OBJECTIVE:The present study aimed to examine facial emotion recognition in a sample from the general population with elevated schizotypal traits, as defined by the four-factor model of schizotypy, and the association of facial emotion recognition and the schizotypal dimensions with psychological well-being. METHOD:Two hundred and thirty-eight participants were allocated into four schizotypal groups and one control group. Following a cross-sectional study design, facial emotion recognition was assessed with a computerized task that included images from the Radboud Faces Database, schizotypal traits were measured with the Schizotypal Personality Questionnaire, and psychological well-being was evaluated with the Flourishing scale. RESULTS:The results revealed distinct patterns of performance across the schizotypal groups and the application of a dimensional approach that included all participants as one group indicated specific associations between the four schizotypal dimensions and psychological well-being. Specifically, (a) negative schizotypes showed poor identification of sadness and fear potentially due to the activation of coping mechanisms, (b) disorganized schizotypes inaccurately recognized surprise, possibly reflecting the effects of disorganized thought on distinguishing this ambiguous emotion, and (c) psychological well-being was predicted by high cognitive-perceptual along with low negative and disorganized schizotypy as well as the accurate recognition of specific emotional states that are common in daily social interactions. CONCLUSIONS:In conclusion, the study findings further advance the identification of emotion-processing difficulties in schizophrenia-vulnerable individuals and further highlight the need for highly personalized early intervention strategies.

OBJECTIVE:To examine cold (based on logical reasoning) versus hot (having emotional components) executive function processes in groups with high individual schizotypal traits.METHOD:Two-hundred and forty-seven participants were administered the Schizotypal Personality Questionnaire and were allocated into schizotypal (cognitive-perceptual, paranoid, negative, disorganized) or control groups according to pre-specified criteria. Participants were also administered a battery of tasks examining working memory, complex selective attention, response inhibition, decision-making and fluid intelligence and their affective counterparts. The outcome measures of each task were reduced to one composite variable thus formulating five cold and five hot cognitive domains. Between-group differences in the cognitive domains were examined with repeated measures analyses of covariance.RESULTS:For working memory, the control and the cognitive-perceptual groups outperformed negative schizotypes, while for affective working memory controls outperformed the disorganized group. Controls also scored higher compared with the disorganized group in complex selective attention, while both the control and the cognitive-perceptual groups outperformed negative schizotypes in complex affective selective attention. Negative schizotypes also had striking difficulties in response inhibition, as they scored lower compared with all other groups. Despite the lack of differences in fluid intelligence, controls scored higher compared with all schizotypal groups (except from cognitive-perceptual schizotypes) in emotional intelligence; the latter group reported higher emotional intelligence compared with negative schizotypes.CONCLUSION:Results indicate that there is no categorical association between the different schizotypal dimensions with solely cold or hot executive function processes and support impoverished emotional intelligence as a core feature of schizotypy.

The near and far transfer effects of Working Memory (WM) training have yielded discrepant findings while there is no literature on the effects of Executive Working Memory (EWM) training. The present study aimed to investigate the far transfer effects of EWM on cognitive flexibility. Community participants ( n = 144) were allocated into a fully-, a partially-trained or a control group. At a baseline assessment, all groups were administered the Wisconsin Card Sorting test and Letter-Number Sequencing (LNS). Following this and for six consecutive days, the fully-trained group were administered the complete LNS, the partially-trained group were administered the LNS up to the three-digit strings while the control group had no involvement in the study. Upon completion of training, all groups were administered the Intra/Extra-Dimensional Shift task (ID/ED). The control group (a) made more errors and completed fewer stages compared with the fully-trained group and (b) had increased response latency and required more trials to complete the ID/ED compared to both the partially- and fully-trained groups. In the total sample, (a) the lack of EWM training was associated with more total errors, trials required to complete the ID/ED, extradimensional-shift errors and prolonged response latency and (b) extended short-term EWM training was associated with more completed stages in the ID/ED. The findings support the far transfer effects of EWM training on cognitive flexibility and are in agreement with studies on WM training. Although preliminary, they hold promise for the enhancement of early intervention programs in populations with cognitive impairments.

The present study aims to explore the association of maternal sleep disturbances during late pregnancy on child neuropsychological and behavioral development in preschool years. The study included 638 mother–child pairs from the prospective Rhea mother–child cohort in Crete, Greece. Information on antenatal sleep disturbances was collected through a computer-assisted interview. Children’s neuropsychological and behavioral development was assessed using the McCarthy Scales of Children’s Abilities (MSCA), the Attention-Deficit Hyperactivity Disorder Test (ADHDT), and the Strengths and Difficulties Questionnaire (SDQ). Multivariate analysis showed that maternal sleep duration less than 8 h was associated with reduced scores in the general cognitive scale (β = –2.28, 95

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify “druggable” targets. Using our meta-analytic data set ( N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing.

Introduction: According to the fully-dimensional approach, schizotypy is a personality trait present in the population in a continuous manner while the quasi-dimensional approach emphasises its extreme presentations. In this study we examined the relationship between sensorimotor gating, a core risk-index of the schizophrenia-spectrum, and four schizotypal factors in a dimensional-wise and a dichotomising-wise approach. Methods: Two-hundred and eighty-three participants were assessed with the Schizotypal Personality Questionnaire and were tested for Prepulse Inhibition (PPI). Associations between the schizotypal factors and startle measures were examined with stepwise regressions (dimensional-wise approach). Individuals in the lower 20% or the upper 20% for each schizotypal factor were identified and between-group comparisons were conducted (dichotomising-wise approach). Results: We found that with both approaches, only high paranoid or negative schizotypy were associated with reduced PPI. The low negative schizotypy group had prolonged onset and peak latencies, indicating that prolonged stimulus detection accompanies superior sensorimotor gating in this group. Conclusions: The findings suggest that although differentiating the effects of the various schizotypal factors is primary, the approach employed is secondary. The study also adds evidence in the literature supporting PPI as a useful endophenotypic marker of the schizophrenia-spectrum and highlights the contribution of specific aspects of schizotypy.

The main aim of the present paper is to assess whether the parental generation exposure to such discharges could cause object recognition deficits in their offspring. Male and female C57Bl/6J mice were put to mate after they were exposed to 7.5% and 15% tannery effluents or water (control group), for 60 days. The male mice were withdrawn from the boxes after 15 days and the female mice remained exposed to the treatment during the gestation and lactation periods. The offspring were subjected to the object recognition test after weaning in order to assess possible cognition losses. The results of the analysis of the novel object recognition index found in the testing session (performed 1 h after the training session) applied to offspring from different experimental groups appeared to be statistically different. The novel object recognition index of the offspring from female mice exposed to tannery effluents (7.5% and 15% groups) was lower than that of the control group, and it demonstrated object recognition deficit in the studied offspring. The present study is the first to report evidences that parental exposure to effluent of tannery (father and mother) can cause object recognition deficit in the offspring, which is related to problems in the central nervous system.

The normal aging process is commonly associated with mild cognitive deficits including memory decline. Previous studies indicate a role of dysregulated messenger ribonucleic acid translation capacity in cognitive defects associated with aging and aging-related diseases, including hyperphosphorylation of eukaryotic elongation factor 2 (eEF2). Phosphorylation of eEF2 by the kinase eEF2K inhibits its activity, hindering general protein synthesis. Here, we sought to determine whether cognitive deficits in aged mice can be improved by genetically deleting eEF2K (eEF2K KO) and consequently reduction of eEF2 phosphorylation. We found that suppression of eEF2K prevented aging-related deficits in novel object recognition memory. Interestingly, deletion of eEF2K did not alter overall protein synthesis in the hippocampus. Ultrastructural analysis revealed increase size and larger active zone lengths of postsynaptic densities in the hippocampus of aged eEF2K KO mice. Biochemical assays showed hippocampal eIF2α hyperphosphorylation in aged eEF2K KO mice, indicating inhibition of translation initiation. Our findings may provide insight into mechanistic understanding and thus development of novel therapeutic strategies for aging-related cognitive decline.

Liability to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and 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 GWAS 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 demonstrating 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, and many of these have been validated by larger, more recent single-phenotype GWAS. 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. Further, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia, but also to the broader biological dimensions that are implicated in both general health outcomes and psychiatric illness.

There is growing evidence associating inflammatory markers in complex, higher order neurological functions, such as cognition and memory. We examined whether high levels of various inflammatory markers are associated with cognitive outcomes at 4 years of age in a mother-child cohort in Crete, Greece (Rhea study). We included 642 children in this cross-sectional study. Levels of several inflammatory markers (IFN-gamma, IL-1 beta, IL-6, IL-8, IL-17 alpha, IL-10, MIP-1 alpha, TNF-alpha and the ratios of IL-6 to IL-10 and TNF-alpha to IL-10) were determined in child serum via immunoassay. Neurodevelopment at 4 years was assessed by means of the McCarthy Scales of Children's Abilities. Multivariate linear regression analyses were used to estimate the associations between the exposures and outcomes of interest after adjustment for various confounders. Our results indicate that children with high TNF-alpha concentrations (>= 90th percentile) in serum demonstrated decreased scores in memory (adjusted beta = 4.0; 95% CI: -7.7, -0.2), working memory (adjusted beta = -4.0; 95% CI: -8.0, -0.1) as well as in memory span scale (adjusted beta = -4.0; 95% CI: -7.9, -0.1). We also found that children with high IFN-gamma serum levels showed lower scores in memory span scale (adjusted beta = -3.4; 95% CI: -7.3, -0.4). Children with elevated TNF-alpha/IL-10 ratio demonstrated decreased quantitative (adjusted beta = -4.3; 95% CI: -8.2, -0.4), motor (adjusted beta = -3.5; 95% CI: -7.5, -0.5), executive function (adjusted beta = -4.8; 95% CI: -8.5, -1.1), general cognitive (adjusted beta = -3.6; 95% CI: -7.3, -0.1), memory (adjusted beta = -3.8; 95% CI: -7.6, -0), working memory (adjusted beta = -3.5; 95% CI: -7.5, -0.5) and memory span scores (adjusted beta = -5.3; 95% CI: -9.1, -1.4) The findings suggest that high levels of TNF-alpha may contribute to reduced memory performance at preschool age.

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to intelligence 3–7 , but much about its genetic underpinnings remains to be discovered. Here, we present the largest genetic association study of intelligence to date (N=279,930), identifying 206 genomic loci (191 novel) and implicating 1,041 genes (963 novel) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and identify 89 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain and specifically in striatal medium spiny neurons and cortical and hippocampal pyramidal neurons. Gene-set analyses implicate pathways related to neurogenesis, neuron differentiation and synaptic structure. We confirm previous strong genetic correlations with several neuropsychiatric disorders, and Mendelian Randomization results suggest protective effects of intelligence for Alzheimer’s dementia and ADHD, and bidirectional causation with strong pleiotropy for schizophrenia. These results are a major step forward in understanding the neurobiology of intelligence as well as genetically associated neuropsychiatric traits.

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.

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'.

Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3–7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer’s disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders. Meta-analysis of genome-wide association studies for cognitive ability identifies 190 new loci and implicates 939 new genes related to neurogenesis, neuron differentiation and synaptic structure.

OBJECTIVE: The study aims to investigate the effect of working memory training on cognitive flexibility in both men and women participants. MATERIAL – METHOD: Ninety-five healthy participants were divided into three groups (matched for demographic variables, schizotypy, impulsivity and baseline cognitive flexibility): a) fully adapted group (participants were fully trained with an executive working memory task, the Letter Number Sequencing task, for six consecutive days), b) partially adapted group (participants were partially trained with the same task for six consecutive days) and c) control group (participants did not receive cognitive training). Following training, all participants were tested in another cognitive flexibility task; the Intra-Extra Dimensional Set Shift Task (ID/EDS). RESULTS: Results showed that the fully adapted group had improved performance on the ID/EDS test, since they made fewer attempts to complete the stages of the test and marginally significantly fewer errors, compared with both the other two groups, who did not differ between each other. There were also significant correlations between the tests used. Specifically, it was found that the number of errors in the Wisconsin Card Sorting Task (WCST) was negatively correlated with the number of errors in the ID/EDS test. Also, it was observed that the Raven test correlates negatively with the number of errors in the WCST and also positively with the number of errors and trials needed to complete the stages of the ID/EDS task. CONCLUSIONS: These findings could have significant implications in the development of therapeutic approaches for the improvement of cognitive deficits in neuropsychiatric disorders.

Hill (2017) 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. 2017). Specifically, Hill offered several inter-related comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG; Turley et al. 2017). In this brief paper, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from “inflation of the false discovery rate”, as suggested by Hill (2017), and are not “more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence.”

Aims. Few epidemiological studies evaluated associations between perinatal complications and maternal mood at the early postpartum period and the findings are inconsistent. We aimed at investigating a wide range of complications during pregnancy, at delivery, and at the early postpartum period as determinants of postpartum depression (PPD) at 8 weeks postpartum. Methods. A total of 1037 women who enrolled in the Rhea mother–child cohort in Crete, Greece participated in the present study. Information on pregnancy, perinatal and postpartum complications was obtained from clinical records or by questionnaires. Postpartum depressive symptoms were assessed at 8 weeks postpartum using the Edinburgh Postnatal Depression Scale (EPDS). Multivariable linear and logistic regression models were fit to estimate the association between pregnancy, perinatal and postpartum complications and maternal depressive symptoms, adjusting also for potential confounders. Results. The prevalence of women with probable depression (EPDS score ≥ 13) was 13.6% at 8 weeks postpartum. Gestational hypertension and/or preeclampsia ( β coefficient 1.86, 95% CI: 0.32, 3.41) and breastfeeding difficulties ( β coefficient 0.77, 95% CI: 0.02, 1.53) were significantly associated with higher PPD symptoms. Sleep patterns during pregnancy, such as sleep deprivation (OR = 3.57, 95% CI: 1.91, 6.67) and snoring (OR = 1.81, 95% CI: 1.11, 2.93), and breastfeeding duration less than 2 months (OR = 1.77, 95% CI: 1.19, 2.64) were significantly associated with increase in the odds for PPD. Some other complications, such as unplanned pregnancy and hospitalisation during pregnancy were also associated with EPDS score, but these associations were explained by socio-demographic characteristics of the mother. Conclusions. We found that several pregnancy, perinatal and postpartum complications may have an adverse effect on maternal mood at the early postpartum period. These findings have considerable implications for developing effective prevention and early psychoeducational intervention strategies for women at risk of developing PPD.

This report describes the Student Counselling Centre (SCC) at the University of Crete. The SCS was established in 2003. Its main areas of activity are individual and group psychological support, crisis intervention, research, prevention, volunteering and awareness. Emphasis is also put on the support provided to students with special needs, which is now the second core service of the SCC.