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1.
Mol Psychiatry ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409883

RESUMO

Disturbance of glucose metabolism may be implicated in cognitive deficits of schizophrenia in its early phases. Many studies have reported the important role of widespread disruption of white matter (WM) connectivity in pathogenesis, cognitive deficit and psychopathology of schizophrenia. However, no study has investigated their inter-relationships in drug-naive first episode (DNFE) patients with schizophrenia. Glucose metabolism parameters including fasting glucose, insulin and homeostasis model of assessment-insulin resistance (HOMA-IR) index, cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB) and the voxel-wised WM fractional anisotropy (FA) values were examined using DTI in 39 DNFE schizophrenia and 31 control subjects. The Positive and Negative Syndrome Scale was utilized for clinical symptoms. The patients showed significantly greater fasting plasma levels of glucose and insulin and HOMA-IR, and poorer cognitive scores, together with widespread reduced FA values in five brain areas, including left and right corpus callosum, superior longitudinal fasciculus, posterior thalamic radiation, and corona radiata (all p < 0.05). Association analysis showed that glucose level was positively associated with Digital Sequence Test and Continuous Performance Test, but negatively with FA values in posterior thalamic radiation and left corpus callosum in patients (all p < 0.05). Furthermore, multiple regression analysis revealed that the interactions of glucose × FA in left corpus callosum, longitudinal fasciculus and corona radiata were independent contributors to the Brief Visuospatial Memory Test (BVMT) of MCCB, while the interaction of glucose × FA in left corpus callosum, or in longitudinal fasciculus was associated with MCCB mazes and Trail Making A Test, respectively. Therefore, abnormal glucose metabolism, cognitive impairment and widespread disruption of WM structure occur in an early course of schizophrenia onset. An interaction between glucose metabolism abnormality and the WM dysconnectivity may lead to cognitive impairment.

2.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 41(4): 336-362, July-Aug. 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1011505

RESUMO

Objectives: Brain imaging studies carried out in patients suffering from generalized anxiety disorder (GAD) have contributed to better characterize the pathophysiological mechanisms underlying this disorder. The present study reviews the available functional and structural brain imaging evidence on GAD, and suggests further strategies for investigations in this field. Methods: A systematic literature review was performed in PubMed, PsycINFO, and Google Scholar, aiming to identify original research evaluating GAD patients with the use of structural and functional magnetic resonance imaging as well as diffusion tensor imaging. Results: The available studies have shown impairments in ventrolateral and dorsolateral prefrontal cortex, anterior cingulate, posterior parietal regions, and amygdala in both pediatric and adult GAD patients, mostly in the right hemisphere. However, the literature is often tentative, given that most studies have employed small samples and included patients with comorbidities or in current use of various medications. Finally, different methodological aspects, such as the type of imaging equipment used, also complicate the generalizability of the findings. Conclusions: Longitudinal neuroimaging studies with larger samples of both juvenile and adult GAD patients, as well as at risk individuals and unaffected relatives, should be carried out in order to shed light on the specific biological signature of GAD.

3.
Pharmacol Biochem Behav ; 183: 56-63, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31158395

RESUMO

The present study evaluated the effects of the coadministration of lithium (Li) and Cel on inflammatory parameters in an animal model of mania induced by dextroamphetamine (D-amph). It was used Wistar rats 60 days old (250-350 g). The animals (n = 10 per group) received D-amph (2 mg/kg) or saline solution of NaCl 0.9% (Sal) intraperitoneally once a day for 14 days. From day eight until 14, the animals from the D-amph and Sal groups received Li (24 mg/kg), Cel (20 mg/kg), Li + Cel or water via gavage. Behavioral analyses were performed using the open-field test. The levels of IL-1ß, IL-4, IL-10, and TNF-α were evaluated. The administration of D-amph induced hyperactivity in the rats, as well increased the IL-4, IL-10, and TNF-α levels in the serum, frontal cortex, and striatum of rats compared to those of the controls, and treatment with Li plus Cel reversed these alterations. In general, the administration of Li or Cel per se did not have effects on the behavioral and biochemical parameters. However, the treatment with Cel per se decreased only the IL-10 levels in the serum of animals. Besides, the treatment with Li or Cel decreased the IL-4 levels in the serum and reversed the effects of D-amph on this parameter in the frontal cortex. The treatment with Li reversed the effects of D-amph on the TNF-α levels in all tissues evaluated, and the administration of Cel reversed this alteration only in the striatum. It can be observed that treatment with Li plus Cel was more effective against damages caused by D-amph when compared to the administration of both treatments per se, suggesting that the coadministration can be more effective to treat BD rather than Li or Cel itself. The treatment with Li plus Cel was effective against the inflammation induced by D-amph.

4.
Magn Reson Imaging ; 61: 16-19, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31078614

RESUMO

PURPOSE: To reduce patient anxiety caused by the MRI scanner acoustic noise. MATERIAL AND METHODS: We developed a simple and low-cost system for patient distraction using visual computer animations that were synchronized to the MRI scanner's acoustic noise during the MRI exam. The system was implemented on a 3T MRI system and tested in 28 pediatric patients with bipolar disorder. The patients were randomized to receive noise-synchronized animations in the form of abstract animations in addition to music (n = 13, F/M = 6/7, age = 10.9 ±â€¯2.5 years) or, as a control, receive only music (n = 15, F/M = 7/8, age = 11.6 ±â€¯2.3 years). After completion of the scans, all subjects answered a questionnaire about their scan experience and the perceived scan duration. RESULTS: The scan duration with multisensory input (animations and music) was perceived to be ~15% shorter than in the control group (43 min vs. 50 min, P < 0.05). However, the overall scan experience was scored less favorably (3.9 vs. 4.6 in the control group, P < 0.04). CONCLUSIONS: This simple system provided patient distraction and entertainment leading to perceived shorter scan times, but the provided visualization with abstract animations was not favored by this patient cohort.

5.
Braz J Psychiatry ; 41(4): 336-362, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31116259

RESUMO

OBJECTIVES: Brain imaging studies carried out in patients suffering from generalized anxiety disorder (GAD) have contributed to better characterize the pathophysiological mechanisms underlying this disorder. The present study reviews the available functional and structural brain imaging evidence on GAD, and suggests further strategies for investigations in this field. METHODS: A systematic literature review was performed in PubMed, PsycINFO, and Google Scholar, aiming to identify original research evaluating GAD patients with the use of structural and functional magnetic resonance imaging as well as diffusion tensor imaging. RESULTS: The available studies have shown impairments in ventrolateral and dorsolateral prefrontal cortex, anterior cingulate, posterior parietal regions, and amygdala in both pediatric and adult GAD patients, mostly in the right hemisphere. However, the literature is often tentative, given that most studies have employed small samples and included patients with comorbidities or in current use of various medications. Finally, different methodological aspects, such as the type of imaging equipment used, also complicate the generalizability of the findings. CONCLUSIONS: Longitudinal neuroimaging studies with larger samples of both juvenile and adult GAD patients, as well as at risk individuals and unaffected relatives, should be carried out in order to shed light on the specific biological signature of GAD.


Assuntos
Transtornos de Ansiedade/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Neuroimagem Funcional , Imagem por Ressonância Magnética , Transtornos de Ansiedade/fisiopatologia , Encéfalo/fisiopatologia , Humanos
6.
Artigo em Inglês | MEDLINE | ID: mdl-31135366

RESUMO

Genome-wide association studies (GWAS) link full genome data to a handful of traits. However, in neuroimaging studies, there is an almost unlimited number of traits that can be extracted for full image-wide big data analyses. Large populations are needed to achieve the necessary power to detect statistically significant effects, emphasizing the need to pool data across multiple studies. Neuroimaging consortia, e.g., ENIGMA and CHARGE, are now analyzing MRI data from over 30,000 individuals. Distributed processing protocols extract harmonized features at each site, and pool together only the cohort statistics using meta analysis to avoid data sharing. To date such MRI projects have focused on single measures such as hippocampal volume, yet voxelwise analyses (e.g., tensor-based morphometry; TBM) may help better localize statistical effects. This can lead to 1013 tests for GWAS and become underpowered. We developed an analytical framework for multi-site TBM by performing multi-channel registration to cohort-specific templates. Our results highlight the reliability of the method and the added power over alternative options while preserving single site specificity and opening the doors for well-powered image-wide genome-wide discoveries.

7.
J Affect Disord ; 253: 240-247, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31060010

RESUMO

BACKGROUND: We studied emotional information processing in youth with pediatric bipolar disorder (pBD) using the late positive potential (LPP), assessing automatic allocation of attentional resources to emotionally salient stimuli, and the occipital P1, assessing early sensory processing. METHODS: Participants were 20 youth with pBD and 26 healthy controls (HC). Participants passively viewed faces with a fearful, neutral or happy expressions. Group differences were tested with general linear models. P1 was included to examine modulating effects on LPP. We calculated Bayes factor (BF) values to express strength of evidence for choosing one hypothesis over another. RESULTS: A significant emotion by group interaction for LPP amplitude was associated with a larger amplitude for happy faces for pBD than HC (F[1,40] = 6.04, p = .018); this was not modulated by P1 amplitude or latency. P1 amplitude did not differ between groups, although P1 peaked earlier for HC (F[1,40] = 5.45, p = .025). BF for LPP was 2.93, suggesting moderate evidence favoring H1. BF for P1 latency of 14.58 suggests strong evidence favoring H1. LIMITATIONS: Inclusion of children and adolescents prohibited careful control for neurodevelopmental effects. CONCLUSIONS: Larger LPP amplitude for happy faces without change in P1 suggests enhanced automatic allocation of attentional resources to positive information in pBD. Delayed P1 latency in pBD suggests slower early processing of emotional information.

8.
J Affect Disord ; 255: 10-14, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31125858

RESUMO

BACKGROUND: The search for biomarkers of bipolar disorder (BD), including epigenetic alterations, has heavily relied on peripheral investigations that do not necessarily reflect brain-specific mechanisms. In this study we aimed to assess peripheral extracellular vesicles (EVs)' microRNAs and determine their use as a novel source of biomarkers in BD. METHODS: We assessed peripheral blood EVs' microRNAs from 20 patients with BD type I and 21 age- and sex-matched healthy controls by microarray, and further explored the predicted biological functions of significantly differentially expressed microRNAs. RESULTS: Our results identified 33 nominally significant microRNAs (p < 0.05 and fold-change >1.5) altered in BD patients, including miRNAs previously reported to be altered in post-mortem tissues of patients. Pathway analyses identified some brain-relevant mechanisms enriched in these miRNAs, including axon guidance by netrin and the serotonin receptor pathway. LIMITATIONS: Relatively small sample size, potential confounding effects of mood states, medication use, and comorbidities, analysis of total rather than brain-specific EVs, and lack of validation of significant miRNAs by other methods. CONCLUSIONS: This study provides important preliminary evidence of the potential use of EVs as a novel source of biomarkers in BD. Overall, our findings of brain-relevant mechanisms in these vesicles suggest their potential use in living patients as a peripheral window to the brain.

10.
Mol Biol Rep ; 46(3): 2867-2875, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30903572

RESUMO

Patients with alcohol use disorder may develop acute ethanol withdrawal syndrome (EWS). Previous studies showed that an epigenetic modification of the N-methyl-D-aspartate (NMDA) receptor, especially NMDA receptor 2B subunit (NR2B), was involved in the pathological process of EWS. However, the relationship between the epigenetic regulation of the NR2B gene in the rat hippocampus region and EWS were inconsistent. The purpose of this study was to explore the role of the histone H3K9 acetylation of the NR2B gene in the rat hippocampus region in EWS. A rat model of chronic ethanol exposure was established. EWS score and the behavioral changes were recorded at different time points. The NR2B expression levels and the histone H3K9 acetylation level in the NR2B gene promoter region were measured using qRT-PCR, Western blot, immunofluorescence, and chromatin immunoprecipitation, respectively. Finally, the relationship between the epigenetic modification of histone H3K9 acetylation of NR2B gene promoter and EWS were examined. Our ultimate results showed that the EWS score was increased at 2 h, peaked at 6 h after withdrawal of ethanol, and reduced to the level parallel to the normal control group at day 3 after ethanol withdrawal. The NR2B mRNA expression and protein levels showed similar patterns. Further correlation analyses indicted that both histone H3K9 acetylation in NR2B gene promoter and the expression levels of NR2B were positively associated with EWS. Our results suggest that chronic ethanol exposure may result in epigenetic modification of histone H3K9 acetylation in NR2B gene promoter in rat hippocampus, and the expression levels of NR2B were found to be positively correlated with ethanol withdrawal syndrome.

11.
Neuropsychology ; 33(4): 482-489, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30855153

RESUMO

OBJECTIVE: Evidence has shown the importance of tumor necrosis factor alpha (TNF-alpha) in the pathophysiological feature in schizophrenia patients. This study aims to determine the impact of a single-nucleotide polymorphism (SNP) in the TNF-alpha gene promoter on the susceptibility, onset age, and cognitive function of schizophrenia. METHOD: The SNP -1031T>C in the TNF-alpha gene was genotyped in 905 patients and 571 healthy controls. The Positive and Negative Syndrome Scale (PANSS) was used to assess the schizophrenia symptoms and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) for cognitive function. RESULTS: There was no significant difference in allele or genotype distribution of the SNP -1031T>C between patients and controls (p = .85, p = .98). This polymorphism had no significant genotypic effect on the symptomatology assessed by the PANSS. Interestingly, this polymorphism was significantly correlated with onset age in schizophrenia patients (p = .004). We found an earlier onset age in patients with the TT genotype compared to those with the CT and CC genotypes (both p < .05). Moreover, there were significant genotypic effects on the immediate memory index, visuospatial/constructional index, and RBANS total score (all p < 0.05) in the patient group. CONCLUSIONS: Our results suggest that the SNP -1031T>C of the TNF-alpha gene may not be associated with susceptibility to schizophrenia but possibly acts as a modulator for its onset age as well as for cognitive deficits. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética , Fator de Necrose Tumoral alfa/genética , Adulto , Idade de Início , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático , China , Cognição/fisiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Regiões Promotoras Genéticas , Adulto Jovem
12.
J Affect Disord ; 250: 391-396, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30877862

RESUMO

OBJECTIVES: Spouses and partners of individuals with bipolar disorder (BD) experience significant burden. As there are some limitations to standard psychosocial caregiver interventions, mobile health technology (mHealth) may be a way to reduce burden and improve well-being in these caregivers. The purpose of this study was to explore how the well-being of spouses or partners of patients with BD can be improved through mHealth technology. METHODS: Using a qualitative design, we conducted five focus groups and one in-depth individual interview to collect information from participants about what they would expect from such a device. The sample consists of thirteen participants (eleven spouses and two partners). The age range was 29-65, with eight females and five males. Data were collected using minimally structured interviews and independently analyzed by the authors using content analysis. RESULTS: Results indicated that the mHealth device many be helpful in at least six areas: reduction of stressors, decreased social isolation, improving communication in the relationship between the spouses, speaking with children about the illness, managing medications, and providing information on resources. CONCLUSION: Mobile health technology may be a feasible, available, and cost-effective support tool for spouses and partners of individuals with BD, especially in reducing caregiver stress. Future research is needed to develop the application and test its effectiveness on health outcomes in a larger trial.


Assuntos
Transtorno Bipolar/psicologia , Cuidadores/psicologia , Casamento/psicologia , Cônjuges/psicologia , Telemedicina , Adaptação Psicológica , Adulto , Transtorno Bipolar/enfermagem , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Isolamento Social , Apoio Social
13.
J Affect Disord ; 245: 1135-1138, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30699857

RESUMO

AIMS: Electroconvulsive Therapy (ECT) is a well-established and effective treatment in mood disorders but the use of ECT in Texas is much lower than the general average among the United States. Our goal is to explore the geographical accessibility of Electroconvulsive Services in Texas. METHODS: 22 ECT Centers in Texas listed in State's 2016 annual ECT report were enrolled and georeferenced. We used Esri's StreetMap Premium Network release 1 network dataset to generate 1-hour drive time service areas for these ECTs. We estimated populations within these service areas based on US Census Tract level population-weighted centroids; generated from the 2015, American Community Survey (ACS) estimates at the US Census Block Group level. RESULTS: About 75% (19,851,802 of 26,538,614) of Texas total population is within a 1-hour drive time to any ECT Services location. When focusing on population below the poverty level from 2015 Block Group level ACS data: 68% (3,046,141 of 4,472,451) are within a 1-hour drive time. CONCLUSIONS: ECT services are geographically accessible in Texas. Other barriers may contribute to lower use of ECT.


Assuntos
Eletroconvulsoterapia/estatística & dados numéricos , Sistemas de Informação Geográfica , Acesso aos Serviços de Saúde/estatística & dados numéricos , Geografia , Humanos , Texas , Estados Unidos
14.
Cogn Neuropsychiatry ; 24(2): 93-107, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30774035

RESUMO

BACKGROUND AND AIMS: Cognitive impairments are primary hallmarks symptoms of bipolar disorder (BD). Whether these deficits are markers of vulnerability or symptoms of the disease is still unclear. This study used a component-wise gradient (CGB) machine learning algorithm to identify cognitive measures that could accurately differentiate pediatric BD, unaffected offspring of BD parents, and healthy controls. METHODS: 59 healthy controls (HC; 11.19 ± 3.15 yo; 30 girls), 119 children and adolescents with BD (13.31 ± 3.02 yo, 52 girls) and 49 unaffected offspring of BD parents (UO; 9.36 ± 3.18 yo; 22 girls) completed the CANTAB cognitive battery. RESULTS: CGB achieved accuracy of 73.2% and an AUROC of 0.785 in classifying individuals as either BD or non-BD on a dataset held out for validation for testing. The strongest cognitive predictors of BD were measures of processing speed and affective processing. Measures of cognition did not differentiate between UO and HC. CONCLUSIONS: Alterations in processing speed and affective processing are markers of BD in pediatric populations. Longitudinal studies should determine whether UO with a cognitive profile similar to that of HC are at less or equal risk for mood disorders. Future studies should include relevant measures for BD such as verbal memory and genetic risk scores.

15.
Sci Rep ; 9(1): 217, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30659208

RESUMO

Recent studies demonstrate that brain-derived neurotrophic factor (BDNF) might be associated with nicotine addiction, and circulating BDNF is a biomarker of memory and general cognitive function. Moreover, studies suggest that a functional polymorphism of the BDNF Val66Met may mediate hippocampal-dependent cognitive functions. We aimed to explore the relationships between smoking, cognitive performance and BDNF in a normal Chinese Han population. We recruited 628 male healthy subjects, inducing 322 smokers and 306 nonsmokers, and genotyped them the BDNF Val66Met polymorphism. Of these, we assessed 114 smokers and 98 nonsmokers on the repeatable battery for the assessment of neuropsychological status (RBANS), and 103 smokers and 89 nonsmokers on serum BDNF levels. Smokers scored lower than the nonsmokers on RBANS total score (p = 0.002), immediate memory (p = 0.003) and delayed memory (p = 0.021). BDNF levels among the smokers who were Val allele carriers were correlated with the degree of cognitive impairments, especially attention, as well as with the carbon monoxide concentrations. Our findings suggest that smoking is associated with cognitive impairment in a male Chinese Han population. The association between higher BDNF levels and cognitive impairment, mainly attention in smokers appears to be dependent on the BDNF Val66Met polymorphism.

16.
J Affect Disord ; 247: 114-119, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30660020

RESUMO

OBJECTIVE: Histories of childhood trauma (CT) are risk factors for affect dysregulation and poor clinical outcomes in women with bipolar disorder (BD). While much is known about the link between BD and CT in adult patients, there is limited data on this research topic in pediatric BD (PBD). The present study aims to investigate the impact of CT on irritability, aggressive and suicidal behaviors in PBD patients across gender types. METHODS: From 2013 to 2015, 59 PBD patients Aged 6-17 (30 female) were administered the Childhood Trauma Questionnaire (CTQ) along with scales assessing irritability (Affective Reactivity Index), aggression (Modified Overt Aggression Scale) and suicidal thoughts and behaviors (Columbia-Suicide Severity Rating Scale). We examined the severity of these behaviors across types of CT and gender using univariate regression analyses. Findings were adjusted for age, number of traumas, and CTQ denial score. RESULTS: In PBD patients, analyses showed that the effect of physical abuse depended on gender, whereby females were more likely than males to engage in suicidal thoughts and behaviors (p < 0.05). Male gender and CT were strong determinants of irritability (p < 0.05). Violence against property and people was found to be reduced in females, and increased in males with a history of emotional and sexual abuse, respectively (p < 0.05). CONCLUSION: These preliminary findings highlight the significant impact of CT in PBD and suggest that gender may predict the risk for dysfunctional behaviors in PBD patients with CT. Future large scale, longitudinal, investigations focusing on fear processing and extinction may provide a deeper understanding of these gender differences, and their role in the course of BD.


Assuntos
Transtorno Bipolar/psicologia , Maus-Tratos Infantis/psicologia , Adolescente , Agressão , Criança , Medo , Feminino , Humanos , Masculino , Abuso Físico/psicologia , Fatores Sexuais , Ideação Suicida , Suicídio/psicologia , Inquéritos e Questionários
17.
Braz J Psychiatry ; 41(3): 254-256, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30540025

RESUMO

OBJECTIVE: Bipolar disorder (BD) is highly heritable. The present study aimed at identifying brain morphometric features that could represent markers of BD vulnerability in non-bipolar relatives of bipolar patients. METHODS: In the present study, structural magnetic resonance imaging brain scans were acquired from a total of 93 subjects, including 31 patients with BD, 31 non-bipolar relatives of BD patients, and 31 healthy controls. Volumetric measurements of the anterior cingulate cortex (ACC), lateral ventricles, amygdala, and hippocampus were completed using the automated software FreeSurfer. RESULTS: Analysis of covariance (with age, gender, and intracranial volume as covariates) indicated smaller left ACC volumes in unaffected relatives as compared to healthy controls and BD patients (p = 0.004 and p = 0.037, respectively). No additional statistically significant differences were detected for other brain structures. CONCLUSION: Our findings suggest smaller left ACC volume as a viable biomarker candidate for BD.


Assuntos
Transtorno Bipolar/patologia , Giro do Cíngulo/patologia , Hipocampo/patologia , Adulto , Transtorno Bipolar/genética , Estudos de Casos e Controles , Endofenótipos , Família , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Neuropsychopharmacology ; 44(7): 1291-1299, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30575805

RESUMO

Bipolar disorder (BD) is a chronic, debilitating illness with a global prevalence of up to 4.8%. The importance of understanding how dysfunctional mitochondria and mitophagy contribute to cell survival and death in BD is becoming increasingly apparent. Therefore, the purpose of this study was to evaluate the mitophagic pathway and NLRP3 inflammasome activation in peripheral blood mononuclear cells (PBMCs) of patients with BD and healthy individuals. Since 18-kDa translocator protein (TSPO) plays an important role in regulating mitochondrial function and since TSPO itself impairs cellular mitophagy, we also investigated the changes in the TSPO-related pathway. Our results showed that patients with BD had lower levels of Parkin, p62/SQSTM1 and LC3A and an upregulation of TSPO pathway proteins (TSPO and VDAC), both in terms of mRNA and protein levels. Additionally, we found a negative correlation between mitophagy-related proteins and TSPO levels, while VDAC correlated negatively with p62/SQSTM1 and LC3 protein levels. Moreover, we found that the gene expression levels of the NLRP3-related proteins NLRP3, ASC, and pro-casp1 were upregulated in BD patients, followed by an increase in caspase-1 activity as well as IL-1ß and IL-18 levels. As expected, there was a strong positive correlation between NLRP3-related inflammasome activation and TSPO-related proteins. The data reported here suggest that TSPO-VDAC complex upregulation in BD patients, the simultaneous downregulation of mitophagic proteins and NLRP3 inflammasome activation could lead to an accumulation of dysfunctional mitochondria, resulting in inflammation and apoptosis. In summary, the findings of this study provide novel evidence that mitochondrial dysfunction measured in peripheral blood is associated with BD.

19.
Transl Psychiatry ; 8(1): 258, 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30498208

RESUMO

Antipsychotic pharmacotherapy is strongly obesogenic and is associated with increased oxidative stress in patients with schizophrenia. However, whether these changes reflect psychopathology, antipsychotic efficacy, or some other factor is not known. Our study aims to investigate the degree of oxidative stress in different BMI categories and to identify clinical symptomatology that may be paired with increased oxidative stress in a schizophrenia population. To this end, we performed a cross-sectional study and recruited 89 long-term inpatients with schizophrenia and collected the following variables: plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), routine biochemical analysis, and psychopathology through the Positive and Negative Syndrome Scale (PANSS). The results indicate that the levels of the lipid peroxidation product, MDA, were significantly higher in the high BMI group than the low (normal) BMI group. As expected, high BMI was associated with an atherogenic lipid profile; however, it was also associated with fewer psychopathological symptoms. Multiple regression analysis found that MDA levels, the PANSS general psychopathology subscore, and triglyceride levels (all p < 0.05) were independent contributors to the BMI in patients. These results suggested that oxidative stress may play an important role in antipsychotic-induced weight gain. Further investigations using the longitudinal design in first-episode schizophrenia patients are needed to explore the beneficial effect of antioxidants on the abnormal lipid metabolism mediated by antipsychotic treatment.

20.
Br J Psychiatry ; : 1-9, 2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30520709

RESUMO

BACKGROUND: Most people with bipolar disorder spend a significant percentage of their lifetime experiencing either subsyndromal depressive symptoms or major depressive episodes, which contribute greatly to the high levels of disability and mortality associated with the disorder. Despite the importance of bipolar depression, there are only a small number of recognised treatment options available. Consecutive treatment failures can quickly exhaust these options leading to treatment-resistant bipolar depression (TRBD). Remarkably few studies have evaluated TRBD and those available lack a comprehensive definition of multi-therapy-resistant bipolar depression (MTRBD).AimsTo reach consensus regarding threshold definitions criteria for TRBD and MTRBD. METHOD: Based on the evidence of standard treatments available in the latest bipolar disorder treatment guidelines, TRBD and MTRBD criteria were agreed by a representative panel of bipolar disorder experts using a modified Delphi method. RESULTS: TRBD criteria in bipolar depression was defined as failure to reach sustained symptomatic remission for 8 consecutive weeks after two different treatment trials, at adequate therapeutic doses, with at least two recommended monotherapy treatments or at least one monotherapy treatment and another combination treatment. MTRBD included the same initial definition as TRBD, with the addition of failure of at least one trial with an antidepressant, a psychological treatment and a course of electroconvulsive therapy. CONCLUSIONS: The proposed TRBD and MTRBD criteria may provide an important signpost to help clinicians, researchers and stakeholders in judging how and when to consider new non-standard treatments. However, some challenging diagnostic and therapeutic issues were identified in the consensus process that need further evaluation and research.Declaration of interestIn the past 3 years, M.B. has received grant/research support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Meat and Livestock Board, Organon, Novartis, Mayne Pharma, Servier, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Eli Lilly, Grunbiotics, Glaxo SmithKline, Janssen Cilag, LivaNova, Lundbeck, Merck, Mylan, Otsuka, Pfizer and Servier. A.C. has received fees for lecturing from pharmaceutical companies namely Lundbeck and Sunovion. A.J.C. has in the past 3 years received honoraria for speaking from Astra Zeneca and Lundbeck, honoraria for consulting from Allergan, Janssen, Lundbeck and LivaNova and research grant support from Lundbeck. G.M.G. holds shares in P1Vital and has served as consultant, advisor or CME speaker for Allergan, Angelini, Compass pathways, MSD, Lundbeck, Otsuka, Takeda, Medscape, Minervra, P1Vital, Pfizer, Servier, Shire and Sun Pharma. J.G. has received research funding from National Institute for Health Research, Medical Research Council, Stanley Medical Research Institute and Wellcome. H.G. received grants/research support, consulting fees or honoraria from Gedeon Richter, Genericon, Janssen Cilag, Lundbeck, Otsuka, Pfizer and Servier. R.H.M.-W. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending advisory boards) from various pharmaceutical companies including Astra Zeneca, Cyberonics, Eli Lilly, Janssen, Liva Nova, Lundbeck, MyTomorrows, Otsuka, Pfizer, Roche, Servier, SPIMACO and Sunovion. R.M. has received research support from Big White Wall, Electromedical Products, Johnson and Johnson, Magstim and P1Vital. S.N. received honoraria from Lundbeck, Jensen and Otsuka. J.C.S. has received funds for research from Alkermes, Pfizer, Allergan, J&J, BMS and been a speaker or consultant for Astellas, Abbott, Sunovion, Sanofi. S.W has, within the past 3 years, attended advisory boards for Sunovion and LivaNova and has undertaken paid lectures for Lundbeck. D.J.S. has received honoraria from Lundbeck. T.S. has reported grants from Pathway Genomics, Stanley Medical Research Institute and Palo Alto Health Sciences; consulting fees from Sunovion Pharamaceuticals Inc.; honoraria from Medscape Education, Global Medical Education and CMEology; and royalties from Jones and Bartlett, UpToDate and Hogrefe Publishing. S.P. has served as a consultant or speaker for Janssen, and Sunovion. P.T. has received consultancy fees as an advisory board member from the following companies: Galen Limited, Sunovion Pharmaceuticals Europe Ltd, myTomorrows and LivaNova. E.V. received grants/ research support, consulting fees or honoraria from Abbott, AB-Biotics, Allergan, Angelini, Dainippon Sumitomo, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka and Sunovion. L.N.Y. has received grants/research support, consulting fees or honoraria from Allergan, Alkermes, Dainippon Sumitomo, Janssen, Lundbeck, Otsuka, Sanofi, Servier, Sunovion, Teva and Valeant. A.H.Y. has undertaken paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders and LivaNova. He has also previously received funding for investigator-initiated studies from AstraZeneca, Eli Lilly, Lundbeck and Wyeth. P.R.A.S. has received research funding support from Corcept Therapeutics Inc. Corcept Therapeutics Inc fully funded attendance at their internal conference in California USA and all related expenses. He has received grant funding from the Medical Research Council UK for a collaborative study with Janssen Research and Development LLC. Janssen Research and Development LLC are providing non-financial contributions to support this study. P.R.A.S. has received a presentation fee from Indivior and an advisory board fee from LivaNova.

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