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BACKGROUND: Poor adherence and negative attitudes to treatment are common clinical problems when treating psychotic disorders. This study investigated how schizophrenia core symptoms and daily functioning affect treatment adherence and attitudes toward antipsychotic medication and to compare patients using clozapine or other antipsychotics. METHOD: A cross-sectional study with data from 275 patients diagnosed with schizophrenia spectrum disorder. Patients adherence, attitudes, insight and side-effects were evaluated using the Attitudes toward Neuroleptic Treatment scale. Overall symptomology was measured using the Brief Psychiatric Rating Scale (BPRS), the Health of the Nation Outcome Scale (HoNOS). The functioning was assessed using activities of daily living scale, instrumental activities of daily living scale and social functioning of daily living scale. RESULTS: Self-reported treatment adherence was high. Of the patients, 83% reported using at least 75% of the prescribed medication. Having more symptoms was related with more negative attitude towards treatment. There was a modest association with functioning and treatment adherence and attitude toward antipsychotic treatment. Attitudes affected on adherence in non-clozapine but not in clozapine groups. CONCLUSION: Early detection of non-adherence is difficult. Systematic evaluation of attitudes toward the treatment could be one way to assess this problem, along with optimized medication, prompt evaluation of side effects and flexible use of psychosocial treatments.
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Antipsicóticos , Esquizofrenia , Atividades Cotidianas , Antipsicóticos/uso terapêutico , Atitude Frente a Saúde , Estudos Transversais , Humanos , Adesão à Medicação , Pacientes Ambulatoriais , Esquizofrenia/tratamento farmacológico , Psicologia do EsquizofrênicoRESUMO
BACKGROUND: Inflammation has been suggested to be one, possibly treatable, cause of cognitive decline and dementia. The purpose of the present article was to investigate whether the herpes simplex virus 1 (HSV-1) or Toxoplasma gondii (T. gondii) infections are related to cognitive decline or dementia. METHOD: The Health 2000 survey, conducted 2000-2001, is a population-representative sample of people over 30â¯years old that involved 7112 participants. The sample was followed up in the year 2011, in the Health 2011 study. At both time points, cognitive performance was assessed with two tests from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) assessing verbal fluency and verbal learning. In addition, the abbreviated Mini-Mental State Examination was administered to people aged over 55. In addition, tests assessing reaction and movement time were performed at baseline. Dementia diagnoses from nationwide health care registers were followed up until the end of year 2013. The presence of HSV-1 and T. gondii immunoglobulin G (IgG) was determined by solid-phase immunoassay at baseline. RESULTS: HSV-1 or T. gondii seropositivity, or IgG antibody levels, were not associated with cognitive decline when investigated as infectionâ¯×â¯time interactions. In addition, the infections were not associated with the risk of dementia. CONCLUSIONS: In a large sample of participants that is representative of the whole country and with a long follow-up, the results suggest that latent HSV-1 or T. gondii infections are not related to either decline in cognitive performance or dementia risk.
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Disfunção Cognitiva/etiologia , Adulto , Idoso , Disfunção Cognitiva/fisiopatologia , Demência , Feminino , Finlândia , Seguimentos , Herpes Simples/fisiopatologia , Herpes Simples/psicologia , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 1/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de Risco , Toxoplasma/imunologia , Toxoplasma/patogenicidade , Toxoplasmose/fisiopatologia , Toxoplasmose/psicologiaRESUMO
BACKGROUND: While group-level functional alterations have been identified in many brain regions of psychotic patients, multivariate machine-learning methods provide a tool to test whether some of such alterations could be used to differentiate an individual patient. Earlier machine-learning studies have focused on data collected from chronic patients during rest or simple tasks. We set out to unravel brain activation patterns during naturalistic stimulation in first-episode psychosis (FEP). METHOD: We recorded brain activity from 46 FEP patients and 32 control subjects viewing scenes from the fantasy film Alice in Wonderland. Scenes with varying degrees of fantasy were selected based on the distortion of the 'sense of reality' in psychosis. After cleaning the data with a novel maxCorr method, we used machine learning to classify patients and healthy control subjects on the basis of voxel- and time-point patterns. RESULTS: Most (136/194) of the voxels that best classified the groups were clustered in a bilateral region of the precuneus. Classification accuracies were up to 79.5% (p = 5.69 × 10-8), and correct classification was more likely the higher the patient's positive-symptom score. Precuneus functioning was related to the fantasy content of the movie, and the relationship was stronger in control subjects than patients. CONCLUSIONS: These findings are the first to show abnormalities in precuneus functioning during naturalistic information processing in FEP patients. Correlational findings suggest that these alterations are associated with positive psychotic symptoms and processing of fantasy. The results may provide new insights into the neuronal basis of reality distortion in psychosis.
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Fantasia , Neuroimagem Funcional/métodos , Aprendizado de Máquina , Lobo Parietal/fisiopatologia , Transtornos Psicóticos/fisiopatologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Filmes Cinematográficos , Adulto JovemRESUMO
BACKGROUND: Delusion is the most characteristic symptom of psychosis. While researchers suggested an association between changes of the cortical salience network (CSN) and delusion, whether these CSN findings are a cause or a consequence of delusion remains unknown. METHOD: To assess the effect of CSN functioning to forthcoming changes in delusion scores, we measured brain activation with 3-T functional magnetic resonance imaging in two independent samples of first-episode psychosis patients (total of 27 patients and 23 healthy controls). During scanning, the patients evaluated statements about whether an individual's psychosis-related experiences should be described as a mental illness, and control statements that were also evaluated by healthy controls. Symptoms were assessed at the baseline and at 2 months follow-up with Brief Psychiatric Rating Scale. RESULTS: Both tasks activated the CSN in comparison with rest. Activation of CSN ('illness evaluation v. control task' contrast) in patients positively correlated with worsening of or less improvement in delusions at the 2-month follow-up assessment. This finding was independent of delusion and clinical insight scores at the baseline evaluation. CONCLUSIONS: Our findings link symptom-evaluation-related CSN functioning to severity of delusion and, importantly, add a new layer of evidence for the contribution of CSN functioning to the longitudinal course of delusions.
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Córtex Cerebral/fisiopatologia , Delusões/fisiopatologia , Progressão da Doença , Rede Nervosa/fisiopatologia , Transtornos Psicóticos/fisiopatologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Delusões/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Transtornos Psicóticos/diagnóstico por imagem , Índice de Gravidade de Doença , Adulto JovemRESUMO
Genes that are differentially expressed between schizophrenia patients and healthy controls may have key roles in the pathogenesis of schizophrenia. We analyzed two large-scale genome-wide expression studies, which examined changes in gene expression in schizophrenia patients and their matched controls. We found calcium/calmodulin (CAM)-dependent protein kinase kinase 2 (CAMKK2) is significantly downregulated in individuals with schizophrenia in both studies. To seek the potential genetic variants that may regulate the expression of CAMKK2, we investigated the association between single-nucleotide polymorphisms (SNPs) within CAMKK2 and the expression level of CAMKK2. We found one SNP, rs1063843, which is located in intron 17 of CAMKK2, is strongly associated with the expression level of CAMKK2 in human brains (P=1.1 × 10(-6)) and lymphoblastoid cell lines (the lowest P=8.4 × 10(-6)). We further investigated the association between rs1063843 and schizophrenia in multiple independent populations (a total of 130 623 subjects) and found rs1063843 is significantly associated with schizophrenia (P=5.17 × 10(-5)). Interestingly, we found the T allele of rs1063843, which is associated with lower expression level of CAMKK2, has a higher frequency in individuals with schizophrenia in all of the tested samples, suggesting rs1063843 may be a causal variant. We also found that rs1063843 is associated with cognitive function and personality in humans. In addition, protein-protein interaction (PPI) analysis revealed that CAMKK2 participates in a highly interconnected PPI network formed by top schizophrenia genes, which further supports the potential role of CAMKK2 in the pathogenesis of schizophrenia. Taken together, these converging lines of evidence strongly suggest that CAMKK2 may have pivotal roles in schizophrenia susceptibility.
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Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/genética , Predisposição Genética para Doença/genética , Esquizofrenia/genética , Psicologia do Esquizofrênico , Alelos , Povo Asiático/genética , Encéfalo/metabolismo , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Estudos de Casos e Controles , Cognição , Bases de Dados Genéticas , Regulação para Baixo , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Personalidade/genética , Polimorfismo de Nucleotídeo Único/genética , Mapas de Interação de Proteínas/genética , População Branca/genéticaRESUMO
Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).
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Transtorno Bipolar/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 16/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtorno Bipolar/complicações , Transtorno Bipolar/epidemiologia , Europa (Continente) , Feminino , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Razão de Chances , Análise de Sequência com Séries de Oligonucleotídeos , Fatores de Risco , Esquizofrenia/complicações , Esquizofrenia/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Increased risk for somatic comorbidity in individuals with schizophrenia has been well established. In addition, psychiatric patients with somatic illnesses are more likely to have more psychiatric readmissions. Increased burden of treatment related to chronic somatic comorbidities may be associated with lower adherence to psychiatric medication. METHODS: Cross-sectional study of 275 patients with schizophrenia spectrum disorder. A general practitioner performed a complete physical health checkup for all participants, including a complete medical examination and laboratory tests. Patients' adherence, attitudes, insight, and side-effects were evaluated using the Attitudes toward Neuroleptic Treatment Scale. Overall symptomatology was measured using the Brief Psychiatric Rating Scale. Regression analysis was used to investigate interactions and associations among health beliefs, disease burden, and treatment adherence. Separate regression models were utilized to account for the complexity of health behavior and treatment adherence pathways. RESULTS: Patients' somatic comorbidity and health behavior were not associated with adherence or attitudes toward antipsychotic treatment. High dose of antipsychotics and obesity were related to the need for medical interventions, while a healthy diet reduced the risk. Higher BPRS score and older age were associated with having somatic symptoms. Somatic comorbidities had no negative effects on treatment adherence or attitudes. CONCLUSION: This study focuses on exploring possible associations between health beliefs and treatment adherence pathways in patients with psychotic disorders. Contrary to our hypotheses, we found no evidence to support our health belief and diseases burden models and their associations.
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Antipsicóticos , Comorbidade , Transtornos Psicóticos , Cooperação e Adesão ao Tratamento , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/psicologia , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Espectro da Esquizofrenia e Outros Transtornos Psicóticos/tratamento farmacológico , Espectro da Esquizofrenia e Outros Transtornos Psicóticos/epidemiologia , Espectro da Esquizofrenia e Outros Transtornos Psicóticos/psicologia , Modelos Lineares , Modelos Logísticos , Antipsicóticos/uso terapêuticoRESUMO
Background: Both overweight and cognitive deficits are common among people with schizophrenia (SZ) and schizoaffective disorder. The results in earlier studies have been inconsistent on whether overweight is associated with cognitive deficits in psychotic disorders. Aims: Our aim in this study was to detect possible associations between obesity and cognitive deficits among study participants with SZ and schizoaffective disorder. Methods: The study sample included 5382 participants with a clinical diagnosis of SZ or schizoaffective disorder selected from the Finnish SUPER study. Obesity was measured both with body-mass index and waist circumference. The cognitive performance was evaluated with two tests from the Cambridge automated neuropsychological test battery: Reaction time was evaluated with the 5-choice serial reaction time task. Visual memory was evaluated with the paired associative learning test. The final analysis included a total sample of 4498 participants applicable for the analysis of the reaction time and 3967 participants for the analysis of the visual memory. Results: Obesity measured with body-mass index was associated with better performance in reaction time task among both female and male participants. Among male participants, overweight was associated with better performance in the visual memory test. The waist circumference was not associated with cognitive measures. Conclusions: The results suggest that obesity in people with SZ or schizoaffective disorder might not be associated with cognitive deficits but instead with better cognitive performance. The results were opposite from earlier literature on the general population. More research is required to better understand whether the results might be partly caused by the differences in the etiology of obesity between the general population and people with SZ.
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BACKGROUND: Both low birthweight and high birthweight have been associated with an increased risk for schizophrenia and cognitive impairments in the general population. We assessed the association between birthweight and cognitive performance in persons with schizophrenia and their unaffected first-degree relatives. METHOD: We investigated a population-based family sample comprising persons with schizophrenia (n = 142) and their unaffected first-degree relatives (n = 277). Both patients and relatives were interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV) and a comprehensive neuropsychological test battery was administered. Information on birthweight was obtained from obstetric records. We used generalized estimating equation (GEE) models to investigate the effect of birthweight, as a continuous variable, on cognitive functioning, adjusting for within-family correlation and relevant covariates. RESULTS: Both low birthweight and high birthweight were associated with lower performance in visuospatial reasoning, processing speed, set-shifting and verbal and visual working memory among persons with schizophrenia and their unaffected first-degree relatives compared to individuals with birthweight in the intermediate range. The group × birthweight interactions were non-significant. CONCLUSIONS: Both low birthweight and high birthweight are associated with deficits in cognition later in life. Schizophrenia does not seem to modify the relationship between birthweight and cognition in families with schizophrenia.
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Peso ao Nascer , Transtornos Cognitivos/psicologia , Família/psicologia , Macrossomia Fetal/psicologia , Recém-Nascido de Baixo Peso/psicologia , Transtornos Psicóticos/psicologia , Esquizofrenia , Psicologia do Esquizofrênico , Adulto , Idoso , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/genética , Feminino , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/genética , Esquizofrenia/epidemiologia , Esquizofrenia/genética , Adulto JovemRESUMO
AIM: We compared the course and outcome of schizophrenia in two groups: (i) hospitalised patients (HP) (n = 5980) who were identified based on their first hospital admission for schizophrenia and (ii) outpatient-treated patients (OTP) who received disability pension because of schizophrenia but who had no hospital admissions for schizophrenia or other psychotic disorder before having been granted a disability pension for schizophrenia (n = 1220). Outcomes were compared using data on mortality, psychiatric hospital utilisation, relapse rate and occupational functioning. METHODS: A nationwide register-based 5-year follow-up study of all first-onset schizophrenia cases between 1998 and 2003 in Finland. The data were linked with the register information of hospital admissions, disability pensions and National Causes of Death Registers. RESULTS: When outcome of treatment was evaluated using mortality rate, relapses, hospital treatment and involuntary admissions as outcome measures, results indicated that OTP group had got along better with their illnesses than HP group. The mortality rates, number of psychiatric treatment days and relapse rate during the 5-year follow up were significantly lower in OTP group. Within the OTP group, there was a notable subgroup of never HP (n = 737, 60.4%), who did not require any psychiatric hospitalisation during the 5-year follow up. CONCLUSIONS: Patients first identified as outpatients had better outcomes than patients first identified following a hospitalisation. Future studies are required to establish whether outpatient treatment is associated with more favourable prognosis, even after fully adjusting for severity of initial symptoms. The higher suicide mortality of hospital-treated patients suggests that hospital treatment of first-onset patients does not protect from suicide.
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Assistência Ambulatorial/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Esquizofrenia/terapia , Adolescente , Adulto , Idade de Início , Idoso , Feminino , Finlândia/epidemiologia , Seguimentos , Hospitais Psiquiátricos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Aposentadoria , Esquizofrenia/mortalidade , Adulto JovemRESUMO
Deletions and reciprocal duplications of the chromosome 16p13.1 region have recently been reported in several cases of autism and mental retardation (MR). As genomic copy number variants found in these two disorders may also associate with schizophrenia, we examined 4345 schizophrenia patients and 35,079 controls from 8 European populations for duplications and deletions at the 16p13.1 locus, using microarray data. We found a threefold excess of duplications and deletions in schizophrenia cases compared with controls, with duplications present in 0.30% of cases versus 0.09% of controls (P=0.007) and deletions in 0.12 % of cases and 0.04% of controls (P>0.05). The region can be divided into three intervals defined by flanking low copy repeats. Duplications spanning intervals I and II showed the most significant (P = 0.00010) association with schizophrenia. The age of onset in duplication and deletion carriers among cases ranged from 12 to 35 years, and the majority were males with a family history of psychiatric disorders. In a single Icelandic family, a duplication spanning intervals I and II was present in two cases of schizophrenia, and individual cases of alcoholism, attention deficit hyperactivity disorder and dyslexia. Candidate genes in the region include NTAN1 and NDE1. We conclude that duplications and perhaps also deletions of chromosome 16p13.1, previously reported to be associated with autism and MR, also confer risk of schizophrenia.
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Aberrações Cromossômicas , Cromossomos Humanos Par 16 , Variações do Número de Cópias de DNA , Esquizofrenia/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Mapeamento Cromossômico , Feminino , Humanos , Masculino , Valores de Referência , Duplicações Segmentares Genômicas/genética , Deleção de Sequência/genética , Adulto JovemRESUMO
A trio of genome-wide association studies recently reported sequence variants at three loci to be significantly associated with schizophrenia. No sequence polymorphism had been unequivocally (P<5 × 10(-8)) associated with schizophrenia earlier. However, one variant, rs1344706[T], had come very close. This polymorphism, located in an intron of ZNF804A, was reported to associate with schizophrenia with a P-value of 1.6 × 10(-7), and with psychosis (schizophrenia plus bipolar disorder) with a P-value of 1.0 × 10(-8). In this study, using 5164 schizophrenia cases and 20,709 controls, we replicated the association with schizophrenia (odds ratio OR = 1.08, P = 0.0029) and, by adding bipolar disorder patients, we also confirmed the association with psychosis (added N = 609, OR = 1.09, P = 0.00065). Furthermore, as it has been proposed that variants such as rs1344706[T]-common and with low relative risk-may also serve to identify regions harboring less common, higher-risk susceptibility alleles, we searched ZNF804A for large copy number variants (CNVs) in 4235 psychosis patients, 1173 patients with other psychiatric disorders and 39,481 controls. We identified two CNVs including at least part of ZNF804A in psychosis patients and no ZNF804A CNVs in controls (P = 0.013 for association with psychosis). In addition, we found a ZNF804A CNV in an anxiety patient (P = 0.0016 for association with the larger set of psychiatric disorders).
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Transtornos de Ansiedade/genética , Transtorno Bipolar/genética , Variações do Número de Cópias de DNA/genética , Fatores de Transcrição Kruppel-Like/genética , Esquizofrenia/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Valores de ReferênciaRESUMO
BACKGROUND: Cognitive deficits in alcohol dependence (AD) have been observed, poorer verbal ability being among the most consistent findings. Genetic factors influence both cognitive ability and AD, but whether these influences overlap is not known. METHOD: A subset of 602 monozygotic (MZ) and dizygotic (DZ) twins from FinnTwin16, a population-based study of Finnish twins, was used to study the associations of verbal ability with DSM-III-R diagnosis and symptoms of AD, the maximum number of drinks consumed in a 24-h period, and the Rutgers Alcohol Problem Index (RAPI) scores. These twins, most of them selected for within-pair discordance or concordance for their RAPI scores at age 18.5 years, were studied with neuropsychological tests and interviewed with the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) in young adulthood (mean age 26.2 years, range 23-30 years). RESULTS: All alcohol problem measures were associated with lower scores on the Vocabulary subtest of the Wechsler Adult Intelligence Scale - Revised (WAIS-R), a measure of verbal ability. In bivariate genetic models, Vocabulary and the alcohol problem measures had moderate heritabilities (0.54-0.72), and their covariation could be explained by correlated genetic influences (genetic correlations -0.20 to -0.31). CONCLUSIONS: Poorer verbal ability and AD have partly overlapping biological etiology. The genetic and environmental influences on the development of cognitive abilities, alcohol problems and risk factors for AD should be studied further with prospective longitudinal designs.
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Alcoolismo/genética , Comportamento Verbal , Adolescente , Adulto , Alcoolismo/psicologia , Distribuição de Qui-Quadrado , Transtornos Cognitivos/complicações , Transtornos Cognitivos/genética , Transtornos Cognitivos/psicologia , Feminino , Finlândia , Humanos , Estudos Longitudinais , Masculino , Gêmeos Dizigóticos/psicologia , Gêmeos Monozigóticos/psicologia , Escalas de Wechsler , Adulto JovemRESUMO
BACKGROUND: Psychiatric co-morbidity is often inadequately controlled for in studies on cognitive functioning in depression. Our recent study established no major deficits in cognition among young adults with a history of pure unipolar depression. The present study extends our previous work by examining the effects of psychiatric co-morbidity and other disorder characteristics on depression-related cognitive functioning. METHOD: Performance in verbal and visual short-term memory, verbal long-term memory and learning, attention, processing speed, and executive functioning was compared between a population-based sample aged 21-35 years with a lifetime history of unipolar depressive disorders (n=126) and a random sample of healthy controls derived from the same population (n=71). Cognitive functioning was also compared between the subgroups of pure (n=69) and co-morbid (n=57) depression. RESULTS: The subgroups of pure and co-morbid depression did not differ in any of the cognitive measures assessed. Only mildly compromised verbal learning was found among depressed young adults in total, but no other cognitive deficits occurred. Received treatment was associated with more impaired verbal memory and executive functioning, and younger age at first disorder onset with more impaired executive functioning. CONCLUSIONS: Psychiatric co-morbidity may not aggravate cognitive functioning among depressed young adults. Regardless of co-morbidity, treatment seeking is associated with cognitive deficits, suggesting that these deficits relate to more distress.
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Transtornos Cognitivos/epidemiologia , Transtorno Depressivo/epidemiologia , Transtornos Mentais/epidemiologia , Testes Neuropsicológicos/estatística & dados numéricos , Adulto , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Estudos de Coortes , Comorbidade , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Feminino , Finlândia , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Rememoração Mental , Psicometria , Valores de Referência , Aprendizagem Verbal , Adulto JovemRESUMO
Disrupted in schizophrenia 1 (DISC1) has been associated with risk of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, autism and Asperger syndrome, but apart from in the original translocation family, true causal variants have yet to be confirmed. Here we report a harmonized association study for DISC1 in European cohorts of schizophrenia and bipolar disorder. We identify regions of significant association, demonstrate allele frequency heterogeneity and provide preliminary evidence for modifying interplay between variants. Whereas no associations survived permutation analysis in the combined data set, significant corrected associations were observed for bipolar disorder at rs1538979 in the Finnish cohorts (uncorrected P=0.00020; corrected P=0.016; odds ratio=2.73+/-95% confidence interval (CI) 1.42-5.27) and at rs821577 in the London cohort (uncorrected P=0.00070; corrected P=0.040; odds ratio=1.64+/-95% CI 1.23-2.19). The rs821577 single nucleotide polymorphism (SNP) showed evidence for increased risk within the combined European cohorts (odds ratio=1.27+/-95% CI 1.07-1.51), even though significant corrected association was not detected (uncorrected P=0.0058; corrected P=0.28). After conditioning the European data set on the two risk alleles, reanalysis revealed a third significant SNP association (uncorrected P=0.00050; corrected P=0.025). This SNP showed evidence for interplay, either increasing or decreasing risk, dependent upon the presence or absence of rs1538979 or rs821577. These findings provide further support for the role of DISC1 in psychiatric illness and demonstrate the presence of locus heterogeneity, with the effect that clinically relevant genetic variants may go undetected by standard analysis of combined cohorts.
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Transtorno Bipolar/genética , Predisposição Genética para Doença , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética , Estudos de Casos e Controles , Estudos de Coortes , Europa (Continente) , Feminino , Frequência do Gene , Genótipo , Humanos , Cooperação Internacional , Masculino , Testes Neuropsicológicos , Razão de Chances , Escalas de Graduação Psiquiátrica , Fatores SexuaisRESUMO
As part of anational Finnish study on reproductive health of women with severe mental disorders, we compared pregnancy- and delivery-, and postpartum-related outcomes between women with schizophrenia (n = 3444) and those with schizoaffective disorder (n = 985), focusing on their singleton pregnancies after illness onset (n = 708 and n = 242, respectively). For comparison, data also included 22,101 controls with 3668 pregnancies. The Finnish Medical Birth Register, the Register of Congenital Malformations and the Child Welfare Register were used. Despite known differences between the two disorders, we found no robust differences between these patient groups.
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Período Pós-Parto/psicologia , Complicações na Gravidez/psicologia , Transtornos Psicóticos/epidemiologia , Sistema de Registros , Esquizofrenia/epidemiologia , Psicologia do Esquizofrênico , Adulto , Feminino , Finlândia/epidemiologia , Humanos , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/epidemiologia , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Esquizofrenia/diagnósticoRESUMO
Schizophrenia is a common and complex mental disorder. Hereditary factors are important for its etiology, but despite linkage signals reported to several chromosomal regions in different populations, final identification of predisposing genes has remained a challenge. Utilizing a large family-based schizophrenia study sample from Finland, we have identified several linked loci: 1q32.2-q42, 2q, 4q31, 5q and 7q22. In this study, an independent sample of 352 nuclear schizophrenia families (n=1626) allowed replication of linkage on 7q21-32. In a sample of 245 nuclear families (n=1074) originating from the same geographical region as the families revealing the linkage, SNP and microsatellite association analyses of the four regional candidate genes, GRM3, RELN, SEMA3A and VGF, revealed no significant association to the clinical diagnosis of schizophrenia. Instead, quantifiable trait component analyses with neuropsychological endophenotypes available from 186 nuclear families (n=861) of the sample showed significant association to RELN variants for traits related to verbal (P=0.000003) and visual working memory (P=0.002), memory (P=0.002) and executive functioning (P=0.002). Trait-associated allele-positive subjects scored lower in the tests measuring working memory (P=0.0004-0.0000000004), memory (P=0.02-0.0001) and executive functioning (P=0.001). Our findings suggest that allelic variants of RELN contribute to the endophenotypes of schizophrenia.
Assuntos
Moléculas de Adesão Celular Neuronais/genética , Cromossomos Humanos Par 22 , Proteínas da Matriz Extracelular/genética , Ligação Genética , Memória/fisiologia , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética , Serina Endopeptidases/genética , Mapeamento Cromossômico , Feminino , Humanos , Masculino , Núcleo Familiar , Fenótipo , Proteína Reelina , Psicologia do EsquizofrênicoRESUMO
Schizophrenia is a heterogeneous disorder characterized by a spectrum of symptoms and many different underlying causes. Thus, instead of using the broad diagnosis, intermediate phenotypes can be used to possibly decrease the underlying complexity of the disorder. Alongside the classical symptoms of delusions and hallucinations, cognitive deficits are a core feature of schizophrenia. To increase our understanding of the biological processes related to these cognitive deficits, we performed a genome-wide gene expression analysis. A battery of 14 neuropsychological tests was administered to 844 individuals from a Finnish familial schizophrenia cohort. We grouped the applied neuropsychological tests into five factors for further analysis. Cognitive endophenotypes, whole blood mRNA, genotype, and medication use data were studied from 47 individuals. Expression level of several RNA probes were significantly associated with cognitive performance. The factor representing Verbal Working Memory was associated with altered expression levels of 11 probes, of which one probe was also associated with a specific sub-measure of this factor (WMS-R Digit span backward). While, the factor Processing speed was related to one probe, which additionally associated among 55 probes with a specific sub-measure of this factor (WAIS-R Digit symbol). Two probes were associated with the measure recognition memory performance. Enrichment analysis of these differentially expressed probes highlighted immunological processes. Our findings are in line with genome-wide genetic discoveries made in schizophrenia, suggesting that immunological processes may be of biological interest for future drug design towards schizophrenia and the cognitive dysfunctions that underlie it.
Assuntos
Transtornos Cognitivos/etiologia , Transtornos Cognitivos/imunologia , Expressão Gênica/fisiologia , Esquizofrenia/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/metabolismo , Feminino , Perfilação da Expressão Gênica , Genótipo , Humanos , Masculino , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Testes Neuropsicológicos , FenótipoRESUMO
BACKGROUND: There is evidence for cognitive dysfunction in unipolar depression among middle-aged and elderly patients, but cognitive functioning among depressed young adults has scarcely been systematically investigated. The aims of the present study were to examine cognitive functioning among depressed young adults identified from the general population and to determine whether cognitive deficits vary as a function of different disorder characteristics, such as severity and age at onset. METHODS: Performance in verbal and visual short-term memory, verbal long-term memory and learning, attention, processing speed, and executive functioning was compared between a population-based sample of 21-35-year-olds with a lifetime history of non-psychotic unipolar depressive disorders without psychiatric comorbidity (n=68) and healthy controls derived from the same population (n=70). RESULTS: Depressed young adults were not found to be impaired in any of the assessed cognitive functions, except for some suggestion of mildly compromised verbal learning. Nevertheless, younger age at depression onset was associated with more impaired executive functioning. LIMITATIONS: The results may slightly underestimate of the true association between depression and cognitive impairments in the young adult population due to possible dropout of participants. Additionally, the problem of multiple testing was not entirely corrected. CONCLUSION: The findings from this study indicate that a lifetime history of non-psychotic unipolar depressive disorders among young adults without psychiatric comorbidity may be associated only with minimal cognitive deficits, even when some residual depressive symptoms are prevalent. However, early-onset depression may represent a more severe form of the disorder, associated with more cognitive dysfunction.
Assuntos
Transtornos Cognitivos/diagnóstico , Transtorno Depressivo/diagnóstico , Adulto , Fatores Etários , Idade de Início , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/psicologia , Comorbidade , Grupos Controle , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Pacientes Desistentes do Tratamento , Índice de Gravidade de DoençaRESUMO
It may be challenging to distinguish autoimmune encephalitis associated with anti-neuronal autoantibodies from primary psychiatric disorders. Here, serum was drawn from patients with a first-episode psychosis (n=70) or a clinical high-risk for psychosis (n=6) and controls (n=34). We investigated the serum prevalence of 24 anti-neuronal autoantibodies: IgG antibodies for anti-N-methyl-d-aspartate-type glutamate receptor (anti-NMDAR), glutamate and γ-aminobutyric acid alpha and beta receptors (GABA-a, GABA-b), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA), glycine receptor (GlyR), metabotropic glutamate receptor 1 and 5 (mGluR1, mGluR5), anti-Tr/Delta/notch-like epidermal growth factor-related receptor (DNER), contactin-associated protein-like 2 (CASPR2), myelin oligodendrocyte glycoprotein (MOG), glutamic acid decarboxylase-65 (GAD65), collapsin response mediator protein 5/crossveinless-2 (CV2), aquaporin-4 (AQP4), anti-dipeptidyl-peptidase-like protein-6 (DPPX), type 1 anti-neuronal nuclear antibody (ANNA-1, Hu), Ri, Yo, IgLON5, Ma2, zinc finger protein 4 (ZIC4), Rho GTPase-activating protein 26, amphiphysin, and recoverin, as well as IgA and IgM for dopamine-2-receptor (DRD2). Anti-NMDA IgG antibodies were positive with serum titer 1:320 in one patient with a clinical high risk for psychosis. He did not receive a diagnosis of encephalitis after comprehensive neurological evaluation. All other antineuronal autoantibodies were negative and there were no additional findings with immunohistochemistry of brain issues.