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Subconcussive head hits (SHH) are common in contact sport athletes and are predictive of the later development of cognitive and brain changes, including chronic traumatic encephalopathy. In this pilot study we determined whether a history of concussion, and SHH acquired during a single season of college football, were associated with changes on retinal biomarkers of central nervous system (CNS) structure and function. College football players with a history of concussion (FB+C; n=9) or without a concussion history (FB-C; n=11), and non-contact sport collegiate athletes (Track/Swim; n=12) underwent visual and cognitive testing, retinal imaging (optical coherence tomography (OCT) and OCT angiography (OCTA)), and electroretinography (ERG) at three time points: pre-season, post-season and 4-month follow-up. The FB+C group demonstrated thicker maculae and exaggerated ERG waveforms (from all retinal neural cell types) compared to the other groups. These changes were generally observed at all timepoints, suggesting long-term changes associated with concussions, rather than effects of recent football activity. However, we also observed significant relationships between the number of head impacts during the season and stronger ERG responses, degree of macula thickening, enlargement of optic disc parameters, and increases in the density of retinal microvasculature relative to controls. These data suggest that retinal biomarkers are sensitive to both long- and short-term CNS changes related to participation in football, even in young athletes.

A subset of individuals with schizophrenia (SZ) are thought to have a microvascular component to their illness with studies demonstrating alterations in retinal superficial, deep, and choroidal microvasculature networks. However, the direction and location of these alterations have differed across studies. In a recent study, we reported that individuals with SZ demonstrated lower superficial layer perfusion density than a healthy control (HC) group. The current study investigated characteristics of the deep vascular layer in SZ. We included 28 individuals with a diagnosis of SZ or schizoaffective disorder, and 37 HCs. Optical coherence tomography angiography (OCTA) data was collected to measure deep retinal layer perfusion density, skeletonized vessel density, vessel diameter index, and fractal dimension. We conducted between-group comparisons to examine differences in these OCTA variables between SZ and HC groups. A trend analysis was conducted to determine if differences reflected a linear trend according to age and illness length, and Spearman correlations were conducted to determine associations between deep and superficial layer density. Individuals with SZ demonstrated significantly lower bilateral perfusion density and vessel diameter index, as well as lower left eye skeletonized vessel density and fractal dimension. There was a significant linear trend in the data indicating that individuals with chronic SZ demonstrated the lowest OCTA values, followed by individuals within two years of their first episode of psychosis who did not differ from older controls, followed by younger controls, who demonstrated the highest values in at least one eye. Lower density values in the deep retinal layer were also significantly associated with lower density values in the superficial layer. Overall, results suggest that microvascular alterations are present in multiple retinal layers in SZ and that they may be useful visual system biomarkers of neurovascular changes in the disorder.

This study investigated relations between a measure of early-stage visual function and self-reported visual anomalies in individuals at clinical high risk for psychosis (CHR-P). Eleven individuals at CHR identified via the Structured Interview for Psychosis-Risk Syndromes (SIPS) were recruited from a CHR-P research program in NYC. The sample was ~36% female, ranging from 16 to 33 years old (M = 23.90, SD = 6.14). Participants completed a contrast sensitivity task on an iPad with five spatial frequencies (0.41–13 cycles/degree) and completed the self-report Audio-Visual Abnormalities Questionnaire. Higher contrast sensitivity (better performance) to low spatial frequencies was associated with higher perceptual (r = 0.616, p = 0.044) and visual disturbances (r = 0.667, p = 0.025); lower contrast sensitivity to a middle spatial frequency was also associated with higher perceptual (r = −0.604, p = 0.049) and visual disturbances (r = −0.606, p = 0.048). This relation between the questionnaire and contrast sensitivity to low spatial frequency may be indicative of a reduction in lateral inhibition and “flooding” of environmental stimuli. The association with middle spatial frequencies, which play a critical role in face processing, may result in a range of perceptual abnormalities. These findings demonstrate that self-reported perceptual anomalies occur in these individuals and are linked to performance on a measure of early visual processing.

Abstract The field of psychiatry is far from perfect in predicting which individuals will transition to a psychotic disorder. Here, we argue that visual system assessment can help in this regard. Such assessments have generated medium-to-large group differences with individuals prior to or near the first psychotic episode or have shown little influence of illness duration in larger samples of more chronic patients. For example, self-reported visual perceptual distortions—so-called visual basic symptoms—occur in up to 2/3rds of those with non-affective psychosis and have already longitudinally predicted an impending onset of schizophrenia. Possibly predictive psychophysical markers include enhanced contrast sensitivity, prolonged backward masking, muted collinear facilitation, reduced stereoscopic depth perception, impaired contour and shape integration, and spatially restricted exploratory eye movements. Promising brain-based markers include visual thalamo-cortical hyperconnectivity, decreased occipital gamma band power during visual detection (MEG), and reduced visually evoked occipital P1 amplitudes (EEG). Potentially predictive retinal markers include diminished cone a- and b-wave amplitudes and an attenuated photopic flicker response during electroretinography. The foregoing assessments are often well-described mechanistically, implying that their findings could readily shed light on the underlying pathophysiological changes that precede or accompany a transition to psychosis. The retinal and psychophysical assessments in particular are inexpensive, well-tolerated, easy to administer, and brief, with few inclusion/exclusion criteria. Therefore, across all major levels of analysis—from phenomenology to behavior to brain and retinal functioning—visual system assessment could complement and improve upon existing methods for predicting which individuals go on to develop a psychotic disorder.

Teachers face significant stressors in relation to their work, placing them at increased risk for burnout and attrition. The COVID-19 pandemic has brought about additional challenges, resulting in an even greater burden. Thus, strategies for reducing stress that can be delivered virtually are likely to benefit this population. Mental and Physical (MAP) Training combines meditation with aerobic exercise and has resulted in positive mental and physical health outcomes in both clinical and subclinical populations. The aim of this pilot study was to evaluate the feasibility and potential effectiveness of virtual MAP Training on reducing stress and improving mood and well-being in teachers. Participants (n = 104) were from recruited online from kindergarten to grade twelve (K-12) schools in the Northeastern region of the United States and randomly assigned to a 6-week program of virtual MAP Training (n = 58) or no training (n = 13). Primary outcomes included pre-intervention and post-intervention ratings on self-report measures of social and emotional health. Changes in cognitive functioning and physical health were also examined in secondary analyses. By intervention end, participants in the MAP Training group reported less anxiety and work-related stress compared to those who received no training (ds = −0.75 to −0.78). Additionally, MAP Training participants reported improvements in depressive symptoms, rumination, work-related quality of life, perceived stress, and self-compassion (ds = 0.38 to −0.82), whereas no changes were observed in the no training group. Participants also reported increased subjective ratings of executive functioning, working memory, cognitive flexibility, and fewer sleep disturbances (ds = −0.41 to −0.74). Together, these results suggest that the combination of meditation and aerobic exercise is an effective virtual intervention for improving mental health and well-being among K-12 teachers and may enhance resilience to stressful life events such as occurred during the coronavirus pandemic.

The predictive coding theory of psychosis posits that individuals with schizophrenia demonstrate abnormalities in the strength of top-down modulation (based on prior experience) of sensory signals. Evidence suggests that difficulty perceiving depth inversion illusions (DIIs) (i.e., more accurate perception of stimuli under conditions in which control subjects perceive these illusions) may reflect this abnormality in people with schizophrenia. This review synthesizes findings from all studies that have investigated DII perception in schizophrenia, high-risk syndromes, and conditions associated with risk for psychosis outside of a psychotic disorder such as those involving cannabis use, alcohol intoxication and withdrawal, and sleep deprivation. Cognitive and biological mechanisms contributing to DII resistance, and strengths and confounds of using the DII task as a measure of predictive coding are also discussed. The available evidence indicates that psychosis is associated with resistance to DIIs, whereas schizophrenia in the absence of active psychosis is less strongly associated with this effect. This may be due to psychosis-related deficiencies in top-down signaling and a compensatory overreliance on bottom-up signaling. Overall, the evidence reviewed suggests that the DII task is a sensitive measure of predictive coding in schizophrenia that could be used as a visual biomarker to predict risk and impending changes in clinical state within the disorder. Additional studies that measure changes longitudinally are necessary to further explore the possibility of using the DII task as a visual biomarker for psychosis in clinical settings.

Abstract Identifying state-sensitive measures of perceptual and cognitive processes implicated in psychosis may allow for objective, earlier, and better monitoring of changes in mental status that are predictive of an impending psychotic episode, relative to traditional self-report-based clinical measures. To determine whether a measure of visual perception that has demonstrated sensitivity to the clinical state of schizophrenia in multiple prior studies is sensitive to features of the at-risk mental state, we examined differences between young people identified as being at clinical high risk for psychosis (CHR; n = 37) and non-psychiatric matched controls (n = 29) on the Mooney Faces Test (MFT). On each trial of the MFT, participants report whether they perceive a face in a degraded face image. The CHR group reported perceiving a greater number of faces in both upright and inverted MFT stimuli. Consistent with prior work, males reported more faces on the MFT than females in both conditions. However, the finding of greater reported face perception among CHR subjects was robustly observed in the female CHR group relative to the female control group. Among male CHR participants, greater reported face perception was related to increased perceptual abnormalities. These preliminary results are consistent with a small but growing literature suggesting that heightened perceptual sensitivity may characterize individuals at increased clinical risk for psychosis. Further studies are needed to determine the contributions of specific perceptual, cognitive, and motivational mechanisms to the findings.

The human retina and retinal imaging technologies continue to increasingly gain the attention of schizophrenia researchers. With the same embryologic origin as the brain, the retina offers a window into neurovascular changes that may underlie disease. Recently, two technologies that have already revolutionized the field of ophthalmology, optical coherence tomography (OCT), and a functional extension of this, optical coherence tomography angiography (OCTA), have gained traction. Together, these non-invasive technologies allow for microscopic imaging of both structural and vascular features of the retina. With ease of use and no side effects, these devices are likely to prove powerful digital health tools in the study and treatment of schizophrenia. They may also prove key to discovering disease relevant biomarkers that underly neurodevelopmental and neurodegenerative aspects of conditions such as schizophrenia.

Visual shape completion recovers object shape, size, and number from spatially segregated edges. Despite being extensively investigated, the process's underlying brain regions, networks, and functional connections are still not well understood. To shed light on the topic, we scanned (fMRI) healthy adults during rest and during a task in which they discriminated pac-man configurations that formed or failed to form completed shapes (illusory and fragmented condition, respectively). Task activation differences (illusory-fragmented), resting-state functional connectivity, and multivariate patterns were identified on the cortical surface using 360 predefined parcels and 12 functional networks composed of such parcels. Brain activity flow mapping (ActFlow) was used to evaluate the likely involvement of resting-state connections for shape completion. We identified 36 differentially-active parcels including a posterior temporal region, PH, whose activity was consistent across 95% of observers. Significant task regions primarily occupied the secondary visual network but also incorporated the frontoparietal, dorsal attention, default mode, and cingulo-opercular networks. Each parcel's task activation difference could be modeled via its resting-state connections with the remaining parcels (r=.62, p

Schizophrenia is characterized by visual distortions in ~60% of cases, and visual hallucinations (VH) in ~25–50% of cases, depending on the sample. These symptoms have received relatively little attention in the literature, perhaps due to the higher rate of auditory vs. visual hallucinations in psychotic disorders, which is the reverse of what is found in other neuropsychiatric conditions. Given the clinical significance of these perceptual disturbances, our aim is to help address this gap by updating and expanding upon prior reviews. Specifically, we: (1) present findings on the nature and frequency of VH and distortions in schizophrenia; (2) review proposed syndromes of VH in neuro-ophthalmology and neuropsychiatry, and discuss the extent to which these characterize VH in schizophrenia; (3) review potential cortical mechanisms of VH in schizophrenia; (4) review retinal changes that could contribute to VH in schizophrenia; (5) discuss relationships between findings from laboratory measures of visual processing and VH in schizophrenia; and (6) integrate findings across biological and psychological levels to propose an updated model of VH mechanisms, including how their content is determined, and how they may reflect vulnerabilities in the maintenance of a sense of self. In particular, we emphasize the potential role of alterations at multiple points in the visual pathway, including the retina, the roles of multiple neurotransmitters, and the role of a combination of disinhibited default mode network activity and enhanced state-related apical/contextual drive in determining the onset and content of VH. In short, our goal is to cast a fresh light on the under-studied symptoms of VH and visual distortions in schizophrenia for the purposes of informing future work on mechanisms and the development of targeted therapeutic interventions.

Abstract Introduction This small pilot study is the first direct comparison of the currently marketed formulations of bromfenac (0.07% solution) and nepafenac (0.3% suspension) using identical dosing regimens and including an extra pre-surgical “pulse” dose in patients undergoing cataract surgery. Methods Adults scheduled for unilateral phacoemulsification with intraocular lens implantation were randomly assigned to bromfenac 0.07% or nepafenac 0.3%, each given once-daily 1 day prior to surgery, on the day of surgery plus an extra dose 1 h before surgery, and for 14 days after surgery. Assessments included summed ocular inflammation score (SOIS), visual acuity (VA), and retinal thickness measured via optical coherence tomography. Results The study population included 49 patients (bromfenac, n = 24; nepafenac, n = 25). The percentage of patients with a SOIS = 0 (no cells or flare) at post-surgical day 15 (primary efficacy endpoint) was statistically similar between the bromfenac (57.1%) and nepafenac (50.0%) treatment groups (intent-to-treat with last observation carried forward) (P = 0.6318). The proportions of patients with an SOIS of 0 at days 3 and 8 were significantly (P

One of the proposed neural mechanisms involved in working memory is coupling between the theta phase and gamma amplitude. For example, evidence from intracranial recordings shows that coupling between hippocampal theta and cortical gamma oscillations increases selectively during working memory tasks. Theta-gamma phase-amplitude coupling can also be measured non-invasively through scalp EEG; however, EEG can only assess coupling within cortical areas, and it is not yet clear if this cortical-only coupling is truly memory-specific, or a more general phenomenon. We tested this directly by measuring cortical coupling during three different conditions: a working memory task, an attention task, and a passive perception condition. We find similar levels of theta-gamma coupling in all three conditions, suggesting that cortical theta-gamma phase-amplitude coupling is not a memory-specific signal, but instead reflects some other attentional or perceptual processes. Implications for understanding the brain dynamics of visual working memory are discussed.

People with schizophrenia exhibit increased intra-individual variability in both behavioral and neural signatures of cognition. Examination of intra-individual variability may uncover a unique functionally relevant aspect of impairment that is not captured by typical between-group comparisons of mean or median values. We and others have observed that retinal activity measured using electroretinography (ERG) is significantly reduced in people with schizophrenia; however, it is currently unclear whether greater intra-individual variability in the retinal response can also be observed. To investigate this, we examined intra-individual variability from 25 individuals with schizophrenia and 24 healthy controls under two fERG conditions: (1) a light-adapted condition in which schizophrenia patients demonstrated reduced amplitudes; and (2) a dark-adapted condition in which the groups did not differ in amplitudes. Intraclass correlation coefficients (ICC) were generated to measure intra-individual variability for each subject, reflecting the consistency of activation values (in μv) across all sampling points (at a 2 kHz sampling rate) within all trials within a condition. Contrary to our predictions, results indicated that the schizophrenia and healthy control groups did not differ in intra-individual variability in fERG responses in either the light- or dark-adapted conditions. This finding remained consistent when variability was calculated as the standard deviation (SD) and coefficient of variation (CV) of maximum positive and negative microvolt values within the a- and b-wave time windows. This suggests that although elevated variability in schizophrenia may be observed at perceptual and cognitive levels of processing, it is not present in the earliest stages of sensory processing in vision.

Background: Recent studies have found evidence of retinal thinning in schizophrenia spectrum disorder patients; however, it is not known whether retinal thinning is present at the first episode of psychosis or whether it is a result of the progression of the disease or related factors (e.g., emergence of medical comorbidities). We hypothesized that first episode patients (FEP) would not differ on any retinal variables when compared to age matched controls, while chronically ill patients would show evidence of retinal thinning compared to age matched controls. Methods: 15 first episode patients, 20 control subjects age-matched to the FEP group, 18 chronically ill patients, and 18 control subjects age-matched to the chronically ill group participated in Spectral Domain OCT scans. We collected data on retinal nerve fiber layer (RNFL) thickness, macula thickness and volume, and ganglion cell-inner plexiform layer (GCL-IPL) thickness as well as cup-to-disc ratio at the optic nerve head. Results: No evidence of retinal structural change was found in the first episode group. In contrast, chronic schizophrenia and schizoaffective disorder patients were characterized by GCL-IPL thinning and overall macula thinning and volume reduction. No evidence of RNFL thinning was observed in the chronic group, however. Discussion: These data suggest that retinal structure is unaffected very early in the course of schizophrenia spectrum disorders but that thinning is an aspect of illness progression, medical comorbidity, and/or long-term antipsychotic medication use in schizophrenia spectrum disorders. Among retinal indices, macula thickness and volume appear to be the most sensitive to the changes associated with illness chronicity.

Investigators have increasingly turned to studying the retina as a window into brain structure and function. In neuropsychiatric diseases, retinal anatomy as assessed by optical coherence tomography (OCT) and retinal cell function as assessed by various forms of electroretinography (ERG) demonstrate notable changes. In addition, many studies indicate significant correlations between retinal changes and clinical features such as cognitive decline, overall illness severity, and progression of illness. Here, we review retinal findings in psychiatric (schizophrenia, autism, mood disorders, attention deficit hyperactivity disorder, anorexia nervosa), and neurologic (multiple sclerosis, Parkinson's disease, Alzheimer's disease and mild cognitive impairment, Huntington's disease, traumatic brain injury) conditions, in terms of their potential as biomarkers of disease onset, progression, severity, and outcomes. Consistency and variability in findings across studies are highlighted, and implications for future research are discussed. Potential confounds and methodological issues central to studies of retinal structure and function in neuropsychiatry are also considered. The review concludes with discussions of: a) recent advances in retinal imaging and their potential applications for studying brain disorders; and b) the potential for applications of artificial intelligence to increasing the predictive validity of retinal data.

Computational modeling is a useful method for generating hypotheses about the contributions of impaired neurobiological mechanisms, and their interactions, to psychopathology. Modeling is being increasingly used to further our understanding of schizophrenia, but to date, it has not been applied to questions regarding the common perceptual disturbances in the disorder. In this article, we model aspects of low-level visual processing and demonstrate how this can lead to testable hypotheses about both the nature of visual abnormalities in schizophrenia and the relationships between the mechanisms underlying these disturbances and psychotic symptoms. Using a model that incorporates retinal, lateral geniculate nucleus (LGN), and V1 activity, as well as gain control in the LGN, homeostatic adaptation in V1, lateral excitation and inhibition in V1, and self-organization of synaptic weights based on Hebbian learning and divisive normalization, we show that (a) prior data indicating 'increased' contrast sensitivity for low-spatial-frequency stimuli in first-episode schizophrenia can be successfully modeled as a function of reduced retinal and LGN efferent activity, leading to overamplification at the cortical level, and (b) prior data on 'reduced' contrast sensitivity and broadened orientation tuning in chronic schizophrenia can be successfully modeled by a combination of reduced V1 lateral inhibition and an increase in the Hebbian learning rate at V1 synapses for LGN input. These models are consistent with many current findings, and they predict several relationships that have not yet been demonstrated. They also have implications for understanding changes in brain and visual function from the first psychotic episode to the chronic stage of illness.

Information theory provides a formal framework within which information processing and its disorders can be described. However, information theory has rarely been applied to modeling aspects of the cognitive neuroscience of schizophrenia. The goal of this article is to highlight the benefits of an approach based on information theory, including its recent extensions, for understanding several disrupted neural goal functions as well as related cognitive and symptomatic phenomena in schizophrenia. We begin by demonstrating that foundational concepts from information theory—such as Shannon information, entropy, data compression, block coding, and strategies to increase the signal-to-noise ratio—can be used to provide novel understandings of cognitive impairments in schizophrenia and metrics to evaluate their integrity. We then describe more recent developments in information theory, including the concepts of infomax, coherent infomax, and coding with synergy, to demonstrate how these can be used to develop computational models of schizophrenia-related failures in the tuning of sensory neurons, gain control, perceptual organization, thought organization, selective attention, context processing, predictive coding, and cognitive control. Throughout, we demonstrate how disordered mechanisms may explain both perceptual/cognitive changes and symptom emergence in schizophrenia. Finally, we demonstrate that there is consistency between some information-theoretic concepts and recent discoveries in neurobiology, especially involving the existence of distinct sites for the accumulation of driving input and contextual information prior to their interaction. This convergence can be used to guide future theory, experiment, and treatment development.

The goal of the current study was to examine the relationships between insight and both cognitive function and depression in schizophrenia and schizoaffective disorder, and to determine if there were similar relationships across diagnostic categories. We examined discrepancies between self and informant reports of function on the Specific levels of function scale as a metric of insight for interpersonal, social acceptance, work and activities. We examined two samples of individuals with schizophrenia and/or schizoaffective disorder (Ns of 188 and 67 respectively). In Sample 1, cognition was measured using the Dot Probe Expectancy Task. In Sample 2, cognition was measured by averaging several subtests from the MATRICS consensus cognitive battery, as well as additional measures of working memory. In both samples, depression was measured using the Brief Psychiatric Rating Scale. In both samples, we found significant relationships between worse cognition and overestimations of work function, as well as between higher depression levels and underestimation of interpersonal function. These relationships were specific to interpersonal and work function, with significantly stronger correlations with interpersonal and work function compared to the other areas of function. Similar results were found across diagnostic categories. These results have important implications for treatment planning, as they suggest the need to take into account depression and cognitive function when evaluating the patient's self-report of function, and highlight the utility of informant reports in evaluating function and treatment planning. Further, they add to the literature on the similarity across schizophrenia and schizoaffective disorder in a variety of pathological mechanisms.

Cognitive control is a cognitive and neural mechanism that contributes to managing the complex demands of day-to-day life. Studies have suggested that functional impairments in cognitive control associated brain circuitry contribute to a broad range of higher cognitive deficits in schizophrenia. To examine this issue, we assessed functional connectivity networks in healthy adults and individuals with schizophrenia performing tasks from two distinct cognitive domains that varied in demands for cognitive control, the RiSE episodic memory task and DPX goal maintenance task. We characterized general and cognitive control-specific effects of schizophrenia on functional connectivity within an expanded frontal parietal network (FPN) and quantified network topology properties using graph analysis. Using the network based statistic (NBS), we observed greater network functional connectivity in cognitive control demanding conditions during both tasks in both groups in the FPN, and demonstrated cognitive control FPN specificity against a task independent auditory network. NBS analyses also revealed widespread connectivity deficits in schizophrenia patients across all tasks. Furthermore, quantitative changes in network topology associated with diagnostic status and task demand were observed. The present findings, in an analysis that was limited to correct trials only, ensuring that subjects are on task, provide critical insights into network connections crucial for cognitive control and the manner in which brain networks reorganize to support such control. Impairments in this mechanism are present in schizophrenia and these results highlight how cognitive control deficits contribute to the pathophysiology of this illness.

Patients with psychosis exhibit a reduced susceptibility to depth inversion illusions (DII) in which a physically concave surface is perceived as convex (e.g., the hollow mask illusion). Here, we examined the extent to which lessened susceptibility to DII characterized youth at ultra high risk (UHR) for psychosis. In this study, 44 UHR participants and 29 healthy controls judged the apparent convexity of face-like human masks, two of which were concave and the other convex. One of the concave masks was painted with realistic texture to enhance the illusion; the other was shown without such texture. Networks involved with top-down and bottom-up processing were evaluated with resting state functional connectivity magnetic resonance imaging (fcMRI). We examined regions associated with the fronto-parietal network and the visual system and their relations with susceptibility to DII. Consistent with prior studies, the UHR group was less susceptible to DII (i.e., they were characterized by more veridical perception of the stimuli) than the healthy control group. Veridical responses were related to weaker connectivity within the fronto-parietal network, and this relationship was stronger in the UHR group, suggesting possible abnormalities of top-down modulation of sensory signals. This could serve as a vulnerability marker and a further clue to the pathogenesis of psychosis.

BackgroundPast studies using the Bonn Scale for the Assessment of Basic Symptoms (hereafter, Bonn Scale) have shown that self-reported perceptual/cognitive disturbances reveal which persons have or will soon develop schizophrenia. Here, we focused specifically on the clinical value of self-reported visual perceptual abnormalities (VPAs) since they are underexplored and have been associated with suicidal ideation, negative symptoms, and objective visual dysfunction.MethodUsing the 17 Bonn Scale vision items, we cross-sectionally investigated lifetime occurrence of VPAs in 21 first-episode psychosis and 22 chronic schizophrenia/schizoaffective disorder (SZ/SA) patients. Relationships were probed between VPAs and illness duration, symptom severity, current functioning, premorbid functioning, diagnosis, and age of onset.ResultsIncreased VPAs were associated with: earlier age of onset; more delusions, hallucinations, bizarre behavior, and depressive symptoms; and worse premorbid social functioning, especially in the childhood and early adolescent phases. SZ/SA participants endorsed more VPAs as compared to those with schizophreniform or psychotic disorder-NOS, especially in the perception of color, bodies, faces, object movement, and double/reversed vision. The range of self-reported VPAs was strikingly similar between first-episode and chronic patients and did not depend on the type or amount of antipsychotic medication. As a comparative benchmark, lifetime occurrence of visual hallucinations did not depend on diagnosis and was linked only to poor premorbid social functioning.ConclusionA brief 17-item interview derived from the Bonn Scale is strongly associated with core clinical features in schizophrenia. VPAs hold promise for clarifying diagnosis, predicting outcome, and guiding neurocognitive investigations.

The power of SNP association studies to detect valid relationships with clinical phenotypes in schizophrenia is largely limited by the number of SNPs selected and non-specificity of phenotypes. To address this, we first assessed performance on two visual perceptual organization tasks designed to avoid many generalized deficit confounds, Kanizsa shape perception and contour integration, in a schizophrenia patient sample. Then, to reduce the total number of candidate SNPs analyzed in association with perceptual organization phenotypes, we employed a two-stage strategy: first a priori SNPs from three candidate genes were selected (GAD1, NRG1 and DTNBP1); then a Hierarchical Classes Analysis (HICLAS) was performed to reduce the total number of SNPs, based on statistically related SNP clusters. HICLAS reduced the total number of candidate SNPs for subsequent phenotype association analyses from 6 to 3. MANCOVAs indicated that rs10503929 and rs1978340 were associated with the Kanizsa shape perception filling in metric but not the global shape detection metric. rs10503929 was also associated with altered contour integration performance. SNPs not selected by the HICLAS model were unrelated to perceptual phenotype indices. While the contribution of candidate SNPs to perceptual impairments requires further clarification, this study reports the first application of HICLAS as a hypothesis-independent mathematical method for SNP data reduction. HICLAS may be useful for future larger scale genotype-phenotype association studies.

Intermittent degradation refers to transient detrimental disruptions in task performance. This phenomenon has been repeatedly observed in the performance data of patients with schizophrenia. Whether intermittent degradation is a feature of the liability for schizophrenia (i.e., schizotypy) is an open question. Further, the specificity of intermittent degradation to schizotypy has yet to be investigated. To address these questions, 92 undergraduate participants completed a battery of self-report questionnaires assessing schizotypy and psychological state variables (e.g., anxiety, depression), and their reaction times were recorded as they did so. Intermittent degradation was defined as the number of times a subject’s reaction time for questionnaire items met or exceeded three standard deviations from his or her mean reaction time after controlling for each item’s information processing load. Intermittent degradation scores were correlated with questionnaire scores. Our results indicate that intermittent degradation is associated with total scores on measures of positive and disorganized schizotypy, but unrelated to total scores on measures of negative schizotypy and psychological state variables. Intermittent degradation is interpreted as potentially derivative of schizotypy and a candidate endophenotypic marker worthy of continued research.

Although visual processing impairments are common in schizophrenia, it is not clear to what extent these originate in the eye vs. the brain. This review highlights potential contributions, from the retina and other structures of the eye, to visual processing impairments in schizophrenia and high-risk states. A second goal is to evaluate the status of retinal abnormalities as biomarkers for schizophrenia. The review was motivated by known retinal changes in other disorders (e.g., Parkinson’s disease, multiple sclerosis), and their relationships to perceptual and cognitive impairments, and disease progression therein. The evidence reviewed suggests two major conclusions. One is that there are multiple structural and functional disturbances of the eye in schizophrenia, all of which could be factors in the visual disturbances of patients. These include retinal venule widening, retinal nerve fiber layer thinning, dopaminergic abnormalities, abnormal ouput of retinal cells as measured by electroretinography (ERG), maculopathies and retinopathies, cataracts, poor acuity, and strabismus. Some of these are likely to be illness-related, whereas others may be due to medication or comorbid conditions. The second conclusion is that certain retinal findings can serve as biomarkers of neural pathology, and disease progression, in schizophrenia. The strongest evidence for this to date involves findings of widened retinal venules, thinning of the retinal nerve fiber layer, and abnormal ERG amplitudes. These data suggest that a greater understanding of the contribution of retinal and other ocular pathology to the visual and cognitive disturbances of schizophrenia is warranted, and that retinal changes have untapped clinical utility.

Impairments in visual perceptual organization abilities are a repeatedly observed cognitive deficit in schizophrenia. These impairments have been found to be most prominent among patients with histories of poor premorbid social functioning, disorganized symptoms, and poor clinical outcomes. Despite the demonstration of significant sex differences for these clinical factors in schizophrenia, the extent of sex differences for visual perceptual organization in schizophrenia is unknown. Therefore, we investigated the extent to which previously known correlates (premorbid social sexual functioning and disorganized symptoms) and a novel factor (participant sex) accounted for performance on two perceptual organization tasks (contour integration and Ebbinghaus illusion) that have previously demonstrated sensitivity to schizophrenia. We also determined the relative degree to which each of these factors predicted task scores over and above the others. Schizophrenia patients (N = 109, 43 female) from different levels of care were ascertained. Female patients demonstrated higher contour integration scores, but lower performance on the context sensitivity index of the Ebbinghaus illusion, compared to males. Contour integration performance was significantly associated with poorer premorbid adolescent social sexual functioning and higher levels of disorganized symptoms, supporting past results that indicate a relationship among poor premorbid social sexual functioning, disorganized symptoms, and visual perceptual abnormalities in schizophrenia. However, analyses of Ebbinghaus illusion performance suggests there is a complex relationship among patient sex, clinical factors and perceptual abilities with relatively intact bottom-up grouping processes in females, but greater problems, compared to males with more top-down mediated context sensitivity. Therefore, sex differences may be an important consideration for future studies of visual perceptual organization in schizophrenia.