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1.
Acta Neurol Scand ; 139(6): 526-532, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30848487

RESUMO

OBJECTIVES: Myotonic dystrophy type 1 (DM1) is a slowly progressive multisystem disorder. Guidelines recommend multidisciplinary follow-up. We aimed to investigate the presence of unmet health and social care needs among patients with DM1 and whether unmet needs correlated with motor function, cognitive impairments, or quality of life. MATERIAL AND METHODS: Patients were 22 adults with DM1. "Needs and Provisions Complexity Scale" (NPCS) was applied to evaluate the individual's needs and provision of health and social services. The Muscular Impairment Rating Scale (MIRS) was used to measure motor function and disease stage. All patients underwent neuropsychological testing. The EQ-5D-3L questionnaire was used to evaluate the patients' health-related quality of life (HRQoL). RESULTS: Median time from diagnosis was 11 years (range: 1-40). Twenty patients had developed needs related to social care, personal care, and rehabilitation that had not been met, whereas need for medical follow-up was largely met. The more pronounced the muscular impairment, the more unmet needs were experienced by DM1 patients (r = 0.50, P = 0.019). Degree of unmet needs did not correlate with full-scale IQ (r = -0.27, P = 0.23) or HRQoL (r = -0.14, P = 0.55). CONCLUSION: Using NPCS, we discovered that patients with DM1 had unmet needs with respect to social care, personal care, and rehabilitation although their need for medical follow-up was met. Thus, the use of NPCS helped bring our practice in better accordance with guidelines. A higher MIRS grade should alert the clinician to the likelihood of unmet needs.


Assuntos
Necessidades e Demandas de Serviços de Saúde , Distrofia Miotônica/psicologia , Distrofia Miotônica/reabilitação , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários
2.
Psychol Med ; : 1-12, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30867076

RESUMO

BACKGROUND: We aimed at exploring potential pathophysiological processes across psychotic disorders, applying metabolomics in a large and well-characterized sample of patients and healthy controls. METHODS: Patients with schizophrenia and bipolar disorders (N = 212) and healthy controls (N = 68) had blood sampling with subsequent metabolomics analyses using electrochemical coulometric array detection. Concentrations of 52 metabolites including tyrosine, tryptophan and purine pathways were compared between patients and controls while controlling for demographic and clinical characteristics. Significant findings were further tested in medication-free subsamples. RESULTS: Significantly decreased plasma concentrations in patients compared to healthy controls were found for 3-hydroxykynurenine (3OHKY, p = 0.0008), xanthurenic acid (XANU, p = 1.5×10-5), vanillylmandelic acid (VMA, p = 4.5×10-5) and metanephrine (MN, p = 0.0001). Plasma concentration of xanthine (XAN) was increased in the patient group (p = 3.5×10-5). Differences of 3OHKY, XANU, VMA and XAN were replicated across schizophrenia spectrum disorders and bipolar disorders subsamples of medication-free individuals. CONCLUSIONS: Although prone to residual confounding, the present results suggest the kynurenine pathway of tryptophan metabolism, noradrenergic and purinergic system dysfunction as trait factors in schizophrenia spectrum and bipolar disorders. Of special interest is XANU, a metabolite previously not found to be associated with bipolar disorders.

3.
Nat Genet ; 51(3): 431-444, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30804558

RESUMO

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.


Assuntos
Transtorno do Espectro Autista/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Dinamarca , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Herança Multifatorial/genética , Fenótipo , Fatores de Risco
5.
Psychol Med ; 49(10): 1749-1757, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30688187

RESUMO

BACKGROUND: Inflammation and immune activation have been implicated in the pathogenesis of severe mental disorders and cardiovascular disease (CVD). Despite high level of comorbidity, many studies of the immune system in severe mental disorders have not systematically taken cardiometabolic risk factors into account. METHODS: We investigated if inflammatory markers were increased in schizophrenia (SCZ) and affective (AFF) disorders independently of comorbid CVD risk factors. Cardiometabolic risk factors (blood lipids, body mass index and glucose) and CVD-related inflammatory markers CXCL16, soluble interleukin-2 receptor (sIL-2R), soluble CD14 (sCD14), macrophage inhibitory factor and activated leukocyte cell adhesion molecule (ALCAM) were measured in n = 992 patients (SCZ, AFF), and n = 647 healthy controls. We analyzed the inflammatory markers before and after controlling for comorbid cardiometabolic risk factors, and tested for association with psychotropic medication and symptom levels. RESULTS: CXCL16 (p = 0.03) and sIL-2R (p = 7.8 × 10-5) were higher, while sCD14 (p = 0.05) were lower in patients compared to controls after controlling for confounders, with significant differences in SCZ for CXCL16 (p = 0.04) and sIL-2R (p = 1.1 × 10-5). After adjustment for cardiometabolic risk factors higher levels of sIL-2R (p = 0.001) and lower sCD14 (p = 0.002) remained, also in SCZ (sIL-2R, p = 3.0 × 10-4 and sCD14, p = 0.01). The adjustment revealed lower ALCAM levels (p = 0.03) in patients. We found no significant associations with psychotropic medication or symptom levels. CONCLUSION: The results indicate that inflammation, in particular enhanced T cell activation and impaired monocyte activation, are associated with severe mental disorders independent of comorbid cardiometabolic risk factors. This suggests a role of novel pathophysiological mechanisms in severe mental disorders, particularly SCZ.

6.
Schizophr Res ; 2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-30126813

RESUMO

BACKGROUND: Although several studies have found reduced plasma BDNF levels in patients with severe mental disorders, the sample sizes have been small and have exhibited variation and heterogeneity. Furthermore, long-term neurobiological changes following childhood trauma and clinical severity have been linked to a reduction in BDNF levels. Accordingly, we aim to clarify, using the largest sample size to date, the role of plasma BDNF in individuals with severe mental disorders in relation to the number of episodes, current remission status, and childhood trauma experiences. METHODS: The study sample comprised 1446 individuals (schizophrenia: SZ [n = 589]; bipolar disorder: BD [n = 254]; and healthy control: HC [n = 603]) all recruited from the same catchment area. A subsample (N = 629) of this larger group had a history of childhood trauma, and some (N = 195) participated in a one-year follow-up study. The level of BDNF in plasma was measured, and childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Diagnoses and episodes were obtained using the Structured Clinical Interview (SCID). RESULTS: Patients with SZ or BD had lower levels of plasma BDNF than did the HC group (p = 0.002, p = 0.003, respectively). Within patients, reduced plasma BDNF levels were associated with more depressive episodes (p = 0.04). Longer time in remission after depressive episodes was associated with higher plasma BDNF levels (p = 0.02), and patients reporting childhood sexual abuse exhibited lower plasma BDNF levels (p = 0.049) than patients without sexual abuse. CONCLUSION: Our study confirms that patients with a severe mental disorder exhibit reduced BDNF levels. While the strongest reduction in BDNF was observed in patients reporting childhood sexual abuse, reduced BDNF levels were also associated with more depressive episodes. Accordingly, further studies are warranted to determine whether treatment that increases BDNF levels may be beneficial to these individuals.

7.
Food Nutr Res ; 622018.
Artigo em Inglês | MEDLINE | ID: mdl-29899685

RESUMO

Persons with intellectual disabilities (ID) are dependent on nutritional policies that have so far not been addressed in a systematic and health-promoting manner in Norway and other nations with a high socioeconomic standard. In many poor countries, such issues have not even been raised nor addressed. Nutritional issues facing persons with ID include the risk of both underweight and overweight. Deficiency in energy, vitamins, essential fatty acids and micronutrients can increase the risk of additional health burdens in already highly vulnerable individuals. According to the World Health Organization, the obesity rates have tripled worldwide the last decades, and recent studies suggest that the prevalence of obesity is even higher for persons with ID than in the general population. This implies additional burdens of life style diseases such as diabetes and hypertension for adults with ID. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5, this group is characterized by intellectual difficulties as well as difficulties in conceptual, social, and practical areas of living. Their reduced intellectual capacity implies that they often have difficulties in making good dietary choices. As a group, they are dependent upon help and guidance to promote a healthy life style. To improve their health, there is a need for improved national services and for more research on lifestyle and nutritional issues in persons with ID. From a human rights perspective, these issues must be put on the agenda both in relevant UN fora and in the respective nations' health policies.

8.
Sci Rep ; 8(1): 5349, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29593239

RESUMO

The Notch signaling pathway plays a crucial role in neurodevelopment and in adult brain homeostasis. We aimed to further investigate Notch pathway activity in bipolar disorder (BD) and schizophrenia (SCZ) by conducting a pathway analysis. We measured plasma levels of Notch ligands (DLL1 and DLK1) using enzyme immunoassays in a large sample of patients (SCZ n = 551, BD n = 246) and healthy controls (HC n = 639). We also determined Notch pathway related gene expression levels by microarray analyses from whole blood in a subsample (SCZ n = 338, BD n = 241 and HC n = 263). We found significantly elevated Notch ligand levels in plasma in both SCZ and BD compared to HC. Significant gene expression findings included increased levels of RFNG and KAT2B (p < 0.001), and decreased levels of PSEN1 and CREBBP in both patient groups (p < 0.001). RBPJ was significantly lower in SCZ vs HC (p < 0.001), and patients using lithium had higher levels of RBPJ (p < 0.001). We provide evidence of altered Notch signaling in both SCZ and BD compared to HC, and suggest that Notch signaling pathway may be disturbed in these disorders. Lithium may ameliorate aberrant Notch signaling. We propose that drugs targeting Notch pathway could be relevant in the treatment of psychotic disorders.

9.
Transl Psychiatry ; 8(1): 55, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29507296

RESUMO

The Wnt signaling pathway plays a crucial role in neurodevelopment and in regulating the function and structure of the adult nervous system. Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders with evidence of subtle neurodevelopmental, structural and functional neuronal abnormalities. We aimed to elucidate the role of aberrant regulation of the Wnt system in these disorders by evaluating plasma levels of secreted Wnt modulators in patients (SCZ = 551 and BD = 246) and healthy controls (HCs = 639) using enzyme immune-assay. We also investigated the expression of 141 Wnt-related genes in whole blood in a subsample (SCZ = 338, BD = 241, and HCs = 263) using microarray analysis. Both SCZ and BD had dysregulated mRNA expression of Wnt-related genes favoring attenuated canonical (beta-catenin-dependent) signaling, and there were also indices of enhanced non-canonical Wnt signaling. In particular, FZD7, which may activate all Wnt pathways, but favors non-canonical signaling, and NFATc3, a downstream transcription factor and readout of the non-canonical Wnt/Ca2+ pathway, were significantly increased in SCZ and BD (p < 3 × 10-4). Furthermore, patients had lower plasma levels of soluble dickkopf 1 and sclerostin (p < 0.01) compared with HC. Our findings suggest that SCZ and BD are characterized by abnormal Wnt gene expression and plasma protein levels, and we propose that drugs targeting the Wnt pathway may have a role in the treatment of severe mental disorders.

11.
Artigo em Inglês | MEDLINE | ID: mdl-29122637

RESUMO

BACKGROUND: Antipsychotic-associated side effects are well known and represent a significant treatment challenge. Still, few large studies have investigated the overall side effect burden of antipsychotics in real-life settings. OBJECTIVE: To describe the occurrence of side effects and perceived burden of antipsychotics in a large naturalistic sample, taking polypharmacy and patient characteristics into account. METHOD: Patients (n=1087) with psychotic disorders were assessed for side effects using the Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale in addition to assessment of clinical and pharmacological data. Statistical analyses were performed controlling for possible confounding factors. RESULTS: Use of antipsychotics showed significant associations to neurologic and sexual symptoms, sedation and weight gain, and >75% of antipsychotics-users reported side effects. More side effects were observed in patients using several antipsychotics (p=0.002), with increasing total dose (p=0.021) and with antipsychotics in combinations with other psychotropic drugs. Patients and investigators evaluated the side effect burden differently, particularly related to severity, gender and antipsychotics dose. Twice as many females described side effect burden as severe (p=0.004). CONCLUSION: Patients with psychotic disorders have a high occurrence of symptoms associated with use of antipsychotics, and polypharmacy and female gender are seemingly risk factors for reporting a severe side effect burden. Due to the cross-sectional design evaluation of causality is tentative, and these findings should be further investigated in prospective studies.

12.
Front Neurosci ; 11: 393, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28744191

RESUMO

Executive functions are often affected in autism spectrum disorders (ASD). The underlying biology is however not well known. In the DSM-5, ASD is characterized by difficulties in two domains: Social Interaction and Repetitive and Restricted Behavior, RRB. Insistence of Sameness is part of RRB and has been reported related to executive functions. We aimed to identify differences between ASD and typically developing (TD) adolescents in Event Related Potentials (ERPs) associated with response preparation, conflict monitoring and response inhibition using a cued Go-NoGo paradigm. We also studied the effect of age and emotional content of paradigm related to these ERPs. We investigated 49 individuals with ASD and 49 TD aged 12-21 years, split into two groups below (young) and above (old) 16 years of age. ASD characteristics were quantified by the Social Communication Questionnaire (SCQ) and executive functions were assessed with the Behavior Rating Inventory of Executive Function (BRIEF), both parent-rated. Behavioral performance and ERPs were recorded during a cued visual Go-NoGo task which included neutral pictures (VCPT) and pictures of emotional faces (ECPT). The amplitudes of ERPs associated with response preparation, conflict monitoring, and response inhibition were analyzed. The ASD group showed markedly higher scores than TD in both SCQ and BRIEF. Behavioral data showed no case-control differences in either the VCPT or ECPT in the whole group. While there were no significant case-control differences in ERPs from the combined VCPT and ECPT in the whole sample, the Contingent Negative Variation (CNV) was significantly enhanced in the old ASD group (p = 0.017). When excluding ASD with comorbid ADHD we found a significantly increased N2 NoGo (p = 0.016) and N2-effect (p = 0.023) for the whole group. We found no case-control differences in the P3-components. Our findings suggest increased response preparation in adolescents with ASD older than 16 years and enhanced conflict monitoring in ASD without comorbid ADHD during a Go-NoGo task. The current findings may be related to Insistence of Sameness in ASD. The pathophysiological underpinnings of executive dysfunction should be further investigated to learn more about how this phenomenon is related to core characteristics of ASD.

13.
Brain Behav Immun ; 65: 342-349, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28619247

RESUMO

BACKGROUND: Several studies have described an association between childhood maltreatment and inflammatory markers in the psychotic disorders (schizophrenia [SZ] and bipolar disorder [BD]). Previous studies have been relatively small (<50 participants), and the severity of abuse and the putative influence of body mass index (BMI) have not been properly investigated. METHODS: The combined effects of childhood abuse severity and clinical diagnosis on inflammatory markers were investigated in a large sample (n=483) of patients with a disorder on the psychosis spectrum and in healthy controls (HCs). Plasma levels of inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], soluble tumor necrosis factor receptor type 1 [TNFR-R1], glycoprotein 130 [gp130]) were analyzed, and BMI and data on childhood trauma events, on the basis of the Childhood Trauma Questionnaire (CTQ), were obtained from all participants. RESULTS: Patients had increased levels of hs-CRP (P<0.001, Cohens d=0.4), lower levels of gp130 (P<0.001, Cohens d=0.5), higher BMI (P<0.001, Cohens d=0.5) and reported more childhood maltreatment experiences (P<0.001, Cohens d=1.2) than the HC group. The severity of childhood abuse (up to three types of abuse: sexual abuse, physical abuse, and emotional abuse) was associated with elevated BMI (f=8.46, P<0.001, Cohen's d=0.5) and hs-CRP (f=5.47, P=0.001, Cohen's d=0.3). Combined effects of patient status and severity of childhood abuse were found for elevated hs-CRP (f=4.76, P<0.001, Cohen's d=0.4). Differences among the groups disappeared when BMI was added to the model. DISCUSSION: Trauma-altered immune activation via elevated hs-CRP in patients with SZ and BD may be mediated by higher BMI; however, the direction of this association needs further clarification.


Assuntos
Transtorno Bipolar/metabolismo , Maus-Tratos Infantis/psicologia , Esquizofrenia/metabolismo , Adulto , Biomarcadores/sangue , Transtorno Bipolar/complicações , Transtorno Bipolar/psicologia , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Criança , Receptor gp130 de Citocina/sangue , Receptor gp130 de Citocina/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Masculino , Obesidade/complicações , Transtornos Psicóticos/complicações , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Esquizofrenia/complicações , Psicologia do Esquizofrênico
14.
Int J Mol Sci ; 18(5)2017 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-28524073

RESUMO

Clinical genetic testing (CGT) of children with autism spectrum disorder (ASD) may have positive and negative effects. Knowledge about parents' attitudes is needed to ensure good involvement of caregivers, which is crucial for accurate diagnosis and effective clinical management. This study aimed to assess parents' attitudes toward CGT for ASD. Parent members of the Norwegian Autism Society were given a previously untested questionnaire and 1455 answered. Linear regression analyses were conducted to evaluate contribution of parent and child characteristics to attitude statements. Provided it could contribute to a casual explanation of their child's ASD, 76% would undergo CGT. If it would improve the possibilities for early interventions, 74% were positive to CGT. Between 49-67% agreed that CGT could have a negative impact on health insurance, increase their concern for the child's future and cause family conflicts. Parents against CGT (9%) were less optimistic regarding positive effects, but not more concerned with negative impacts. The severity of the children's ASD diagnosis had a weak positive association with parent's positive attitudes to CGT (p-values range from <0.001 to 0.975). Parents prefer that CGT is offered to those having a child with ASD (65%), when the child's development deviates from normal (48%), or before pregnancy (36%). A majority of the parents of children with ASD are positive to CGT due to possibilities for an etiological explanation.


Assuntos
Atitude , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/genética , Testes Genéticos , Pais/psicologia , Transtorno Autístico/diagnóstico , Transtorno Autístico/genética , Feminino , Humanos , Modelos Lineares , Masculino , Noruega , Inquéritos e Questionários
15.
Schizophr Bull ; 43(4): 881-890, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28049760

RESUMO

Objective: A proinflammatory imbalance in the tumor necrosis factor (TNF) system may contribute to the pathogenesis of schizophrenia (SCZ) and bipolar disorders (BDs) and related comorbidities. We investigated the relative distribution of TNF-related molecules in blood and dorsolateral prefrontal cortex (DLPFC) in these disorders. Method: We measured plasma levels of TNF, soluble TNF receptor 1 (sTNFR1), soluble TNF receptor 2 (sTNFR2), and a disintegrin and metalloprotease-17 (ADAM17) using enzyme immunoassays and calculated the TNF/sTNFRs ratio (TNF/sTNFR1+sTNFR2) in a sample of 816 SCZ and BD spectrum patients and 624 healthy controls (HCs). TNF, TNFRSF1A (TNFR1), TNFRSF1B (TNFR2), and ADAM17 mRNA levels were determined in whole blood, and postmortem DLPFC obtained from an independent cohort (n = 80 SCZ, n = 44 BD, and n = 86 HC). Results: In peripheral blood, we show increased TNF-related measures in patients compared to HC, with an increased TNF/sTNFRs ratio (p = 6.00 × 10-5), but decreased TNF mRNA expression (p = 1 × 10-4), with no differences between SCZ and BD. Whole blood ADAM17 mRNA expression was markedly higher in BD vs SCZ patients (p = 1.40 × 10-14) and vs HC (p = 1.22 × 10-8). In postmortem DLPFC, we found no significant differences in mRNA expression of TNF pathway genes between any groups. Conclusions: SCZ and BD patients have increased plasma TNF pathway markers without corresponding increase in blood cell gene expression. ADAM17 expression in leukocytes is markedly different between the two disorders, while alterations in TNF-related gene expression in DLPFC are uncertain. Further studies are necessary to elucidate the aberrant regulation of the TNF pathway in severe mental disorders.


Assuntos
Proteína ADAM17/metabolismo , Transtorno Bipolar/metabolismo , Córtex Pré-Frontal/metabolismo , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Esquizofrenia/metabolismo , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Proteína ADAM17/sangue , Adulto , Transtorno Bipolar/sangue , Feminino , Expressão Gênica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Esquizofrenia/sangue , Fator de Necrose Tumoral alfa/sangue
16.
Schizophr Res ; 178(1-3): 44-49, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27595553

RESUMO

BACKGROUND: There are indications that low S-25(OH)D is associated with increased disease severity in psychotic disorder. Our first aim was to investigate the relations between low S-25(OH)D and positive, negative and depressive symptoms. Our second aim was to explore if associations between S-25(OH)D and symptoms were influenced by levels of inflammatory markers. METHODS: Participants (N=358) with a medical history of one or more psychotic episodes were recruited. Current symptomatology was assessed by The Structured Interview for the Positive and Negative Syndrome Scaleanalyzed by a five-factor model. The Calgary Depression Scale for Schizophrenia was used to assess depression and suicidal ideation. Blood samples were analyzed for S-25(OH)D, CRP, sTNF-R1, IL-Ra and OPG. We performed bivariate correlations and multiple regression models to evaluate the effect of S-25(OH)D on the outcomes. RESULTS: Low S-25(OH)D was significantly associated with negative symptoms (adjusted R2=0.113, F(6,357)=8.58, p<0.001) and with depression (adjusted R2=0.045, F(4,357)=5.233, p<0.001) when adjusting for possible confounding factors (i.e. gender, education, diagnose, hospitalization status, ethnicity, season and thyroid status). CRP was correlated with both S-25(OH)D (rho=-0.13, p=0.02) and negative symptoms (rho=0.14, p=0.01), but did not act as a mediator. The correlations between S-25(OH)D and the inflammatory markers sTNF-R1, IL-Ra and OPG were not significant. CONCLUSION: There is a strong association between low S-25(OH)D and higher negative and depressive symptoms in psychotic disorders. Randomized controlled trials should be performed to investigate the effect of vitamin D supplementation as adjuvant treatment strategy in patients with prominent negative or depressive symptoms.


Assuntos
Depressão/sangue , Depressão/complicações , Transtornos Psicóticos/complicações , Transtornos Psicóticos/psicologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/psicologia , Adulto , Biomarcadores/sangue , Estudos Transversais , Depressão/imunologia , Feminino , Humanos , Entrevista Psicológica , Masculino , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/sangue , Transtornos Psicóticos/imunologia , Análise de Regressão , Esquizofrenia/sangue , Esquizofrenia/complicações , Esquizofrenia/imunologia , Psicologia do Esquizofrênico , Ideação Suicida , Deficiência de Vitamina D/imunologia
17.
Psychoneuroendocrinology ; 67: 189-97, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26923849

RESUMO

BACKGROUND: Inflammation and immune activation have been implicated in the pathophysiology of severe mental disorders. Previous studies of inflammatory markers, however, have been limited with somewhat inconsistent results. AIMS: We aimed to determine the effect sizes of inflammatory marker alterations across diagnostic groups of the psychosis continuum and investigate association to antipsychotic medications. METHODS: Plasma levels of soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin 1 receptor antagonist (IL-1Ra), osteoprotegerin (OPG), and von Willebrand factor (vWf) were measured in patients (n=992) with schizophrenia spectrum (SCZ, n=584), schizoaffective disorder (SA, n=93), affective spectrum disorders (AFF, n=315), and healthy controls (HC, n=638). RESULTS: Levels of sTNF-R1 (p=1.8×10(-8), d=0.23) and IL-1Ra (p=0.002, d=0.16) were increased in patients compared to HC. The SCZ group had higher levels of sTNF-R1 (p=8.5×10(-8), d=0.27) and IL-1Ra (p=5.9×10(-5), d=0.25) compared to HC, and for sTNF-R1 this was also seen in the SA group (p=0.01, d=0.3) and in the AFF group (p=0.002, d=0.12). Further, IL-1Ra (p=0.004, d=0.25) and vWf (p=0.02, d=0.21) were increased in the SCZ compared to the AFF group. There was no significant association between inflammatory markers and use of antipsychotic medication. CONCLUSION: We demonstrate a small increase in sTNF-R1 and IL-1Ra in patients with severe mental disorders supporting a role of inflammatory mechanisms in disease pathophysiology. The increase was more pronounced in SCZ compared to AFF supporting a continuum psychosis model related to immune factors.


Assuntos
Inflamação/sangue , Proteína Antagonista do Receptor de Interleucina 1/sangue , Transtornos do Humor/sangue , Osteoprotegerina/sangue , Transtornos Psicóticos/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Esquizofrenia/sangue , Fator de von Willebrand/metabolismo , Adulto , Antipsicóticos/sangue , Antipsicóticos/uso terapêutico , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/complicações , Masculino , Modelos Psicológicos , Transtornos do Humor/complicações , Transtornos do Humor/tratamento farmacológico , Transtornos Psicóticos/complicações , Transtornos Psicóticos/tratamento farmacológico , Psicotrópicos/uso terapêutico , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico , Adulto Jovem
18.
Schizophr Res ; 165(2-3): 188-94, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25956633

RESUMO

BACKGROUND: The mechanisms underlying cognitive impairment in schizophrenia and bipolar disorders are largely unknown. Immune abnormalities have been found in both disorders, and inflammatory mediators may play roles in cognitive function. We investigated if inflammatory markers are associated with general cognitive abilities. METHODS: Participants with schizophrenia spectrum (N=121) and bipolar spectrum (N=111) disorders and healthy controls (N=241) were included. General intellectual abilities were assessed using the Wechsler Abbreviated Scale of Intelligence (WASI). Serum concentrations of the following immune markers were measured: Soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin 1 receptor antagonist (IL-1Ra), osteoprotegerin, von Willebrand factor, C-reactive protein, interleukin-6 and CD40 ligand. RESULTS: After adjusting for age, sex and diagnostic group, significant negative associations with general cognitive function were found for sTNF-R1 (p=2×10(-5)), IL-1Ra (p=0.002) and sCD40 ligand (p=0.003). Among patients, the associations remained significant (p=0.006, p=0.005 and p=0.02) after adjusting for possible confounders including education, smoking, psychotic and affective symptoms, body mass index, cortisol, medication and time of blood sampling. Subgroup analysis, showed that general cognitive abilities were significantly associated with IL-1Ra and sTNF-R1 in schizophrenia patients, with sCD40L and IL-1Ra in bipolar disorder patients and with sTNF-R1 in healthy controls. CONCLUSION: The study shows significant negative associations between inflammatory markers and general cognitive abilities after adjusting for possible confounders. The findings strongly support a role for inflammation in the neurophysiology of cognitive impairment.


Assuntos
Biomarcadores/sangue , Transtorno Bipolar/complicações , Transtornos Cognitivos/sangue , Transtornos Cognitivos/etiologia , Citocinas/sangue , Esquizofrenia/complicações , Adulto , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Adulto Jovem
19.
Schizophr Res ; 161(2-3): 222-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25433965

RESUMO

BACKGROUND: Increased inflammation, endothelial dysfunction, and structural brain abnormalities have been reported in both schizophrenia and bipolar disorder, but the relationships between these factors are unknown. We aimed to identify associations between markers of inflammatory and endothelial activation and structural brain variation in psychotic disorders. METHODS: We measured von Willebrand factor (vWf) as a marker of endothelial cell activation and six inflammatory markers (tumor necrosis factor-receptor 1, osteoprotegerin, interleukin-1-receptor antagonist, interleukin-6, C-reactive protein, CD40 ligand) in plasma and 16 brain structures obtained from MRI scans of 356 individuals (schizophrenia spectrum; n=121, affective spectrum; n=95, healthy control subjects; n=140). The relationship between the inflammatory and endothelial markers and brain measurements were investigated across groups. RESULTS: There was a positive association (p=2.5×10(-4)) between plasma levels of vWf and total volume of the basal ganglia which remained significant after correction for multiple testing. Treatment with first generation antipsychotics was associated with basal ganglia volume only (p=0.009). After adjusting for diagnosis and antipsychotic medication, vWf remained significantly associated with increased basal ganglia volume (p=0.008), in particular the right globus pallidus (p=3.7×10(-4)). The relationship between vWf and basal ganglia volume was linear in all groups, but the intercept was significantly higher in the schizophrenia group (df=2, F=8.2, p=3.4×10(-4)). CONCLUSION: Our results show a strong positive correlation between vWf levels and basal ganglia volume, in particular globus pallidus, independent of diagnosis. vWf levels were significantly higher in schizophrenia, which could indicate a link between endothelial cell activation and basal ganglia morphology in schizophrenia patients.


Assuntos
Proteínas Sanguíneas/metabolismo , Encéfalo/patologia , Citocinas/sangue , Transtornos Psicóticos/sangue , Transtornos Psicóticos/patologia , Adulto , Proteína C-Reativa/metabolismo , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Modelos Lineares , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/sangue , Escalas de Graduação Psiquiátrica , Adulto Jovem , Fator de von Willebrand/metabolismo
20.
Schizophr Res ; 145(1-3): 36-42, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23403415

RESUMO

BACKGROUND: Previous studies suggest elevated inflammation in schizophrenia and bipolar disorder, with increased activity of the Interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor (TNF)-alpha, von Willebrand factor (vWf) and osteoprotegerin (OPG). It is unclear how immune activation is involved in the psychopathology. We investigated if elevated inflammation was associated with disease severity (trait) or current symptom level (state), comparing psychotic with general characteristics. METHODS: Plasma levels of sTNF receptor 1 (sTNF-R1), IL-1 receptor antagonist (IL-1Ra), IL-6, vWf and OPG were measured with ELISA techniques in 322 patients with schizophrenia spectrum and bipolar disorder. Current symptom level (state) was measured with Global Assessment of Functioning (GAF) and Positive and Negative Syndrome Scale (PANSS). Disease severity (trait) was measured with premorbid adjustment scale (PAS), age at onset, number of psychotic episodes and number and length of hospitalizations. RESULTS: After controlling for confounders, IL-1Ra and TNF-R1 were independently associated with GAF, and significantly correlated with PANSS negative and positive, respectively. In addition, Il-1Ra was associated with PAS, and sTNF-R1 with number of hospitalizations and psychotic episodes. VWf was significantly correlated with psychotic episodes, OPG with hospitalizations and IL-6 with history of psychosis. Linear regression analysis showed that GAF remained associated with sTNF-R1 and IL-1Ra with PANSS, after controlling for the other clinical measures. CONCLUSIONS: This supports that inflammatory markers, particularly IL-1Ra and sTNF-R1 are associated with both general disease severity and psychotic features. This supports a role of immune activation in the core pathological mechanisms of severe mental disorders.


Assuntos
Transtorno Bipolar/complicações , Proteína Antagonista do Receptor de Interleucina 1/sangue , Transtornos Psicóticos/etiologia , Receptores do Fator de Necrose Tumoral/sangue , Esquizofrenia/complicações , Adolescente , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/sangue , Escalas de Graduação Psiquiátrica , Análise de Regressão , Esquizofrenia/metabolismo , Índice de Gravidade de Doença , Adulto Jovem , Fator de von Willebrand/metabolismo
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