Different learning aberrations relate to delusion-like beliefs with different contents.

The prediction error account of delusions has had success. However, its explanation of delusions with different contents has been lacking. Persecutory delusions and paranoia are the common unfounded beliefs that others have harmful intentions towards us. Other delusions include believing that one's thoughts or actions are under external control, or that events in the world have specific personal meaning. We compare learning on two different cognitive tasks, probabilistic reversal learning (PRL) and Kamin blocking, that have relationships to paranoid and non-paranoid delusion-like beliefs, respectively. We find that Clinical High-Risk status alone does not result in different behavioral results on the PRL task but that an individual's level of paranoia is associated with excessive switching behavior. During the Kamin blocking task, paranoid individuals learned inappropriately about the blocked cue. However, they also had decreased learning about the control cue, suggesting more general learning impairments. Non-paranoid delusion-like belief conviction (but not paranoia) was associated with aberrant learning about the blocked cue but intact learning about the control cue, suggesting specific impairments in learning related to cue combination. We fit task-specific computational models separately to behavioral data to explore how latent parameters vary within individuals between tasks, and how they can explain symptom-specific effects. We find that paranoia is associated with low learning rates on the PRL task as well as the blocking task. Non-paranoid delusion-like belief conviction was instead related to parameters controlling the degree and direction of similarity between cue updating during simultaneous cue presentation. These results suggest that paranoia and other delusion-like beliefs involve dissociable deficits in learning and belief updating, which - given the transdiagnostic status of paranoia - may have differential utility in predicting psychosis.

Assessing Trial-by-Trial Electrophysiological and Behavioral Markers of Attentional Control and Sensory Precision in Psychotic and Mood Disorders.

BACKGROUND AND HYPOTHESIS: The current study investigated the extent to which changes in attentional control contribute to performance on a visual perceptual discrimination task, on a trial-by-trial basis in a transdiagnostic clinical sample. STUDY DESIGN: Participants with schizophrenia (SZ; N = 58), bipolar disorder (N = 42), major depression disorder (N = 51), and psychiatrically healthy controls (N = 92) completed a visual perception task in which stimuli appeared briefly. The design allowed us to estimate the lapse rate and the precision of perceptual representations of the stimuli. Electroencephalograms (EEG) were recorded to examine pre-stimulus activity in the alpha band (8-13 Hz), overall and in relation to behavior performance on the task. STUDY RESULTS: We found that the attention lapse rate was elevated in the SZ group compared with all other groups. We also observed group differences in pre-stimulus alpha activity, with control participants showing the highest levels of pre-stimulus alpha when averaging across trials. However, trial-by-trial analyses showed within-participant fluctuations in pre-stimulus alpha activity significantly predicted the likelihood of making an error, in all groups. Interestingly, our analysis demonstrated that aperiodic contributions to the EEG signal (which affect power estimates across frequency bands) serve as a significant predictor of behavior as well. CONCLUSIONS: These results confirm the elevated attention lapse rate that has been observed in SZ, validate pre-stimulus EEG markers of attentional control and their use as a predictor of behavior on a trial-by-trial basis, and suggest that aperiodic contributions to the EEG signal are an important target for further research in this area, in addition to alpha-band activity.

Performance on a contour integration task as a function of contour shape in schizophrenia and controls.

Contour Integration (CI) is the ability to integrate elemental features into objects and is a basic visual process essential for object perception and recognition, and for functioning in visual environments. It is now well documented that people with schizophrenia (SZ), in addition to having cognitive impairments, also have several visual perceptual deficits, including in CI. Here, we retrospectively characterize the performance of both SZ and neurotypical individuals (NT) on a series of contour shapes, made up of Gabor elements, that varied in terms of closure and curvature. Participants in both groups performed a CI training task that included 7 different families of shapes (Lines, Ellipse, Blobs, Squiggles, Spiral, Circle and Letters) for up to 40 sessions. Two parameters were manipulated in the training task: Orientation Jitter (OJ, i.e., orientation deviations of individual Gabor elements from ideal for each shape) and Inducer Number (IN, i.e., number of Gabor elements defining the shape). Results show that both OJ and IN thresholds significantly differed between the groups, with higher (OJ) and lower (IN) thresholds observed in the controls. Furthermore, we found significant effects as a function of the contour shapes, with differences between groups emerging with contours that were considered more complex, e.g., due to having a higher degree of curvature (Blobs, Spiral, Letters). These data can inform future work that aims to characterize visual integration impairments in schizophrenia.

Stronger tilt aftereffects in individuals diagnosed with schizophrenia spectrum disorders but not bipolar disorder.

An altered use of context and experience to interpret incoming information has been posited to explain schizophrenia symptoms. The visual system can serve as a model system for examining how context and experience guide perception and the neural mechanisms underlying putative alterations. The influence of prior experience on current perception is evident in visual aftereffects, the perception of the "opposite" of a previously viewed stimulus. Aftereffects are associated with neural adaptation and concomitant change in strength of lateral inhibitory connections in visually responsive neurons. In a previous study, we observed stronger aftereffects related to orientation (tilt aftereffects) but not luminance (negative afterimages) in individuals diagnosed with schizophrenia, which we interpreted as potentially suggesting altered cortical (but not subcortical) adaptability and local changes in excitatory-inhibitory interactions. Here, we tested whether stronger tilt aftereffects were specific to individuals with schizophrenia or extended to individuals with bipolar disorder. We measured tilt aftereffects and negative afterimages in 32 individuals with bipolar disorder, and compared aftereffect strength to a previously reported group of 36 individuals with schizophrenia and 22 healthy controls. We observed stronger tilt aftereffects, but not negative afterimages, in individuals with schizophrenia as compared to both controls and individuals with bipolar disorder, who did not differ from each other. These results mitigate concerns that stronger tilt aftereffects in schizophrenia are a consequence of medication or of the psychosocial consequences of a severe mental illness.

Specific association between retinal neural layer thinning and neurological soft signs in schizophrenia.

There is growing evidence of disproportionate retinal thinning in schizophrenia, but doubts are still raised regarding its significance in the context of the neurobiology of the disease. Therefore, we examined whether these abnormalities are significantly associated with neurological soft signs (NSS) which are closely related to the risk of schizophrenia. This cross-sectional study analyzing linear correlations between variables involved 56 schizophrenia inpatients and 60 controls. The results confirmed such relationships, and only in the patient sample. In addition, retinal abnormalities and NSS were significantly correlated with duration of illness. These findings provide further evidence for linked neurodevelopmental and neurodegenerative aspects of schizophrenia.

A Transdiagnostic Study of Effort-Cost Decision-Making in Psychotic and Mood Disorders.

BACKGROUND: Research suggests that effort-cost decision-making (ECDM), the estimation of work required to obtain reward, may be a relevant framework for understanding motivational impairment in psychotic and mood pathology. Specifically, research has suggested that people with psychotic and mood pathology experience effort as more costly than controls, and thus pursue effortful goals less frequently. This study examined ECDM across psychotic and mood pathology. HYPOTHESIS: We hypothesized that patient groups would show reduced willingness to expend effort compared to controls. STUDY DESIGN: People with schizophrenia (N = 33), schizoaffective disorder (N = 28), bipolar disorder (N = 39), major depressive disorder (N = 40), and controls (N = 70) completed a physical ECDM task. Participants decided between completing a low-effort or high-effort option for small or larger rewards, respectively. Reward magnitude, reward probability, and effort magnitude varied trial-by-trial. Data were analyzed using standard and hierarchical logistic regression analyses to assess the subject-specific contribution of various factors to choice. Negative symptoms were measured with a clinician-rated interview. STUDY RESULTS: There was a significant effect of group, driven by reduced choice of high-effort options in schizophrenia. Hierarchical logistic regression revealed that reduced choice of high-effort options in schizophrenia was driven by weaker contributions of probability information. Use of reward information was inversely associated with motivational impairment in schizophrenia. Surprisingly, individuals with major depressive disorder and bipolar disorder did not differ from controls. CONCLUSIONS: Our results provide support for ECDM deficits in schizophrenia. Additionally, differences between groups in ECDM suggest a seemingly similar behavioral phenotype, reduced motivation, could arise from disparate mechanisms.

Diagnostic profiles and trauma history among treatment-seeking young adults with positive post-traumatic stress disorder screens: Findings and implications for public mental health care.

OBJECTIVES: This study examined diagnostic profiles and trauma history among treatment-seeking young adults with positive PTSD screens in public mental health care. METHODS: Screening for trauma history and PTSD symptoms was implemented in a community mental health service system. 266 treatment-seeking young adults (aged 18-35) endorsed trauma exposure with a score of at least 45 on the DSM-IV PTSD Checklist, indicating probable PTSD. RESULTS: Young adults with positive PTSD screens were predominantly female, minority, and diagnosed with mood disorders. Of those with positive screens, only 15% had a chart diagnosis of PTSD; 17.3% (ages 18-24) versus 14.1% (ages 25-35). Variables significantly associated with a decreased likelihood of PTSD detection included a diagnosis of schizophrenia or bipolar disorder, exposure to fewer types of traumatic events, male gender, and white race. CONCLUSION: Routine PTSD screening for young adults receiving public mental health care should be prioritized to address long-term impacts of trauma.

Retina as a potential biomarker in schizophrenia spectrum disorders: a systematic review and meta-analysis of optical coherence tomography and electroretinography.

INTRODUCTION: Abnormal findings on optical coherence tomography (OCT) and electroretinography (ERG) have been reported in participants with schizophrenia spectrum disorders (SSDs). This study aims to reveal the pooled standard mean difference (SMD) in retinal parameters on OCT and ERG among participants with SSDs and healthy controls and their association with demographic characteristics, clinical symptoms, smoking, diabetes mellitus, and hypertension. METHODS: Using PubMed, Scopus, Web of Science, and PSYNDEX, we searched the literature from inception to March 31, 2023, using specific search terms. This study was registered with PROSPERO (CRD4202235795) and conducted according to PRISMA 2020. RESULTS: We included 65 studies in the systematic review and 44 in the meta-analysis. Participants with SSDs showed thinning of the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer- inner plexiform cell layer, and retinal thickness in all other segments of the macula. A meta-analysis of studies that excluded SSD participants with diabetes and hypertension showed no change in results, except for pRNFL inferior and nasal thickness. Furthermore, a significant difference was found in the pooled SMD of pRNFL temporal thickness between the left and right eyes. Meta-regression analysis revealed an association between retinal thinning and duration of illness, positive and negative symptoms. In OCT angiography, no differences were found in the foveal avascular zone and superficial layer foveal vessel density between SSD participants and controls. In flash ERG, the meta-analysis showed reduced amplitude of both a- and b-waves under photopic and scotopic conditions in SSD participants. Furthermore, the latency of photopic a-wave was significantly shorter in SSD participants in comparison with HCs. DISCUSSION: Considering the prior report of retinal thinning in unaffected first-degree relatives and the results of the meta-analysis, the findings suggest that retinal changes in SSDs have both trait and state aspects. Future longitudinal multimodal retinal imaging studies are needed to clarify the pathophysiological mechanisms of these changes and to clarify their utility in individual patient monitoring efforts.

Comparing a Computerized Digit Symbol Test to a Pen-and-Paper Classic.

Background and Hypothesis: Processing speed dysfunction is a core feature of psychosis and predictive of conversion in individuals at clinical high risk (CHR) for psychosis. Although traditionally measured with pen-and-paper tasks, computerized digit symbol tasks are needed to meet the increasing demand for remote assessments. Therefore we: (1) assessed the relationship between traditional and computerized processing speed measurements; (2) compared effect sizes of impairment for progressive and persistent subgroups of CHR individuals on these tasks; and (3) explored causes contributing to task performance differences. Study Design: Participants included 92 CHR individuals and 60 healthy controls who completed clinical interviews, the Brief Assessment of Cognition in Schizophrenia Symbol Coding test, the computerized TestMyBrain Digit Symbol Matching Test, a finger-tapping task, and a self-reported motor abilities measure. Correlations, Hedges' g, and linear models were utilized, respectively, to achieve the above aims. Study Results: Task performance was strongly correlated (r = 0.505). A similar degree of impairment was seen between progressive (g = -0.541) and persistent (g = -0.417) groups on the paper version. The computerized task uniquely identified impairment for progressive individuals (g = -477), as the persistent group performed similarly to controls (g = -0.184). Motor abilities were related to the computerized version, but the paper version was more related to symptoms and psychosis risk level. Conclusions: The paper symbol coding task measures impairment throughout the CHR state, while the computerized version only identifies impairment in those with worsening symptomatology. These results may be reflective of sensitivity differences, an artifact of existing subgroups, or evidence of mechanistic differences.

Retinal Neurodegeneration as a Potential Biomarker of Accelerated Aging in Schizophrenia Spectrum Disorders.

BACKGROUND AND HYPOTHESES: Several biological markers are believed to reflect accelerated aging in schizophrenia spectrum disorders; however, retinal neural changes have not yet been explored as potential CNS biomarkers of accelerated aging in this population. The aim of this study was to determine whether retinal neural layer thinning is more strongly related to age in schizophrenia and schizoaffective disorder patients (SZ) than in a psychiatrically healthy control group (CON). STUDY DESIGN: Schizophrenia (n = 60) and CON participants (n = 69) underwent spectral domain optical coherence tomography (OCT) scans to examine the following variables in both eyes: retinal nerve fiber layer (RNFL) thickness, macula central subfield (CSF) thickness, macula volume, ganglion cell layer-inner plexiform layer (GCL-IPL) thickness, optic cup volume, and cup-to-disc ratio. Eleven participants in each group had diabetes or hypertension. STUDY RESULTS: Significant negative relationships between age and RNFL thickness, macula volume, and GCL-IPL thickness were observed in the SZ group, while no significant relationships were observed in the CON group. However, many of the findings in the SZ group lost significance when participants with diabetes/hypertension were removed from analyses. A notable exception to this was that the age × SZ interaction accounted for a unique proportion of variance in GCL-IPL thinning over and above the effect of diabetes/hypertension. CONCLUSIONS: The results suggest that retinal atrophy occurs at an increased rate in schizophrenia spectrum disorders, potentially reflecting accelerated aging inherent to these conditions, with considerable contributions from systemic medical diseases closely linked to this population.

Managing EEG studies: How to prepare and what to do once data collection has begun.

In this paper, we provide guidance for the organization and implementation of EEG studies. This work was inspired by our experience conducting a large-scale, multi-site study, but many elements could be applied to any EEG project. Section 1 focuses on study activities that take place before data collection begins. Topics covered include: establishing and training study teams, considerations for task design and piloting, setting up equipment and software, development of formal protocol documents, and planning communication strategy with all study team members. Section 2 focuses on what to do once data collection has already begun. Topics covered include: (1) how to effectively monitor and maintain EEG data quality, (2) how to ensure consistent implementation of experimental protocols, and (3) how to develop rigorous preprocessing procedures that are feasible for use in a large-scale study. Links to resources are also provided, including sample protocols, sample equipment and software tracking forms, sample code, and tutorial videos (to access resources, please visit: https://osf.io/wdrj3/).

Transdiagnostic Predictors of Everyday Functioning: Examining the Relationships of Depression and Reinforcement Learning.

BACKGROUND AND HYPOTHESIS: Impairments in function (ie, the ability to independently accomplish daily tasks) have been established in psychotic disorders. Identifying factors that contribute to these deficits is essential to developing effective interventions. The current study had several goals: examine potential differential relationships across domains of neurocognition, assess whether reinforcement learning is related to function, identify if predictors of function are transdiagnostic, determine whether depression and positive symptoms contribute to function, and to explore whether the modality of assessment impacts observed relationships. STUDY DESIGN: Data from 274 participants were examined with schizophrenia/schizoaffective disorder (SZ; n = 195) and bipolar disorder (BD; n = 79). To reduce dimensionality, a PCA was completed on neurocognitive tasks which resulted in 3 components. These components and clinical interview data were used to investigate predictors of functional domains across measures of function (self- and informant-report SLOF and UPSA). RESULTS: Two components, working memory/processing speed/episodic memory (ßs = 0.18-0.42), and negative/positive reinforcement learning (ß = -0.04), predicted different functional domains. Predictors of function were largely transdiagnostic with two exceptions: reinforcement learning had a positive association with self-reported interpersonal relationships for SZ and a negative association for BD (ß = 0.34), and the negative association between positive symptoms and self-reported social acceptability was stronger for BD than for SZ (ß = 0.93). Depression robustly predicted self-reported but not informant-reported function, and anhedonia predicted all domains of informant-reported function. CONCLUSIONS: These findings imply that reinforcement learning may differentially relate to function across disorders, traditional domains of neurocognition can be effective transdiagnostic targets for interventions, and positive symptoms and depression play a critical role in self-perceived functional impairments.

Effects of Punctal Occlusion on Ocular Itching and Conjunctival Redness Associated with Allergic Conjunctivitis.

PURPOSE: Punctal occlusion using punctal plugs has been successfully used to treat the signs and symptoms of dry eye disease. However, the effects of punctal occlusion on the symptoms of allergic conjunctivitis (AC) have been less well documented. There is some concern among clinicians that punctal occlusion may make signs/symptoms of allergic conjunctivitis worse by trapping allergens on the eye. The objective of this post hoc analysis was to address this question and thus assess the effect of punctal occlusion alone on ocular itching and conjunctival redness associated with AC. METHODS: This was a pooled post hoc analysis of three randomized, double-blind, placebo insert-controlled clinical trials in subjects with AC. Enrolled subjects were generally healthy adults with ocular allergies and a positive skin test reaction to perennial and/or seasonal allergens. The study used a modified version of the traditional conjunctival allergen challenge (CAC) model, which included multiple, repeated allergen challenges following placement of the intracanalicular insert. Subjects were rechallenged on Days 6, 7 and 8; Days 13, 14 and 15; and Days 26, 27 and 28. RESULTS: The data set included 128 subjects that were administered placebo. Baseline mean (SD) ocular itching and conjunctival redness scores were 3.52 (0.44) and 2.97 (0.39), respectively. On post-insertion Days 7, 14 and 28, mean itching scores were 2.62, 2.26 and 1.91, respectively, representing 26%, 36% and 46% itching reductions, respectively (p < 0.001). On Days 7, 14 and 28, mean conjunctival redness scores were 1.98, 1.90, and 2.08, respectively, representing 33%, 36%, and 30% redness reductions, respectively (p < 0.001). CONCLUSIONS: Based on this post hoc pooled analysis, punctal occlusion with a resorbable hydrogel intracanalicular insert did not worsen ocular itching or conjunctival redness in this patient population.

Post-Traumatic Cognitions Inventory (PTCI): psychometric properties in clients with serious mental illness and co-occurring PTSD.

BACKGROUND: People with post-traumatic stress disorder (PTSD) exhibit negative cognitions, predictive of PTSD severity. The Post-Traumatic Cognitions Inventory (PTCI) is a widely used instrument measuring trauma-related cognitions and beliefs with three subscales: negative thoughts of self (SELF), negative cognitions about the world (WORLD), and self-blame (BLAME). AIMS: The current study attempted to validate the use of the PTCI in people with serious mental illness (SMI), who have greater exposure to trauma and elevated rates of PTSD, using confirmatory factor analysis (CFA) and examining convergent and divergent correlations with relevant constructs. METHOD: Participants were 432 individuals with SMI and co-occurring PTSD diagnosis based on the Clinician Administered PTSD Scale, who completed PTCI and other clinical ratings. RESULTS: CFAs provided adequate support for Foa's three-factor model (SELF, WORLD, BLAME), and adequate support for Sexton's four-factor model that also included a COPE subscale. Both models achieved measurement invariance at configural, metric and scalar levels for three diagnostic groups: schizophrenia, bipolar and major depression, as well as for ethnicity (White vs Black), and gender (male vs female). Validity of both models was supported by significant correlations between PTCI subscales, and self-reported and clinician assessed PTSD symptoms and associated symptoms. CONCLUSIONS: Findings provide support for the psychometric properties of the PTCI and the conceptualization of Sexton's four-factor and Foa's three-factor models of PTCI among individuals diagnosed with SMI (Foa et al., ).

Self-reported Gesture Interpretation and Performance Deficits in Individuals at Clinical High Risk for Psychosis.

BACKGROUND AND HYPOTHESIS: Deficits in performing and interpreting communicative nonverbal behaviors, such as gesture, have been linked to varied psychopathology and dysfunction. Some evidence suggests that individuals at risk for psychosis have deficits in gesture interpretation and performance; however, individuals with internalizing disorders (eg, depression) may have similar deficits. No previous studies have examined whether gesture deficits in performance and interpretation are specific to those at risk for psychosis. Additionally, the underlying mechanisms (eg, cognition) and consequences (eg, functioning) of these deficits are poorly understood. STUDY DESIGN: This study examined self-reported gesture interpretation (SRGI) and performance (SRGP) in those at clinical high risk for psychosis (CHR; N = 88), those with internalizing disorders (INT; N = 51), and healthy controls (HC; N = 53). Participants completed questionnaires, clinical interviews, and neurocognitive tasks. STUDY RESULTS: Results indicated that the CHR group was characterized by significantly lower SRGI scores than the HC or INT groups (d = 0.41); there were no differences among groups in SRGP. Within CHR participants, greater deficits in SRGP were associated with lower verbal learning and memory (r = -.33), but not general intelligence or processing speed. Furthermore, gesture deficits were associated with higher cross-sectional risk for conversion to a full psychotic disorder in the CHR group. CONCLUSIONS: Overall, these findings suggest that specific subdomains of gesture may reflect unique vulnerability for psychosis, self-report may be a viable assessment tool in understanding these phenomena, and gesture dysfunction may signal risk for transition to psychosis.

The reliability and validity of the revised Green et al. paranoid thoughts scale in individuals at clinical high-risk for psychosis.

INTRODUCTION: Paranoia is a common and impairing psychosis symptom, which exists along a severity continuum that extends into the general population. Individuals at clinical high-risk for psychosis (CHR) frequently experience paranoia and this may elevate their risk for developing full psychosis. Nonetheless, limited work has examined the efficient measurement of paranoia in CHR individuals. The present study aimed to validate an often-used self-report measure, the revised green paranoid thoughts scale (RGPTS), in this critical population. METHOD: Participants were CHR individuals (n = 103), mixed clinical controls (n = 80), and healthy controls (n = 71) who completed self-report and interview measures. Confirmatory factor analysis (CFA), psychometric indices, group differences, and relations to external measures were used to evaluate the reliability and validity of the RGPTS. RESULTS: CFA replicated a two-factor structure for the RGPTS and the associated reference and persecution scales were reliable. CHR individuals scored significantly higher on both reference and persecution, relative to both healthy (ds = 1.03, 0.86) and clinical controls (ds = 0.64, 0.73). In CHR participants, correlations between reference and persecution and external measures were smaller than expected, though showed evidence of discriminant validity (e.g., interviewer-rated paranoia, r = 0.24). When examined in the full sample, correlation magnitude was larger and follow-up analyses indicated that reference related most specifically to paranoia (ß = 0.32), whereas persecution uniquely related to poor social functioning (ß = -0.29). CONCLUSION: These results demonstrate the reliability and validity of the RGPTS, though its scales related more weakly to severity in CHR individuals. The RGPTS may be useful in future work aiming to develop symptom-specific models of emerging paranoia in CHR individuals.

Association Between Retinal Features From Multimodal Imaging and Schizophrenia.

Importance: The potential association of schizophrenia with distinct retinal changes is of clinical interest but has been challenging to investigate because of a lack of sufficiently large and detailed cohorts. Objective: To investigate the association between retinal biomarkers from multimodal imaging (oculomics) and schizophrenia in a large real-world population. Design, Setting, and Participants: This cross-sectional analysis used data from a retrospective cohort of 154 830 patients 40 years and older from the AlzEye study, which linked ophthalmic data with hospital admission data across England. Patients attended Moorfields Eye Hospital, a secondary care ophthalmic hospital with a principal central site, 4 district hubs, and 5 satellite clinics in and around London, United Kingdom, and had retinal imaging during the study period (January 2008 and April 2018). Data were analyzed from January 2022 to July 2022. Main Outcomes and Measures: Retinovascular and optic nerve indices were computed from color fundus photography. Macular retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (mGC-IPL) thicknesses were extracted from optical coherence tomography. Linear mixed-effects models were used to examine the association between schizophrenia and retinal biomarkers. Results: A total of 485 individuals (747 eyes) with schizophrenia (mean [SD] age, 64.9 years [12.2]; 258 [53.2%] female) and 100 931 individuals (165 400 eyes) without schizophrenia (mean age, 65.9 years [13.7]; 53 253 [52.8%] female) were included after images underwent quality control and potentially confounding conditions were excluded. Individuals with schizophrenia were more likely to have hypertension (407 [83.9%] vs 49 971 [48.0%]) and diabetes (364 [75.1%] vs 28 762 [27.6%]). The schizophrenia group had thinner mGC-IPL (-4.05 µm, 95% CI, -5.40 to -2.69; P = 5.4 × 10-9), which persisted when investigating only patients without diabetes (-3.99 µm; 95% CI, -6.67 to -1.30; P = .004) or just those 55 years and younger (-2.90 µm; 95% CI, -5.55 to -0.24; P = .03). On adjusted analysis, retinal fractal dimension among vascular variables was reduced in individuals with schizophrenia (-0.14 units; 95% CI, -0.22 to -0.05; P = .001), although this was not present when excluding patients with diabetes. Conclusions and Relevance: In this study, patients with schizophrenia had measurable differences in neural and vascular integrity of the retina. Differences in retinal vasculature were mostly secondary to the higher prevalence of diabetes and hypertension in patients with schizophrenia. The role of retinal features as adjunct outcomes in patients with schizophrenia warrants further investigation.

Association between visual impairment and psychosis: A longitudinal study and nested case-control study of adults.

BACKGROUND: Theories propose that visual impairment might increase the risk of psychosis, and vice versa. We aimed to investigate the relationship between visual impairment and psychosis in the UK Biobank cohort. STUDY DESIGN: In a nested case control study of ~116,000 adults, we tested whether a Schizophrenia Spectrum Disorder (SSD) diagnosis as exposure was associated with visual impairment. We also tested longitudinally whether poorer visual acuity, and thinner retinal structures on Optical Coherence Tomography (OCT) scans in 2009 were associated with psychotic experiences in 2016. We adjusted for age, sex, depression and anxiety symptoms; and socioeconomic variables and vascular risk factors where appropriate. We compared complete case with multiple imputation models, designed to reduce bias potentially introduced by missing data. RESULTS: People with visual impairment had greater odds of SSD than controls in multiply imputed data (Adjusted Odds Ratio [AOR] 1.42, 95 % Confidence Interval [CI] 1.05-1.93, p = 0.021). We also found evidence that poorer visual acuity was associated with psychotic experiences during follow-up (AOR per 0.1 point worse visual acuity score 1.06, 95 % CI 1.01-1.11, p = 0.020; and 1.04, 95 % CI 1.00-1.08, p = 0.037 in right and left eye respectively). In complete case data (15 % of this cohort) we found no clear association, although confidence intervals included the multiple imputation effect estimates. OCT measures were not associated with psychotic experiences. CONCLUSIONS: Our findings highlight the importance of eye care for people with psychotic illnesses. We could not conclude whether visual impairment is a likely causal risk factor for psychosis.