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The pineal gland (PG) is a small interhemispheric brain structure that influences human physiology in many ways, most importantly via secretion of the hormone melatonin which is known to regulate sleep and wakefulness. Here, we systematically reviewed existing neuroimaging studies of PG structure, and/or melatonin release (MLT) in psychosis and mood disorders. Medline, PubMed, and Web of Science databases were searched (on 3 February 2023), yielding 36 studies (8 PG volume, 24 MLT). The findings showed smaller-than-normal PG volume in people with schizophrenia, regardless of symptom severity and illness stage; and smaller-than-normal PG volume in major depression, with some indication of this being present only in certain subgroups, or in those with high scores on the 'loss of interest' symptom. There was considerable evidence of lower-than-normal MLT as well as aberrant MLT secretion pattern in schizophrenia. A similar picture, though less consistent than that seen in schizophrenia, emerged in major depression and bipolar disorder, with some evidence of a transient lowering of MLT following the initiation of certain antidepressants in drug-withdrawn patients. Overall, PG and MLT aberrations appear to represent transdiagnostic biomarkers for psychosis and mood disorders, but further work is needed to establish their clinical correlates and treatment implications. [ABSTRACT FROM AUTHOR]

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]

In recent years there has been a surge of interest and corresponding accumulation of knowledge about the role of sleep disturbance in schizophrenia. In this review, we provide an update on the current status of experimentally controlled sleep deprivation (SD) as an experimental medicine model of psychosis, and also consider, given the complexity and heterogeneity of schizophrenia, whether this (state) model can be usefully combined with other state or trait model systems to more powerfully model the pathophysiology of psychosis. We present evidence of dose-dependent aberrations that qualitatively resemble positive, negative and cognitive symptoms of schizophrenia as well as deficits in a range of translational biomarkers for schizophrenia, including prepulse inhibition, smooth pursuit and antisaccades, following experimentally controlled SD, relative to standard sleep, in healthy volunteers. Studies examining the combination of SD and schizotypy, a trait model of schizophrenia, revealed only occasional, task-dependent superiority of the combination model, relative to either of the two models alone. Overall, we argue that experimentally controlled SD is a valuable experimental medicine model of schizophrenia to advance our understanding of the pathophysiology of the clinical disorder and discovery of more effective or novel treatments. Future studies are needed to test its utility in combination with other, especially state, model systems of psychosis such as ketamine. [ABSTRACT FROM AUTHOR]

Background: Both chronic cannabis use and psychotic disorders are associated with abnormalities in visual attentional processing. Using functional magnetic resonance imaging (fMRI), we sought to determine whether there would be a difference in functional connectivity in patients and controls with and without a history of cannabis use in the visual and dorsal attention networks. Methods: Restingstate fMRI data were acquired in patients with early psychosis with (EPC = 29) and without (EPNC = 25); and controls with (HCC = 16) and without (HCNC = 22) cannabis use. Results: There was a patient effect in both Visual- Dorsal Attention Internetwork (F(1,87) = 5.326, P = .023) and the Visual Network (F(1,87) = 4.044, P = .047) and a cannabis effect in the Dorsal Attention Network (F(1,87) = 4.773, P = .032). These effects were specific to the networks examined with no evidence for significant patient or cannabis effects in other canonical networks. Patients with a history of cannabis use showed increased connectivity in the Dorsal Attention Network (134%, P = .019) and Visual Dorsal Attention Internetwork (285%, P = .036) compared to non-using controls. In the EPC group connectivity of the Visual Network (ρ = 0.379, P = .042) and Visual-Dorsal Attention Internetwork (ρ = 0.421, P = .023) correlated with visual hallucinations which were significantly different from EPNC (P = .011). Dorsal attention network strength correlated with severity of dependence for cannabis (ρ = 0.215, P = .04). Conclusion: We demonstrate specific cannabis and patient effects in networks associated with visual attentional processing. There is a differential association with hallucinatory symptoms in patients with and without a history of cannabis use. This may indicate that dysconnectivity in these networks serves different roles in the context of cannabis use. [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]

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. [ABSTRACT FROM AUTHOR]

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, n519 controls and n517 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. [ABSTRACT FROM AUTHOR]

Current antipsychotic medications fail to satisfactorily reduce negative and cognitive symptoms and produce many unwanted side effects, necessitating the development of new compounds. Cross-species, experimental behavioural model systems can be valuable to inform the development of such drugs. The aim of the current study was to further test the hypothesis that controlled sleep deprivation is a safe and effective model system for psychosis when combined with oculomotor biomarkers of schizophrenia. Using a randomized counterbalanced within-subjects design, we investigated the effects of 1 night of total sleep deprivation in 32 healthy participants on smooth pursuit eye movements (SPEM), prosaccades (PS), antisaccades (AS), and self-ratings of psychosis-like states. Compared with a normal sleep control night, sleep deprivation was associated with reduced SPEM velocity gain, higher saccadic frequency at 0.2 Hz, elevated PS spatial error, and an increase in AS direction errors. Sleep deprivation also increased intra-individual variability of SPEM, PS, and AS measures. In addition, sleep deprivation induced psychosis-like experiences mimicking hallucinations, cognitive disorganization, and negative symptoms, which in turn had moderate associations with AS direction errors. Taken together, sleep deprivation resulted in psychosis-like impairments in SPEM and AS performance. However, diverging somewhat from the schizophrenia literature, sleep deprivation additionally disrupted PS control. Sleep deprivation thus represents a promising but possibly unspecific experimental model that may be helpful to further improve our understanding of the underlying mechanisms in the pathophysiology of psychosis and aid the development of antipsychotic and pro-cognitive drugs. [ABSTRACT FROM AUTHOR]

Translational biomarkers, such as prepulse inhibition (PPI) of the acoustic startle response, are playing an increasingly important role in the development of antipsychotic drugs for schizophrenia and related conditions. However, attempts to reliably induce a PPI deficit by psychotomimetic drugs have not been successful, leaving an unmet need for a cross-species psychosis model sensitive to this widely studied surrogate treatment target. Sleep deprivation (SD) might be such a model as it has previously been shown to induce PPI deficits in rats, which could be selectively prevented with antipsychotic but not anxiolytic or antidepressant compounds. Here, in a first proof-of-concept study we tested whether SD induces a deficit in PPI and an increase in psychosis-like symptoms in healthy humans. In two counterbalanced sessions, acoustic PPI and self-reported psychosis-like symptoms (Psychotomimetic States Inventory) were measured in 24 healthy human volunteers after a normal night's sleep and after a night of total SD. SD decreased PPI (p = 0.001) without affecting the magnitude or habituation of the startle response (all p > 0.13). SD also induced perceptual distortions, cognitive disorganization, and anhedonia (all p < 0.02). Thus, extending previous rodent work, we conclude that SD, in combination with the PPI biomarker, might be a promising translational surrogate model for psychosis as this method represents a possibility to partially and reversibly mimic the pathogenesis of psychotic states. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: There is strong evidence for significant contributions of genetic factors to the risk of schizophrenia. In the past 10 years, studies employing linkage and association approaches have identified multiple putative schizophrenia risk genes. For most of these, the evidence for association with schizophrenia remains weak and attempts of replication not always successful nor easy to interpret. Aim: To give an overview of new developments in genetic research of schizophrenia. Methods: The present literature on schizophrenia genetics was reviewed with special emphasis on new developments such as genome-wide association studies (GWAS), associations of copy number variations (CNVs) with schizophrenia and the role of endophenotypes in genetic research. Results: The first GWAS of schizophrenia have identified new putative candidate risk genes and opened avenues for investigating how multiple genes may act in functional biological pathways forming the genetic basis of schizophrenia and other complex diseases. There is growing evidence that rare de novo CNVs as well as some inherited CNVs contribute to the susceptibility to several neuropsychiatric disorders including schizophrenia. Schizophrenia endophenotypes, which possibly better represent biological phenomena than the complex clinical phenotype, are turning out to be helpful for investigating neurobiological pathways of putative risk genes. Conclusions: Recent studies suggest that individual common gene variants make relatively small contributions to risk of schizophrenia but some rare CNVs may be associated with much higher risk when present. Future studies employing new technologies for identifying common and rare risk markers are likely to deepen our understanding of the genetic architecture of schizophrenia. [ABSTRACT FROM AUTHOR]

The article presents a meta-analysis, database, and meta-regression of 98 structural imaging studies in bipolar disorder. This research aims to employ meta-analytical techniques to study structural brain changes in bipolar disorder and to evaluate the effect of medication use and demographic and clinical variables. Findings indicate that meta-analyses illustrated robust but regionally nonspecific alternations of brain structure in bipolar disorder. It also mentions that the provision of online databases may effect a more refined design and analysis of structural imaging data sets in bipolar disorder.

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]

The article examines the volume of the thalamus and the presence of the adhesio interthalamica in monozygotic twins with or without schizophrenia by means of magnetic resonance imaging. Results reveal that volumetric thalamic abnormalities in schizophrenia occur in twin pairs concordant for schizophrenia. These abnormalities may mark the genetic contribution to the illness seen in concordant twin pairs, while the adhesio interthalamica is unlikely to be affected by schizophrenia.

We investigated whether prepulse inhibition of the startle response is reduced in siblings of schizophrenia patients compared to age- and sex-matched healthy controls. Nineteen unaffected biological siblings and 19 controls were assessed on prepulse inhibition by monaural and binaural acoustic prepulse stimuli, with the startle stimuli always presented binaurally. There was significantly less prepulse inhibition in siblings, compared to controls, with binaural prepulse stimuli, as also seen previously in schizophrenia patients. The difference between siblings and controls in prepulse inhibition with the left or right ear prepulse stimuli was not significant because of a pronounced increase in prepulse inhibition with monaural, relative to binaural, prepulses in the sibling group. High schizotypal ratings were mildly associated with reduced prepulse inhibition. Prepulse inhibition may provide a useful measure in the search for schizophrenia genes. [ABSTRACT FROM AUTHOR]

Abstract: Individuals with schizophrenia, compared to healthy individuals, are known to exhibit deficient prepulse inhibition (PPI) of the startle response as well as reduced performance on the antisaccade task. There is evidence for genetic transmission of both PPI and antisaccadic abnormalities in schizophrenia. It has been suggested that PPI and antisaccade measures identify separate endophenotypes, on the basis of a lack of relationship between PPI and antisaccade deficits in patients with schizotypal personality disorder. However, given that patients with schizotypal personality disorder are unlikely to manifest all the abnormalities associated with schizophrenia, it is important to determine that there is no relationship present between these two abnormalities in people affected with schizophrenia. The main objective of this investigation therefore was to establish the lack of the association between PPI and antisaccade deficits in schizophrenia in two independent studies. Study 1 involved 39 patients with schizophrenia and 14 healthy controls and study 2 involved 35 patients with schizophrenia and 22 healthy controls. PPI (uninstructed paradigm) of the acoustically elicited startle (eye blink) was measured electromyographically. Antisaccadic eye movements (standard, non-overlap version) were measured using infrared oculography. Patients displayed reduced PPI and a lower percentage of correct antisaccades relative to healthy controls in both studies. As expected, no relationship occurred between PPI and the percentage of correct antisaccade responses in either group. It is concluded that PPI and antisaccade abnormalities in schizophrenia represent separate endophenotypes, reflecting the functions of different genetic aetiologies and different or only partially overlapping neural systems. [Copyright &y& Elsevier]

Objective: The authors investigated the structural brain correlates of antisaccade performance. Method: Magnetic resonance imaging was used to measure the volumes of the prefrontal, premotor, sensorimotor and occipitoparietal cortices as well as the caudate, thalamus, cerebellar vermis, and cerebrum in 20 first-episode Psychosis patients and 18 healthy comparison subjects, Antisaccades were recorded by using infrared oculography. Results: Groups significantly differed in terms of antisaccade error rate and amplitude gain and tended to differ in terms of latency but not brain region volumes. Premotor cortex volume predicted antisaccade error rate among comparison subjects, in the patient group, caudate volume was related to latency and amplitude gain, Negative symptoms, independent of structural volumes, predicted error rate. Conclusions: These findings point to altered structure-function relationships in first-episode psychosis. [ABSTRACT FROM AUTHOR]

Background Oculomotor abnormalities are among the most widely replicated findings in psychotic disorders with impairments in Smooth Pursuit Eye Movements (SPEM) and Antisaccades (AS) tasks. Cannabis-use may be a clinically relevant demarcating factor in early psychosis seen in around half of FEP patients at presentation and indicative of worse prognosis. No study to date has aimed at differentiating cannabis-using from non-using patients using AS and SPEM. Differences in eye movement measures between groups would indicate altered neurobiology between cannabis-using and non-using patients. We thus aimed to determine whether abnormalities in SPEM and AS are indicative of neurobiological differences between Early Psychosis patients who use cannabis (EPC) and those who do not use cannabis (EPNC). Methods We undertook the EfCiP study (the Effect of Cannabis in Psychosis) consisting of four groups: Early Psychosis patients who used cannabis (EPC) (n=28), Early Psychosis patients who did not use cannabis (EPNC) (n=25), healthy controls who used cannabis (HCC) (n=16) and healthy controls who did not use cannabis (HCNC) (n=22). The smooth pursuit stimulus used a sinusoidal waveform at three target frequencies (0.2, 0.4 and 0.6 Hz) across a horizontal range. Participants performed 40 antisaccade trials using a horizontal step task with an equal number of left and right stimuli in randomised order. As primary outcomes we tested measures robustly associated with abnormalities in psychosis: maintenance gain to index smooth pursuit and antisaccade percentage errors. We used one-way ANCOVA on four levels (EPC, EPNC, HCC and HCNC) with post-hoc Bonferroni correction. Covariates entered into the model were age, sex, AUDIT and Fagerstrom's scores. Results EPC and EPNC were clinically indistinguishable with no difference across clinical measures: including GAF, PANSS, duration since diagnosis, days spent in hospital, chlorpromazine equivalents, proportion with affective component to psychosis or schizophreniform spectrum disorder. Participants with EPC had higher indices of cannabis use and also scored higher on Fagerstrom's and AUDIT scores to index smoking and alcohol use respectively. Repeated measures ANCOVA revealed a significant effect of task, indicating that mean gain decreased as SPEM frequency increased. There was a significant Group effect (F3,83=3.514, p=0.019, ηp2=0.113). Post-hoc tests revealed significantly reduced mean gain for EPNC vs EPC (p=0.021). There was no significant difference between HCC and HCNC (p=1). There was no significant effect on SPEM gain for any covariate. When controls were combined there was a significant reduction in SPEM gain for EPNC vs EPC (Hedge's g=0.830, p=0.014) and trend level reduced gain for EPNC vs all controls (Hedge's g=0.594, p=0.058) but no difference between EPC and all controls (p=0.998) There was a numerical decrease in antisaccades percentage error rate such that EPC≈EPNC>HCC>HCNC but there was no significant group effect (p>0.35). Discussion This study demonstrates neurobiological distinction between cannabis using and non-using patients. There is evidence of impairment of SPEM in the EPNC group but not in the EPC group, whereas there is no discernable effect of cannabis use on SPEM gain in the healthy situation. This is consistent with lower psychosis liability in EPC than EPNC and suggests an additive component for cannabis use in the EPC group. Differential performance in SPEM and AS may indicate impairments in specific circuitry between groups. Further work should look to delineate the neurobiological substrates for this distinction. [ABSTRACT FROM AUTHOR]

Background: Cortical neuroanatomical abnormalities have been reported along a continuum between individuals with chronic schizophrenia, first-episode psychosis, clinical high risk for psychosis, and healthy individuals self-reporting subclinical psychotic-like experiences (or schizotypy). Recently, the Schizophrenia Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium provided meta-analytic evidence for robust cortical thickness abnormalities in schizophrenia, while also indicating that these abnormalities are influenced by illness severity and treatment with antipsychotic medications. In this context, schizotypy research allows the investigation of cortical neuroanatomy associated with the expression of subclinical psychotic-like symptoms without the potential influence of a psychotic illness, its severity, or the use of antipsychotics. This study presents the first large-scale imaging meta-analysis of cortical thickness in schizotypy using standardized methods from 23 datasets worldwide. Methods: Cortical thickness and surface area were assessed in MRI scans of 2,695 healthy individuals (mean [range] age of 29.1 [17–55.8], 46.3% male) who had also completed validated self-report schizotypy questionnaires. Each site processed their local T1-weighted MRI scans using FreeSurfer and, following the protocol outlined in the ENIGMA Schizophrenia Working Group study, extracted cortical thickness for 70 Desikan-Killiany (DK) atlas regions (34 regions per hemisphere + left and right hemisphere mean thickness). At each site, partial correlation analyses were performed between regional cortical thickness by ROI and total schizotypy scores in R, predicting the left, right and mean cortical thickness, adjusting for sex, age and site. Random-effects meta-analyses of partial correlation effect sizes for each of the DK atlas regions were performed using R’s metafor package. False discovery rate (pFDR < .05) was used to control for multiple comparisons. Results: We found significant positive associations between subclinical psychotic-like experiences and mean cortical thickness of the medial orbitofrontal cortex (r = .077; pFDR = .006) and the frontal pole (r = .073; pFDR = .006). When assessed separately by hemisphere, meta-analysis revealed a significant positive association between subclinical psychotic-like experiences and cortical thickness of the left medial orbitofrontal cortex (r = .066; pFDR = .044), and at trend-level with the right medial orbitofrontal cortex (r = .062; pFDR = .053) and the left frontal pole (r = .062; pFDR = .053). No significant associations were observed for surface area. Discussion: Worldwide cooperative analyses of large-scale brain imaging data support a profile of cortical thickness abnormalities involving prefrontal cortical regions positively related to schizotypy in healthy individuals. These findings are not secondary to potential influences of disease chronicity or antipsychotic medication on the neuroanatomical correlates of psychotic-like experiences. The directionality of the observed meta-analytical effects in schizotypy is opposite to those previously reported in patients with schizophrenia (i.e., thinner cortex). The present findings of increased thickness may indicate early microstructural deficits (e.g. in myelination) that contribute to vulnerability for psychosis. Alternatively, these may reflect mechanisms of resilience associated with the expression of subclinical manifestations of psychotic symptoms in otherwise healthy individuals. [ABSTRACT FROM AUTHOR]

Objective: Deficiency in antisaccade performance has been proposed as a schizophrenia endophenotype. Method: The authors assessed performance on an antisaccade task (and a prosaccade control condition) by 10 monozygotic twin pairs discordant for DSM-IV schizophrenia and 10 monozygotic healthy twin pairs matched for age, sex, and parental socioeconomic status. The authors computed antisaccade gain, latency, and error rate, as well as prosaccade gain and latency. Results: The schizophrenic twins made more antisaccade reflexive errors than the nonschizophrenic co-twins and comparison twins, who did not significantly differ from each other. The nonschizophrenic members of discordant pairs performed worse than the comparison twins on antisaccade gain and latency but did not differ from their schizophrenic co-twins on these variables. There were no differences on prosaccade performance. Antisaccade errors were correlated with negative symptoms in the patients. Conclusions: Antisaccade spatial accuracy and latency deficits may serve as markers of genetic liability for schizophrenia. [ABSTRACT FROM AUTHOR]

Investigates the thalamic volumes in patients with first-episode psychosis through magnetic resonance imaging in London, England. Use of the Positive and Negative Syndrome Scale in rating patients symptoms; Absence of correlation between thalamic volumes and symptom scores; Possible localization of abnormalities to specific nuclei.

Abstract: Disturbances of the oculomotor system are promising endophenotypes for schizophrenia. Increased error rates in the antisaccade task and prolonged antisaccade latencies have been found in patients with schizophrenia and their first degree relatives. We investigated oculomotor performance in 41 parents of schizophrenia patients and 22 controls with a prosaccade task and an antisaccade task. Parents were grouped into parents with a positive family history for schizophrenia (N =9) and parents with a negative family history for schizophrenia (N =32). An overlap-paradigm was applied; eye movements were recorded using infrared oculography. The combined group of parents made more antisaccade direction errors than controls (p =0.005) and there was a linear increase in direction errors from controls via negative family history parents to positive family history parents (p =0.008). Antisaccade latencies were prolonged in the combined parent group (p =0.057) compared to controls and there was a linear increase in latency with genetic loading (p =0.018). No group differences were found for prosaccade parameters. These results support the hypothesis that antisaccade impairment is associated with genetic loading for schizophrenia. [Copyright &y& Elsevier]

Abstract: Background: P300 amplitude reduction is reliably seen in schizophrenia. Inconsistent reports of isolated frontal and/or parietal deficits in unaffected family members may be clarified using a task that places greater load on frontal function. Method: Go and No–Go versions of the auditory oddball task were performed by eighteen schizophrenia patients, age-matched unaffected siblings and healthy controls matched closely to unaffected siblings on age, sex, education, socioeconomic-status, handedness and ethnicity. Groups were compared on P300 and N100 amplitude and latency. Spearman correlations were used to test the relationship between ERP amplitudes and neuropsychological measures of executive function and memory. The relationship between schizotypy – as measured using the structured interview – and ERPs was explored in a combined group of siblings and controls. Results: Independent of task, patients had lower P300 than controls and reduced parietal amplitude compared to siblings. Siblings had enhanced frontocentral N100 compared to controls. No–Go P300 amplitude and N100 latency was associated with executive function measures. There were significant intraclass correlations between patients and siblings for No–Go P300 amplitude, particularly at the central midline electrode. Frontocentral N100 and P300 amplitude were positively correlated with anxiety-related aspects of schizotypy. Conclusion: Enhanced N100 is present in unaffected siblings. Parietal P300 is intact in unaffected siblings, but reduced in patients. The No–Go-oddball is more sensitive than the Go-oddball to executive function deficits in patients and as an index of heritability. [Copyright &y& Elsevier]