.825, p < 0.0001). The cut-off point for the NDDI-E determined with receiver operating characteristic (ROC) curve analysis is 15 (sensitivity = 85.0%, specificity = 87.64%). CONCLUSION: The Chinese version of the NDDI-E adapted for the Taiwanese population is a reliable and valid self-reported questionnaire for detecting MDE in Taiwanese PWE.
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Trastorno Depresivo Mayor , Epilepsia , Adulto , Niño , Depresión/diagnóstico , Depresión/epidemiología , Depresión/etiología , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/epidemiología , Epilepsia/complicaciones , Epilepsia/diagnóstico , Epilepsia/epidemiología , Humanos , Escalas de Valoración Psiquiátrica , Psicometría , Curva ROC , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: The efficacy and safety of lurasidone in schizophrenia has been demonstrated in multiple controlled trials, primarily in US and European populations. The aim of the current study was To evaluate lurasidone for the treatment of schizophrenia among patients in Japan, Korea, and Taiwan. METHODS: Hospitalized patients (N = 460) with schizophrenia were randomized to 6 weeks of fixed-dose lurasidone 40 mg/d, lurasidone 80 mg/d, risperidone 4 mg/d, or placebo. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S). RESULTS: No significant endpoint differences in PANSS total score were found for lurasidone or risperidone vs placebo. Lurasidone was safe and well tolerated, with minimal effects on weight and metabolic parameters. DISCUSSION: The current study was inconclusive regarding the efficacy of lurasidone in schizophrenia but further confirmed its safety and tolerability.
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Antipsicóticos/uso terapéutico , Clorhidrato de Lurasidona/uso terapéutico , Risperidona/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Clorhidrato de Lurasidona/efectos adversos , Masculino , Persona de Mediana Edad , Risperidona/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Carbon monoxide (CO) poisoning has recently become a serious health problem in some Asian countries, including Taiwan. The aims of this study are to evaluate the changing trend of CO poisoning and to demonstrate the association between myocardial injury and neurological sequelae of CO poisoning in Taiwan between 1990 and 2011. METHODS: This retrospective cohort study included all eligible patients with acute CO poisoning reported to the Taiwan National Poison Control Center during the study period. The changing trend of CO poisoning and its impacts on the primary outcomes, i.e., persistent neurological sequelae (PNS) and delayed neurological sequelae (DNS), were then assessed. RESULTS: 786 CO poisoned cases were reported. Among them, 467 cases were intentional. Intentional CO exposure started to become the major cause of CO poisoning in Taiwan in 2002. Increase in the number of intentional CO poisoning significantly correlated with the increase in the overall number of CO poisoning (r = 0.972, p < 0.001). Patients who took tranquilizer (OR = 3.89; 95% CI:1.94-7.77), had myocardial injury (OR = 1.70; 95% CI:1.03-2.82), had been stayed in intensive care unit (OR = 2.03; 95% CI:1.13-3.62), presented with GCS less than 9 (OR = 4.05; 95% CI:2.32-7.08) and had abnormal brain image (OR = 14.46; 95% CI:5.83-35.83) had a higher risk of PNS. Moreover, patients who were older age (OR = 1.04; 95% CI:1.02-1.07), had psychiatric disorder history (OR = 2.82; 95% CI:1.35-5.89), had myocardial injury (OR = 1.33; 95% CI:1.16-1.53), and presented with GCS less than 9 (OR = 3.23; 95% CI:1.65-6.34) had a higher risk of DNS. CONCLUSION: The pattern of CO poisoning had changed markedly during the study period, with a significant increase in both the numbers of intentional and overall CO poisoning. Moreover, intentional CO poisoning was associated with a higher risk of neurological sequelae, which was mediated by various indicators of poisoning severity such as myocardial injury and GCS less than 9.
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Intoxicación por Monóxido de Carbono/complicaciones , Cardiomiopatías/etiología , Enfermedades del Sistema Nervioso/etiología , Enfermedad Aguda , Adulto , Femenino , Humanos , Oxigenoterapia Hiperbárica , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/etiología , Estudios RetrospectivosRESUMEN
99mTc-TRODAT-1 is a type of drug that can bind to dopamine transporters in living organisms and is often used in SPCT imaging for observation of changes in the activity uptake of dopamine in the striatum. Therefore, it is currently widely used in studies on clinical diagnosis of Parkinson's disease (PD) and movement-related disorders. In conventional 99mTc-TRODAT-1 SPECT image evaluation, visual inspection or manual selection of ROI for semiquantitative analysis is mainly used to observe and evaluate the degree of striatal defects. However, these methods are dependent on the subjective opinions of observers, which lead to human errors, have shortcomings such as long duration, increased effort, and have low reproducibility. To solve this problem, this study aimed to establish an automatic semiquantitative analytical method for 99mTc-TRODAT-1. This method combines three drug templates (one built-in SPECT template in SPM software and two self-generated MRI-based and HMPAO-based TRODAT-1 templates) for the semiquantitative analysis of the striatal phantom and clinical images. At the same time, the results of automatic analysis of the three templates were compared with results from a conventional manual analysis for examining the feasibility of automatic analysis and the effects of drug templates on automatic semiquantitative analysis results. After comparison, it was found that the MRI-based TRODAT-1 template generated from MRI images is the most suitable template for 99mTc-TRODAT-1 automatic semiquantitative analysis.
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Cuerpo Estriado/diagnóstico por imagen , Enfermedad de Parkinson/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodos , Adulto , Anciano , Anciano de 80 o más Años , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Compuestos de Organotecnecio/metabolismo , Compuestos de Organotecnecio/farmacocinética , Enfermedad de Parkinson/metabolismo , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tropanos/metabolismo , Tropanos/farmacocinética , Adulto JovenRESUMEN
BACKGROUND: Mild cognitive impairment (MCI) is characterized by a decrease in cognitive abilities that does not affect the ability to perform activities of daily living (ADLs). Therefore, this condition is easily overlooked. The prevalence and factors of influence for MCI in older people living in publicly managed congregate housing are currently unknown. PURPOSE: This study investigated the prevalence and distribution of MCI in older people living in publicly managed congregate housing and assessed the correlations among quality of life (QoL), ADL, and MCI. METHODS: This study applied a correlational study design. The participants were older people who met the study criteria and who lived in public housing in Wanhua District, Taipei City, Taiwan. One-on-one interviews were conducted to measure the cognitive abilities of the participants, and 299 valid samples were collected. RESULTS: The prevalence of MCI in older people living in publicly managed congregate housing was 16.1%. The χ test was employed to evaluate the distribution of MCI prevalence and indicated that the group with higher MCI prevalence exhibited the following characteristics: older than 81 years; married; lived in public housing for more than 20 years; cohabiting; had a history of drinking; and exhibited severe memory regression, physical disabilities, psychological distress, and low QoL. The difference between the groups achieved statistical significance (p < .05). After performing logistical regression analysis to control demographic variables, we found that QoL and ADL were critical for predicting MCI. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study confirmed that QoL and ADL correlate significantly with MCI in older people. Maintaining an open and supportive community enables older people to maintain sufficient mental activity, which has been shown to reduce MCI. These findings may provide an important reference for policy makers, educators, researchers, and community practitioners in their development of service strategies for older people.
Asunto(s)
Actividades Cotidianas , Envejecimiento/fisiología , Disfunción Cognitiva/complicaciones , Hogares para Ancianos/estadística & datos numéricos , Casas de Salud/estadística & datos numéricos , Calidad de Vida , Anciano , Anciano de 80 o más Años , Disfunción Cognitiva/epidemiología , Femenino , Evaluación Geriátrica , Humanos , Masculino , Prevalencia , Taiwán/epidemiologíaRESUMEN
BACKGROUND: Reduced brain serotonin transporter (SERT) has been demonstrated in bipolar disorder (BD). The aim of this study was to explore the potential role of cytokines on reduced SERT in BD. METHODS: Twenty-eight BD type I patients and 28 age- and gender-matched healthy controls (HCs) were recruited. Single photon emission computed tomography with the radiotracer 123I ADAM was used for SERT imaging. Regions of interest included the midbrain, thalamus, putamen and caudate. Seven cytokines, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1α (IL-1α), IL-1ß, IL-4, IL-6 and IL-10, were measured using an enzyme linked immune-sorbent assay. RESULTS: SERT availability in the midbrain and caudate was significantly lower in BD compared to HCs. IL-1ß was significantly lower, whereas IL-10 was significantly higher in BD compared to HCs. Multiple linear regression analyses revealed that there were associations between cytokines, IL-1α, IL-1ß, IL-6 and SERT availability in the midbrain but not in the thalamus, putamen and caudate. Furthermore, linear mixed effect analyses demonstrated that these associations were not different between HCs and BD. CONCLUSION: While many cytokines have been proposed to be important in the pathophysiology of BD, our results demonstrated that significant associations between cytokines and SERT availability may explain the role of cytokines in mood regulation. However, these associations were not different between HCs and BD, which imply the role of these cytokines is not specific for BD.
Asunto(s)
Trastorno Bipolar/fisiopatología , Citocinas/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Adulto , Trastorno Bipolar/sangre , Trastorno Bipolar/metabolismo , Encéfalo/metabolismo , Cinanserina/análogos & derivados , Cinanserina/metabolismo , Citocinas/sangre , Femenino , Neuroimagen Funcional , Humanos , Masculino , Tomografía Computarizada de Emisión de Fotón Único , Adulto JovenRESUMEN
Converging evidence indicates the hypothalamus-pituitary-adrenal axis and serotonergic neurons exert reciprocal modulatory actions. Likewise, brain-derived neurotrophic factor (BDNF) has been implicated as a growth and differentiation factor in the development of serotonergic neurons. The aim of this study was to examine the interaction of cortisol and BDNF on serotonin transporter (SERT) in bipolar disorder (BD). Twenty-eight BD and 28 age- and gender-matched healthy controls (HCs) were recruited. (123)I-ADAM with single-photon emission computed tomography (SPECT) was applied for measurement of SERT availability in the brain, which included the midbrain, thalamus, putamen and caudate. Ten milliliters of venous blood was withdrawn, when the subject underwent SPECT, for the measurement of the plasma concentration of cortisol and BDNF. SERT availability was significantly decreased in the midbrain and caudate of BD compared with HCs, whereas plasma concentration of cortisol and BDNF did not show a significant difference. The linear mixed-effect model revealed that there was a significant interaction of group and cortisol on SERT availability of the midbrain, but not BDNF. Linear regression analyses by groups revealed that cortisol was associated with SERT availability in the midbrain in the HCs, but not in BD. Considering previous studies, which showed a significant association of cortisol with SERT availability in the HCs and major depressive disorder (MDD), our result replicated a similar finding in HCs. However, the negative finding of the association of cortisol and SERT availability in BD, which was different from MDD, suggests a different role for cortisol in the pathophysiology of mood disorder.
Asunto(s)
Trastorno Bipolar/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hidrocortisona/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Adulto , Trastorno Bipolar/diagnóstico por imagen , Trastorno Bipolar/patología , Encéfalo/diagnóstico por imagen , Estudios de Casos y Controles , Cinanserina/análogos & derivados , Cinanserina/farmacología , Femenino , Humanos , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Unión Proteica/efectos de los fármacos , Radioquímica , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician's clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms.