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1.
Psychiatry Res ; 323: 115184, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37015164

RESUMO

BACKGROUND: People with schizophrenia spectrum disorders (SSD) frequently present cognitive impairments. Here, we investigated whether the exposome score for schizophrenia (ES-SCZ) - a cumulative environmental exposure score - was associated with impairments of neurocognition, social cognition, and perception in patients with SSD, their unaffected siblings, and healthy controls. METHODS: This cross-sectional sample consisted of 1200 patients, 1371 siblings, and 1564 healthy controls. Neurocognition, social cognition, and perception were assesed using a short version of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), the Degraded Facial Affect Recognition Task (DFAR), and the Benton Facial Recognition Test (BFR), respectively. Regression models were used to analyze the association between ES-SCZ and cognitive domains in each group. RESULTS: There were no statistically significant associations between ES-SCZ and cognitive domains in SSD. ES-SCZ was negatively associated with T-score of cognition in siblings (B=-0.40, 95% CI -0.76 to -0.03) and healthy controls (B=-0.63, 95% CI -1.06 to -0.21). Additionally, ES-SCZ was positively associated with DFAR-total in siblings (B=0.83, 95% CI 0.26 to 1.40). Sensitivity analyses excluding cannabis use history from ES-SCZ largely confirmed the main findings. CONCLUSIONS: Longitudinal cohorts may elucidate how environmental exposures influence the onset and course of cognitive impairments in trans-syndromic psychosis spectrum.


Assuntos
Cognição , Expossoma , Psicologia do Esquizofrênico , Adulto , Humanos , Estudos Transversais , Esquizofrenia/epidemiologia , Irmãos/psicologia , Estudos de Casos e Controles , Transtornos Cognitivos/epidemiologia , Masculino , Feminino
2.
Eur Neuropsychopharmacol ; 63: 47-59, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36055075

RESUMO

Schizophrenia is frequently accompanied with social cognitive disturbances. Cannabis represents one established environmental factor associated with the onset and progression of schizophrenia. The present cross-sectional study aimed to investigate the association of facial emotion recognition (FER) performance with cannabis use in 2039 patients with schizophrenia, 2141 siblings, and 2049 healthy controls (HC). FER performance was measured using the Degraded Facial Affect Recognition Task (DFAR). Better FER performance as indicated by higher DFAR-total scores was associated with lifetime regular cannabis use in schizophrenia (B = 1.36, 95% CI 0.02 to 2.69), siblings (B = 2.17, 95% CI 0.79 to 3.56), and HC (B = 3.10, 95% CI 1.14 to 5.06). No associations were found between DFAR-total and current cannabis use. Patients with schizophrenia who started to use cannabis after the age of 16 showed better FER performance than patients who started earlier (B = 2.50, 95% CI 0.15 to 4.84) and non-users (B = 3.72, 95 CI 1.96 to 5.49). Better FER performance was found also in siblings who started to use cannabis after 16 compared to non-users (B = 2.37, 95% CI 0.58 to 4.16), while HC using cannabis performed better than non-users at DFAR-total regardless of the age at onset. Our findings suggest that lifetime regular cannabis use may be associated with better FER regardless of the psychosis risk, but that FER might be moderated by age at first use in people with higher genetic risk. Longitudinal studies may clarify whether there is a cause-and-effect relationship between cannabis use and FER performance in psychotic and non-psychotic samples.


Assuntos
Cannabis , Reconhecimento Facial , Transtornos Psicóticos , Esquizofrenia , Agonistas de Receptores de Canabinoides , Estudos Transversais , Emoções , Humanos , Transtornos Psicóticos/psicologia , Esquizofrenia/complicações , Irmãos/psicologia
3.
Psychoneuroendocrinology ; 129: 105242, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33975150

RESUMO

This study aimed to identify yet unavailable blood biomarkers for the responsive and the hyporesponsive hypothalamic-pituitary-adrenal (HPA) axis subtypes of posttraumatic stress disorder (PTSD). As, I, we recently discovered the intranasal neuropeptide oxytocin to reduce experimentally provoked PTSD symptoms, II, expression of its receptor (OXTR) has hitherto not been assessed in PTSD patients, and III, oxytocin and OXTR have previously been related to the HPA axis, we considered both as suitable candidates. During a Trier Social Stress Test (TSST), we compared serum oxytocin and blood OXTR mRNA concentrations between female PTSD patients, their HPA axis reactivity subtypes and sex and age-matched healthy controls (HC). At baseline, both candidates differentiated the hyporesponsive HPA axis subtype from HC, however, only baseline OXTR mRNA discriminated also between subtypes. Furthermore, in the hyporesponsive HPA axis subgroup, OXTR mRNA levels correlated with PTSD symptoms and changed markedly during the TSST. To assess the influence of (traumatic) stress on the cerebral expression of oxytocin and its receptor and to test their suitability as biomarkers for the mouse PTSD-like syndrome, we then analyzed oxytocin, its mRNA (Oxt) and Oxtr mRNA in three relevant brain regions and Oxt in blood of a PTSD mouse model. To further explore the HPA axis reactivity subtype dependency of OXTR, we compared cerebral OXTR protein expression between mice exhibiting two different HPA axis reactivity traits, i.e., FK506 binding protein 51 knockout vs. wildtype mice. In summary, blood OXTR mRNA emerged as a potential biomarker of the hyporesponsive HPA axis PTSD subtype and prefrontal cortical Oxtr and Oxt of the mouse PTSD-like syndrome. Moreover, we found first translational evidence for a HPA axis responsivity trait-dependent regulation of OXTR expression. The lack of a cohort of the (relatively rare) hyporesponsive HPA axis subtype of HC is a limitation of our study.


Assuntos
Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Receptores de Ocitocina/metabolismo , Transtornos de Estresse Pós-Traumáticos/classificação , Transtornos de Estresse Pós-Traumáticos/metabolismo , Adulto , Animais , Biomarcadores/análise , Biomarcadores/sangue , Feminino , Humanos , Masculino , Camundongos , Ocitocina/análise , Ocitocina/sangue , Ocitocina/genética , RNA Mensageiro/análise , Receptores de Ocitocina/genética , Transtornos de Estresse Pós-Traumáticos/genética
4.
Elife ; 102021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33646943

RESUMO

We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.


Assuntos
Metilação de DNA , Epigenoma , Transtornos Psicóticos/fisiopatologia , Esquizofrenia Resistente ao Tratamento/fisiopatologia , Adulto , Idoso , Inglaterra , Feminino , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/genética , Esquizofrenia Resistente ao Tratamento/genética , Escócia , Suécia , Adulto Jovem
5.
Psychol Med ; 51(4): 623-633, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32327005

RESUMO

BACKGROUND: The 'jumping to conclusions' (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ. METHODS: A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia. RESULTS: The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI -0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25-0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = -1.7, 95% CI -2.8 to -0.5, p = 0.006), but did not relate to delusions in patients. CONCLUSIONS: Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.


Assuntos
Inteligência , Transtornos Psicóticos/psicologia , Adolescente , Adulto , Viés , Estudos de Casos e Controles , Cognição , Disfunção Cognitiva/psicologia , Delusões/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resolução de Problemas , Adulto Jovem
6.
Lancet Psychiatry ; 6(5): 427-436, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30902669

RESUMO

BACKGROUND: Cannabis use is associated with increased risk of later psychotic disorder but whether it affects incidence of the disorder remains unclear. We aimed to identify patterns of cannabis use with the strongest effect on odds of psychotic disorder across Europe and explore whether differences in such patterns contribute to variations in the incidence rates of psychotic disorder. METHODS: We included patients aged 18-64 years who presented to psychiatric services in 11 sites across Europe and Brazil with first-episode psychosis and recruited controls representative of the local populations. We applied adjusted logistic regression models to the data to estimate which patterns of cannabis use carried the highest odds for psychotic disorder. Using Europe-wide and national data on the expected concentration of Δ9-tetrahydrocannabinol (THC) in the different types of cannabis available across the sites, we divided the types of cannabis used by participants into two categories: low potency (THC <10%) and high potency (THC ≥10%). Assuming causality, we calculated the population attributable fractions (PAFs) for the patterns of cannabis use associated with the highest odds of psychosis and the correlation between such patterns and the incidence rates for psychotic disorder across the study sites. FINDINGS: Between May 1, 2010, and April 1, 2015, we obtained data from 901 patients with first-episode psychosis across 11 sites and 1237 population controls from those same sites. Daily cannabis use was associated with increased odds of psychotic disorder compared with never users (adjusted odds ratio [OR] 3·2, 95% CI 2·2-4·1), increasing to nearly five-times increased odds for daily use of high-potency types of cannabis (4·8, 2·5-6·3). The PAFs calculated indicated that if high-potency cannabis were no longer available, 12·2% (95% CI 3·0-16·1) of cases of first-episode psychosis could be prevented across the 11 sites, rising to 30·3% (15·2-40·0) in London and 50·3% (27·4-66·0) in Amsterdam. The adjusted incident rates for psychotic disorder were positively correlated with the prevalence in controls across the 11 sites of use of high-potency cannabis (r = 0·7; p=0·0286) and daily use (r = 0·8; p=0·0109). INTERPRETATION: Differences in frequency of daily cannabis use and in use of high-potency cannabis contributed to the striking variation in the incidence of psychotic disorder across the 11 studied sites. Given the increasing availability of high-potency cannabis, this has important implications for public health. FUNDING SOURCE: Medical Research Council, the European Community's Seventh Framework Program grant, São Paulo Research Foundation, National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King's College London and the NIHR BRC at University College London, Wellcome Trust.


Assuntos
Abuso de Maconha/epidemiologia , Transtornos Psicóticos/epidemiologia , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Abuso de Maconha/complicações , Pessoa de Meia-Idade , Razão de Chances , Transtornos Psicóticos/etiologia , Adulto Jovem
7.
Psychol Med ; 49(8): 1378-1391, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30282569

RESUMO

BACKGROUND: The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment. METHOD: This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions. RESULTS: A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions. CONCLUSIONS: Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.


Assuntos
Psicopatologia , Transtornos Psicóticos/classificação , Transtornos Psicóticos/psicologia , Esquizofrenia/classificação , Psicologia do Esquizofrênico , Adulto , Transtornos Psicóticos Afetivos , Transtorno Bipolar/psicologia , Depressão/psicologia , Europa (Continente) , Feminino , Humanos , Masculino , Modelos Psicológicos , Escalas de Graduação Psiquiátrica , Curva ROC , Adulto Jovem
8.
Epigenomics ; 8(5): 593-8, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27092400

RESUMO

Alterations in DNA methylation have been associated with cognitive decline and Alzheimer's disease. A recent study of mild cognitive impairment (MCI) reported a significant association between annual decline in cognitive function and the rs11887120 SNP located in DNMT3A, a gene implicated in DNA methylation. Here, we aimed to replicate this finding in two independent MCI cohorts (n = 1024); however, no significant association was observed in either cohort or the pooled dataset. In stratified analyses for conversion to Alzheimer's disease status, no association between rs11887120 and cognitive decline was observed in either converters or nonconverters. In conclusion, our analyses provide no support for the hypothesis that genetic variants in DNMT3A are implicated in cognitive performance decline in individuals with MCI.


Assuntos
Doença de Alzheimer/genética , Disfunção Cognitiva/genética , DNA (Citosina-5-)-Metiltransferases/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Estudos de Casos e Controles , Cognição , Disfunção Cognitiva/psicologia , DNA Metiltransferase 3A , Progressão da Doença , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
9.
Schizophr Bull ; 34(6): 1066-82, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18791076

RESUMO

Concern is building about high rates of schizophrenia in large cities, and among immigrants, cannabis users, and traumatized individuals, some of which likely reflects the causal influence of environmental exposures. This, in combination with very slow progress in the area of molecular genetics, has generated interest in more complicated models of schizophrenia etiology that explicitly posit gene-environment interactions (EU-GEI. European Network of Schizophrenia Networks for the Study of Gene Environment Interactions. Schizophrenia aetiology: do gene-environment interactions hold the key? [published online ahead of print April 25, 2008] Schizophr Res; S0920-9964(08) 00170-9). Although findings of epidemiological gene-environment interaction (G x E) studies are suggestive of widespread gene-environment interactions in the etiology of schizophrenia, numerous challenges remain. For example, attempts to identify gene-environment interactions cannot be equated with molecular genetic studies with a few putative environmental variables "thrown in": G x E is a multidisciplinary exercise involving epidemiology, psychology, psychiatry, neuroscience, neuroimaging, pharmacology, biostatistics, and genetics. Epidemiological G x E studies using indirect measures of genetic risk in genetically sensitive designs have the advantage that they are able to model the net, albeit nonspecific, genetic load. In studies using direct molecular measures of genetic variation, a hypothesis-driven approach postulating synergistic effects between genes and environment impacting on a final common pathway, such as "sensitization" of mesolimbic dopamine neurotransmission, while simplistic, may provide initial focus and protection against the numerous false-positive and false-negative results that these investigations engender. Experimental ecogenetic approaches with randomized assignment may help to overcome some of the limitations of observational studies and allow for the additional elucidation of underlying mechanisms using a combination of functional enviromics and functional genomics.


Assuntos
Esquizofrenia/epidemiologia , Esquizofrenia/genética , Psicologia do Esquizofrênico , Meio Social , Estudos Transversais , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Predisposição Genética para Doença/psicologia , Genótipo , Humanos , Pesquisa , Fatores de Risco
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