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1.
Am J Hum Genet ; 105(2): 334-350, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374203

RESUMO

Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected ("concordant") direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive ("discordant") relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophrenia at p < 5 × 10-8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs. Many of these have been validated by larger, more recent single-phenotype GWASs. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms-early neurodevelopmental pathways that characterize concordant allelic variation and adulthood synaptic pruning pathways-that were linked to the paradoxical positive genetic association between education and schizophrenia. Furthermore, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia but also to the broader biological dimensions implicated in both general health outcomes and psychiatric illness.

3.
Psychiatry Res ; 273: 422-429, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30684787

RESUMO

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 (n = 65; SR), multiplex (n = 35; MR) relatives and controls (n = 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.

4.
Twin Res Hum Genet ; 21(5): 394-397, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30001766

RESUMO

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88) presented a critique of our recently published paper in Cell Reports entitled 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' (Lam et al., Cell Reports, Vol. 21, 2017, 2597-2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229-237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from 'inflation in the FDR [false discovery rate]', as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88), and are not 'more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence'.

5.
Nat Commun ; 9(1): 2098, 2018 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-29844566

RESUMO

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

6.
Schizophr Bull ; 44(suppl_2): S468-S479, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-29684178

RESUMO

Elucidating schizotypal traits is important if we are to understand the various manifestations of psychosis spectrum liability and to reliably identify individuals at high risk for psychosis. The present study examined the network structures of (1) 9 schizotypal personality domains and (2) 74 individual schizotypal items, and (3) explored whether networks differed across gender and culture (North America vs China). The study was conducted in a sample of 27001 participants from 12 countries and 21 sites (M age = 22.12; SD = 6.28; 37.5% males). The Schizotypal Personality Questionnaire (SPQ) was used to assess 74 self-report items aggregated in 9 domains. We used network models to estimate conditional dependence relations among variables. In the domain-level network, schizotypal traits were strongly interconnected. Predictability (explained variance of each node) ranged from 31% (odd/magical beliefs) to 55% (constricted affect), with a mean of 43.7%. In the item-level network, variables showed relations both within and across domains, although within-domain associations were generally stronger. The average predictability of SPQ items was 27.8%. The network structures of men and women were similar (r = .74), node centrality was similar across networks (r = .90), as was connectivity (195.59 and 199.70, respectively). North American and Chinese participants networks showed lower similarity in terms of structure (r = 0.44), node centrality (r = 0.56), and connectivity (180.35 and 153.97, respectively). In sum, the present article points to the value of conceptualizing schizotypal personality as a complex system of interacting cognitive, emotional, and affective characteristics.

7.
Schizophr Res ; 199: 128-134, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29567403

RESUMO

BACKGROUND: Schizotypal traits are expressions of underlying vulnerability to psychotic disorders which have a potential impact on mental health status, neurocognition, quality of life, and daily functioning. To date, little research has examined epidemiologic landscape of schizotypal traits at the cross-national level. Our aim was to study the expression of schizotypal traits by sex, age, and country in a combined sample gathered from 12 countries. METHODS: A total of 27,001 participants completed the Schizotypal Personality Questionnaire (SPQ). The mean age of participants was 22.12 (SD=6.28); 37.5% (n=10,126) were males. RESULTS: Schizotypal traits varied according to sex, age, and country. Females scored higher than males in the positive dimension, whereas males scored higher in the disorganization dimension. By age, a significant decrease in the positive schizotypal traits was observed. Epidemiological expression of schizotypal traits varied by country. Moreover, several interactions by sex, age, and country were found. CONCLUSIONS: This pattern is similar to those found in patients with psychosis and psychotic-like experiences. These findings provide new insights and the opportunity to explore the phenotypic expression of schizotypal traits at cross-national level.

8.
Schizophr Res ; 198: 52-59, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29287625

RESUMO

Sensorimotor gating measured by prepulse inhibition (PPI) of the acoustic startle response (ASR) has been proposed as one of the most promising electrophysiological endophenotypes of schizophrenia. During the past decade, a number of publications have reported significant associations between genetic polymorphisms and PPI in samples of schizophrenia patients and healthy volunteers. However, an overall evaluation of the robustness of these results has not been published so far. Therefore, we performed the first meta-analysis of published and unpublished associations between gene polymorphisms and PPI of ASR. Unpublished associations between genetic polymorphisms and PPI were derived from three independent samples. In total, 120 single observations from 16 independent samples with 2660 study participants and 43 polymorphisms were included. After correction for multiple testing based on false discovery rate and considering the number of analyzed polymorphisms, significant associations were shown for four variants, even though none of these associations survived a genome-wide correction (P<5∗10-8). These results imply that PPI might be modulated by four genotypes - COMT rs4680 (primarily in males), GRIK3 rs1027599, TCF4 rs9960767, and PRODH rs385440 - indicating a role of these gene variations in the development of early information processing deficits in schizophrenia. However, the overall impact of single genes on PPI is still rather small suggesting that PPI is - like the disease phenotype - highly polygenic. Future genome-wide analyses studies with large sample sizes will enhance our understanding on the genetic architecture of PPI.

9.
Schizophr Bull ; 44(2): 338-347, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29036523

RESUMO

Schizotypal personality traits may increase proneness to psychosis and likely index familial vulnerability to schizophrenia (SZ), implying shared genetic determinants with SZ. Here, we sought to investigate the contribution of common genetic risk variation for SZ on self-reported schizotypy in 2 ethnically homogeneous cohorts of healthy young males during compulsory military service, enrolled in the Athens Study of Proneness and Incidence of Schizophrenia (ASPIS, N = 875) and the Learning on Genetics of Schizophrenia Spectrum study (LOGOS, N = 690). A follow-up psychometric assessment was performed in a sub-sample of the ASPIS (N = 121), 18 months later at military service completion. Polygenic risk scores (PRS) for SZ were derived based on genome-wide association meta-analysis results from the Psychiatric Genomics Consortium. In the ASPIS, higher PRSSZ significantly associated with lower levels of positive (ie, perceptual distortions), disorganization and paranoid facets of schizotypy, whereas no association with negative (ie, interpersonal) facets was noted. Importantly, longitudinal data analysis in the ASPIS subsample revealed that PRSSZ was inversely associated with positive schizotypy at military induction (stressed condition) but not at follow-up (nonstressed condition), providing evidence for environmental rather than SZ-implicated genetic influences. Moreover, consistent with prior reports, PRSSZ was positively correlated with trait anxiety in the LOGOS and additionally the recruits with higher PRSSZ and trait anxiety exhibited attenuated paranoid ideation. Together, these findings do not support an etiological link between increased polygenic liability for SZ and schizotypy, suggesting that psychosocial stress or trait anxiety may impact schizotypal phenotypic expressions among healthy young adults not genetically predisposed to SZ.


Assuntos
Ansiedade , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Militares/estatística & dados numéricos , Herança Multifatorial , Esquizofrenia , Transtorno da Personalidade Esquizotípica , Estresse Psicológico , Adulto , Ansiedade/epidemiologia , Ansiedade/genética , Ansiedade/fisiopatologia , Seguimentos , Grécia/epidemiologia , Humanos , Masculino , Esquizofrenia/epidemiologia , Esquizofrenia/genética , Esquizofrenia/fisiopatologia , Transtorno da Personalidade Esquizotípica/epidemiologia , Transtorno da Personalidade Esquizotípica/genética , Transtorno da Personalidade Esquizotípica/fisiopatologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia , Adulto Jovem
10.
Cell Rep ; 21(9): 2597-2613, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29186694

RESUMO

Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum). Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth.


Assuntos
Estudo de Associação Genômica Ampla/métodos , Nootrópicos/farmacologia , Cefotaxima/análogos & derivados , Cefotaxima/farmacologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Feminino , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Sinapses/efeitos dos fármacos , Sinapses/metabolismo
11.
Schizophr Res ; 2017 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-29113776

RESUMO

The Schizotypal Personality Questionnaire-Brief (SPQ-B) was developed with the aim of examining variations in healthy trait schizotypy, as well as latent vulnerability to psychotic-spectrum disorders. No previous study has studied the cross-cultural validity of the SPQ-B in a large cross-national sample. The main goal of the present study was to analyze the reliability and the internal structure of SPQ-B scores in a multinational sample of 28,426 participants recruited from 14 countries. The mean age was 22.63years (SD=7.08; range 16-68years), 37.7% (n=10,711) were men. The omega coefficients were high, ranging from 0.86 to 0.92 for the total sample. Confirmatory factor analysis revealed that SPQ-B items were grouped either in a theoretical structure of three first-order factors (Cognitive-Perceptual, Interpersonal, and Disorganized) or in a bifactor model (three first-order factors plus a general factor of schizotypal personality). In addition, the results supported configural but not strong measurement invariance of SPQ-B scores across samples. These findings provide new information about the factor structure of schizotypal personality, and support the validity and utility of the SPQ-B, a brief and easy tool for assessing self-reported schizotypal traits, in cross-national research. Theoretical and clinical implications for diagnostic systems, psychosis models, and cross-national mental health strategies are derived from these results.

12.
Arch Clin Neuropsychol ; 32(8): 1010-1025, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28383650

RESUMO

Objective: The aim of the study was to compare the neurocognitive profile of unaffected first-degree relatives of schizophrenia patients with control individuals, controlling for different schizotypal traits. Method: One hundred and fifteen adult unaffected first-degree relatives of schizophrenia-spectrum patients and 122 controls were tested for schizotypy with the Schizotypal Personality Questionnaire. They also underwent a thorough neurocognitive assessment with a range of tasks covering several aspects of executive functioning. Between-group differences in cognition were examined first with multivariate analysis of variance and then with a series of multivariate analyses of covariance, including the schizotypal dimensions as covariates. Results: The relatives had higher scores on all schizotypal dimensions compared with controls and poorer planning, problem solving, strategy formation and working memory, irrespective of schizotypal traits. They also scored lower in executive working memory and verbal fluency. The difference in executive working memory was sensitive to the effects of paranoid and negative schizotypy (both dimensions abolished the between-group difference) whereas the difference in verbal fluency was sensitive only to the effects of paranoid schizotypy. Neither cognitive-perceptual nor disorganized schizotypy accounted for any differences in neurocognition between relatives and the controls. Conclusions: Impairments in planning, problem solving, strategy formation and working memory are "core" impairments in the schizophrenia-spectrum, possibly due to high heritability effects in these functions. Impairments in executive working memory and verbal fluency are associated with paranoid and negative schizotypy, possibly due to alterations in a common fronto-temporo-parietal neural network.


Assuntos
Disfunção Cognitiva/etiologia , Família/psicologia , Transtorno da Personalidade Esquizotípica/complicações , Transtorno da Personalidade Esquizotípica/genética , Adulto , Disfunção Cognitiva/diagnóstico , Feminino , Humanos , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Análise de Componente Principal , Escalas de Graduação Psiquiátrica , Transtorno da Personalidade Esquizotípica/classificação
13.
J Affect Disord ; 208: 512-520, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-27810272

RESUMO

INTRODUCTION: Although cognitive deficits are consistent endophenotypes of schizophrenia and bipolar disorder, findings in psychotic bipolar disorder (BDP) are inconsistent. In this study we compared adult unaffected first-degree relatives of schizophrenia and BDP patients on cognition, psychopathology, social functioning and quality of life. METHODS: Sixty-six unaffected first-degree relatives of schizophrenia patients (SUnR), 36 unaffected first-degree relatives of BDP patients (BDPUnR) and 102 controls participated in the study. Between-group differences were examined and Discriminant Function Analysis (DFA) predicted group membership. RESULTS: Visual memory, control inhibition, working memory, cognitive flexibility and abstract reasoning were linearly impaired in the relatives' groups. Poorer verbal fluency and processing speed were evident only in the SUnR group. The SUnR group had higher depressive and somatization symptoms while the BDPUnR group had higher anxiety and lower social functioning compared with the controls. Individuals with superior cognition were more likely to be classified as controls; those with higher social functioning, prolonged processing speed and lower anxiety were more likely to be classified as SUnR. LIMITATIONS: The relatives' sample is quite heterogeneous; the effects of genetic or environmental risk-factors were not examined. CONCLUSIONS: Cognitive functions mediated by a fronto-parietal network, show linear impairments in unaffected relatives of BDP and schizophrenia patients; processing speed and verbal fluency impairments were evident only in schizophrenia relatives. Self-perceived symptomatology and social functioning also differ between schizophrenia and BDP relatives. The continuum seen in patients in several indices was also seen in the cognitive impairments in unaffected relatives of schizophrenia and BDP patients.


Assuntos
Transtorno Bipolar , Cognição , Família/psicologia , Esquizofrenia , Adulto , Estudos de Casos e Controles , Transtornos Cognitivos/psicologia , Endofenótipos , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Psicopatologia , Transtornos Psicóticos , Qualidade de Vida , Risco , Ajustamento Social
14.
Compr Psychiatry ; 71: 39-48, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27621208

RESUMO

BACKGROUND: Increased schizotypal traits are observed in a percentage of the general population and in the schizophrenia-spectrum and have been associated with impairments in working memory. In this study we examined the effects of four schizotypal dimensions [Negative (NegS), Paranoid (ParS), Cognitive-Perceptual (CPS), Disorganized (DiS)] on executive working memory (EWM), as mediated by set-shifting, planning and control inhibition. We also examined whether these associations are moderated by family-history of psychosis. METHODS: Our sample consisted of 110 unaffected first-degree relatives of schizophrenia-spectrum patients and 120 control individuals. Schizotypy was assessed with the Schizotypal Personality Questionnaire. Participants were also tested with the Letter-Number Sequencing, Wisconsin Card Sorting, Stroop Color-Word and Stockings of Cambridge tasks. The effects of set-shifting, control inhibition and planning on the relationship between schizotypy and EWM were examined with mediation analyses. Moderated-mediation analyses examined potential moderating effects of group membership (unaffected relative/community participant). RESULTS: All mediators were significant in the relationship between NegS and EWM. The effects of ParS were mediated only by set-shifting and planning. Planning and control inhibition were the only significant mediators on the effects of CPS and DiS on EWM, respectively. The moderated-mediation analyses revealed that these findings apply only in the community group. CONCLUSIONS: We found that the effects of different schizotypal dimensions on EWM are mediated by other cognitive processes in individuals without personal/family history of psychosis. This is probably due to either more severe impairments in the cognitive processes of the relatives or restrictions in our sample and study-design.


Assuntos
Família/psicologia , Transtornos da Memória/psicologia , Transtorno da Personalidade Esquizotípica/psicologia , Adolescente , Adulto , Saúde da Família , Feminino , Humanos , Masculino , Transtornos da Memória/complicações , Memória de Curto Prazo , Pessoa de Meia-Idade , Testes Neuropsicológicos , Transtornos Psicóticos/psicologia , Transtorno da Personalidade Esquizotípica/complicações , Adulto Jovem
15.
J Clin Exp Neuropsychol ; 38(9): 1050-63, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27295077

RESUMO

INTRODUCTION: Studies assessing the effects of schizotypal dimensions (i.e., positive, negative, and disorganized) on cognitive functions have yielded mixed findings. In the present study, we administered an extensive battery of cognitive tasks to a community sample and defined the schizotypal dimensions according to a more analytical four-factor model, whereby positive schizotypy is further divided into cognitive-perceptual and paranoid. METHOD: Two hundred healthy community participants were assessed for schizotypy with the Schizotypal Personality Questionnaire; assessment of cognitive functions included set shifting, working memory, processing speed, verbal fluency, attention switching, planning/problem solving, strategy formation, and abstract reasoning. Associations between cognitive tasks and schizotypy were examined with hierarchical multiple linear regressions. We also divided our subjects into groups based on whether or not their scores in the negative, positive, and cognitive-perceptual factors fell in the upper 10% of the scores of a large community normative sample in Greece and examined between-group differences. RESULTS: Applying both dimensional and categorical approaches, we showed that (a) attention-switching impairment is a "core" deficit of both negative and paranoid schizotypy, (b) impaired working memory and set shifting are associated mainly with negative and to a lesser extent paranoid schizotypy, (c) paranoid schizotypy is associated with reduced performance in tasks requiring intact frontotemporal connectivity, and (d) cognitive-perceptual and disorganized schizotypy are not associated with any cognitive functions. CONCLUSIONS: Our findings further support the more analytical four-factor categorization of schizotypy and suggest that the discrepancies in the findings so far might be due to a more "generalized" definition of the schizotypal dimensions. They also add further in the early formulation of the profile of the high-schizotypal individuals seeking psychiatric help so that their overall management is directed towards a more targeted approach.


Assuntos
Atenção , Cognição , Memória de Curto Prazo , Personalidade , Transtorno da Personalidade Esquizotípica/psicologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Testes Neuropsicológicos , Inquéritos e Questionários , Adulto Jovem
16.
Scand J Psychol ; 57(3): 256-70, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27119257

RESUMO

Schizotypy refers to a personality structure indicating "proneness" to schizophrenia. Around 10% of the general population has increased schizotypal traits, they also share other core features with schizophrenia and are thus at heightened risk for developing schizophrenia and spectrum disorders. A key aspect in schizophrenia-spectrum pathology is the impairment observed in emotion-related processes. This review summarizes findings on impairments related to central aspects of emotional processes, such as emotional disposition, alexithymia, facial affect recognition and speech prosody, in high schizotypal individuals in the general population. Although the studies in the field are not numerous, the current findings indicate that all these aspects of emotional processing are deficient in psychometric schizotypy, in accordance to the schizophrenia-spectrum literature. A disturbed frontotemporal neural network seems to be the critical link between these impairments, schizotypy and schizophrenia. The limitations of the current studies and suggestions for future research are discussed.


Assuntos
Emoções , Transtorno da Personalidade Esquizotípica/psicologia , Adolescente , Adulto , Sintomas Afetivos/complicações , Reconhecimento Facial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Transtorno da Personalidade Esquizotípica/complicações , Fala , Percepção da Fala , Adulto Jovem
17.
PeerJ ; 4: e1830, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27019787

RESUMO

Background. The revised Temperament and Character Inventory (TCI-R) measures Cloninger's psychobiological model of personality. The average effects of individual temperament and character traits have been associated with schizotypy and with impaired regulation of affect and cognition. We extended prior research by testing predictions about the association of specific multidimensional configurations of temperament and character traits on schizotypy, affect balance, and self-perceived cognitive functioning. Method. A well-educated sample of native Greeks (N = 483), completed a new Greek translation of the TCI-R, as well as the Schizotypal Personality Questionnaire (SPQ), the Positive/Negative Affect Schedule (PANAS) and the Cognitive Failures Questionnaire (CFQ). The factor structure of the TCI-R was examined with exploratory and confirmatory tests. Associations between reported measures were examined with correlational and regression analyses. Results. The TCI-R had good psychometric properties as expected from studies in other countries. As predicted, specific configurations of temperament and character were associated with schizotypy, negative affect balance, and cognitive lapses. The "Borderline/Explosive temperament" (high Novelty Seeking, high Harm Avoidance, low Reward Dependence), "Schizotypal/Disorganized character" (low Self-directedness, low Cooperativeness, high Self-transcendence), and "Low Ego Strength/Fragile" profile (high Harm Avoidance, low Persistence, low Self-Directedness) were each strongly associated with higher stereotypy, negative affect balance (low positive affect and high negative affect), and subjective cognitive lapses compared to their contrast groups. Discussion. Multidimensional TCI profiles are strongly related to individual differences in schizotypy and self-reported regulation of affect and cognition. The Greek translation of the TCI-R is psychometrically sound and useful for clinical assessment and research.

18.
Biol Psychiatry ; 79(12): 988-96, 2016 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-26212897

RESUMO

BACKGROUND: Prepulse inhibition (PPI) of the startle reflex has been suggested as a candidate endophenotype for schizophrenia research, as it shows high heritability and has been found deficient in schizophrenia spectrum disorders. The objectives of the study were to 1) identify common genetic variants associated with baseline startle and PPI; 2) estimate the single nucleotide polymorphism heritability; and 3) examine the relationship of polygenic score for schizophrenia with baseline startle and PPI. METHODS: A cohort of healthy young male subjects (n = 1493) originating from the Learning on Genetics of Schizophrenia Spectrum project was assessed for baseline startle and PPI. The most recent genome-wide association study in schizophrenia from the Psychiatric Genomics Consortium 2 was used to calculate polygenic scores. RESULTS: Eleven loci showed suggestive association (p < 10(-6)) with baseline startle and PPI in the discovery cohort. Additional genotyping in a replication cohort identified genome-wide significant association at two loci (rs61810702 and rs4718984). These loci were co-localized with expression quantitative trait loci associated with gene expression of nerve growth factor (NGF) and calneuron 1 (CALN1) genes. Estimation of the genetic and environmental contributions to baseline startle and PPI showed a substantial single nucleotide polymorphism heritability for 120-ms PPI stimuli. Increased polygenic risk score for schizophrenia was associated with reduced PPI. CONCLUSIONS: Common genetic variation has an important role in the etiology of schizophrenia and PPI impairments. Overall, these data support the idea that PPI is a valid endophenotype that can be used to explore the genetic architecture of schizophrenia.


Assuntos
Endofenótipos , Inibição Pré-Pulso/genética , Reflexo de Sobressalto/genética , Esquizofrenia/genética , Adolescente , Adulto , Estudos de Coortes , Estudo de Associação Genômica Ampla , Humanos , Masculino , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Inibição Pré-Pulso/fisiologia , Locos de Características Quantitativas , Reflexo de Sobressalto/fisiologia , Esquizofrenia/fisiopatologia , Adulto Jovem
19.
Compr Psychiatry ; 62: 51-62, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26343467

RESUMO

BACKGROUND: The Schizotypal Personality Questionnaire (SPQ) is a widely used scale for measuring schizotypal characteristics modeled on DSM-III-R criteria for schizotypal personality disorder (SPD). The aim of this study was to examine the factorial structure of the Greek SPQ, its factorial invariance across gender and different age groups and possible gender and age group differences at latent mean level. METHODS: Eight hundred sixty-five community participants completed the Greek version of the SPQ. RESULTS: With regard to the factorial structure of the original first-order model, the results showed that a seven-factor model (sub-scales "no close friends" with "constricted affect" and "ideas of reference" with "unusual perceptual experiences" were combined) was replicated adequately. Furthermore, the second-order "paranoid" model provided also adequate fit. With regard to the factorial invariance of the SPQ across gender and age, the analysis revealed that both, the first- and second-order models showed measurement invariance (configural, metric and structural) across gender and age groups (17-35 vs. 36-70). Latent mean differences across gender and age groups were also found. CONCLUSIONS: Based on these findings, we can conclude that the Greek version of the SPQ is a psychometrically sound instrument for measuring schizotypal characteristics and a useful screening tool for SPD across gender and age.


Assuntos
Inventário de Personalidade/normas , Transtorno da Personalidade Esquizotípica/diagnóstico , Adolescente , Adulto , Fatores Etários , Idoso , Manual Diagnóstico e Estatístico de Transtornos Mentais , Grupos Étnicos , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Psicometria , Transtorno da Personalidade Esquizotípica/psicologia , Fatores Sexuais , Adulto Jovem
20.
Am J Med Genet B Neuropsychiatr Genet ; 168B(5): 363-73, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25951819

RESUMO

Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genome-wide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability ("g") in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts. Using cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy individuals), we examined the relationship between g and variants associated with educational attainment. We next conducted meta-analyses with 24,189 individuals with neurocognitive data from the educational attainment studies, and then with 53,188 largely independent individuals from a recent GWAS of cognition. A SNP (rs1906252) located at chromosome 6q16.1, previously associated with years of schooling, was significantly associated with g (P = 1.47 × 10(-4) ) in COGENT. The first joint analysis of 43,381 non-overlapping individuals for this a priori-designated locus was strongly significant (P = 4.94 × 10(-7) ), and the second joint analysis of 68,159 non-overlapping individuals was even more robust (P = 1.65 × 10(-9) ). These results provide independent replication, in a large-scale dataset, of a genetic locus associated with cognitive function and education. As sample sizes grow, cognitive GWAS will identify increasing numbers of associated loci, as has been accomplished in other polygenic quantitative traits, which may be relevant to psychiatric illness.


Assuntos
Transtornos Cognitivos/genética , Cognição/fisiologia , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Feminino , Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade
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