RESUMO
BACKGROUND: Strategies of prevention for psychiatric disorders need a deep understanding of the aetiological factors involved in the psychopathological processes. Our twin study aims at disentangling the contributions of genes and environment to schizotypal and hypomanic dimensions, considering the role of stressful life events (LEs) and the quality of family relationships. METHODS: The Magical Ideation Scale (MIS) and Perceptual Aberration Scale (PAS) were used to assess positive schizotypy, while Hypomanic Personality Scale (HPS) and its sub-scales were used to investigate proneness to affective disorders. 268 twins (54.5 % female; aged 18.0 ± 6.68) were included. Participants filled out a questionnaire on LEs and their parents provided an evaluation of intra-family relationship (Relationship Quality Index, RQI). Classic univariate twin models for quantitative traits were fitted for scales, and the effects of covariates (LEs and RQI) were assessed. RESULTS: For MIS, HPS and its sub-scales, significant common and unique environmental effects were detected, with genetic factors affecting only HPS Social Vitality sub-scale. Unique environment was the only source of variance of PAS score. The number of recent LEs influenced MIS and PAS models, while RQI score affected MIS model. LIMITATIONS: The main limitation of the study is the small sample size, which reduces statistical power and may potentially lead to an underestimation of heritability. Additionally, the cross-sectional design limits the possibility to draw causal considerations. CONCLUSIONS: Findings provide preliminary evidence for a significant environmental role in modulating states of vulnerability. Moreover, the expression of positive schizotypy resulted influenced by recent stressors and intra-family relationships.
Assuntos
Transtorno Bipolar , Acontecimentos que Mudam a Vida , Transtorno da Personalidade Esquizotípica , Humanos , Feminino , Masculino , Transtorno da Personalidade Esquizotípica/genética , Transtorno da Personalidade Esquizotípica/psicologia , Adulto , Adolescente , Adulto Jovem , Transtorno Bipolar/genética , Transtorno Bipolar/psicologia , Interação Gene-Ambiente , Inquéritos e Questionários , Relações Familiares , Família/psicologia , Gêmeos Dizigóticos/genética , Gêmeos Dizigóticos/psicologia , Escalas de Graduação PsiquiátricaRESUMO
PURPOSE OF THE ARTICLE: Schizophrenia with persistent negative symptoms (PNS) may have different characteristics regarding negative symptom dimensions and heritability patterns. This study aimed to investigate the dimensional characteristics of PNS and their relationships with schizotypal features in first-degree relatives (FDRs). MATERIALS AND METHODS: The study included 142 patients, 142 FDRs, and 71 healthy controls (HC). Patients were evaluated with the Positive and Negative Symptom Scale (PANSS), Brief Negative Symptom Scale (BNSS), Calgary Depression Scale for Schizophrenia (CDSS), and Simpson-Angus Scale (SAS). Schizotypy Personality Questionnaire was applied to FDR and HC groups. Clinical symptoms were compared between primary-PNS, secondary-PNS, and non-PNS groups. In addition, schizotypy scores were compared between FDRs and HCs. Then, the relationship between the symptoms of the patients in the PNS group and the schizotypy scores of their relatives was evaluated by multiple regression analysis. RESULTS: All negative symptom dimension scores were similar in primary-PNS and secondary-PNS and lowest in non-PNS. PNS-FDR had higher in all schizotypy scores than non-PNS-FDR and HC, except for lack of close friends and social anxiety. In the PNS group, positive symptom severity and PANSS experiential deficit scores significantly predicted positive and negative schizotypy scores in relatives. Negative schizotypy was associated with asociality. CONCLUSIONS: The PNS is likely a subtype in which the genetic basis of negative symptoms is stronger and is associated with genetic abnormalities shared by positive and negative schizotypy dimensions in relatives. Family-based genetic studies will be beneficial in enlightening the genetic etiology of PNS.
Assuntos
Esquizofrenia , Transtorno da Personalidade Esquizotípica , Humanos , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Transtorno da Personalidade Esquizotípica/diagnóstico , Transtorno da Personalidade Esquizotípica/genética , Análise de Regressão , Inquéritos e QuestionáriosRESUMO
Introduction: Clinical and family studies suggest that alterations of theory of mind (ToM) represent a marker of genetic liability to schizophrenia. Findings regarding ToM in schizotypy are less consistent. The study aimed to explore whether this might be due to an insufficient account of the heterogeneity of schizotypy in prior research and/or the fact that in psychometric schizotypy ToM alterations could manifest as subtle peculiarities rather than overt errors of mentalising.Methods: Individuals without a family history of psychosis (n = 150) were assigned to low, positive, negative, and high mixed schizotypy classes based on a cluster analysis of 1322 subjects who completed the Schizotypal Personality Questionnaire. The classes were compared on their performance of faux pas tasks with 77 adult first-degree relatives of schizophrenia patients, who represent individuals at genetic risk for schizophrenia. Besides overt errors, subtle alterations in ToM were analysed using expert judgment.Results: The relatives tended to make overt errors and demonstrated specific features of intentional reasoning. None of the schizotypal classes showed similar trends.Conclusions: The results complement the literature on the subjective-objective disjunction in psychometric schizotypes and did not provide evidence that ToM anomalies are a marker of genetic liability to schizophrenia in this cohort.
Assuntos
Transtornos Psicóticos , Esquizofrenia , Transtorno da Personalidade Esquizotípica , Teoria da Mente , Adulto , Humanos , Esquizofrenia/genética , Psicometria , Transtorno da Personalidade Esquizotípica/genéticaRESUMO
BACKGROUND: Psychotic disorders and schizotypal traits aggregate in the relatives of probands with schizophrenia. It is currently unclear how variability in symptom dimensions in schizophrenia probands and their relatives is associated with polygenic liability to psychiatric disorders. AIMS: To investigate whether polygenic risk scores (PRSs) can predict symptom dimensions in members of multiplex families with schizophrenia. METHOD: The largest genome-wide data-sets for schizophrenia, bipolar disorder and major depressive disorder were used to construct PRSs in 861 participants from the Irish Study of High-Density Multiplex Schizophrenia Families. Symptom dimensions were derived using the Operational Criteria Checklist for Psychotic Disorders in participants with a history of a psychotic episode, and the Structured Interview for Schizotypy in participants without a history of a psychotic episode. Mixed-effects linear regression models were used to assess the relationship between PRS and symptom dimensions across the psychosis spectrum. RESULTS: Schizophrenia PRS is significantly associated with the negative/disorganised symptom dimension in participants with a history of a psychotic episode (P = 2.31 × 10-4) and negative dimension in participants without a history of a psychotic episode (P = 1.42 × 10-3). Bipolar disorder PRS is significantly associated with the manic symptom dimension in participants with a history of a psychotic episode (P = 3.70 × 10-4). No association with major depressive disorder PRS was observed. CONCLUSIONS: Polygenic liability to schizophrenia is associated with higher negative/disorganised symptoms in participants with a history of a psychotic episode and negative symptoms in participants without a history of a psychotic episode in multiplex families with schizophrenia. These results provide genetic evidence in support of the spectrum model of schizophrenia, and support the view that negative and disorganised symptoms may have greater genetic basis than positive symptoms, making them better indices of familial liability to schizophrenia.
Assuntos
Transtorno Depressivo Maior , Transtornos Psicóticos , Esquizofrenia , Transtorno da Personalidade Esquizotípica , Humanos , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Transtorno da Personalidade Esquizotípica/diagnóstico , Transtorno da Personalidade Esquizotípica/genética , Transtorno da Personalidade Esquizotípica/psicologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/genética , Transtornos Psicóticos/genética , Transtornos Psicóticos/psicologia , Fatores de RiscoRESUMO
Recent evidence shows that genetic and environmental risk factors for psychotic disorders are associated with higher levels of schizotypy (or psychosis proneness) in the general population. However, little is known about how these risk factors interact. We specifically examined whether genetic loading for schizophrenia moderates the association between childhood trauma severity and schizotypy. Schizotypy was measured using the Schizotypal Personality Questionnaire (SPQ), and childhood trauma severity was measured with the Childhood Trauma Questionnaire (CTQ) among a total of 168 participants (comprising 51 healthy individuals, 56 diagnosed with schizophrenia, and 61 with bipolar disorder). Polygenic risk scores (PRS) for schizophrenia were calculated for all participants and examined as a potential moderator of associations between total scores on the CTQ and schizotypy total scores and dimensions (i.e., cognitive-perceptual, interpersonal, disorganised). Multiple linear regression models revealed associations between childhood trauma and all dimensions of schizotypy, but no associations between PRS and schizotypy. A significant interaction between PRS and childhood trauma was evident for the interpersonal and disorganised dimensions of schizotypy, as well as the total score, reflecting positive associations between childhood trauma severity and these two schizotypal dimensions, only for individuals with low or average PRS for schizophrenia. This suggests that trauma may be able to increase risk for psychosis independently of any genetic vulnerability. The present findings are consistent with the idea of several risk pathways for the development of psychotic disorders.
Assuntos
Experiências Adversas da Infância , Transtornos Psicóticos , Esquizofrenia , Transtorno da Personalidade Esquizotípica , Humanos , Herança Multifatorial , Transtornos Psicóticos/genética , Esquizofrenia/epidemiologia , Transtorno da Personalidade Esquizotípica/epidemiologia , Transtorno da Personalidade Esquizotípica/genéticaRESUMO
Mismatch negativity (MMN) amplitude is reliably reduced in psychotic disorders. While several studies have examined this effect in first-degree relatives of individuals with schizophrenia, few have sought to quantify deficits in relatives of individuals with other psychotic disorders. While some conclude that, compared to healthy subjects, first-degree relatives of schizophrenia show reduced MMN, others contradict this finding. Furthermore, though MMN is often shown to be associated with cognitive impairments and clinical symptoms in psychotic disorders, to our knowledge no studies have sought to fully examine these relationships in studies of first-degree relatives. The present study sought to clarify the extent of MMN amplitude reductions in a large sample of siblings of individuals with diverse psychotic disorders (n = 67), compared to probands with psychosis (n = 221) and never psychotic comparison subjects (n = 251). We further examined associations of MMN amplitude with cognition and schizotypal symptoms across these groups. We found that MMN amplitude was intact in siblings compared to probands. MMN amplitude was associated with cognition and schizotypal symptoms dimensionally across levels of familial risk. The present results imply that MMN reductions do not reflect genetic risk for psychotic disorders per se, and instead emerge as a result of, or in conjunction with, clinical features associated with psychosis. Such findings carry important implications for the utility of MMN amplitude as an indicator of inherited risk, and suggest that this component may be best conceptualized as an endophenotype for clinical symptoms and cognitive impairments, rather than risk for psychosis per se.
Assuntos
Transtornos Psicóticos , Esquizofrenia , Transtorno da Personalidade Esquizotípica , Cognição , Eletroencefalografia , Potenciais Evocados Auditivos , Humanos , Transtornos Psicóticos/complicações , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Transtorno da Personalidade Esquizotípica/complicações , Transtorno da Personalidade Esquizotípica/genéticaRESUMO
The traditional medical model of schizophrenia assumes a categorical view of the syndrome. On the contrary, the dimensional approach to schizophrenia infers that schizophrenia is not a discrete illness entity, but that psychotic symptoms differ in quantitative ways from normal experiences and behaviours. Schizotypy comprise a set of inherited traits reflected in personality organization, which presents as qualitatively similar to schizophrenia. Schizotipy is in line with continuum hypothesis of schizophrenia where different combinations of genes and environmental risk factors result in a range of different phenotypic expressions lying on a continuum from normal through to clinical psychosis. We discuss evidences for the continuity of psychotic symptoms to normal experiences and theoretical and future research implications of such a continuum.
Assuntos
Transtornos Psicóticos , Esquizofrenia , Transtorno da Personalidade Esquizotípica , Humanos , Personalidade , Fenótipo , Esquizofrenia/genética , Transtorno da Personalidade Esquizotípica/diagnóstico , Transtorno da Personalidade Esquizotípica/genéticaRESUMO
There is a relative dearth of research on features of schizotypal personality in children, in part due to lack of instrumentation. This study tests 5 competing models of the factor structure of the self-report Schizotypal Personality Questionnaire for Children (SPQ-C) and examines its relationship with a family history of schizotypal personality disorder (SPD), child abuse, and stability over time. Hypotheses were tested on 454 11- to 12-year-old schoolchildren and their caregivers. Confirmatory factor analyses supported a 3-factor structure of the SPQ-C (cognitive-perceptual, interpersonal, and disorganized). Test-retest stability was relatively robust over 3 months (r = .67), 6 months (r = .64), and 12 months (r = .55), with acceptable internal reliabilities (r = .84 to .91). Regarding construct validity, children with a biological family history of SPD had higher scores on all 3 factors (d =.51). Abused children had higher schizotypy scores (d = .55). A genetic × environment interaction was observed, with schizotypy highest in those with both a family history of schizotypy and also child abuse. Findings are the first in the child schizotypy field to document a gene × environment interaction and the independence of child abuse from confounding genetic influences. Results support the utility of the SPQ-C in future family and clinical studies of schizotypal personality and provide an avenue for much-needed and neglected research into the early antecedents of child schizotypal personality.
Assuntos
Maus-Tratos Infantis , Interação Gene-Ambiente , Predisposição Genética para Doença , Escalas de Graduação Psiquiátrica/normas , Psicometria/normas , Transtorno da Personalidade Esquizotípica/diagnóstico , Transtorno da Personalidade Esquizotípica/etiologia , Criança , Análise Fatorial , Feminino , Humanos , Masculino , Psicometria/instrumentação , Reprodutibilidade dos Testes , Transtorno da Personalidade Esquizotípica/genética , AutorrelatoRESUMO
There is a well-established relationship between cannabis use and psychosis, although the exact nature of this relationship is not fully understood. Recent studies have observed significant genetic overlap between a diagnosis of schizophrenia and lifetime cannabis use. Expanding on this work, the current study aimed to examine whether genetic overlap also occurs for subclinical psychosis (schizotypy) and cannabis use, as well as examining the phenotypic association between the traits. Phenotypic correlations were calculated for a variety of schizotypy and cannabis phenotypes in the UK Biobank (UKB), and single nucleotide polymorphism (SNP)-based heritability estimates and genetic correlations were calculated for these UKB phenotypes as well as for several other variables taken from recent genomewide association studies. Positive phenotypic correlations were observed between 11 out of 12 pairs of the cannabis use and schizotypy phenotypes (correlation range .05-.18), indicating a robust association between increased symptoms of schizotypy and cannabis use. SNP-based heritability estimates for two schizotypy phenotypes remained significant after multiple testing correction: social anhedonia (h2SNP = .08, SE = .02, N = 4025) and ever seen an unreal vision (h2SNP = .35, SE = .10, N = 150,717). Finally, one significant genetic correlation was observed between schizotypy and cannabis use, a negative correlation between social anhedonia and number of times used cannabis (rg = -.30, p = .012). The current study suggests the relationship between cannabis use and psychosis is also seen in subclinical symptoms of psychosis, but further research with larger samples is needed to determine the biological mechanisms underlying this association.
Assuntos
Uso da Maconha/genética , Transtornos Psicóticos , Transtorno da Personalidade Esquizotípica , Cannabis , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único , Transtornos Psicóticos/genética , Transtorno da Personalidade Esquizotípica/genéticaRESUMO
BACKGROUND: Schizotypal traits are considered as inheritable traits and the endophenotype for schizophrenia. A common variant in the NOTCH4 gene, rs204993, has been linked with schizophrenia, but the neural underpinnings are largely unknown. METHODS: In present study, we compared the differences of brain functions between different genotypes of rs204993 and its relationship with schizotypal traits among 402 Chinese Han healthy volunteers. The brain function was evaluated with functional connectivity strength (FCS) using the resting-state functional magnetic resonance image(rs-fMRI). The schizotypal traits were measured by the schizotypal personality questionnaire (SPQ). RESULTS: Our results showed that carriers with the AA genotype showed reduced FCS in the left occipital cortex when compared with carriers with the AG and GG genotypes, and the carriers with the AG genotype showed reduced FCS in the left occipital cortex when compared with carriers with the GG genotype. The FCS values in the left occipital lobe were negatively associated with the SPQ scores and its subscale scores within the carriers with the GG genotype, but not within the carriers with AA or AG genotype. CONCLUSION: Our results suggested that the common variant in the NOTCH4 gene, rs204993, modulates the function of the occipital cortex, which may contribute to schizotypal traits. These findings provide insight for genetic effects on schizotypal traits and its potential neural substrate.
Assuntos
Esquizofrenia , Transtorno da Personalidade Esquizotípica , Genótipo , Humanos , Imageamento por Ressonância Magnética , Lobo Occipital/diagnóstico por imagem , Receptor Notch4 , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genética , Transtorno da Personalidade Esquizotípica/diagnóstico por imagem , Transtorno da Personalidade Esquizotípica/genéticaRESUMO
BACKGROUND: Genetic risk is thought to drive clinical variation on a spectrum of schizophrenia-like traits, but the underlying changes in brain structure that mechanistically link genomic variation to schizotypal experience and behavior are unclear. METHODS: We assessed schizotypy using a self-reported questionnaire and measured magnetization transfer as a putative microstructural magnetic resonance imaging marker of intracortical myelination in 68 brain regions in 248 healthy young people (14-25 years of age). We used normative adult brain gene expression data and partial least squares analysis to find the weighted gene expression pattern that was most colocated with the cortical map of schizotypy-related magnetization. RESULTS: Magnetization was significantly correlated with schizotypy in the bilateral posterior cingulate cortex and precuneus (and for disorganized schizotypy, also in medial prefrontal cortex; all false discovery rate-corrected ps < .05), which are regions of the default mode network specialized for social and memory functions. The genes most positively weighted on the whole-genome expression map colocated with schizotypy-related magnetization were enriched for genes that were significantly downregulated in two prior case-control histological studies of brain gene expression in schizophrenia. Conversely, the most negatively weighted genes were enriched for genes that were transcriptionally upregulated in schizophrenia. Positively weighted (downregulated) genes were enriched for neuronal, specifically interneuronal, affiliations and coded a network of proteins comprising a few highly interactive "hubs" such as parvalbumin and calmodulin. CONCLUSIONS: Microstructural magnetic resonance imaging maps of intracortical magnetization can be linked to both the behavioral traits of schizotypy and prior histological data on dysregulated gene expression in schizophrenia.
Assuntos
Esquizofrenia , Transtorno da Personalidade Esquizotípica , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Esquizofrenia/genética , Transtorno da Personalidade Esquizotípica/genéticaRESUMO
BACKGROUND: There is consistent evidence that theory of mind (ToM) is impaired in schizophrenia (SZ); however, it remains unclear whether such deficits are trait- or state-dependent. We evaluated ToM in patients with schizophrenia spectrum disorders (SSDs), their healthy first-degree relatives, and controls to test its suitability as an endophenotypic marker. We also studied the modifying effect of markers of clinical and genetic liability to SZ (schizotypy and genetic variability in the oxytocin receptor gene: OXTR) on ToM in healthy individuals. METHODS: The sample included 38 stable SSD patients, 80 unaffected first-degree relatives, and 81 controls. ToM was assessed using the Hinting Task (HT) and schizotypy via the Schizotypal Personality Questionnaire-Brief (SPQ-B), which generates interpersonal (SPQ-IP), cognitive-perceptual (SPQ-CP), and disorganization (SPQ-D) scores. The polymorphism rs53576 of OXTR was genotyped. RESULTS: Patients presented poorer HT performance than relatives and controls (p = 0.003 and p < 0.001). High SPQ-IP and SPQ-CP scores correlated with poorer ToM performance in relatives (p = 0.010 and p = 0.030), but not in controls. OXTR was not associated with HT scores, but it showed a modifying effect within controls; high SPQ-CP was related to HT poorer performance conditional to GG genotype (p = 0.007). CONCLUSIONS: ToM deficits were present in patients but not in unaffected relatives or controls. However, our data indicate the usefulness of clinical and genetic liability markers to characterize differences in ToM abilities within healthy individuals. Then, the observed link between ToM and SZ liability suggests the putative role of ToM as an endophenotypic marker. Nevertheless, new analyses in larger samples are needed.
Assuntos
Genótipo , Personalidade , Receptores de Ocitocina/genética , Transtorno da Personalidade Esquizotípica/genética , Teoria da Mente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Esquizofrenia/complicações , Inquéritos e QuestionáriosRESUMO
Schizophrenia patients have a higher probability of altered structural and functional differences between the left and right hemisphere. Schizotypy as its nonclinical manifestation has been related to a higher incidence of non-right-handedness and atypical right-hemispheric language dominance. It has been suggested that genes involved in cilia function might link brain asymmetry and neurodevelopmental disorders. We assessed DNA methylation in the promoter regions of seven candidate genes involved in cilia function and psychiatric disorders from buccal cells and investigated their association with schizotypy and language lateralization in 60 healthy adults. Moreover, we determined microstructural properties of the planum temporale in a subsample of 52 subjects using neurite orientation dispersion and density imaging (NODDI). We found a significant association between schizotypy and DNA methylation in the AHI1 promoter region. Moreover, AHI1 DNA methylation significantly predicted language lateralization and asymmetry in estimated planum temporale neurite density. Finally, stronger leftward asymmetry in estimated neurite density was associated with a more pronounced right ear advantage (left hemisphere dominance) in the forced-right condition of the dichotic listening task, measuring attentional modulation of language lateralization. Our results are in line with a shared molecular basis of schizotypy and functional hemispheric asymmetries that is based on cilia function.
Assuntos
Proteínas Adaptadoras de Transporte Vesicular/genética , Encéfalo/fisiopatologia , Cílios/genética , Transtorno da Personalidade Esquizotípica/genética , Transtorno da Personalidade Esquizotípica/fisiopatologia , Atenção , Percepção Auditiva , Mapeamento Encefálico , Metilação de DNA , Lateralidade Funcional , Humanos , Idioma , Imageamento por Ressonância Magnética , Masculino , Mucosa Bucal , Esquizofrenia/fisiopatologia , Lobo Temporal/fisiopatologiaRESUMO
Schizotypy is a multidimensional risk phenotype distributed in the general population, constituting of subclinical, psychotic-like symptoms. It is associated with psychosis proneness, and several risk genes for psychosis are associated with schizotypy in non-clinical populations. Schizotypy might also modulate cognitive abilities as it is associated with attentional deficits in healthy subjects. In this study, we tested the hypothesis that established genetic risk variants ZNF804A rs1344706 and CACNA1C rs1006737 are associated with psychometric schizotypy and that schizotypy mediates their effect on attention or vice versa. In 615 healthy subjects from the FOR2107 cohort study, we analysed the genetic risk variants ZNF804A rs1344706 and CACNA1C rs1006737, psychometric schizotypy (schizotypal personality questionnaire-brief SPQB), and a neuropsychological measure of sustained and selective attention (d2 test). ZNF804A rs1344706 C (non-risk) alleles were significantly associated with higher SPQ-B Cognitive-Perceptual subscores in women and with attention deficits in both sexes. This schizotypy dimension also mediated the effect of ZNF804A on attention in women, but not in men. CACNA1C rs1006737-A showed a significant sex-modulated negative association with Interpersonal schizotypy only in men, and no effect on attention. Our multivariate model demonstrates differential genetic contributions of two psychosis risk genes to dimensions of schizotypy and, partly, to attention. This supports a model of shared genetic influence between schizotypy and cognitive functions impaired in schizophrenia.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Disfunção Cognitiva/genética , Transtorno da Personalidade Esquizotípica/genética , Adolescente , Adulto , Idoso , Estudos de Coortes , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/genética , Esquizofrenia/genética , Adulto JovemRESUMO
The maternally expressed imprinted gene UBE3A has been implicated in autism, schizophrenia and psychosis. The phenotype of Angelman syndrome, caused by loss of UBE3A expression, involves autism spectrum traits, while Prader-Willi syndrome, where the genotype of maternal disomy increases dosage of UBE3A, shows high penetrance for the development of psychosis. Maternal duplications of the 15q11-q13 chromosome region that overlap the imprinted region also show an association with schizophrenia, further implying a connection between increased dosage of UBE3A and the development of schizophrenia and psychosis. We phenotyped a large population of typical individuals for autism spectrum and schizotypal traits and genotyped them for a set of SNPs in UBE3A. Genetic variation of rs732739, an intronic SNP tagging a large haplotype spanning nearly the entire range of UBE3A, was significantly associated with variation in total schizotypy. Our results provide an independent line of evidence, connecting the imprinted UBE3A gene to the schizophrenia spectrum.
Assuntos
Impressão Genômica , Herança Materna , Transtornos Psicóticos/genética , Transtorno da Personalidade Esquizotípica/genética , Ubiquitina-Proteína Ligases/genética , Síndrome de Angelman/genética , Transtorno Autístico/genética , Cromossomos Humanos Par 15/genética , Feminino , Dosagem de Genes , Genótipo , Humanos , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Síndrome de Prader-Willi/genéticaRESUMO
Studies comparing cognitive processes between familial and sporadic schizophrenia have yielded inconsistent findings. In this study we examined differences in neurocognition and schizotypal traits in unaffected relatives of schizophrenia-spectrum patients with either the familial (multiplex) or the sporadic (simplex) subtype of the disorder, taking paternal age at birth into consideration. Simplex (nâ¯=â¯65; SR), multiplex (nâ¯=â¯35; MR) relatives and controls (nâ¯=â¯114) were compared on several cognitive functions and schizotypal traits; between-group differences were evaluated with and without including paternal age in the analyses. SR and MR had higher negative and paranoid traits compared with controls, but paternal age abolished the differences between the SR and control groups. When taking into account schizotypal traits and participants' age, controls outperformed MR in strategy formation and set-shifting and SR in psychomotor speed, set-shifting and executive working memory. After including paternal age in the analyses, controls outperformed MR in strategy formation, working memory and executive working memory and both groups in psychomotor speed and set-shifting. These findings suggest that multiplex relatives present with a "riskier" personality and cognitive profile when considering the effects of paternal age. Nevertheless, simplex relatives are impaired in fundamental cognitive processes, thus highlighting the detrimental effects of paternal age on neurocognition.
Assuntos
Cognição , Família/psicologia , Idade Paterna , Esquizofrenia , Psicologia do Esquizofrênico , Transtorno da Personalidade Esquizotípica/psicologia , Adulto , Cognição/fisiologia , Feminino , Humanos , Masculino , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Transtorno da Personalidade Paranoide/diagnóstico , Transtorno da Personalidade Paranoide/genética , Transtorno da Personalidade Paranoide/psicologia , Fenótipo , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Transtorno da Personalidade Esquizotípica/diagnóstico , Transtorno da Personalidade Esquizotípica/genética , Inquéritos e QuestionáriosRESUMO
The ZNF804A gene and cannabis use are risk factors for psychosis and both have also been associated with schizotypal traits. This study aimed to investigate: i) the association of lifetime cannabis use (and its dose effect) with schizotypal personality traits, and ii) whether the genetic variability at ZNF804A gene modulates that association. Our sample consisted of 385 Spanish non-clinical subjects (43.1% males, mean ageâ¯=â¯21.11(2.19)). Schizotypy was evaluated using the three factors of the Schizotypal Personality Questionnaire-Brief (SPQ-B): Cognitive-Perceptual (SPQ-CP), Interpersonal (SPQ-I) and Disorganized (SPQ-D). Subjects were classified according to their frequency of cannabis consumption, and dichotomized as users or non-users. The effects of a genetic variant of ZNF804A (rs1344706) and cannabis use, as well as their interaction, on each of the three SPQ-B factors were assessed using linear models and permutation tests. Sex, SCL anxiety scores and use of other drugs were included as covariates. Our analysis showed a significant relationship between ZNF804A and SPQ-I: AA genotype was associated with higher scores (ßâ¯=â¯0.885 pFDRâ¯=â¯.018). An interaction between the AA genotype and lifetime cannabis use was found in SPQ-CP (ßâ¯=â¯1.297 pFDRâ¯=â¯0.018). This interaction showed a dose-effect pattern among AA subjects: schizotypy scores increased with increasing frequency of cannabis use (sporadic users: ßâ¯=â¯0.746 pFDRâ¯=â¯0.208; monthly users: ßâ¯=â¯1.688 pFDRâ¯=â¯0.091; intense users: ßâ¯=â¯1.623 pFDRâ¯=â¯0.038). These results add evidence on that the ZNF804A gene is associated with schizotypy and suggest that the interaction between cannabis use and ZNF804A genotype could modulate psychosis proneness.
Assuntos
Fatores de Transcrição Kruppel-Like/genética , Uso da Maconha/genética , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/genética , Transtorno da Personalidade Esquizotípica/epidemiologia , Transtorno da Personalidade Esquizotípica/genética , Cannabis , Feminino , Interação Gene-Ambiente , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/complicações , Transtornos Psicóticos/psicologia , Transtorno da Personalidade Esquizotípica/complicações , Transtorno da Personalidade Esquizotípica/psicologia , Adulto JovemRESUMO
The COMT Val158Met polymorphism affects the availability of synaptic dopamine in the prefrontal cortex and has been widely studied as a genetic risk factor for psychosis. Schizotypy is associated with an increased risk of psychosis, with some studies implicating similar neurobiological mechanisms to schizophrenia. The present study sought to interrogate the link between the COMT Val158Met polymorphism and schizotypy using electroencephalogram (EEG) to identify neurophysiological mechanisms underpinning psychosis risk. Neurotypical (N = 91) adults were genotyped for the COMT Val158Met polymorphism, completed the Schizotypal Personality Questionnaire (SPQ), and had eyes open resting-state EEG recorded for 4 min. SPQ suspiciousness subscale scores were higher for individuals homozygous for Val/Val and Met/Met versus Val/Met genotypes. Delta, theta, alpha-2, beta-1, and beta-2 amplitudes were lower for Val/Val than Met/Met individuals. Lower theta amplitudes were correlated with higher total SPQ scores (P = 0.050), and multiple regression revealed that higher delta, and lower theta and beta-2 amplitudes (but not COMT genotype) best predicted total SPQ scores (P = 0.014). This study demonstrates the importance of COMT genotype in determining trait suspiciousness and EEG oscillatory activity. It also highlights relationships between dopaminergic alterations, EEG and schizotypy that are dissimilar to those observed in schizophrenia.
Assuntos
Encéfalo/fisiopatologia , Catecol O-Metiltransferase/genética , Transtorno da Personalidade Esquizotípica/genética , Transtorno da Personalidade Esquizotípica/fisiopatologia , Eletroencefalografia , Feminino , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
Common alleles associated with psychiatric disorders are often regarded as deleterious genes that influence vulnerability to disease, but they may also be considered as mediators of variation in adaptively structured cognitive phenotypes among healthy individuals. The schizophrenia-associated gene GRIN2A (glutamate ionotropic receptor NMDA type subunit 2a) codes for a protein subunit of the NMDA (N-methyl-D-aspartate) receptor that underlies central aspects of human cognition. Pharmacological NMDA blockage recapitulates the major features of schizophrenia in human subjects, and represents a key model for the neurological basis of this disorder. We genotyped two functional GRIN2A polymorphisms in a large population of healthy individuals who were scored for schizotypy and mental imagery/manipulation (the mental rotation test). Rare-allele homozygosity of the promoter microsatellite rs3219790 was associated with high total schizotypy (after adjustment for multiple comparisons) and with enhanced mental rotation ability (nominally, but not after adjustment for multiple comparisons), among males. These findings provide preliminary evidence regarding a genetic basis to previous reports of enhanced mental imagery in schizophrenia and schizotypy. The results also suggest that some schizophrenia-related alleles may be subject to cognitive tradeoffs involving both positive and negative effects on psychological phenotypes, which may help to explain the maintenance of psychiatric-disorder risk alleles in human populations.
Assuntos
Imaginação/fisiologia , Processos Mentais/fisiologia , Polimorfismo Genético/genética , Receptores de N-Metil-D-Aspartato/genética , Transtorno da Personalidade Esquizotípica/genética , Transtorno da Personalidade Esquizotípica/fisiopatologia , Análise de Variância , Feminino , Frequência do Gene , Humanos , Masculino , Testes Psicológicos , Transtorno da Personalidade Esquizotípica/psicologia , Estudantes , UniversidadesRESUMO
There is fundamental doubt about whether the natural unit of measurement for temperament and personality corresponds to single traits or to multi-trait profiles that describe the functioning of a whole person. Biogenetic researchers of temperament usually assume they need to focus on individual traits that differ between individuals. Recent research indicates that a shift of emphasis to understand processes within the individual is crucial for identifying the natural building blocks of temperament. Evolution and development operate on adaptation of whole organisms or persons, not on individual traits or categories. Adaptive functioning generally depends on feedback among many variable processes in ways that are characteristic of complex adaptive systems, not machines with separate parts. Advanced methods of unsupervised machine learning can now be applied to genome-wide association studies and brain imaging in order to uncover the genotypic-phenotypic architecture of traits like temperament, which are strongly influenced by complex interactions, such as genetic epistasis, pleiotropy and gene-environment interactions. We have found that the heritability of temperament can be nearly fully explained by a large number of genetic variants that are unique for multi-trait profiles, not single traits. The implications of this finding for research design and precision medicine are discussed.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.