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Schizophrenia is associated with various deficits in social cognition that remain relatively unaltered by antipsychotic treatment. While faulty glutamate signaling has been associated with general cognitive deficits as well as negative symptoms of schizophrenia, no direct link between manipulation of glutamate signaling and deficits in mentalizing has been demonstrated thus far. Here, we experimentally investigated whether ketamine, an uncompetitive N-methyl-D-aspartate receptor antagonist known to induce psychotomimetic effects, influences mentalizing and its neural correlates. In a randomized, placebo-controlled between-subjects experiment, we intravenously administered ketamine or placebo to healthy participants performing a video-based social cognition task during functional magnetic resonance imaging. Psychotomimetic effects of ketamine were assessed using the Positive and Negative Syndrome Scale. Compared to placebo, ketamine led to significantly more psychotic symptoms and reduced mentalizing performance (more “no mentalizing” errors). Ketamine also influenced blood oxygen level dependent (BOLD) response during mentalizing compared to placebo. Specifically, ketamine increased BOLD in right posterior superior temporal sulcus (pSTS) and increased connectivity between pSTS and anterior precuneus. These increases may reflect a dysfunctional shift of attention induced by ketamine that leads to mentalizing deficits. Our findings show that a psychotomimetic dose of ketamine impairs mentalizing and influences its neural correlates, a result compatible with the notion that deficient glutamate signaling may contribute to deficits in mentalizing in schizophrenia. The results also support efforts to seek novel psychopharmacological treatments for psychosis and schizophrenia targeting glutamatergic transmission. [ABSTRACT FROM AUTHOR]

In this paper, we present a review of how the various aspects of any study using an eye tracker (such as the instrument, methodology, environment, participant, etc.) affect the quality of the recorded eye-tracking data and the obtained eye-movement and gaze measures. We take this review to represent the empirical foundation for reporting guidelines of any study involving an eye tracker. We compare this empirical foundation to five existing reporting guidelines and to a database of 207 published eye-tracking studies. We find that reporting guidelines vary substantially and do not match with actual reporting practices. We end by deriving a minimal, flexible reporting guideline based on empirical research (Section "An empirically based minimal reporting guideline"). [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Minimal reporting guideline for research involving eye tracking (2023 edition)" published in the journal Behavior Research Methods. The correction includes the addition of a funding note acknowledging support from various organizations. The authors state that the content of the article is their responsibility and does not necessarily reflect the views of the funding organizations. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. The document also lists the names of the authors involved in the article. [Extracted from the article]

The article titled "Retraction Note: Eye tracking: empirical foundations for a minimal reporting guideline" has been retracted by the authors due to the use of two references that should not have been included. The authors, along with a large number of contributors, agree with this retraction. The publisher, Springer Nature, remains neutral in regards to jurisdictional claims and institutional affiliations. The full list of authors is provided in the document. [Extracted from the article]

Rationale: Nicotine has been widely studied for its pro-dopaminergic effects. However, at the behavioural level, past investigations have yielded heterogeneous results concerning effects on cognitive, affective, and motor outcomes, possibly linked to individual differences at the level of genetics. A candidate polymorphism is the 40-base-pair variable number of tandem repeats polymorphism (rs28363170) in the SLC6A3 gene coding for the dopamine transporter (DAT). The polymorphism has been associated with striatal DAT availability (9R-carriers > 10R-homozygotes), and 9R-carriers have been shown to react more strongly to dopamine agonistic pharmacological challenges than 10R-homozygotes. Objectives: In this preregistered study, we hypothesized that 9R-carriers would be more responsive to nicotine due to genotype-related differences in DAT availability and resulting dopamine activity. Methods: N=194 non-smokers were grouped according to their genotype (9R-carriers, 10R-homozygotes) and received either 2-mg nicotine or placebo gum in a between-subject design. Spontaneous blink rate (SBR) was obtained as an indirect measure of striatal dopamine activity and smooth pursuit, stop signal, simple choice and affective processing tasks were carried out in randomized order. Results: Reaction times were decreased under nicotine compared to placebo in the simple choice and stop signal tasks, but nicotine and genotype had no effects on any of the other task outcomes. Conditional process analyses testing the mediating effect of SBR on performance and how this is affected by genotype yielded no significant results. Conclusions: Overall, we could not confirm our main hypothesis. Individual differences in nicotine response could not be explained by rs28363170 genotype. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Although research on goal-directed, proactive inhibitory control (IC) and stimulus-driven, reactive IC is growing, no previous study has compared proactive IC in conditions of uncertainty with regard to upcoming inhibition to conditions of certain upcoming IC. Therefore, we investigated effects of certainty and uncertainty on behavior and blood oxygen level dependent (BOLD) signal in proactive and reactive IC. In two studies, healthy adults performed saccadic go/no-go and prosaccade/antisaccade tasks. The certainty manipulation had a highly significant behavioral effect in both studies, with inhibitory control being more successful under certain than uncertain conditions on both tasks (p ≤ 0.001). Saccadic go responses were significantly less efficient under conditions of uncertainty than certain responding (p < 0.001). Event-related functional magnetic resonance imaging (fMRI) (one study) revealed a dissociation of certainty- and uncertainty-related proactive inhibitory neural correlates in the go/no-go task, with lateral and medial prefrontal and occipital cortex showing stronger deactivations during uncertainty than during certain upcoming inhibition, and lateral parietal cortex being activated more strongly during certain upcoming inhibition than uncertainty or certain upcoming responding. In the antisaccade task, proactive BOLD effects arose due to stronger deactivations in uncertain response conditions of both tasks and before certain prosaccades than antisaccades. Reactive inhibition-related BOLD increases occurred in inferior parietal cortex and supramarginal gyrus (SMG) in the go/no-go task only. Proactive IC may imply focusing attention on the external environment for encoding salient or alerting events as well as inhibitory mechanisms that reduce potentially distracting neural processes. SMG and inferior parietal cortex may play an important role in both proactive and reactive IC of saccades. [ABSTRACT FROM AUTHOR]

Saccadic eye movements are well-described markers of cerebral function and have been widely studied in schizophrenia spectrum populations. However, less is known about saccades in individuals clinically at risk for schizophrenia. Therefore, we studied individuals in an at-risk mental state (ARMS) (N = 160), patients in their first episode of schizophrenia (N = 32) and healthy controls (N = 75). N = 88 ARMS participants showed an early at-risk mental state (E-ARMS), defined by cognitive-perceptive basic symptoms (COPER) or a combination of risk and loss of function, whereas N = 72 were in a late at-risk mental state (L-ARMS), defined by attenuated psychotic symptoms or brief limited intermittent psychotic symptoms. We examined prosaccades, reflecting overt attentional shifts, and antisaccades, measuring inhibitory control, as well as their relationship as an indicator of the interplay of bottom–up and top–down influences. L-ARMS but not E-ARMS participants had increased antisaccade latencies compared to controls. First-episode patients had higher antisaccade error rates compared to E-ARMS participants and controls, and increased latencies compared to all other groups. Prosaccade latencies did not differ between groups. We observed the expected negative correlation between prosaccade latency and antisaccade error rate, indicating that individuals with shorter prosaccade latencies made more antisaccade errors. The magnitude of the association did not differ between groups. No saccadic measure predicted conversion to psychosis within 2 years. These findings confirm the existence of antisaccade impairments in patients with schizophrenia and provide evidence that volitional response generation in the antisaccade task may be affected even before onset of clinically overt psychosis. [ABSTRACT FROM AUTHOR]

While impairments in executive functions have been well established in major depressive disorder (MDD), specific deficits in proactive control have scarcely been studied so far. Proactive control refers to cognitive processes during anticipation of a behaviorally relevant event that facilitate readiness to react. In this study, cerebral blood flow responses were investigated in MDD patients during a precued antisaccade task requiring preparatory attention and proactive inhibition. Using functional transcranial Doppler sonography, blood flow velocities in the middle cerebral arteries of both hemispheres were recorded in 40 MDD patients and 40 healthy controls. In the task, a target appeared left or right of the fixation point 5 s after a cuing stimulus; subjects had to move their gaze to the target (prosaccade) or its mirror image position (antisaccade). Video-based eye-tracking was applied for ocular recording. A right dominant blood flow increase arose during prosaccade and antisaccade preparation, which was smaller in MDD patients than controls. Patients exhibited a higher error rate than controls for antisaccades but not prosaccades. The smaller blood flow response may reflect blunted anticipatory activation of the dorsolateral prefrontal and inferior parietal cortices in MDD. The patients' increased antisaccade error rate suggests deficient inhibitory control. The findings support the notion of impairments in proactive control in MDD, which are clinically relevant as they may contribute to the deficits in cognition and behavioral regulation that characterize the disorder. [ABSTRACT FROM AUTHOR]

Rationale: The non-selective nicotinic acetylcholine receptor (nAChR) agonist nicotine has been argued to improve attention via enhanced filtering of irrelevant stimuli. Here, we tested this hypothesis in the context of smooth pursuit eye movements (SPEMs), an oculomotor function previously shown to improve with nicotine in some but not all studies. Objectives: In order to test whether nicotine improves performance particularly when the inhibition of distracting stimuli is required, SPEM was elicited in conditions with or without peripheral distractors. Additionally, different target frequencies were employed in order to parametrically vary general processing demands on the SPEM system. Methods: Healthy adult non-smokers (N = 18 females, N = 13 males) completed a horizontal sinusoidal SPEM task at different target frequencies (0.2 Hz, 0.4 Hz, 0.6 Hz) in the presence or absence of peripheral distractors in a double-blind, placebo-controlled, cross-over design using a 2 mg nicotine gum. Results: Nicotine increased peak pursuit gain relative to placebo (p <.001), but an interaction with distractor condition (p =.001) indicated that this effect was most pronounced in the presence of distractors. Catch-up saccade frequency was reduced by nicotine (p =.01), particularly at higher target frequencies (two-way interaction, p =.04). However, a three-way interaction (p =.006) indicated that the reduction with nicotine was strongest at the highest target frequency (0.6 Hz) only without distractors, whereas in the presence of distractors, it was strongest at 0.4-Hz target frequency. There were no effects of nicotine on subjective state measures. Conclusions: Together, these findings support a role of both distractor inhibition and general processing load in the effects of nicotine on smooth pursuit. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Relationships of physical resemblance to personality similarity and social affiliation have generated considerable discussion among behavioral science researchers. A “twin-like” experimental design (involving genetically unrelated look-alikes, U-LAs) explores associations among resemblance in appearance, the Big Five personality traits, self-esteem, and social attraction within an evolutionary framework. The Personality for Professionals Inventory (PfPI), NEO/NEO-FFI-3, Rosenberg Self-Esteem Scale, and a Social Relationship Survey were variously completed by 45 U-LA pairs, identified from the “I’m Not a Look-Alike” project, Mentorn Media, and personal referrals. The mean U-LA intraclass correlations were negligible for all Big Five personality traits on the PfPI and NEO/NEO-FFI-3 (ri = −.02 and − .04, respectively). In contrast, mean ri values of.53 and.15 for monozygotic (MZA) and dizygotic (DZA) reared-apart twins, respectively, have been reported for these personality measures. The U-LA self-esteem correlation (ri = −.18) was also below the correlations reported for MZ and DZ reared-together twins (ri =.31 and.13, respectively). Finally, far fewer U-LAs expressed close social relationships (20%) than MZA (80%) and DZA (65%) twins. The present study extends earlier findings indicating that appearance is not meaningfully related to personality similarity and social relatedness. The criticism that MZ twins are alike in personality because their matched looks invite similar treatment by others is refuted. A more judicious interpretation is reactive genotype-environment correlation, namely that MZ twins’ similar personalities evoke similar reactions from others. MZ twins’ close social relations most likely derive from their perceptions of genetically based within-pair similarities that are lacking in U-LAs. [ABSTRACT FROM AUTHOR]

We developed a cued pro- and antisaccade paradigm (CPAP) to explore automatic components of sexual interest. Heterosexual participants (n = 32 women, n = 25 men) had to perform fast eye movements toward and away from sexually relevant or irrelevant stimuli across a congruent (i.e., prosaccade toward sexually relevant stimuli, antisaccade away from sexually irrelevant stimuli) and an incongruent condition (i.e., prosaccade toward sexually irrelevant stimuli, antisaccade away from sexually relevant stimuli). We hypothesized that pro- and antisaccade performance would be influenced by the sexual interest-specific relevance of the presented stimulus (i.e., nude female or male stimulus) and the instructed task (i.e., pro- or antisaccade) and, thus, differ meaningfully between conditions. Results for prosaccades toward sexually relevant stimuli in the congruent condition showed that error rates were lower and latencies were shorter compared with prosaccades toward sexually irrelevant stimuli in the incongruent condition, but only for male participants. In addition, error rates for antisaccades away from sexually irrelevant stimuli in the congruent condition were lower than for antisaccades away from sexually relevant stimuli in the incongruent condition, for both female and male participants. Latencies of antisaccades, however, did not differ between conditions. In comparison with established indirect sexual interest paradigms, the CPAP benefits from measuring highly automated processes less prone to deliberate control. To this end, the CPAP could be applied to explore the interplay of early automatic and deliberate components of sexual information processing. [ABSTRACT FROM AUTHOR]

Nicotine is a cholinergic agonist with known pro-cognitive effects in the domains of alerting and orienting attention. However, its effects on attentional top-down functions such as response inhibition and interference control are less well characterised. Here, we investigated the effects of 7 mg transdermal nicotine on performance on a battery of response inhibition and interference control tasks. A sample of N = 44 healthy adult non-smokers performed antisaccade, stop signal, Stroop, go/no-go, flanker, shape matching and Simon tasks, as well as the attentional network test (ANT) and a continuous performance task (CPT). Nicotine was administered in a within-subjects, double-blind, placebo-controlled design, with order of drug administration counterbalanced. Relative to placebo, nicotine led to significantly shorter reaction times on a prosaccade task and on CPT hits but did not significantly improve inhibitory or interference control performance on any task. Instead, nicotine had a negative influence in increasing the interference effect on the Simon task. Nicotine did not alter inter-individual associations between reaction times on congruent trials and error rates on incongruent trials on any task. Finally, there were effects involving order of drug administration, suggesting practice effects but also beneficial nicotine effects when the compound was administered first. Overall, our findings support previous studies showing positive effects of nicotine on basic attentional functions but do not provide direct evidence for an improvement of top-down cognitive control through acute administration of nicotine at this dose in healthy non-smokers. [ABSTRACT FROM AUTHOR]

Impairment of inhibition-related functions is one of the most pronounced cognitive deficits found in attention-deficit/hyperactivity disorder (ADHD). Compelling evidence from studies of unaffected relatives of patients with ADHD and of ADHD-like traits in healthy subjects suggest the continuous distribution of ADHD symptoms in the population. A more subtle inhibitory deficit can also be found in healthy relatives of patients and in subjects with high ADHD-like traits. Here, we examined the relationship between inhibitory performance and ADHD-like traits, for the first time, in a large sample of healthy adults by applying multiple, widely used tests of inhibition-related functions. ADHD-like traits, in general, were independently predicted by Stroop interference score and, at trend level, by go/no-go commission error rate while controlling for socio-demographic factors, verbal intelligence and neuroticism. Additionally, higher inattentive traits were related to worse Stroop performance at trend level, and higher hyperactive/impulsive traits were significantly associated with more go/no-go commission errors. ADHD-like traits were strongly related to neuroticism. The study shows that individual differences in ADHD-like traits are related to variance in fundamental inhibition-related functions over and above effects of negative affect regulation, but the relationships tend to be small. The results suggest the quasi-dimensionality of ADHD and raise further questions about the relationship between genetic factors and the deficit of inhibition-related functions in the ADHD spectrum. [ABSTRACT FROM AUTHOR]

Rationale: Most cognitive domains show only minimal improvement following typical or atypical antipsychotic treatments in schizophrenia, and some may even worsen. One domain that may worsen is procedural learning, an implicit memory function relying mainly on the integrity of the fronto-striatal system. Objectives: We investigated whether switching to atypical antipsychotics would improve procedural learning and task-related neural activation in patients on typical antipsychotics. Furthermore, we explored the differential effects of the atypical antipsychotics risperidone and olanzapine. Methods: Thirty schizophrenia patients underwent functional magnetic resonance imaging during a 5-min procedural (sequence) learning task on two occasions: at baseline and 7-8 weeks later. Of 30 patients, 10 remained on typical antipsychotics, and 20 were switched randomly in equal numbers to receive either olanzapine (10-20 mg) or risperidone (4-8 mg) for 7-8 weeks. Results: At baseline, patients (all on typical antipsychotics) showed no procedural learning. At follow-up, patients who remained on typical antipsychotics continued to show a lack of procedural learning, whereas those switched to atypical antipsychotics displayed significant procedural learning ( p = 0.001) and increased activation in the superior-middle frontal gyrus, anterior cingulate and striatum (cluster-corrected p < 0.05). These neural effects were present as a linear increase over five successive 30-s blocks of sequenced trials. A switch to either risperidone or olanzapine resulted in comparable performance but with both overlapping and distinct task-related activations. Conclusions: Atypical antipsychotics restore procedural learning deficits and associated neural activity in schizophrenia. Furthermore, different atypical antipsychotics produce idiosyncratic task-related neural activations, and this specificity may contribute to their differential long-term clinical profiles. [ABSTRACT FROM AUTHOR]

We pharmacologically challenged catecholamine reuptake, using methylphenidate, to investigate its effects on brain activity during a motor response inhibition task as a function of the 3′-UTR variable number of tandem repeats (VNTR) polymorphism of the dopamine transporter (DAT) gene (SLC6A3) and the availability of DATs in the striatum. We measured the cerebral hemodynamic response of 50 healthy males during a Go/No-Go task, a measure of cognitive control, under the influence of 40 mg methylphenidate and placebo using 3T functional magnetic resonance imaging. Subjects were grouped into 9-repeat (9R) carriers and 10/10 homozygotes on the basis of the SLC6A3 VNTR. During successful no-go trials compared with oddball trials, methylphenidate induced an increase of blood oxygen level-dependent (BOLD) signal for carriers of the SLC6A3 9R allele but a decrease in 10/10 homozygotes in a thalamocortical network. The same pattern was observed in caudate and inferior frontal gyrus when successful no-go trials were compared with successful go trials. We additionally investigated in a subset of 35 participants whether baseline striatal DAT availability, ascertained with 123I-FP-CIT single photon emission computed tomography, predicted the amount of methylphenidate-induced change in hemodynamic response or behavior. Striatal DAT availability was nominally greater in 9R carriers compared with 10/10 homozygotes (d=0.40), in line with meta-analyses, but did not predict BOLD or behavioral changes following MPH administration. We conclude that the effects of acute MPH administration on brain activation are dependent on DAT genotype, with 9R carriers showing enhanced BOLD following administration of a prodopaminergic compound. [ABSTRACT FROM AUTHOR]

Rationale: Prepulse inhibition (PPI) of the acoustic startle response, a measure of sensorimotor gating, can be enhanced by nicotine. Moreover, the TT genotype of the nicotinic acetylcholine receptor (nAChR) α3-subunit ( CHRNA3) rs1051730 polymorphism has previously been associated with diminished PPI and nicotine dependence. Objectives: We tested whether this CHRNA3 polymorphism also modulates the nicotine-induced enhancement of PPI. Methods: We assessed the effect of nicotine on PPI, startle reactivity, and habituation in 52 healthy nonsmoking volunteers genotyped for CHRNA3 rs1051730 in a double-blind, placebo-controlled, counterbalanced, within-subjects design. Additionally, cotinine plasma levels were measured. Results: Nicotine significantly enhanced PPI in TT homozygotes only and tended to worsen PPI in TC and CC carriers. Additionally, nicotine significantly reduced startle habituation. Conclusions: The present findings imply that the effect of nicotine on sensorimotor gating is modulated by nAChR α3-subunits. Thus, genetic variation in nicotinic receptor genes might be an important connecting link between early attentional processes and smoking behavior. [ABSTRACT FROM AUTHOR]

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, )). 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rationale: Nicotinergic agents are currently examined as possible pro-cognitive drugs for a variety of clinical conditions marked by cognitive deficits, such as attention deficit hyperactivity disorder (ADHD) or schizophrenia. The response to acute nicotine is heterogeneous across subjects and samples; however, only a few reliable predictors of response have been identified. Objectives: We tested the hypothesis that baseline performance level in cognitive control may be a predictor of the cognitive effects of nicotine. Methods: We tested 28 healthy Caucasian, male, non-smoking volunteers with the antisaccade task, an oculomotor measure of cognitive control. Participants were given a 7-mg nicotine patch in a double-blind, placebo-controlled, counterbalanced, within-subjects design. Subjects were stratified into high and low performers based on their antisaccade error rate in the placebo condition (median split). Results: Nicotine tended to reduce response time variability of prosaccade latency ( p = 0.06). There was no main effect of nicotine on antisaccade error rate ( p = 0.31). However, nicotine significantly reduced antisaccade error rate in the low-accuracy probands while leaving performance of the high-accuracy probands unaffected (interaction, p < 0.05). Furthermore, we found a nicotine-induced reduction of response time variability of antisaccade latency at one target location in the low-performing group (interaction, p < 0.05). Conclusions: The present results demonstrate the importance of baseline performance differences for the effectiveness of pharmacological enhancement of cognitive control. More generally, the results suggest that stimulation of the nicotinic acetylcholine receptor system might be an effective way of improving cognition in people with poor cognitive performance, such as patients with ADHD or schizophrenia. [ABSTRACT FROM AUTHOR]

Rationale: Working memory dysfunction is frequently observed in schizophrenia. The neural mechanisms underlying this dysfunction remain unclear, with functional neuroimaging studies reporting increased, decreased or unchanged activation compared to controls. Objectives: We investigated the neural correlates of spatial working memory in schizophrenia with particular consideration of effects of antipsychotic treatment and relation to performance levels in the patient group. Method: We used functional magnetic resonance imaging and studied the blood-oxygen-level-dependent (BOLD) response of 45 schizophrenia outpatients and 19 healthy controls during a parametric spatial n-back task. Results: Performance in both groups deteriorated with increasing memory load (0-back, 1-back, 2-back), but the two groups did not significantly differ in performance overall or as a function of load. Patients produced stronger BOLD signal in occipital and lateral prefrontal cortex during task performance than controls. This difference increased with increasing working memory load in the prefrontal areas. We also found that in patients with good task performance, the BOLD response in left prefrontal cortex showed a stronger parametric increase with working memory load than in patients with poor performance. Second-generation antipsychotics were independently associated with left prefrontal BOLD increase in response to working memory load, whereas first-generation antipsychotics were associated with BOLD decrease with increasing load in this area. Conclusions: Together, these findings suggest that in schizophrenia patients, normal working memory task performance may be achieved through compensatory neural activity, especially in well-performing patients and in those treated with second-generation antipsychotics. [ABSTRACT FROM AUTHOR]

Attentional gating deficits, commonly measured by prepulse inhibition (PPI) of the acoustic startle response (ASR), have been established as an endophenotype of schizophrenia. Prepulse inhibition is heritable and has been associated with polymorphisms in serotonin and dopamine system genes. Prepulse inhibition can be enhanced by nicotine, and therefore it has been proposed that schizophrenia patients smoke to ameliorate their early attentional deficits. The PPI-enhancing effects of nicotine in rodents are strain dependent, suggesting a genetic contribution to PPI within the nicotinic acetylcholine receptor (nAChR) system. Recent human genetic studies also imply that tobacco dependence is affected by polymorphisms in the α3/α5 subunits of the nAChR (CHRNA3/CHRNA5) gene cluster. We, therefore, investigated the impact of two common CHRNA3 polymorphisms (rs1051730/rs1317286) on PPI, startle reactivity, and habituation of the ASR in two independent samples of 107 healthy British volunteers and 73 schizophrenia patients hailing from Germany. In both samples, PPI was influenced by both CHRNA3 polymorphisms (combined p-value=0.0027), which were strongly linked. Moreover, CHRNA3 genotype was associated with chronicity, treatment, and negative symptoms in the schizophrenia sample. These results suggest that sensorimotor gating is influenced by variations of the CHRNA3 gene, which might also have an impact on the course and severity of schizophrenia. [ABSTRACT FROM AUTHOR]

Neuregulin-1 (NRG-1) is a putative susceptibility gene for schizophrenia but the neurocognitive processes that may involve NRG-1 in schizophrenia are unknown. Deficits in antisaccade (AS) and smooth pursuit eye movements (SPEM) are promising endophenotypes, which may be associated with brain dysfunctions underlying the pathophysiology of schizophrenia. The aim of this study was to investigate the associations of NRG-1 genotypes with AS and SPEM in schizophrenia patients and healthy controls . Patients ( N = 113) and controls ( N = 106) were genotyped for two NRG-1 single nucleotide polymorphisms (SNPs); SNP8NRG222662, a surrogate marker for the originally described Icelandic NRG-1 risk haplotype, and SNP8NRG243177, which has recently been associated with individual differences in brain function. Subjects underwent infrared oculographic assessment of AS and SPEM. The study replicates previous findings of impaired AS and SPEM performance in schizophrenia patients (all P < 0.005; all d = 0.5–1.5). SNP8NRG243177 risk allele carriers had marginally increased variability of AS spatial error ( P = 0.050, d = 0.3), but there were no significant genotype effects on other eye movement variables and no significant diagnosis-by-genotype interactions. Generally, risk allele carriers (G allele for SNP8NRG222662 and T allele for SNP8NRG243177) had numerically worse performance than non-carriers on most AS and SPEM variables. The results do not suggest that NRG-1 genotype significantly affects AS and SPEM task performance. However, the power of the sample to identify small effects is limited and the possibility of a type II error must be kept in mind. Larger samples may be needed to reliably investigate such gene effects on oculomotor endophenotypes. [ABSTRACT FROM AUTHOR]

The catechol-O-methyltransferase (COMT) val158met single nucleotide polymorphism (rs4680) has been shown to be associated with brain activation during a number of neurocognitive and emotional tasks. The present study evaluated genotypic associations with brain function during measurement of cognitive stability (prosaccades) and plasticity (antisaccades). A total of 36 healthy volunteers were genotyped for rs4680 and underwent functional magnetic resonance imaging (fMRI) at 1.5 T. Individuals with at least one val158 allele (val158 carriers, N=24) showed lower blood oxygen level-dependent (BOLD) response in ventromedial and dorsomedial prefrontal cortex during antisaccades compared to val158 noncarriers, whereas met158 homozygotes (N=12) showed lower BOLD response in a cluster in the posterior cingulate and precuneus during prosaccades compared to val158 carriers. These findings suggest that associations of COMT val158met genotype with brain function may be mediated by task characteristics. The findings may be compatible with a hypothesis on the role of COMT val158met genotype in tonic and phasic dopamine levels in brain and differential effects on cognitive measures of stability (eg prosaccades) and plasticity (eg antisaccades).Neuropsychopharmacology (2008) 33, 3046–3057; doi:10.1038/sj.npp.1301658; published online 30 January 2008 [ABSTRACT FROM AUTHOR]

Deficits in antisaccade (AS) and smooth pursuit eye movements (SPEM) are promising endophenotypes in genetic studies of schizophrenia. The Icelandic population lends itself ideally to genetic studies due to its ethnic homogeneity and well-documented genealogy. The primary aim of this study was to assess AS and SPEM performance in a large Icelandic sample. Additional aims were to investigate the relationship between AS and SPEM task performance and to assess internal consistency, within-session performance changes and effects of SPEM target velocity on performance. Patients with schizophrenia ( N = 118) and healthy controls ( N = 109) matched for age and gender underwent infrared oculographic assessment of AS and SPEM (at target velocities of 12°, 24° and 36°/s). On the AS task patients displayed significantly more reflexive errors, longer latency, increased intra-individual latency variability, and reduced amplitude gain compared to controls. On the SPEM task, patients had significantly lower velocity gain and more frequent saccades during pursuit at all velocities, but group differences in velocity gain increased with increasing target velocity. Internal consistency of performance was high for all variables in both groups (Cronbach’s alpha >0.77 for AS and >0.85 for SPEM) except for AS spatial error in patients (alpha = 0.38). A moderate association was found between AS and SPEM performance. By and large, patients and controls showed similar patterns of systematic within-session performance changes. Our findings confirm the existence of robust eye movement deficits in schizophrenia in a large sample. These measures may be studied as endophenotypes in future studies of potential schizophrenia risk genotypes in the genetically homogenous Icelandic population. [ABSTRACT FROM AUTHOR]

Event-related potentials (ERPs) have been suggested as possible endophenotypes of schizophrenia. We investigated the test–retest reliabilities and heritabilities of three ERP components in healthy monozygotic and dizygotic twin pairs. ERP components (P300, P50 and MMN) were recorded using a 19-channel electroencephalogram (EEG) in 40 healthy monozygotic twin pairs, 19 of them on two separate occasions, and 30 dizygotic twin pairs. Zygosity was determined using DNA genotyping. High reliabilities were found for the P300 amplitude and its latency, MMN amplitude, and P50 suppression ratio components. Intra-class correlation (ICC) = 0.86 and 0.88 for the P300 amplitude and P300 latency respectively. Reliability of MMN peak amplitude and mean amplitude were 0.67 and 0.66 respectively. P50 T/C ratio reliability was 0.66. Model fitting analyses indicated a substantial heritability or familial component of variance for these ERP measures. Heritability estimates were 63 and 68% for MMN peak amplitude and mean amplitude respectively. For P50 T/C ratio, 68% heritability was estimated. P300 amplitude heritability was estimated at 69%, and while a significant familiality effect was found for P300 latency there was insufficient power to distinguish between shared environment and genetic factors. The high reliability and heritability of the P300 amplitude, MMN amplitude, and P50 suppression ratio components supports their use as candidate endophenotypes for psychiatric research. [ABSTRACT FROM AUTHOR]

Smooth pursuit eye movement (SPEM) and antisaccade deficits are observed in the schizophrenia spectrum and have been used to study the pathophysiology as well as the genetic basis of this condition. The neurotransmitter acetylcholine has been implicated in a number of cognitive processes thought to underlie SPEM and antisaccade performance. This study investigates effects on eye movements of procyclidine, an anticholinergic drug often administered to schizophrenic patients. A total of 13 patients completed a double-blind placebo-controlled crossover design, receiving 15 mg procyclidine and placebo. Seven participants received procyclidine first and placebo second, six participants were tested in the reverse order. SPEM and antisaccade (as well as fixation and prosaccade) eye movements were recorded using infrared oculography. Results showed that procyclidine overall, relative to placebo, mildly worsened SPEM performance, as indicated by nonsignificantly reduced gain (p=0.08) and increased frequency of intrusive anticipatory saccades during pursuit (p=0.06). A significant interaction of group and order of administration indicated that procyclidine increased the rate of antisaccade reflexive errors only when administered first; the opposite pattern was observed when placebo was administered first, likely due to the operation of practice effects at second assessment. These findings indicate that acute administration of a clinically relevant dose of procyclidine leads to mild impairments in eye movement performance in schizophrenic patients, suggesting the need to consider this compound in oculomotor studies in schizophrenia. The action of this anticholinergic drug on oculomotor performance is consistent with the hypothesized role of the cholinergic system in the cognitive mechanisms of attention and working memory, processes thought to underlie SPEM and antisaccade performance. Effects of order of administration and practice on the antisaccade task suggest that these factors need to be taken into consideration in future pharmacological studies. [ABSTRACT FROM AUTHOR]

A guideline is proposed that comprises the minimum items to be reported in research studies involving an eye tracker and human or non-human primate participant(s). This guideline was developed over a 3-year period using a consensus-based process via an open invitation to the international eye tracking community. This guideline will be reviewed at maximum intervals of 4 years. [ABSTRACT FROM AUTHOR]

There is increasing recognition of 'higher preference for eveningness' as a potential independent risk factor for poor mental health. To examine the chronotype-mental health relationship while also quantifying the potential roles of poor sleep quality, relevant personality traits, and childhood trauma, we assessed 282 young adults (18-40 years; 195 females) residing in North India, between January and March 2023 (to control for seasonal variation), using self-report measures of diurnal preference, sleep patterns, mental health (depression, anxiety, and stress), personality traits (extraversion, neuroticism, schizotypy, and impulsivity), and childhood trauma. The results showed a significant association between eveningness and poor mental health but this association was fully mediated by poor sleep quality. Neuroticism, emotional abuse and cognitive disorganisation were correlated with eveningness as well as with poor mental health and sleep quality. Neuroticism and emotional abuse, but not cognitive disorganisation, also had indirect effects on mental health via sleep quality. Our findings highlight the crucial role played by sleep quality in the chronotype-mental health relationship., (© 2024. The Author(s).)

Temporal discounting (TD), the tendency to devalue future rewards as a function of delay until receipt, is aberrant in many mental disorders. Identifying symptom patterns and transdiagnostic dimensions associated with TD could elucidate mechanisms responsible for clinically impaired decision-making and facilitate identifying intervention targets. Here, we tested in a general population sample (N = 731) the extent to which TD was related to different symptom patterns and whether effects of time framing (dates/delay units) and monetary magnitude (large/small) had particularly strong effects in people scoring higher on specific symptom patterns. Analyses revealed that TD was related to symptom patterns loading on anxious-depression and inattention-impulsivity-overactivity dimensions. Moreover, TD was lower in the date than the delay version and with higher magnitudes, especially in people scoring higher on the inattention-impulsivity-overactivity dimension. Overall, this study provides evidence for TD as a transdiagnostic process across affective and impulsivity-related dimensions. Future studies should test framing interventions in clinical populations characterized by impulsivity.Preregistration: This research was preregistered at https://osf.io/fg9sc ., (© 2024. The Author(s).)