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Inhibitory control (IC) aberrations are present in various psychopathologies, including schizophrenia spectrum and personality disorders, especially in association with antisocial or violent behaviour. We investigated behavioural and neural associations between IC and psychopathology-related traits of schizotypy [Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE)], psychopathy [Triarchic Psychopathy Measure (TriPM)], and impulsivity [Barratt Impulsiveness Scale (BIS-11)], using a novel Go/No-Go Task (GNG) featuring human avatars in 78 healthy adults (25 males, 53 females; mean age = 25.96 years, SD = 9.85) and whole-brain functional magnetic resonance imaging (fMRI) in a separate sample of 22 right-handed healthy individuals (7 males, 15 females; mean age = 24.13 years, SD = 5.40). Behaviourally, O-LIFE Impulsive Nonconformity (impulsive, anti-social, and eccentric behaviour) significantly predicted 16 % of variance in false alarms (FAs). O-LIFE Unusual Experiences (positive schizotypy) and BIS-11 Motor Impulsivity predicted 15 % of d prime (d') (sensitivity index) for the fastest (400 ms) GNG trials. When examined using fMRI, higher BIS-11 Motor Impulsivity uniquely, and also together with Unusual Experiences, was associated with lower activity in the left lingual gyrus during successful inhibition (correct No-Go over baseline). Additionally, higher Impulsive Nonconformity was associated with lower activity in the caudate nucleus and anterior cingulate during No-Go compared to Go stimuli reactions. Positive schizotypy, motor, and antisocial-schizotypal impulsivity correlate with some common but mostly distinct neural activation patterns during response inhibition in areas within or associated with the ventral attention network., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: Deficits in metacognition, the ability to monitor one's own mental states, are key elements of the functional pathology of schizophrenia spectrum disorders. Little is known, however, about the integrity of metacognitive processes in subclinical schizotypy. The purpose of the present investigation was two-fold: First, we conducted a preregistered, systematic literature review to synthesize previous research efforts on the role of metacognition in schizotypy. Second, we investigated the relationship between self-reported dimensions of schizotypy and psychometric as well as behavioral measures of metacognition in a preregistered online study., Methods: A large sample (N = 330) completed a questionnaire battery and an episodic memory experiment; task-based metacognition was tapped via trial-by-trial confidence ratings., Results: In keeping with findings from our literature review, higher schizotypy was associated with diminished introspective insight and an overly self-referential and maladaptive metacognitive style in metacognition questionnaires. Importantly, low task-based metacognitive efficiency was predictive of high levels of cognitive disorganization, whereas task-related overconfidence (i.e., increased metacognitive bias) was linked with positive schizotypy., Limitations: Due to the comparatively small number of k = 20 studies meeting our inclusion criteria, the systematic literature review provides only preliminary indications for potential conclusions. Furthermore, control over potential disturbing influences in the experimental study was limited due to its online format., Conclusions: Overall, we provide evidence for specific metacognitive deficits in schizotypy and discuss a potential continuity of preserved and impaired aspects of metacognitive monitoring along the psychosis continuum., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Schizotypy is a putative risk phenotype for psychosis liability, but the overlap of its genetic architecture with schizophrenia is poorly understood., Methods: We tested the hypothesis that dimensions of schizotypy (assessed with the SPQ-B) are associated with a polygenic risk score (PRS) for schizophrenia in a sample of 623 psychiatrically healthy, non-clinical subjects from the FOR2107 multi-centre study and a second sample of 1133 blood donors., Results: We did not find correlations of schizophrenia PRS with either overall SPQ or specific dimension scores, nor with adjusted schizotypy scores derived from the SPQ (addressing inter-scale variance). Also, PRS for affective disorders (bipolar disorder and major depression) were not significantly associated with schizotypy., Conclusions: This important negative finding demonstrates that despite the hypothesised continuum of schizotypy and schizophrenia, schizotypy might share less genetic risk with schizophrenia than previously assumed (and possibly less compared to psychotic-like experiences).

Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, p FDR  = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, p spin  = 0.024), but not BD (r = 0.166, p spin  = 0.205) or MDD (r = -0.274, p spin  = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = -0.690, p spin  = 0.006), BD (rho = -0.672, p spin  = 0.009), and MDD (rho = -0.692, p spin  = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype., (© 2021. The Author(s).)

Schizotypal personality traits show similarity with schizophrenia at various levels of analysis. It is generally agreed that schizotypal personality is multidimensional; however, it is still debated whether impulsive nonconformity should be incorporated into theories and measurement of schizotypy. In addition, relatively little is known about the network structure of the four-dimensional model of schizotypal personality. To estimate the network structure of schizotypy, we used data from participants recruited from the community (N = 11,807) who completed the short version of the Oxford-Liverpool Inventory of Feelings and Experiences, a widespread self-report instrument that assesses the positive, negative, disorganised and impulsive domains of schizotypy. We performed community detection, then examined differences between communities in terms of centralities and compared the strength of edges within and between communities. We found communities that almost perfectly corresponded to the a priori-defined subscales (93% overlap, normalised mutual information = 0.74). Items in the disorganisation community had higher closeness centrality relative to items in the other communities (Cliff's Δs ranged from 0.55 to 0.83) and weights of edges within the disorganisation community were stronger as compared to the negative schizotypy and impulsive nonconformity communities (Cliff's Δs = 0.33). Our findings imply that the inclusion of impulsive nonconformity items does not dilute the classical three-factor structure of positive, negative and disorganised schizotypy. The high closeness centrality of disorganisation concurs with theories positing that cognitive slippage and associative loosening are core features of the schizophrenic phenotype.

Deficits on saccade tasks, particularly antisaccade performance, have been reliably reported in schizophrenia. However, less evidence is available on saccade performance in relation to schizotypy, a personality constellation harboring risk for schizophrenia. Here, we report a large empirical study of the associations of schizotypy and neuroticism with antisaccade and prosaccade performance (Study I). Additionally, we carried out meta-analyses of the association between schizotypy and antisaccade error rate (Study II). In Study I, N = 526 healthy individuals from the general population aged 18-54 years completed prosaccade and antisaccade tasks as well as the Schizotypal Personality Questionnaire (SPQ). Schizotypy was significantly associated with increased antisaccade error rate, with the disorganized dimension emerging as strongest predictor (β = .118, p = .007). Neuroticism emerged as a significant predictor for prosaccade gain (β = .103, p = .023) and antisaccade latency (β = .101, p = .025). In Study II, random-effects meta-analyses were performed on the published data and those from Study I. Meta-analyses revealed significant associations (all p ≤ .003) of antisaccade error rate with positive (g = 0.37), negative (g = 0.26), disorganized (g = 0.36) and overall schizotypy (g = 0.37). Overall, the present work replicates the association between antisaccade direction errors and schizotypy. Significant findings from meta-analyses provide further evidence of the antisaccade error rate as a putative schizophrenia spectrum marker., (© 2020 The Authors. Psychophysiology published by Wiley Periodicals LLC On behalf of Society for Psychophysiological Research.)

Background: Schizotypy, a putative schizophrenia endophenotype, has been associated with brain-structural variations partly overlapping with those in psychotic disorders. Variations in precuneus structure have been repeatedly reported, whereas the involvement of fronto-striatal networks - as in schizophrenia - is less clear. While shared genetic architecture is thought to increase vulnerability to environmental insults, beneficial factors like general intelligence might buffer their effect., Methods: To further investigate the role of fronto-striatal networks in schizotypy, we examined the relationship of voxel- and surface-based brain morphometry and a measure of schizotypal traits (Schizotypal Personality Questionnaire, with subscores Cognitive-Perceptual, Interpersonal, Disorganised) in 115 healthy participants [54 female, mean age (s.d.) = 27.57(8.02)]. We tested intelligence (MWT-B) as a potential moderator., Results: We found a positive association of SPQ Cognitive-Perceptual with putamen volume (p = 0.040, FWE peak level-corrected), moderated by intelligence: with increasing IQ, the correlation of SPQ Cognitive-Perceptual and striatal volume decreased (p = 0.022). SPQ Disorganised was positively correlated with precentral volume (p = 0.013, FWE peak level-corrected). In an exploratory analysis (p < 0.001, uncorrected), SPQ total score was positively associated with gyrification in the precuneus and postcentral gyrus, and SPQ Disorganised was negatively associated with gyrification in the inferior frontal gyrus., Conclusions: Our findings support the role of fronto-striatal networks for schizotypal features in healthy individuals, and suggest that these are influenced by buffering factors like intelligence. We conclude that protective factors, like general cognitive capacity, might attenuate the psychosis risk associated with schizotypy. These results endorse the idea of a continuous nature of schizotypy, mirroring similar findings in schizophrenia.

Several studies suggest that highly schizotypal individuals display a deficit in smooth pursuit eye movements (SPEM), which are considered an important biomarker of schizophrenia. In schizophrenia, abnormal SPEM is thought to be driven by impairments in motion perception. In schizotypy, the processes underlying reduced SPEM performance have not been examined so far, and there are no studies on motion perception deficits in schizotypy. Thus, in this registered report, we aimed to investigate whether motion perception is impaired in highly schizotypal individuals, and how it contributes to SPEM performance. On an exploratory basis, we were interested in the association between schizotypy and prediction, another mechanism underlying SPEM. To address this issue, participants with high total scores of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE short form) and control participants with low scores (N = 86 in each group) performed a standard sinusoidal SPEM task, random dot kinematograms to measure motion perception, and a blanking SPEM task to assess prediction abilities. Group comparisons as well as mediator analyses were carried out to identify whether motion perception or prediction are responsible for SPEM performance in schizotypy. We found reduced blanking SPEM performance in schizotypes compared to controls, but no group differences regarding sinusoidal SPEM and motion perception. Although no significant mediators were identified for SPEM performance in schizotypes, an exploratory analysis revealed an association between motion perception and SPEM gain in high, but not in low schizotypy. Our findings imply that despite the schizotypy-related impairment in prediction, motion perception seems to be a more important predictor of SPEM performance in schizotypes. A deficit in prediction that does not relate to SPEM performance suggests that protective factors (e.g., other cognitive processes) might operate in schizotypal individuals to maintain SPEM performance on a healthy level., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Patients with obsessive-compulsive disorder (OCD) show dysfunctions of the fronto-striatal circuitry, which imply corresponding oculomotor deficits including smooth pursuit eye movements (SPEM). However, evidence for a deficit in SPEM is inconclusive, with some studies reporting reduced velocity gain while others did not find any SPEM dysfunctions in OCD patients. Interestingly, psychosis-like traits have repeatedly been linked to both OCD and impaired SPEM. Here, we examined a large sample of n = 168 patients with OCD, n = 93 unaffected first-degree relatives and n = 171 healthy control subjects to investigate whether elevated levels of schizotypy and SPEM deficits represent potential endophenotypes of OCD. We applied a SPEM task with high demands on predictive pursuit that is more sensitive to assess executive dysfunctions than a standard task with continuous visual feedback, as episodes of target blanking put increased demands on basal ganglia and prefrontal involvement. Additionally, we examined the relation between schizotypy and SPEM performance in OCD patients and their relatives. Results indicate that OCD patients and unaffected relatives do not show deficient performance in either standard or predictive SPEM. Yet, both patients and relatives exhibited elevated levels of schizotypy, and schizotypy was significantly correlated with velocity gain during standard trials in unmedicated and depression-free OCD patients. These findings highlight the role of schizotypy as a candidate endophenotype of OCD and add to the growing evidence for predisposing personality traits in OCD. Furthermore, intact gain may represent a key characteristic that distinguishes the OCD and schizophrenia patient populations.

Model systems of psychosis play an important role in pathophysiology and drug development research. Schizotypal individuals display similar cognitive impairments as schizophrenia patients in several domains. Therefore, schizotypy may be interpreted as a trait model system of psychosis. In addition, experimentally controlled sleep deprivation is a putative state psychosis model that evokes subclinical psychosis-like states. We aimed to further validate these model systems by examining them in relation to central cognitive biomarkers of schizophrenia. Most of all, we were interested in investigating, for the first time, effects of their combination on cognitive function. Healthy subjects with high (N = 17) or low (N = 19) levels of schizotypy performed a cognitive task battery after one night of normal sleep and after 24 h of sleep deprivation. Sleep deprivation impaired performance in the go/nogo and n-back tasks relative to the normal sleep control condition. No differences between groups or interactions of group with sleep condition were found. The role of sleep deprivation as a model of psychosis is thus supported to some extent by impairments in inhibitory control. However, classical measures of cognition may be less able to detect deficits in schizotypy, in line with evidence of more basic information processing dysfunctions in schizotypy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The latent structure of schizotypy and psychosis-spectrum symptoms remains poorly understood. Furthermore, molecular genetic substrates are poorly defined, largely due to the substantial resources required to collect rich phenotypic data across diverse populations. Sample sizes of phenotypic studies are often insufficient for advanced structural equation modeling approaches. In the last 50 years, efforts in both psychiatry and psychological science have moved toward (1) a dimensional model of psychopathology (eg, the current Hierarchical Taxonomy of Psychopathology [HiTOP] initiative), (2) an integration of methods and measures across traits and units of analysis (eg, the RDoC initiative), and (3) powerful, impactful study designs maximizing sample size to detect subtle genomic variation relating to complex traits (the Psychiatric Genomics Consortium [PGC]). These movements are important to the future study of the psychosis spectrum, and to resolving heterogeneity with respect to instrument and population. The International Consortium of Schizotypy Research is composed of over 40 laboratories in 12 countries, and to date, members have compiled a body of schizotypy- and psychosis-related phenotype data from more than 30000 individuals. It has become apparent that compiling data into a protected, relational database and crowdsourcing analytic and data science expertise will result in significant enhancement of current research on the structure and biological substrates of the psychosis spectrum. The authors present a data-sharing infrastructure similar to that of the PGC, and a resource-sharing infrastructure similar to that of HiTOP. This report details the rationale and benefits of the phenotypic data collective and presents an open invitation for participation.

Schizotypy is defined as a time-stable multidimensional personality trait consisting of positive, negative, and disorganized facets. Schizotypy is considered as a model system of psychosis, as there is considerable overlap between the 2 constructs. High schizotypy is associated with subtle but fairly widespread cognitive alterations, which include poorer performance in tasks measuring cognitive control. Similar but more pronounced impairments in cognitive control have been described extensively in psychosis. We here sought to provide a quantitative estimation of the effect size of impairments in schizotypy in the updating, shifting, and inhibition dimensions of cognitive control. We included studies of healthy adults from both general population and college samples, which used either categorical or correlative designs. Negative schizotypy was associated with significantly poorer performance on shifting (g = 0.32) and updating (g = 0.11). Positive schizotypy was associated with significantly poorer performance on shifting (g = 0.18). There were no significant associations between schizotypy and inhibition. The divergence in results for positive, negative, and disorganized schizotypy emphasizes the importance of examining relationships between cognition and the facets of schizotypy rather than using the overall score. Our findings also underline the importance of more detailed research to further understand and define this complex personality construct, which will also be of importance when applying schizotypy as a model system for psychosis.

The ability to inhibit inappropriate responses and suppress irrelevant information is a core feature of executive control. In this study, we provide a detailed analysis of prepotent response inhibition and interference in patients with schizophrenia. To further test the role of genetic factors and subclinical schizophrenia-like traits, we additionally studied clinically unaffected, first-degree relatives of schizophrenia patients and assessed dimensions of schizotypy in both relatives and healthy controls. Inhibition and interference control were assessed using a battery comprising the antisaccade, Stroop, stop signal, go/no-go, flanker, and Simon tasks. Schizophrenia patients differed from both relatives and controls in making more errors on the antisaccade task and having longer response times on the Stroop task, especially the incongruent condition. Patients also had general, that is, condition independent, increases in reaction times on the go/no-go and flanker tasks and made more errors on the flanker and Simon tasks, suggesting general performance impairments independent of inhibitory demand. Relatives were characterized by hypometric antisaccade amplitude gain despite normal prosaccades, suggesting a selective deficit in non-standard sensorimotor transformations. Schizotypy was correlated with inhibitory performance across a number of tasks in both relatives and controls. Generally, these effects were independent of verbal intelligence levels. Overall, the findings point to rather selective impairments of inhibitory control in the schizophrenia spectrum and confirm a previously observed deficit in antisaccade spatial accuracy as an endophenotype of schizophrenia., (© 2017 The British Psychological Society.)

Altered striatocortical functional connectivity has been suggested to be a trait marker of schizophrenia spectrum disorders, including schizotypal personality. In the present study, we examined the association between schizotypal personality traits and striatocortical functional connectivity in a sample of healthy adults. The German version of the Schizotypal Personality Questionnaire was obtained from N = 111 participants recruited from the general public. Resting-state functional magnetic resonance imaging scans were acquired at 3T. Six striatal seed regions in each hemisphere were defined and striatocortical resting-state functional connectivity (rsFC) as well as its lateralization indices was calculated. Regression analysis showed that schizotypy scores, especially from the positive dimension, were positively correlated with rsFC between ventral striatum and frontal cortex and negatively associated with rsFC between dorsal striatum and posterior cingulate. No significant associations were found between negative dimension schizotypy and striatocortical rsFC. We also found positive correlations between schizotypy total scores and lateralization index of right dorsal caudate and right rostral putamen. In conclusion, the present study extends previous evidence of altered striatocortical rsFC in the schizophrenia spectrum. The observed associations resemble in part the alterations observed in psychotic patients and their relatives, providing support for dimensionality from schizotypal personality to the clinical disorder. Hum Brain Mapp 39:288-299, 2018. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Model systems of psychosis, such as schizotypy or sleep deprivation, are valuable in informing our understanding of the etiology of the disorder and aiding the development of new treatments. Schizophrenia patients, high schizotypes, and sleep-deprived subjects are known to share deficits in oculomotor biomarkers. Here, we aimed to further validate the schizotypy and sleep deprivation models and investigated, for the first time, their interactive effects on smooth pursuit eye movements (SPEM), prosaccades, antisaccades, predictive saccades, and measures of psychotomimetic states, anxiety, depression, and stress. To do so, n = 19 controls and n = 17 high positive schizotypes were examined after both a normal sleep night and 24 h of sleep deprivation. Schizotypes displayed higher SPEM global position error, catch-up saccade amplitude, and increased psychotomimetic states. Sleep deprivation impaired SPEM, prosaccade, antisaccade, and predictive saccade performance and increased levels of psychotomimetic experiences. Additionally, sleep deprivation reduced SPEM gain in schizotypes but not controls. We conclude that oculomotor impairments are observed in relation to schizotypy and following sleep deprivation, supporting their utility as biomarkers in model systems of psychosis. The combination of these models with oculomotor biomarkers may be particularly fruitful in assisting the development of new antipsychotic or pro-cognitive drugs., (© 2017 Society for Psychophysiological Research.)

Schizotypy refers to a set of personality traits thought to reflect the subclinical expression of the signs and symptoms of schizophrenia. Here, we review the cognitive and brain functional profile associated with high questionnaire scores in schizotypy. We discuss empirical evidence from the domains of perception, attention, memory, imagery and representation, language, and motor control. Perceptual deficits occur early and across various modalities. While the neural mechanisms underlying visual impairments may be linked to magnocellular dysfunction, further effects may be seen downstream in higher cognitive functions. Cognitive deficits are observed in inhibitory control, selective and sustained attention, incidental learning, and memory. In concordance with the cognitive nature of many of the aberrations of schizotypy, higher levels of schizotypy are associated with enhanced vividness and better performance on tasks of mental rotation. Language deficits seem most pronounced in higher-level processes. Finally, higher levels of schizotypy are associated with reduced performance on oculomotor tasks, resembling the impairments seen in schizophrenia. Some of these deficits are accompanied by reduced brain activation, akin to the pattern of hypoactivations in schizophrenia spectrum individuals. We conclude that schizotypy is a construct with apparent phenomenological overlap with schizophrenia and stable interindividual differences that covary with performance on a wide range of perceptual, cognitive, and motor tasks known to be impaired in schizophrenia. The importance of these findings lies not only in providing a fine-grained neurocognitive characterization of a personality constellation known to be associated with real-life impairments, but also in generating hypotheses concerning the aetiology of schizophrenia., (© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Schizotypy, defined in terms of commonly occurring personality traits related to the schizophrenia spectrum, has been an important construct for understanding the neurodevelopment and stress-diathesis of schizophrenia. However, as schizotypy nears its sixth decade of application, it is important to acknowledge its impressively rich literature accumulating outside of schizophrenia research. In this article, we make the case that schizotypy has considerable potential as a conceptual framework for understanding individual differences in affective and social functions beyond those directly involved in schizophrenia spectrum pathology. This case is predicated on (a) a burgeoning literature noting anomalies in a wide range of social functioning, affiliative, positive and negative emotional, expressive, and social cognitive systems, (b) practical and methodological features associated with schizotypy research that help facilitate empirical investigation, and (c) close ties to theoretical constructs of central importance to affective and social science (eg, stress diathesis, neural compensation). We highlight recent schizotypy research, ie providing insight into the nature of affective and social systems more generally. This includes current efforts to clarify the neurodevelopmental, neurobiological, and psychological underpinnings of affiliative drives, hedonic capacity, social cognition, and stress responsivity systems. Additionally, we discuss neural compensatory and resilience factors that may mitigate the expression of stress-diathesis and functional outcome, and highlight schizotypy's potential role for understanding cultural determinants of social and affective functions., (© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Patients with schizophrenia as well as individuals with high levels of schizotypy are known to have deficits in smooth pursuit eye movements (SPEM). Here, we investigated, for the first time, the neural mechanisms underlying SPEM performance in high schizotypy. Thirty-one healthy participants [N = 19 low schizotypes, N = 12 high schizotypes (HS)] underwent functional magnetic resonance imaging at 3T with concurrent oculographic recording while performing a SPEM task with sinusoidal stimuli at two velocities (0.2 and 0.4 Hz). Behaviorally, a significant interaction between schizotypy group and velocity was found for frequency of saccades during SPEM, indicating impairments in HS in the slow but not the fast condition. On the neural level, HS demonstrated lower brain activation in different regions of the occipital lobe known to be associated with early sensory and attentional processing and motion perception (V3A, middle occipital gyrus, and fusiform gyrus). This group difference in neural activation was independent of target velocity. Together, these findings replicate the observation of altered pursuit performance in highly schizotypal individuals and, for the first time, identify brain activation patterns accompanying these performance changes. These posterior activation differences are compatible with evidence of motion processing deficits from the schizophrenia literature and, therefore, suggest overlap between schizotypy and schizophrenia both on cognitive-perceptual and neurophysiological levels. However, deficits in frontal motor areas observed during pursuit in schizophrenia were not seen here, suggesting the operation of additional genetic and/or illness-related influences in the clinical disorder., (© 2014 Wiley Periodicals, Inc.)

Rationale: The increasing demand to develop more efficient compounds to treat cognitive impairments in schizophrenia has led to the development of experimental model systems. One such model system combines the study of surrogate populations expressing high levels of schizotypy with oculomotor biomarkers., Objectives: We aimed (1) to replicate oculomotor deficits in a psychometric schizotypy sample and (2) to investigate whether the expected deficits can be remedied by compounds shown to ameliorate impairments in schizophrenia., Methods: In this randomized double-blind, placebo-controlled study 233 healthy participants performed prosaccade (PS), antisaccade (AS) and smooth pursuit eye movement (SPEM) tasks after being randomly assigned to one of four drug groups (nicotine, risperidone, amisulpride, placebo). Participants were classified into medium- and high-schizotypy groups based on their scores on the Schizotypal Personality Questionnaire (SPQ, Raine (Schizophr Bull 17:555-564, 1991))., Results: AS error rate showed a main effect of Drug (p < 0.01), with nicotine improving performance, and a Drug by Schizotypy interaction (p = 0.04), indicating higher error rates in medium schizotypes (p = 0.01) but not high schizotypes under risperidone compared to placebo. High schizotypes had higher error rates than medium schizotypes under placebo (p = 0.03). There was a main effect of Drug for saccadic peak velocity and SPEM velocity gain (both p ≤ 0.01) indicating impaired performance with risperidone., Conclusions: We replicate the observation of AS impairments in high schizotypy under placebo and show that nicotine enhances performance irrespective of group status. Caution should be exerted in applying this model as no beneficial effects of antipsychotics were seen in high schizotypes.

Schizotypy is phenotypically associated with neuroticism. To reveal the origin of this association, we assessed 3,349 (1,449 monozygotic, 1,105 dizygotic [DZ] same-sex and 795 DZ opposite-sex) twins on a 12-item version of Chapman's Psychosis-Proneness Scales and the short form of the Eysenck Personality Questionnaire-Revised as measures of schizotypy and neuroticism. A substantial proportion (0.51 with 95 % CI from 0.38 to 0.64) of the phenotypic correlation of 0.37 between neuroticism and the perceptual and ideational components of schizotypy was accounted for by shared genetic influences on these two traits. Moreover, a Cholesky decomposition including anhedonia, hypomania and impulsivity fully accounted for the heritable variance in perceptual and ideational components of schizotypy. These findings suggest a shared genetic etiology between neuroticism and perceptual and ideational components of schizotypy and affect future investigations on the etiology of these phenotypically overlapping traits and affective and psychotic disorders.

Dimensional models of psychosis assume a continuum between schizotypy and schizophrenia. However, little is known about the overlap in brain functional alterations between schizotypy and schizophrenia. Fifty-four healthy volunteers underwent functional magnetic resonance imaging during an antisaccade task, a measure of cognitive control known to be impaired in schizophrenia, and a prosaccade task. Higher positive schizotypy was correlated with higher antisaccade error rates. Associations between reduced blood oxygenation level dependent signal and higher schizotypy were found during antisaccades in the putamen, thalamus, cerebellum, and visual cortex and during prosaccades in the visual cortex, supplementary eye field, and posterior intraparietal sulcus. These findings show that increased schizotypy is associated with decreased antisaccade performance and reduced brain function in regions also affected in schizophrenia, therefore providing evidence of neurocognitive and neurophysiological overlap between schizotypy and schizophrenia., (Copyright © 2011 Society for Psychophysiological Research.)

Objective: In the present study the relationship between behavioural adjustment following cognitive conflict and schizotypy was investigated using a Stroop colour naming paradigm. Previous research has found deficits with behavioural adjustment in schizophrenia patients. Based on these findings, we hypothesized that individual differences in schizotypy, a personality trait reflecting the subclinical expression of the schizophrenia phenotype, would be associated with behavioural adjustment. Additionally, we investigated whether such a relationship would be explained by individual differences in neuroticism, a non-specific measure of negative trait emotionality known to be correlated with schizotypy., Methods: 106 healthy volunteers (mean age: 25.1, 60% females) took part. Post-conflict adjustment was measured in a computer-based version of the Stroop paradigm. Schizotypy was assessed using the Schizotypal Personality Questionnaire (SPQ) and Neuroticism using the NEO-FFI., Results: We found a negative correlation between schizotypy and post-conflict adjustment (r = -.30, p<.01); this relationship remained significant when controlling for effects of neuroticism. Regression analysis revealed that particularly the subscale No Close Friends drove the effect., Conclusion: Previous findings of deficits in cognitive control in schizophrenia patients were extended to the subclinical personality expression of the schizophrenia phenotype and found to be specific to schizotypal traits over and above the effects of negative emotionality.

Previous research has suggested that there may be overlap between schizophrenia and attention-deficit hyperactivity disorder (ADHD). The relationship between schizotypal personality traits, ADHD features and polymorphisms was evaluated in dopamine-related genes. Thirty-one healthy, Caucasian men completed the Rust Inventory of Schizotypal Cognitions (RISC) and the ADHD Self-Report Scale (ASRS). Catechol-O-methyltransferase (COMT) Val158Met, dopamine receptors of the D3 type (DRD3) Ser9Gly, DRD4 variable number of tandem repeats (VNTR), and SLC6A3 VNTR polymorphisms were analyzed. RISC score was correlated with ASRS score (r = 0.54, P = 0.003). COMT Met homozygotes had higher ASRS scores than Val homozygotes (P = 0.005). These findings are consistent with evidence of overlap between schizophrenia and ADHD and support an involvement of COMT genotype in ADHD features.

We investigated the relationships of anti- and prosaccades with psychometric schizotypy. One aim was to estimate the role of negative emotionality and general psychopathology (i.e. neuroticism) in this relationship. 115 non-clinical volunteers underwent infrared oculographic assessment of antisaccades and prosaccades. Schizotypy was assessed with the Personality Syndrome Questionnaire (PSQ-80), the Rust Inventory of Schizotypal Cognitions (RISC), and Eysenck Personality Questionnaire-Revised (EPQ-R) Psychoticism. Higher positive schizotypy scores predicted increased antisaccade errors (RISC) and greater prosaccade spatial error (PSQ-80 Unreality). Greater thought disorder (PSQ-80 Activity) predicted shorter prosaccade latencies. EPQ-R Neuroticism was substantially correlated with schizotypy but was not related to saccadic measures and did not account for their relationship with schizotypy. We conclude that saccadic performance patterns in schizotypy are not due to negative emotionality or general psychopathology, but specific to schizophrenia spectrum signs and symptoms.

Schizotypy refers to a set of personality traits that bear resemblance, at subclinical level, to psychosis. Despite evidence of similarity at multiple levels of analysis, direct comparisons of schizotypy and clinical psychotic disorders are rare. Therefore, we used functional magnetic resonance imaging (fMRI) to examine the neural correlates and task-based functional connectivity (psychophysiological interactions; PPI) of smooth pursuit eye movements (SPEM) in patients with recent onset psychosis (ROP; n = 34), participants with high levels of negative (HNS; n = 46) or positive (HPS; n = 41) schizotypal traits, and low-schizotypy control participants (LS; n = 61) using machine-learning. Despite strong previous evidence that SPEM is a highly reliable marker of psychosis, patients and controls could not be significantly distinguished based on SPEM performance or blood oxygen level dependent (BOLD) signal during SPEM. Classification was, however, significant for the right frontal eye field (FEF) seed region in the PPI analyses but not for seed regions in other key areas of the SPEM network. Applying the right FEF classifier to the schizotypal samples yielded decision scores between the LS and ROP groups, suggesting similarities and dissimilarities of the HNS and HPS samples with the LS and ROP groups. The very small difference between groups is inconsistent with previous studies that showed significant differences between patients with ROP and controls in both SPEM performance and underlying neural mechanisms with large effect sizes. As the current study had sufficient power to detect such differences, other reasons are discussed. [ABSTRACT FROM AUTHOR]

Environmental noise causes cognitive impairment, particularly in executive function and episodic memory domains, in healthy populations. However, the possible moderating influences on this relationship are less clear. This study assessed 54 healthy participants (24 men) on a cognitive battery (measuring psychomotor speed, attention, executive function, working memory, and verbal learning and memory) under three (quiet, urban, and social) noise conditions. IQ, subjective noise sensitivity, sleep, personality, paranoia, depression, anxiety, stress, and schizotypy were assessed on a single occasion. We found significantly slower psychomotor speed (urban), reduced working memory and episodic memory (urban and social), and more cautious decision-making (executive function, urban) under noise conditions. There was no effect of sex. Variance in urban noise-induced changes in psychomotor speed, attention, Trail Making B-A (executive function), and immediate recall and social noise-induced changes in verbal fluency (executive function) and immediate recall were explained by a combination of baseline cognition and paranoia, noise sensitivity, sleep, or cognitive disorganization. Higher baseline cognition (but not IQ) predicted greater impairment under urban and social noise for most cognitive variables. Paranoia predicted psychomotor speed, attention, and executive function impairment. Subjective noise sensitivity predicted executive function and memory impairment. Poor sleep quality predicted less memory impairment. Finally, lower levels of cognitive disorganization predicted slower psychomotor speed and greater memory impairment. The identified moderators should be considered in studies aiming to reduce the detrimental effects of occupational and residential noise. These results highlight the importance of studying noise effects in clinical populations characterized by high levels of the paranoia, sleep disturbances, noise sensitivity, and cognitive disorganization. [ABSTRACT FROM AUTHOR]

Schizotypy refers to a constellation of personality traits that are believed to mirror the subclinical expression of schizophrenia in the general population. Evidence from pharmacological studies indicates that dopamine (DA) is involved in the etiology of schizophrenia. Based on the assumption of a continuum between schizophrenia and schizotypy, researchers have begun investigating the association between DA and schizotypy using a wide range of methods. In this article, we review published studies on this association from the following areas of work: (1) experimental investigations of the interactive effects of dopaminergic challenges and schizotypy on cognition, motor control, and behavior (2), dopaminergically supported cognitive functions (3), studies of associations between schizotypy and polymorphisms in genes involved in dopaminergic neurotransmission, and (4) molecular imaging studies of the association between schizotypy and markers of the DA system. Together, data from these lines of evidence suggest that DA is important to the expression and experience of schizotypy and associated behavioral biases. An important observation is that the experimental designs, methods, and manipulations used in this research are highly heterogeneous. Future studies are required to replicate individual observations, to enlighten the link between DA and different schizotypy dimensions (positive, negative, cognitive disorganization), and to guide the search for solid DA-sensitive behavioral markers. Such studies are important in order to clarify inconsistencies between studies. Morework is also needed to identify differences between dopaminergic alterations in schizotypy compared to the dysfunctions observed in schizophrenia. [ABSTRACT FROM AUTHOR]

Objectives. Schizophrenia is associated with replicable grey matter volume reductions in fronto-temporo-limbic and subcortical regions. Psychometric schizotypy refers to a set of behavioural traits and cognitions thought to represent the subclinical manifestation of schizophrenia in the general population. While there is evidence of a continuum between schizophrenia and schizotypy at phenotypic, genetic and cognitive levels, no previous study has observed grey matter volume reductions associated with increased psychometric schizotypy levels in healthy individuals. Such evidence would provide further support for a relationship between non-clinical schizophrenia-like traits in the general population and the full-blown clinical condition of schizophrenia. Methods. We used magnetic resonance imaging to investigate the relationship between psychometric schizotypy and brain structure in 55 clinically unaffected and unmedicated volunteers. We performed a voxel-based morphometry analysis of grey matter volume data obtained at 1.5 Tesla. Results. Covarying for age and gender, higher scores of self-report positive schizotypy were significantly associated with reduced grey matter volume in medial prefrontal, orbitofrontal, and temporal cortical regions. Conclusions. These findings show that psychometric schizotypy in healthy individuals is associated with volume reductions in cortical areas known to be altered in schizophrenia, thereby providing neurobiological evidence of a continuum between schizotypy and schizophrenia. [ABSTRACT FROM AUTHOR]

Antipsychotic drugs are the mainstay of treatment for schizophrenia but they have little effect on core negative symptoms or cognitive impairment. To meet the deficiencies of current treatments, novel potential compounds are emerging from preclinical research but translation to clinical success has been poor. This article evaluates the possibility that cognitive and physiological abnormalities in schizophrenia can be used as central nervous system biomarkers to predict, in healthy volunteers, the likely efficacy of entirely new pharmacological approaches to treatment. Early detection of efficacy would focus resource on rapidly developing, effective drugs. We review the relevance of selected cognitive and physiological abnormalities as biomarkers in schizophrenia and three of its surrogate populations: (i) healthy volunteers with high trait schizotypy; (ii) unaffected relatives of patients; and (iii) healthy volunteers in a state of cortical glutamate disinhibition induced by low-dose ketamine. Several biomarkers are abnormal in these groups and in some instances there has been exploratory work to determine their sensitivity to drug action. They are generally insensitive to current antipsychotics and therefore their predictive validity cannot be established until novel, therapeutically useful drugs are discovered. Until then such biomarker studies can provide evidence of drugs engaging with the mechanism of interest and encouragement of the concept. [ABSTRACT FROM PUBLISHER]

The article focuses on the research about the genetic traits which contribute to the development of schizophrenia. The research shows that neurocognitive deficits are seen as possible factors for the development of schizophrenia. An overview of the methodology, analyses, and results of the research are presented. The research concludes that shared genetic variability is explained by the 92 percent phenotypic correlation between intelligence and schizophrenia based on the application of the bivariate genetic model.

Objective: Several components of event-related potentials—P50 suppression, P300 amplitude and latency, and mismatch negativity—have been proposed as potential endophenotypes for schizophrenia on the basis of family studies. The present study used a twin design to estimate the extent of genetic overlap between these indices and the liability to schizophrenia. Method: The authors measured mismatch negativity, P300, and P50 suppression in 16 monozygotic twin pairs concordant for schizophrenia, nine monozygotic twin pairs discordant for schizophrenia, and 78 healthy comparison twin pairs. The study design was based on a power calculation. Structural equation modeling was used to quantify the genetic and environmental contributions to the phenotypic covariance between schizophrenia and each of the event-related potential indices. Results: Significant phenotypic correlation with schizophrenia was found for each of the event-related potential components. Genetic factors were the main source of the phenotypic correlations. PS0 suppression had the greatest genetic correlation with schizophrenia, followed by P300 amplitude, P300 latency, and mismatch negativity. Conclusions: All four event-related potential indices are potentially valid endophenotypes for schizophrenia, but P50 suppression and P300 amplitude show the closest genetic relationship to schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract: A number of compounds aimed at improving cognition in schizophrenia have failed to demonstrate efficacy in Phase 2 clinical trials. Translational studies using biomarkers in surrogate populations, such as schizotypy, could be used to assess the efficacy of novel compounds. In this study, we aimed to validate the sensitivity and inter-site reliability of cognitive biomarkers (working memory (N-back), spatial working memory (SWM) and verbal fluency (VF) tasks) to detect the schizotypy phenotype and its reversal by psychotropic drugs. Healthy volunteers scoring high or average on a schizotypal personality measure (122 in each group) were randomized to receive a single dose of risperidone, amisulpride, nicotine or placebo in a double-blind, between-subject design. We found evidence for a poorer performance on N-back and VF tasks in the high schizotypy group, replicating previous research. This effect was counteracted by amisulpride on N-back: it improved working memory in high schizotypy group but impaired the controls. A similar pattern was seen in SWM and VF. We interpret this finding in the light of the dopamine enhancing action of amisulpride when given in low doses. In contrast, risperidone impaired both groups and nicotine had a beneficial effect for the low baseline performers only. These effects were consistent across sites. These data demonstrates the utility of biomarkers in detecting the effect of schizotypy and its reversal by drugs that enhance dopamine and cholinergic function. Studies using similar design could help the early assessment of potential of compounds designed to improve cognition in schizophrenia. [Copyright &y& Elsevier]