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Psychotic symptoms, that we defined as delusions or hallucinations, are common in bipolar disorders (BD). This systematic review and meta-analysis aims to synthesise the literature on both lifetime and point prevalence rates of psychotic symptoms across different BD subtypes, including both BD type I (BDI) and BD type II (BDII). We performed a systematic search of Medline, PsycINFO, Embase and Cochrane Library until 5 August 2021. Fifty-four studies (N = 23 461) of adults with BD met the predefined inclusion criteria for evaluating lifetime prevalence, and 24 studies (N = 6480) for evaluating point prevalence. Quality assessment and assessment of publication bias were performed. Prevalence rates were calculated using random effects meta-analysis, here expressed as percentages with a 95% confidence interval (CI). In studies of at least moderate quality, the pooled lifetime prevalence of psychotic symptoms in BDI was 63% (95% CI 57.5-68) and 22% (95% CI 14-33) in BDII. For BDI inpatients, the pooled lifetime prevalence was 71% (95% CI 61-79). There were no studies of community samples or inpatient BDII. The pooled point prevalence of psychotic symptoms in BDI was 54% (95 CI 41-67). The point prevalence was 57% (95% CI 47-66) in manic episodes and 13% (95% CI 7-23.5) in depressive episodes. There were not enough studies in BDII, BDI depression, mixed episodes and outpatient BDI. The pooled prevalence of psychotic symptoms in BDI may be higher than previously reported. More studies are needed for depressive and mixed episodes and community samples.Prospero registration number: CRD 42017052706.
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Transtorno Bipolar , Transtornos Psicóticos , Adulto , Humanos , Transtorno Bipolar/epidemiologia , Prevalência , Alucinações , ManiaRESUMO
OBJECTIVE: Apathy is a central predictor of a poor functional outcome in schizophrenia. Schizophrenia polygenic risk scores (PRSs) are used to detect genetic associations to key clinical phenotypes in schizophrenia. We explored the associations between schizophrenia PRS and apathy levels in schizophrenia spectrum disorders (n = 281) and matched healthy controls (n = 298), and further how schizophrenia PRS contributed in predicting apathy when added to premorbid and clinical factors in the patient sample. METHOD: Schizophrenia PRSs were computed for each participant. Apathy was assessed with the Apathy Evaluation Scale. Bivariate correlation analyses were used to investigate associations between schizophrenia PRS and apathy, and between apathy and premorbid and clinical factors. Multiple hierarchical regression analyses were employed to evaluate the contributions of clinical variables and schizophrenia PRS to apathy levels. RESULTS: We found no significant associations between schizophrenia PRS and apathy in patients and healthy controls. Several premorbid and clinical characteristics significantly predicted apathy in patients, but schizophrenia PRS did not. CONCLUSION: Since the PRSs are based on common genetic variants, our results do not preclude associations to other types of genetic factors. The results could also indicate that environmentally based biological or psychological factors contribute to apathy levels in schizophrenia.
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Apatia , Herança Multifatorial/genética , Esquizofrenia/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Fenótipo , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: Associations between suicidality and lipid dysregulation are documented in mental illness, but the potential role of leptin remains unclear. We examined the association between leptin and suicidal behaviour in schizophrenia, together with the influence of other clinical and biological indices. METHOD: We recruited a sample of 270 participants with schizophrenia spectrum diagnoses. Blood samples were analysed for leptin, while symptom severity was assessed by Positive and Negative Syndrome Scale (PANSS) and Inventory of Depressive Symptomatology (IDS-C). Patients' history of suicidal behaviour was categorized into three subgroups based on IDS-C suicide subscale: No suicidal behaviour, mild/moderate suicidal behaviour and severe suicidal behaviour with/without attempts. RESULTS: Mild/moderate suicidal behaviour was present in 17.4% and severe suicidal behaviour in 34.8%. Both groups were significantly associated with female gender (OR = 6.0, P = 0.004; OR = 5.9, P = 0.001), lower leptin levels (OR = 0.4, P = 0.008; OR = 0.5, P = 0.008) and more severe depression (OR = 1.2, P < 0.001; OR = 1.1, P < 0.001) respectively. Smoking (OR = 2.6, P = 0.004), younger age of onset (OR = 0.9, P = 0.003) and less use of leptin-increasing medications (OR = 0.5, P = 0.031) were associated with severe/attempts group, while higher C-reactive protein CRP (OR = 1.3, P = 0.008) was associated with mild/moderate group. CONCLUSION: Lower leptin levels were associated with higher severity of suicidal behaviour in schizophrenia.
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Leptina/metabolismo , Esquizofrenia/sangue , Suicídio/psicologia , Adulto , Idade de Início , Proteína C-Reativa/análise , Estudos Transversais , Transtorno Depressivo/complicações , Transtorno Depressivo/psicologia , Feminino , Humanos , Masculino , Psicotrópicos/efeitos adversos , Fatores de Risco , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Índice de Gravidade de Doença , Fumar/epidemiologia , Fumar/psicologia , Ideação Suicida , Suicídio/tendênciasRESUMO
OBJECTIVE: While CVD risk has decreased in the general population during the last decade, the situation in patients with schizophrenia (SCZ) and bipolar disorder (BD) is unknown. METHODS: We compared CVD risk factors in patients with SCZ and BD recruited from 2002-2005 (2005 sample, N = 270) with patients recruited from 2006-2017 (2017 sample, N = 1011) from the same catchment area in Norway. The 2017 sample was also compared with healthy controls (N = 922) and the general population (N range = 1285-4587, Statistics Norway) from the same area and period. RESULTS: Patients with SCZ and BD in the 2017 sample had significantly higher level of most CVD risk factors compared to healthy controls and the general population. There was no significant difference in the prevalence of CVD risk factors in SCZ between the 2005 and 2017 samples except a small increase in glucose in the 2017 sample. There were small-to-moderate reductions in hypertension, obesity, total cholesterol, low-density lipoprotein, systolic and diastolic blood pressure in the BD 2017 sample compared to the 2005 sample. CONCLUSION: Despite major advances in health promotion during the past decade, there has been no reduction in the level of CVD risk factors in patients with SCZ and modest improvement in BD.
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Transtorno Bipolar/epidemiologia , Doenças Cardiovasculares/epidemiologia , Esquizofrenia/epidemiologia , Adulto , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: This study examines if YKL-40 is increased in individuals with psychotic disorders and if elevated YKL-40 levels at baseline is associated with subsequent development of type 2 diabetes. METHOD: A total of 1383 patients with a diagnosis of schizophrenia or affective psychosis and 799 healthy controls were recruited in the period 2002-2015. Plasma YKL-40 and metabolic risk factors were measured and medication was recorded. Using national registry data, association between baseline risk factors and later development of type 2 diabetes was assessed using Cox proportional hazards models. RESULTS: Plasma YKL-40 was higher in patients vs. healthy controls also after adjusting for metabolic risk factors, with no difference between the schizophrenia and affective psychosis groups. Patients were diagnosed with type 2 diabetes at a significantly younger age. Multivariate Cox regression analyses showed that elevated YKL-40 (hazard ratio (HR) = 5.6, P = 0.001), elevated glucose (HR = 3.6, P = 0.001), and schizophrenia diagnosis (HR = 3.0, P = 0.014) at baseline were associated with subsequent development of type 2 diabetes. CONCLUSIONS: Patients with psychotic disorders have at baseline increased levels of YKL-40 beyond the effect of comorbid type 2 diabetes and metabolic risk factors. Elevated YKL-40 level at baseline is associated with later development of type 2 diabetes.
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Biomarcadores/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Diabetes Mellitus Tipo 2/etiologia , Transtornos Psicóticos/sangue , Adulto , Transtornos Psicóticos Afetivos/sangue , Transtornos Psicóticos Afetivos/complicações , Transtornos Psicóticos Afetivos/diagnóstico , Comorbidade , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/psicologia , Feminino , Voluntários Saudáveis/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Transtornos Psicóticos/complicações , Transtornos Psicóticos/diagnóstico , Fatores de Risco , Esquizofrenia/sangue , Esquizofrenia/complicações , Esquizofrenia/diagnósticoRESUMO
BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) are heritable, polygenic disorders with shared clinical and genetic components, suggesting a psychosis continuum. Cannabis use is a well-documented environmental risk factor in psychotic disorders. In the current study, we investigated the relationship between SZ genetic load and cannabis use before illness onset in SZ and BD spectrums. Since frequent early cannabis use (age <18 years) is believed to increase the risk of developing psychosis more than later use, follow-up analyses were conducted comparing early use to later use and no use. METHODS: We assigned a SZ-polygenic risk score (PGRS) to each individual in our independent sample (N = 381 SZ spectrum cases, 220 BD spectrum cases and 415 healthy controls), calculated from the results of the Psychiatric Genomics Consortium (PGC) SZ case-control study (N = 81 535). SZ-PGRS in patients who used cannabis weekly to daily in the period before first illness episode was compared with that of those who never or infrequently used cannabis. RESULTS: Patients with weekly to daily cannabis use before illness onset had the highest SZ-PGRS (p = 0.02, Cohen's d = 0.33). The largest difference was found between patients with daily or weekly cannabis use before illness onset <18 years of age and patients with no or infrequent use of cannabis (p = 0.003, Cohen's d = 0.42). CONCLUSIONS: Our study supports an association between high SZ-PGRS and frequent cannabis use before illness onset in psychosis continuum disorders.
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Transtorno Bipolar/genética , Cannabis/efeitos adversos , Abuso de Maconha/epidemiologia , Esquizofrenia/genética , Adolescente , Adulto , Transtorno Bipolar/induzido quimicamente , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Herança Multifatorial , Noruega , Escalas de Graduação Psiquiátrica , Fatores de Risco , Esquizofrenia/induzido quimicamente , Adulto JovemRESUMO
BACKGROUND: Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. METHODS: This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). RESULTS: Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (ß std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. CONCLUSIONS: Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
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Córtex Pré-Frontal/patologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia , Adulto , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Internacionalidade , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Escalas de Graduação Psiquiátrica , Psicologia do EsquizofrênicoRESUMO
This corrects the article DOI: 10.1038/mp.2016.244.
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The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P<5 × 10-8). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e.=0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness.
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Cognição/fisiologia , Transtornos Neurocognitivos/genética , Adulto , Alelos , Feminino , Frequência do Gene/genética , Estudos de Associação Genética/métodos , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , População Branca/genéticaRESUMO
BACKGROUND: Early trauma is linked to higher symptom levels in bipolar and psychotic disorders, but the translating mechanisms are not well understood. This study examines whether the relationship between early emotional abuse and depressive symptoms is mediated by metacognitive beliefs about thoughts being uncontrollable/dangerous, and whether this pathway extends to influence positive symptoms. METHOD: Patients (N = 261) with psychotic or bipolar disorders were assessed for early trauma experiences, metacognitive beliefs, and current depression/anxiety and positive symptoms. Mediation path analyses using ordinary least-squares regressions tested if the effect of early emotional abuse on depression/anxiety was mediated by metacognitive beliefs, and if the effect of early emotional abuse on positive symptoms was mediated by metacognitive beliefs and depression/anxiety. RESULTS: Metacognitive beliefs about thoughts being uncontrollable/dangerous significantly mediated the relationship between early emotional abuse and depression/anxiety. Metacognitive beliefs and depression/anxiety significantly mediated the relationship between early emotional abuse and positive symptoms. The models explained a moderate amount of the variance in symptoms (R 2 = 0.21-0.29). CONCLUSION: Our results indicate that early emotional abuse is relevant to depression/anxiety and positive symptoms in bipolar and psychotic disorders, and suggest that metacognitive beliefs could play a role in an affective pathway to psychosis. Metacognitive beliefs could be relevant treatment targets with regards to depression/anxiety and positive symptoms in bipolar and psychotic disorders.
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Sobreviventes Adultos de Maus-Tratos Infantis , Ansiedade/fisiopatologia , Transtorno Bipolar/fisiopatologia , Depressão/fisiopatologia , Emoções/fisiologia , Metacognição/fisiologia , Transtornos Psicóticos/fisiopatologia , Adulto , Ansiedade/etiologia , Transtorno Bipolar/etiologia , Depressão/etiologia , Feminino , Humanos , Masculino , Transtornos Psicóticos/etiologia , Adulto JovemRESUMO
BACKGROUND: Excessive alcohol use is associated with brain damage but less is known about brain effects from moderate alcohol use. Previous findings indicate that patients with severe mental illness, particularly schizophrenia, are vulnerable to alcohol-related brain damage. We investigated the association between levels of alcohol consumption and cortical and subcortical brain structures in schizophrenia and bipolar disorder patients and healthy controls, and investigated for group differences for this association. METHOD: 1.5 T structural magnetic resonance images were acquired of 609 alcohol-using participants (165 schizophrenia patients, 172 bipolar disorder patients, 272 healthy controls), mean (s.d.) age 34.2 (9.9) years, 52% men. Past year alcohol use was assessed with the Alcohol Use Disorder Identification Test - Consumption part (AUDIT-C). General linear models were used to investigate associations between AUDIT-C score and cortical thickness, surface area, and total brain and subcortical volumes. RESULTS: Increasing AUDIT-C score was linearly associated with thinner cortex in medial and dorsolateral frontal and parieto-occipital regions, and with larger left lateral ventricle volume. There was no significant interaction between AUDIT-C score and diagnostic group. The findings remained significant after controlling for substance use disorders, antipsychotic medication and illness severity. CONCLUSION: The results show a dose-dependent relationship between alcohol use and thinner cortex and ventricular expansion. The findings are present also at lower levels of alcohol consumption and do not differ between schizophrenia or bipolar disorder patients compared to healthy controls. Our results do not support previous findings of increased vulnerability for alcohol-related brain damage in severe mental illness.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/patologia , Transtorno Bipolar/patologia , Córtex Cerebral/patologia , Ventrículos Cerebrais/patologia , Esquizofrenia/patologia , Adulto , Transtorno Bipolar/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Ventrículos Cerebrais/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Esquizofrenia/diagnóstico por imagemRESUMO
BACKGROUND: Childhood trauma increases risk of a range of mental disorders including psychosis. Whereas the mechanisms are unclear, previous evidence has implicated atypical processing of emotions among the core cognitive models, in particular suggesting altered attentional allocation towards negative stimuli and increased negativity bias. Here, we tested the association between childhood trauma and brain activation during emotional face processing in patients diagnosed with psychosis continuum disorders. In particular, we tested if childhood trauma was associated with the differentiation in brain responses between negative and positive face stimuli. We also tested if trauma was associated with emotional ratings of negative and positive faces. METHOD: We included 101 patients with a Diagnostic and Statistical Manual of Mental Disorders (DSM) schizophrenia spectrum or bipolar spectrum diagnosis. History of childhood trauma was obtained using the Childhood Trauma Questionnaire. Brain activation was measured with functional magnetic resonance imaging during presentation of faces with negative or positive emotional expressions. After the scanner session, patients performed emotional ratings of the same faces. RESULTS: Higher levels of total childhood trauma were associated with stronger differentiation in brain responses to negative compared with positive faces in clusters comprising the right angular gyrus, supramarginal gyrus, middle temporal gyrus and the lateral occipital cortex (Cohen's d = 0.72-0.77). In patients with schizophrenia, childhood trauma was associated with reporting negative faces as more negative, and positive faces as less positive (Cohen's d > 0.8). CONCLUSIONS: Along with the observed negativity bias in the assessment of emotional valence of faces, our data suggest stronger differentiation in brain responses between negative and positive faces with higher levels of trauma.
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Adultos Sobreviventes de Eventos Adversos na Infância , Transtorno Bipolar/fisiopatologia , Córtex Cerebral/fisiopatologia , Emoções/fisiologia , Expressão Facial , Reconhecimento Facial/fisiologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Percepção Social , Adulto , Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Transtorno Bipolar/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Masculino , Transtornos Psicóticos/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: Many studies have shown associations between a history of childhood trauma and more severe or complex clinical features of bipolar disorders (BD), including suicide attempts and earlier illness onset. However, the psychopathological mechanisms underlying these associations are still unknown. Here, we investigated whether affective lability mediates the relationship between childhood trauma and the severe clinical features of BD. METHOD: A total of 342 participants with BD were recruited from France and Norway. Diagnosis and clinical characteristics were assessed using the Diagnostic Interview for Genetic Studies (DIGS) or the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Affective lability was measured using the short form of the Affective Lability Scale (ALS-SF). A history of childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Mediation analyses were performed using the SPSS process macro. RESULTS: Using the mediation model and covariation for the lifetime number of major mood episodes, affective lability was found to statistically mediate the relationship between childhood trauma experiences and several clinical variables, including suicide attempts, mixed episodes and anxiety disorders. No significant mediation effects were found for rapid cycling or age at onset. CONCLUSIONS: Our data suggest that affective lability may represent a psychological dimension that mediates the association between childhood traumatic experiences and the risk of a more severe or complex clinical expression of BD.
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Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Transtornos de Ansiedade/fisiopatologia , Transtorno Bipolar/fisiopatologia , Transtornos Psicóticos/fisiopatologia , Tentativa de Suicídio/psicologia , Adolescente , Adulto , Adultos Sobreviventes de Eventos Adversos na Infância/estatística & dados numéricos , Idade de Início , Idoso , Transtornos de Ansiedade/epidemiologia , Transtorno Bipolar/epidemiologia , Comorbidade , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Transtornos Psicóticos/epidemiologia , Tentativa de Suicídio/estatística & dados numéricos , Adulto JovemRESUMO
Inbreeding depression refers to lower fitness among offspring of genetic relatives. This reduced fitness is caused by the inheritance of two identical chromosomal segments (autozygosity) across the genome, which may expose the effects of (partially) recessive deleterious mutations. Even among outbred populations, autozygosity can occur to varying degrees due to cryptic relatedness between parents. Using dense genome-wide single-nucleotide polymorphism (SNP) data, we examined the degree to which autozygosity associated with measured cognitive ability in an unselected sample of 4854 participants of European ancestry. We used runs of homozygosity-multiple homozygous SNPs in a row-to estimate autozygous tracts across the genome. We found that increased levels of autozygosity predicted lower general cognitive ability, and estimate a drop of 0.6 s.d. among the offspring of first cousins (P=0.003-0.02 depending on the model). This effect came predominantly from long and rare autozygous tracts, which theory predicts as more likely to be deleterious than short and common tracts. Association mapping of autozygous tracts did not reveal any specific regions that were predictive beyond chance after correcting for multiple testing genome wide. The observed effect size is consistent with studies of cognitive decline among offspring of known consanguineous relationships. These findings suggest a role for multiple recessive or partially recessive alleles in general cognitive ability, and that alleles decreasing general cognitive ability have been selected against over evolutionary time.
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Cognição/fisiologia , Depressão por Endogamia/genética , Adulto , Alelos , Mapeamento Cromossômico/métodos , Feminino , Genoma Humano/genética , Estudo de Associação Genômica Ampla , Homozigoto , Humanos , Depressão por Endogamia/fisiologia , Masculino , Polimorfismo de Nucleotídeo Único/genética , População Branca/genéticaRESUMO
The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.
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Encéfalo/patologia , Esquizofrenia/patologia , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Estudos de Casos e Controles , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Estudos Prospectivos , Esquizofrenia/genéticaRESUMO
OBJECTIVE: The effect of antipsychotic medication on brain structure remains unclear. Given the prevalence of weight gain as a side-effect, body mass index (BMI) change could be a confounder. METHOD: Patients with first-episode psychosis (n = 78) and healthy controls (n = 119) underwent two 1.5T MRI scans with a 1-year follow-up interval. siena (fsl 5.0) was used to measure whole-brain volume change. Weight and height were measured at both time points. Antipsychotic medication use at baseline and follow-up was converted into chlorpromazine equivalent dose and averaged. RESULTS: Patients did not show significantly larger brain volume loss compared with healthy controls. In the whole sample (n = 197), BMI change was negatively associated with brain volume change (ß = -0.19, P = 0.008); there was no interaction effect of group. Among patients, higher antipsychotic medication dosage was associated with greater brain volume loss (ß = -0.45, P < 0.001). This association was not affected by adjusting for BMI change. CONCLUSION: Weight gain was related to brain volume reductions to a similar degree among patients and controls. Antipsychotic dosage-related reductions of brain volume were not confounded by BMI change. Generalizability to contexts involving severe weight gain needs to be established. Furthermore, disentangling effects of medication from illness severity remains a challenge.
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Antipsicóticos/uso terapêutico , Encéfalo/diagnóstico por imagem , Clorpromazina/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Adulto , Antipsicóticos/farmacologia , Índice de Massa Corporal , Encéfalo/efeitos dos fármacos , Clorpromazina/farmacologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: We evaluated if plasma levels of inflammatory markers are persistently altered in severe mental disorders with psychotic symptoms or associated with state characteristics in a longitudinal study. METHODS: Soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin-1 receptor antagonist (IL-1Ra), von Willebrand factor (VWF), and osteoprotegerin (OPG) were measured in schizophrenia (n = 69) and affective (n = 55) spectrum patients at baseline and at one-year follow-up, and compared to healthy controls (HC) (n = 92) with analysis of covariance. Association between change in symptoms and inflammatory markers was analyzed with mixed-effects models. RESULTS: sTNF-R1 was higher in the schizophrenia (P < 0.0001) and affective disorders (P = 0.02) compared to HC, while IL-1Ra was higher in schizophrenia (P = 0.01) compared to HC at one year follow-up. There were no significant differences between schizophrenia and affective groups; however, levels in the affective group were in between schizophrenia and HC for sTNF-R1 and IL-1Ra. There were no significant associations between change in symptoms and inflammatory markers. CONCLUSION: Persistently increased sTNF-R1 and IL-1Ra after one year in patients with severe mental disorders primarily reflecting data from the schizophrenia group may suggest that inflammation is a trait phenomenon, and not only the result of stress-related mechanisms associated with acute episodes.
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Transtorno Bipolar/sangue , Transtorno Depressivo Maior/sangue , Inflamação/sangue , Proteína Antagonista do Receptor de Interleucina 1/sangue , Osteoprotegerina/sangue , Transtornos Psicóticos/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Esquizofrenia/sangue , Fator de von Willebrand/análise , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: Based on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia. METHOD: This prospective meta-analysis includes data from 1987 individuals with schizophrenia collected at seventeen centres around the world that contribute to the ENIGMA Schizophrenia Working Group. STG thickness measures were extracted from T1-weighted brain scans using FreeSurfer. The study performed a meta-analysis of effect sizes across sites generated by a model predicting left or right STG thickness with a positive symptom severity score (harmonized SAPS or PANSS-positive scores), while controlling for age, sex and site. Secondary models investigated relationships between antipsychotic medication, duration of illness, overall illness severity, handedness and STG thickness. RESULTS: Positive symptom severity was negatively related to STG thickness in both hemispheres (left: ßstd = -0.052; P = 0.021; right: ßstd = -0.073; P = 0.001) when statistically controlling for age, sex and site. This effect remained stable in models including duration of illness, antipsychotic medication or handedness. CONCLUSION: Our findings further underline the important role of the STG in hallmark symptoms in schizophrenia. These findings can assist in advancing insight into symptom-relevant pathophysiological mechanisms in schizophrenia.
Assuntos
Imageamento por Ressonância Magnética/métodos , Esquizofrenia/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Masculino , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Esquizofrenia/patologia , Psicologia do Esquizofrênico , Lobo Temporal/patologiaRESUMO
INTRODUCTION: Abstract thinking is important in modern understanding of neurocognitive abilities, and a symptom of thought disorder in psychosis. In patients with psychosis, we assessed if socio-developmental background influences abstract thinking, and the association with executive functioning and clinical psychosis symptoms. METHODS: Participants (n = 174) had a diagnosis of psychotic or bipolar disorder, were 17-65 years, intelligence quotient (IQ) > 70, fluent in a Scandinavian language, and their full primary education in Norway. Immigrants (N = 58) were matched (1:2) with participants without a history of migration (N = 116). All participants completed a neurocognitive and clinical assessment. Socio-developmental background was operationalised as human developmental index (HDI) of country of birth, at year of birth. Structural equation modelling was used to assess the model with best fit. RESULTS: The model with best fit, χ2 = 96.591, df = 33, p < .001, confirmed a significant indirect effect of HDI scores on abstract thinking through executive functioning, but not through clinical psychosis symptoms. CONCLUSIONS: This study found that socio-developmental background influences abstract thinking in psychosis by indirect effect through executive functioning. We should take into account socio-developmental background in the interpretation of neurocognitive performance in patients with psychosis, and prioritise cognitive remediation in treatment of immigrant patients.
Assuntos
Transtorno Bipolar/psicologia , Transtornos Cognitivos/psicologia , Transtornos Psicóticos/psicologia , Pensamento , Adolescente , Adulto , Idoso , Transtorno Bipolar/etnologia , Transtornos Cognitivos/etnologia , Emigrantes e Imigrantes/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Noruega , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/etnologia , Adulto JovemRESUMO
BACKGROUND: Cannabis use disorder is associated with an earlier age at onset and a more severe outcome of schizophrenia spectrum disorders. The role of cannabis use before the onset of illness (premorbid cannabis use) has not been fully investigated. We here examined how amount and type of premorbid cannabis use was associated with the later course of illness including current substance use, symptoms and level of functioning in schizophrenia spectrum disorder. METHOD: We used a naturalistic sample of patients with DSM-IV schizophrenia spectrum disorders with a comprehensive history of illness and substance use. Data on premorbid substance use was obtained from comprehensive self-report. The relationship to outcome was investigated using regression models that included current substance use and premorbid functioning. RESULTS: Pre-schizophrenia cannabis use was significantly associated with more severe psychotic symptoms and impaired functioning. Higher levels of premorbid cannabis use were associated with higher levels of current psychotic symptoms. These associations were independent of current substance use and premorbid functioning. Early use of cannabis (age <17 years) was associated with earlier age at onset of psychosis, independently of potential confounders. CONCLUSIONS: Pre-psychosis cannabis use affects illness outcome in schizophrenia spectrum disorders, and is associated with lower age at onset of psychosis. These findings of independent negative effects of premorbid cannabis use in schizophrenia suggest that a limitation of the general use of cannabis may have beneficial health effects.