Publications by authors named "Steven M Silverstein"

180 Publications

Reliability and Replicability of Implicit and Explicit Reinforcement Learning Paradigms in People With Psychotic Disorders.

Schizophr Bull 2021 04;47(3):731-739

Department of Psychology, University of Minnesota, Minneapolis, MN.

Background: Motivational deficits in people with psychosis may be a result of impairments in reinforcement learning (RL). Therefore, behavioral paradigms that can accurately measure these impairments and their change over time are essential.

Methods: We examined the reliability and replicability of 2 RL paradigms (1 implicit and 1 explicit, each with positive and negative reinforcement components) given at 2 time points to healthy controls (n = 75), and people with bipolar disorder (n = 62), schizoaffective disorder (n = 60), and schizophrenia (n = 68).

Results: Internal consistency was acceptable (mean α = 0.78 ± 0.15), but test-retest reliability was fair to low (mean intraclass correlation = 0.33 ± 0.25) for both implicit and explicit RL. There were no clear effects of practice for these tasks. Largely, performance on these tasks shows intact implicit and impaired explicit RL in psychosis. Symptom presentation did not relate to performance in any robust way.

Conclusions: Our findings replicate previous literature showing spared implicit RL and impaired explicit reinforcement in psychosis. This suggests typical basal ganglia dopamine release, but atypical recruitment of the orbitofrontal and dorsolateral prefrontal cortices. However, we found that these tasks have only fair to low test-retest reliability and thus may not be useful for assessing change over time in clinical trials.
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http://dx.doi.org/10.1093/schbul/sbaa165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084427PMC
April 2021

Using Computational Modelling to Capture Schizophrenia-Specific Reinforcement Learning Differences and Their Implications on Patient Classification.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 Apr 17. Epub 2021 Apr 17.

Background: Psychiatric diagnosis and treatment have historically taken a symptom-based approach, with less attention on identifying underlying symptom-producing mechanisms. Recent efforts have illuminated the extent to which different underlying circuitry can produce phenotypically similar symptomatology (e.g. psychosis in bipolar disorder vs schizophrenia). Computational modelling makes it possible to identify and mathematically differentiate behaviorally-unobservable, specific reinforcement-learning (RL) differences in schizophrenia (SZ) patients versus other disorders, likely due to a higher reliance on prediction-error(PE)-driven learning associated with basal ganglia, and under-reliance on explicit value representations associated with OFC.

Methods: We use a well-established probabilistic-RL task to replicate those findings in individuals with schizophrenia both on (N=120) and off (N=44) anti-psychotic medications, and include a patient comparison group of bipolar patients with psychosis (N=60) and healthy controls (n=72).

Results: Using accuracy, there was a main effect of group (F(3,279)=7.87, p<0.001, such that all patients groups were less accurate than controls. Using computationally derived parameters, both medicated and unmediated individuals with SZ, but not bipolar patients, demonstrated a reduced "mixing" parameter (F(3,295)=13.91,p<0.001), indicating less dependence on learning explicit value representations, as well as greater learning decay between training and test (F(1,289)=12.81, p<0.001). Unmedicated SZ also showed greater decision noise (F(3,295)=2.67, p=0.04).

Conclusions: Both medicated and unmedicated patients show overreliance on PE-driven learning, as well as significantly higher noise and value-related memory decay, compared to the healthy controls and the bipolar patients. Additionally, the computational model parameters capturing these processes can significantly improve patient/control classification, potentially providing useful diagnosis insight.
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http://dx.doi.org/10.1016/j.bpsc.2021.03.017DOI Listing
April 2021

Brain network mechanisms of visual shape completion.

Neuroimage 2021 Apr 18;236:118069. Epub 2021 Apr 18.

Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, 197 University Ave 07102, USA.

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<10), suggesting that such connections undergird shape completion. Functional connections from the dorsal attention network were key in modelling task activation differences in the secondary visual network. Dorsal attention and frontoparietal connections could also model activations in the remaining networks. Taken together, these results suggest that shape completion relies upon a sparsely distributed but densely interconnected network coalition that is centered in the secondary visual network, coordinated by the dorsal attention network, and inclusive of at least three other networks.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118069DOI Listing
April 2021

Management of repository corticotropin injection therapy for non-infectious uveitis: a Delphi study.

Acta Ophthalmol 2021 Mar 9. Epub 2021 Mar 9.

Massachusetts Eye Research & Surgery Institution (MERSI), Waltham, MA, USA.

Purpose: Diagnosis and management of non-infectious uveitis (NIU), a major cause of blindness worldwide, are challenging. Corticosteroids, the cornerstone of therapy, are not appropriate for long-term use, and while non-biologic and biologic immunomodulators may be used for some patients, data on their efficacy and safety in this population are limited. Repository corticotropin injection (RCI), believed to affect uveitis by multiple mechanisms, has received regulatory approval for treatment of ophthalmic diseases including posterior uveitis, but is not widely used or discussed in guidelines for the management of uveitis and ocular inflammatory diseases.

Methods: The index study employed a modified Delphi process with a panel of 14 US-based ophthalmologists. Consensus recommendations were developed through a series of three questionnaires. Panellists rated statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree).

Results: The Delphi panel provided consensus recommendations on examinations and testing needed for diagnosis, treatment goals, and the use of corticosteroids, as well as the use of non-biologic and biologic immunomodulators. The panel reached consensus that RCI may be considered for posterior and pan-uveitis, and dosing should be individualized for each patient. Dose reduction/discontinuation should be considered for excessive RCI-related toxicity, hyperglycaemia and/or diabetic complications, excessive costs, or remission ≥ 2 years. Patients should be weaned from RCI if uveitis is stable and well controlled. Adverse events during RCI therapy can be managed by appropriate interventions, with dose reduction/discontinuation considered if events are severe or recurrent.

Conclusions: Expert consensus suggests RCI may be an appropriate treatment option for some patients with uveitis when other therapies are ineffective or intolerable.
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http://dx.doi.org/10.1111/aos.14702DOI Listing
March 2021

Oculomics in Schizophrenia Research.

Schizophr Bull 2021 04;47(3):577-579

Department of Psychiatry, Yale University, New Haven, CT.

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http://dx.doi.org/10.1093/schbul/sbab011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084449PMC
April 2021

Sex differences in macular thickness of the retina in patients with psychosis spectrum disorders.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Feb 7;110:110280. Epub 2021 Feb 7.

Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Institute of Mental Health, Belgrade, Serbia.

Introduction: Imaging of retinal structure in psychosis spectrum disorders (PSD) is a novel approach to studying effect of this illness class on CNS structure. Studies of optical coherence tomography (OCT) have revealed significant reductions in regarding: retinal nerve fiber layer (RNFL), macular thickness (MT), ganglion cell-inner plexiform layer (GC-IPL) and macular volume (MV). Sex differences in retinal structure in PSD have not been previously explored.

Methods: This cross-sectional pilot study included 81 participant of age matched patients and controls. There were no differences between genders regarding illness duration and antipsychotic daily dose in the patient group. SD-OCT assessed RNFL, GC-IPL, MT, MV, and optic nerve cup-to-disc (C/D) ratio. In order to assess the main effects of illness, sex, and illness × sex interaction on the retinal parameters, general linear model was performed.

Results: Patients demonstrated abnormalities on all OCT indices. Effects of sex were observed for central subfield MT and C/D ratio, which were lower in females. An illness × sex interaction effect was observed for the left MT, indicating greater thinning in female patients.

Conclusion: Sex differences in OCT findings in PSD appear to be most prominent considering macular parameters. These preliminary data may have important implications for the valid interpretation of OCT findings as potential biomarkers for PSD.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110280DOI Listing
February 2021

Absence of Excess Intra-Individual Variability in Retinal Function in People With Schizophrenia.

Front Psychiatry 2020 20;11:543963. Epub 2020 Nov 20.

University Behavioral Health Care, Rutgers University, Piscataway, NJ, United States.

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.
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http://dx.doi.org/10.3389/fpsyt.2020.543963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714716PMC
November 2020

Predicting Attention-Shaping Response in People With Schizophrenia.

J Nerv Ment Dis 2021 03;209(3):203-207

Rutgers University, Behavioral Health Care, Piscataway Township, New Jersey.

Abstract: People with schizophrenia often experience attentional impairments that hinder learning during psychological interventions. Attention shaping is a behavioral technique that improves attentiveness in this population. Because reinforcement learning (RL) is thought to be the mechanism by which attention shaping operates, we investigated if preshaping RL performance predicted level of response to attention shaping in people with schizophrenia. Contrary to hypotheses, a steeper attentiveness growth curve was predicted by less intact pretreatment RL ability and lower baseline attentiveness, accounting for 59% of the variance. Moreover, baseline attentiveness accounted for over 13 times more variance in response to attention shaping than did RL ability. Results suggest attention shaping is most effective for lower-functioning patients, and those high in RL ability may already be close to ceiling in terms of their response to reinforcers. Attention shaping may not be a primarily RL-driven intervention, and other mechanisms of its effects should be considered.
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http://dx.doi.org/10.1097/NMD.0000000000001286DOI Listing
March 2021

Stronger tilt aftereffects in persons with schizophrenia.

J Abnorm Psychol 2021 Feb 10;130(2):186-197. Epub 2020 Dec 10.

Department of Psychology.

Individuals with schizophrenia may fail to appropriately use temporal context and apply past environmental regularities to the interpretation of incoming sensory information. Here we use the visual system as a test bed for investigating how prior experience shapes perception in individuals with schizophrenia. Specifically, we use visual aftereffects, illusory percepts resulting from prior exposure to visual input, to measure the influence of prior events on current processing. At a neural level, visual aftereffects arise due to attenuation in the responses of neurons that code the features of the prior stimulus (neuronal adaptation) and subsequent disinhibition of neurons signaling activity at the opposite end of the feature dimension. In the current study, we measured tilt aftereffects and negative afterimages, 2 types of aftereffects that reflect, respectively, adaptation of cortical orientation-coding neurons and adaptation of subcortical and retinal luminance-coding cells in persons with schizophrenia (PSZ; n = 36) and demographically matched healthy controls (HC; n = 22). We observed stronger tilt aftereffects in PSZ compared to HC, but no difference in negative afterimages. Stronger tilt aftereffects were related to more severe negative symptoms. These data suggest oversensitivity to recent regularities, in the form of stronger visual adaptation, at cortical, but not subcortical, levels in schizophrenia. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/abn0000653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100990PMC
February 2021

Visual Impairment and Mental Health: Unmet Needs and Treatment Options.

Clin Ophthalmol 2020 3;14:4229-4251. Epub 2020 Dec 3.

Departments of Psychiatry, Neuroscience, and Ophthalmology, University of Rochester, Rochester, NY, USA.

Purpose: An estimated 2.2 billion people are visually impaired worldwide. Given that age-related vision loss is a primary cause of vision impairment, this number is projected to rise with increases in average lifespan. Vision loss often results in significant disability and is associated with a substantial economic burden, reduced quality-of-life, concurrent medical issues, and mental health problems. In this review, the mental health needs of people with vision impairment are examined.

Patients And Methods: A review of recent literature on mental health outcomes and current treatments in people with visual impairment was conducted.

Results: Considerable data indicate that rates of depression and anxiety are elevated among people with visual impairments. Moreover, individuals of lower socioeconomic status may be at increased risk for vision impairment and subsequent mental health problems. Existing psychosocial interventions for improving mental health in people with visual impairment show some promise, but are limited by low adherence and lack generalizability.

Conclusion: In order to improve outcomes, a better understanding of the mechanisms linking visual impairment and poor mental health is needed. It will also be essential to develop more effective interventions and expand access to services to improve the detection and treatment of mental health problems in this population.
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http://dx.doi.org/10.2147/OPTH.S258783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721280PMC
December 2020

Flash Electroretinography Parameters and Parkinson's Disease.

J Parkinsons Dis 2021 ;11(1):251-259

Department of Psychiatry, Rutgers - Robert Wood Johnson Medical School, Piscataway, NJ, USA.

Background: Parkinson's disease (PD) is known to affect retinal structure and activity. As such, retinal evaluations may be used to develop objective and possibly early PD diagnostic tools.

Objective: The aim of this study was to investigate the effects of Parkinson's disease (PD) manifestation and treatment on retinal activity.

Methods: Data were collected on 21 participants diagnosed with PD, including the number of medications taken, clinical scales and flash electroretinography (fERG) measurements, under light-adapted and dark-adapted conditions. The fERG parameters measured included a-wave and b-wave amplitude and implicit time (i.e., latency). First, we investigated correlations between symptom measure scores and the fERG parameters. Next, we divided participants into two groups based on their antiparkinsonian medication load and analyzed differences between these groups' fERG parameters.

Results: fERG parameters were strongly correlated with a number of clinical variables, including motor and non-motor symptoms and age at PD onset. Photoreceptor cell implicit time was longer among participants taking one or less antiparkinsonian medication as compared to those taking two or more. However, overall there was not strong evidence of a relationship between the number of antiparkinsonian medications taken and the fERG parameters.

Conclusion: Findings suggest that fERG may be a useful, non-intrusive measure of retinal, and, perhaps overall CNS function, in PD. However, additional studies in larger samples are needed to clarify this association.
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http://dx.doi.org/10.3233/JPD-191830DOI Listing
January 2021

Opposite effects of smoking and nicotine intake on cognition.

Psychiatry Res 2020 11 3;293:113357. Epub 2020 Aug 3.

Federal University of Paraiba, Department of Psychology, Joao Pessoa, Brazil; Perception, Neuroscience, and Behaviour Laboratory, Joao Pessoa, Brazil.

Our main purpose was to investigate how smoking and nicotine interacted with specific aspects of cognitive functioning. The research was conducted in two parts: (i) an investigation of cognition in heavy smokers and healthy nonsmokers, and (ii) an investigation of cognition in healthy nonsmokers enrolled in a clinical trial involving administration of nicotine gum. Results indicated that the relationship between smoking and nicotine was characterized by an inverted U-shaped effect. On the one hand, cognitive test performance of the heavy smokers group was reduced on all of the cognitive tasks used here. On the other hand, healthy nonsmokers who used 2-mg of nicotine gum performed better, whilst the 4-mg group performed worse than the 2-mg and the placebo group. Demographic data were not related to the cognitive tasks. These data suggest that small doses of nicotine can have an activating function that leads to improved cognition, while heavy smoking on a chronic (and possibly acute) basis leads to cognitive impairment.
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http://dx.doi.org/10.1016/j.psychres.2020.113357DOI Listing
November 2020

Both unmedicated and medicated individuals with schizophrenia show impairments across a wide array of cognitive and reinforcement learning tasks.

Psychol Med 2020 Aug 17:1-11. Epub 2020 Aug 17.

Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.

Background: Schizophrenia is a disorder characterized by pervasive deficits in cognitive functioning. However, few well-powered studies have examined the degree to which cognitive performance is impaired even among individuals with schizophrenia not currently on antipsychotic medications using a wide range of cognitive and reinforcement learning measures derived from cognitive neuroscience. Such research is particularly needed in the domain of reinforcement learning, given the central role of dopamine in reinforcement learning, and the potential impact of antipsychotic medications on dopamine function.

Methods: The present study sought to fill this gap by examining healthy controls (N = 75), unmedicated (N = 48) and medicated (N = 148) individuals with schizophrenia. Participants were recruited across five sites as part of the CNTRaCS Consortium to complete tasks assessing processing speed, cognitive control, working memory, verbal learning, relational encoding and retrieval, visual integration and reinforcement learning.

Results: Individuals with schizophrenia who were not taking antipsychotic medications, as well as those taking antipsychotic medications, showed pervasive deficits across cognitive domains including reinforcement learning, processing speed, cognitive control, working memory, verbal learning and relational encoding and retrieval. Further, we found that chlorpromazine equivalency rates were significantly related to processing speed and working memory, while there were no significant relationships between anticholinergic load and performance on other tasks.

Conclusions: These findings add to a body of literature suggesting that cognitive deficits are an enduring aspect of schizophrenia, present in those off antipsychotic medications as well as those taking antipsychotic medications.
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http://dx.doi.org/10.1017/S003329172000286XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095353PMC
August 2020

Development and Evaluation of a Visual Remediation Intervention for People with Schizophrenia.

J Psychiatr Brain Sci 2020 20;5. Epub 2020 Jul 20.

Clinical Research Department, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA.

It is now well documented that schizophrenia is associated with impairments in visual processing at all levels of vision, and that these disturbances are related to deficits in multiple higher-level cognitive and social cognitive functions. Visual remediation methods have been slow to appear in the literature as a potential treatment strategy to target these impairments, however, in contrast to interventions that aim to improve auditory and higher cognitive functions in schizophrenia. In this report, we describe a National Institute of Mental Health (NIMH)-funded R61/R33 grant that uses a phased approach to optimize and evaluate a novel visual remediation intervention for people with schizophrenia. The goals of this project are: (1) in the R61 phase, to establish the optimal components and dose (number of sessions) of a visual remediation intervention from among two specific visual training strategies (and their combination) for improving low and mid-level visual functions in schizophrenia; and (2) in the R33 phase, to determine the extent to which the optimal intervention improves not only visual processing but also higher-level cognitive and role functions. Here we present the scientific background for and innovation of the study, along with our methods, hypotheses, and preliminary data. The results of this study will help determine the utility of this novel intervention approach for targeting visual perceptual, cognitive, and functional impairments in schizophrenia.
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http://dx.doi.org/10.20900/jpbs.20200017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418924PMC
July 2020

Enhancing Psychosis Risk Prediction Through Computational Cognitive Neuroscience.

Schizophr Bull 2020 12;46(6):1346-1352

Departments of Psychology, Psychiatry, Medical Social Sciences, Institutes for Policy Research (IPR) and Innovations in Developmental Sciences (DevSci), Evanston and Chicago, IL.

Research suggests that early identification and intervention with individuals at clinical high risk (CHR) for psychosis may be able to improve the course of illness. The first generation of studies suggested that the identification of CHR through the use of specialized interviews evaluating attenuated psychosis symptoms is a promising strategy for exploring mechanisms associated with illness progression, etiology, and identifying new treatment targets. The next generation of research on psychosis risk must address two major limitations: (1) interview methods have limited specificity, as recent estimates indicate that only 15%-30% of individuals identified as CHR convert to psychosis and (2) the expertise needed to make CHR diagnosis is only accessible in a handful of academic centers. Here, we introduce a new approach to CHR assessment that has the potential to increase accessibility and positive predictive value. Recent advances in clinical and computational cognitive neuroscience have generated new behavioral measures that assay the cognitive mechanisms and neural systems that underlie the positive, negative, and disorganization symptoms that are characteristic of psychotic disorders. We hypothesize that measures tied to symptom generation will lead to enhanced sensitivity and specificity relative to interview methods and the cognitive intermediate phenotype measures that have been studied to date that are typically indicators of trait vulnerability and, therefore, have a high false positive rate for conversion to psychosis. These new behavioral measures have the potential to be implemented on the internet and at minimal expense, thereby increasing accessibility of assessments.
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http://dx.doi.org/10.1093/schbul/sbaa091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707066PMC
December 2020

Structural imaging of the retina in psychosis spectrum disorders: current status and perspectives.

Curr Opin Psychiatry 2020 09;33(5):476-483

Institute for Mental Health, Belgrade, Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Purpose Of Review: Structural changes of the retina in schizophrenia and other psychotic disorders seem plausible as these conditions are accompanied by widespread morphological abnormalities of the brain. Advances in structural retinal imaging have led to the possibility of precise quantification of individual retinal layers, using optical coherence tomography (OCT) scanners.

Recent Findings: The aggregation of information related to OCT findings in schizophrenia has resulted in three metaanalyses, which are currently described. Areas where retinal changes were reported include retinal nerve fiber layer (RNFL), ganglion cell layer complex (GCC), macular volume, and macular thickness, but findings on affected retinal segments vary to some extent across studies. Discrepancies in individual studies could be because of small samples, heterogeneity within schizophrenia (phase of the illness, illness duration, predominant symptomatology), inconsistent reporting of antipsychotic therapy, insufficient control of confounding variables (somatic comorbidities, smoking, and so on), and use of the different types of OCT scanners.

Summary: Exploration of potential disturbances in retinal architecture could provide new insights into neuronal changes associated with psychosis spectrum disorders, with potential to elucidate the nature and timing of developmental, progressive, inflammatory, and degenerative aspects of neuropathology and pathophysiology, and to assist with characterizing heterogeneity and facilitating personalized treatment approaches.
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http://dx.doi.org/10.1097/YCO.0000000000000624DOI Listing
September 2020

Modeling perception and behavior in individuals at clinical high risk for psychosis: Support for the predictive processing framework.

Schizophr Res 2020 12 24;226:167-175. Epub 2020 Jun 24.

Yale University School of Medicine and the Connecticut Mental Health Center, New Haven, CT, United States of America. Electronic address:

Early intervention in psychotic spectrum disorders is critical for maximizing key clinical outcomes. While there is some evidence for the utility of intervention during the prodromal phase of the illness, efficacy of interventions is difficult to assess without appropriate risk stratification. This will require biomarkers that robustly help to identify risk level and are also relatively easy to obtain. Recent work highlights the utility of computer-based behavioral tasks for understanding the pathophysiology of psychotic symptoms. Computational modeling of performance on such tasks may be particularly useful because they explicitly and formally link performance and symptom expression. Several recent studies have successfully applied principles of Bayesian inference to understanding the computational underpinnings of hallucinations. Within this framework, hallucinations are seen as arising from an over-weighting of prior beliefs relative to sensory evidence. This view is supported by recently-published data from two tasks: the Conditioned Hallucinations (CH) task, which determines the degree to which participants use expectations in detecting a target tone; and a Sine-Vocoded Speech (SVS) task, in which participants can use prior exposure to speech samples to inform their understanding of degraded speech stimuli. We administered both of these tasks to two samples of participants at clinical high risk for psychosis (CHR; N = 19) and healthy controls (HC; N = 17). CHR participants reported both more conditioned hallucinations and more pre-training SVS detection. In addition, relationships were found between participants' performance on both tasks. On computational modeling of behavior on the CH task, CHR participants demonstrate significantly poorer recognition of task volatility as well as a trend toward higher weighting of priors. A relationship was found between this latter effect and performance on both tasks. Taken together, these results support the assertion that these two tasks may be driven by similar latent factors in perceptual inference, and highlight the potential utility of computationally-based tasks in identifying risk.
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http://dx.doi.org/10.1016/j.schres.2020.04.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774587PMC
December 2020

Visual Impairments in Schizophrenia: Their Significance and Unrealized Clinical Potential.

Psychiatr Danub 2020 ;32(1):72-73

Department of Psychiatry, University of Rochester Medical Center, 300 Crittenden Boulevard, Rochester, NY 14642, USA,

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January 2021

The place of the retina in psychiatry: Uniting neurobiological and neurodevelopmental research with clinical research in psychiatric disorders.

Schizophr Res 2020 05 3;219:1-4. Epub 2020 Apr 3.

Department of Psychiatry University of Rochester Medical Center. Electronic address:

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http://dx.doi.org/10.1016/j.schres.2020.03.028DOI Listing
May 2020

The effects of a staff-training program in behavior management and social-learning principles on staff-patient interactions within a psychiatric rehabilitation inpatient unit.

Am J Orthopsychiatry 2020 5;90(4):419-431. Epub 2020 Mar 5.

Department of Psychiatry.

Despite the existence of effective behavioral interventions for people diagnosed with serious mental illness (SMI), these continue to be underutilized. Barriers to implementation include a low frequency of staff-patient interactions, as well as a lack of knowledge about, and negative attitudes toward, behavioral interventions. Therefore, we examined the effects of a mandatory behavioral staff-training program on staff-patient interactions on a long-term psychiatric inpatient program for individuals with SMI. Staff-training consisted of two-phases: didactic training followed by a written exam, and in vivo training and assessment. From pre- to posttraining, all staff demonstrated increased positive and therapeutic behaviors and decreased negative behaviors when interacting with patients. Additionally, at baseline, nonmedical staff (psychologists, social workers) displayed significantly more therapeutic and fewer negative behaviors compared with medical staff (psychiatrists, nurses, mental health workers), and this pattern persisted at posttraining despite improvements in both groups. Importantly, completion of the staff-training program was associated with improvements in patient behavior. Although both written and in vivo test scores significantly predicted change in negative staff behaviors toward patients, the in vivo test performance increased predictive ability over and above that of written test performance. Staff who disagreed with behavioral management principles displayed less improvement in negative behaviors from pre- to postassessment. These data have implications for clarifying staff training needs in programs for chronically ill people with SMI. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/ort0000443DOI Listing
March 2021

Progress, Possibilities, and Pitfalls in Electroretinography Research in Psychiatry.

Biol Psychiatry 2020 02;87(3):202-203

Department of Psychiatric Rehabilitation and Counseling Professions, Rutgers University, Piscataway, New Jersey.

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http://dx.doi.org/10.1016/j.biopsych.2019.10.028DOI Listing
February 2020

Relationships Between Working Alliance and Outcomes in Group Therapy for People Diagnosed with Schizophrenia.

Psychosis 2020 16;12(4):348-358. Epub 2020 Jun 16.

Rutgers University, Behavioral Health Care, 671 Hoes Ln W, Piscataway Township, NJ 08854.

Working alliance (WA) is an important predictor of treatment outcomes in therapy. Forming a strong WA can be challenging with people diagnosed with schizophrenia, and differences between client-rated and clinician-rated WA have been found in this population. This project examined WA in people diagnosed with schizophrenia who completed a skills training and attention shaping group intervention. Paired samples t-tests revealed differences between client and clinician ratings on the Working Alliance Inventory Short Form (WAI-S). Clinician-rated WAI-S scores were related to symptom severity, cognitive functioning, and attention during group sessions. Yet, the primary hypothesis was not supported as WAI-S scores were unrelated to clients' treatment response. Clinician-rated WAI-S was found to partially mediate the relationship between negative symptoms and overall attention. Client-rated WAI-S scores were associated with client measures of self-efficacy and mastery. Results reinforce the importance of working alliance in the treatment of those diagnosed with schizophrenia and indicate clinical and functional factors that may influence the quality of WA.
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http://dx.doi.org/10.1080/17522439.2020.1779796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958934PMC
June 2020

Dynamic reorganization of the frontal parietal network during cognitive control and episodic memory.

Cogn Affect Behav Neurosci 2020 02;20(1):76-90

Imaging Research Center, University of California at Davis, Sacramento, CA, USA.

Higher cognitive functioning is supported by adaptive reconfiguration of large-scale functional brain networks. Cognitive control (CC), which plays a vital role in flexibly guiding cognition and behavior in accordance with our goals, supports a range of executive functions via distributed brain networks. These networks process information dynamically and can be represented as functional connectivity changes between network elements. Using graph theory, we explored context-dependent network reorganization in 56 healthy adults performing fMRI tasks from two cognitive domains that varied in CC and episodic-memory demands. We examined whole-brain modular structure during the DPX task, which engages proactive CC in the frontal-parietal cognitive-control network (FPN), and the RiSE task, which manipulates CC demands at encoding and retrieval during episodic-memory processing, and engages FPN, the medial-temporal lobe and other memory-related networks in a context dependent manner. Analyses revealed different levels of network integration and segregation. Modularity analyses revealed greater brain-wide integration across tasks in high CC conditions compared to low CC conditions. Greater network reorganization occurred in the RiSE memory task, which is thought to require coordination across multiple brain networks, than in the DPX cognitive-control task. Finally, FPN, ventral attention, and visual systems showed within network connectivity effects of cognitive control; however, these cognitive systems displayed varying levels of network reorganization. These findings provide insight into how brain networks reorganize to support differing task contexts, suggesting that the FPN flexibly segregates during focused proactive control and integrates to support control in other domains such as episodic memory.
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http://dx.doi.org/10.3758/s13415-019-00753-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018593PMC
February 2020

Retinal structural abnormalities in young adults with psychosis spectrum disorders.

Prog Neuropsychopharmacol Biol Psychiatry 2020 03 21;98:109825. Epub 2019 Nov 21.

Clinic for Psychiatry, Clinical Centre of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Background: Structural retinal architecture in living organisms became measurable with the development of optical coherence tomography (OCT) scanners. Single-layer analysis with spectral-domain OCT, among other techniques, may provide further insight into pathological changes in complex brain disorders such as psychosis spectrum disorders (PSD).

Methods: This study investigated potential thinning of retinal layers (retinal nerve fiber layer - RNFL, macular volume, macular thickness, ganglion cell-inner plexiform layer- GC-IPL, optic cup volume and cup-to-disk ratio) using a spectral-domain OCT device in 33 non-acute PSD patients (illness duration 5.9 ± 3.9 years) and 35 healthy controls.

Results: In comparison to age and gender matched controls, patients had bilateral reductions in GC-IPL layer thickness and macular volume. Macular central subfield thinning was found in the right eye, while average macular thickness was lower in the left eye only. RNFL thinning was not observed in patients in comparison to controls, but we noticed that status of this layer could be affected by daily dose of antipsychotics and by illness duration.

Conclusion: Taken together, our results reveal that retinal thinning is present in young adults with PSDs, but in comparison to the literature we found more prominent changes in both GC-IPL and macular volume/thickness, than in RNFL. Our findings may reflect synaptic loss and neuronal atrophy in non-acute young patients with psychosis.
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http://dx.doi.org/10.1016/j.pnpbp.2019.109825DOI Listing
March 2020

Issues in the Aggregation of Data on Retinal Structure and Function in Schizophrenia.

Schizophr Bull 2020 01;46(1):15-16

Departments of Psychiatry and Ophthalmology, Rutgers University - Robert Wood Johnson Medical School, New Brunswick, NJ.

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http://dx.doi.org/10.1093/schbul/sbz108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079813PMC
January 2020

Smaller visual arrays are harder to integrate in schizophrenia: Evidence for impaired lateral connections in early vision.

Psychiatry Res 2019 12 16;282:112636. Epub 2019 Nov 16.

Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA; University Behavioral Health Care, Rutgers Biomedical and Health Sciences, Rutgers University, Piscataway, NJ 08854, USA; Center for Cognitive Science, Rutgers University, Piscataway, NJ 08854, USA.

Long-range horizontal connections in early vision undergird a well-studied "collinear facilitation" effect, wherein a central low-contrast target becomes more detectable when flanked by collinear elements. Collinear facilitation is weaker in schizophrenia. Might lateral connections be responsible? To consider the possibility, we had 38 schizophrenia patients and 49 well-matched healthy controls judge the presence of a central low-contrast element flanked by collinear or orthogonal high-contrast elements.   The display (target+flankers) was scaled in size to produce a lower and higher spatial frequency ("SF") condition (4 and 10 cycles/deg, respectively).  Larger stimulus arrays bias processing towards feedback connections from higher-order visual areas; smaller arrays bias processing toward lateral connections. Patients had impaired facilitation relative to controls at higher but not lower SFs. Combining data from a past study on "contour integration" (in which subjects sought to detect chains of co-circular elements), we found correlated integration and facilitation performance at the higher SF and a similar effect of spatial scaling across SF, suggesting a common mechanism. In an exploratory analysis, worse contrast thresholds (without facilitation) correlated strongly with more premorbid dysfunction. In schizophrenia, inter-element filling-in worsens at smaller spatial scales potentially because of its increased reliance on impaired lateral connections in early vision.
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http://dx.doi.org/10.1016/j.psychres.2019.112636DOI Listing
December 2019

Schizophrenia and the retina: Towards a 2020 perspective.

Schizophr Res 2020 05 7;219:84-94. Epub 2019 Nov 7.

Rutgers University, Department of Psychology, United States. Electronic address:

Background: Differences between people with schizophrenia and psychiatrically healthy controls have been consistently demonstrated on measures of retinal function such as electroretinography (ERG), and measures of retinal structure such as optical coherence tomography (OCT). Since our 2015 review of this literature, multiple new studies have been published using these techniques. At the same time, the accumulation of data has highlighted the "fault lines" in these fields, suggesting methodological considerations that need greater attention in future studies.

Methods: We reviewed studies of ERG and OCT in schizophrenia, as well as data from studies whose findings are relevant to interpreting these papers, such as those on effects of the following on ERG and OCT data: comorbid medical conditions that are over-represented in schizophrenia, smoking, antipsychotic medication, substance abuse, sex and gender, obesity, attention, motivation, and influences of brain activity on retinal function.

Results: Recent ERG and OCT studies continue to support the hypothesis of retinal structural and functional abnormalities in schizophrenia, and suggest that these are relevant to understanding broader aspects of pathophysiology, neurodevelopment, and neurodegeneration in this disorder. However, there are differences in findings which suggest that the effects of multiple variables on ERG and OCT data need further clarification.

Conclusions: The retina, as the only component of the CNS that can be imaged directly in live humans, has potential to clarify important aspects of schizophrenia. With greater attention to specific methodological issues, the true potential of ERG and OCT as biomarkers for important clinical phenomena in schizophrenia should become apparent.
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http://dx.doi.org/10.1016/j.schres.2019.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202990PMC
May 2020

Bromfenac Ophthalmic Solution 0.07% Versus Nepafenac Ophthalmic Suspension 0.3% for Post-Cataract Surgery Inflammation: A Pilot Study of Identical Dosing Regimens with Pre-Surgical "Pulse" Dose.

Ophthalmol Ther 2019 Dec 24;8(4):577-587. Epub 2019 Sep 24.

Silverstein Eye Centers, Kansas City, MO, USA.

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 < 0.05) higher in the bromfenac group (23.8 and 52.4%, respectively) versus the nepafenac group (0.0 and 20.8%, respectively). Visual acuity was similar between groups at each study visit, as were mean retinal thickness and change from baseline in retinal thickness. Rescue medication (typically difluprednate) was given on or before day 15 to 13 patients in each treatment group (bromfenac, 54.2%; nepafenac, 52.0%). There were no adverse events considered to be related to either treatment.

Conclusions: The results of this small pilot study suggest that once-daily bromfenac 0.07% produces similar benefits with regard to postsurgical inflammation, VA, and retinal thickness as once-daily nepafenac 0.3%, and possibly has a faster onset of anti-inflammatory action, when compared using identical dosing regimens.

Funding: Bausch & Lomb Incorporated.

Trial Registration: NCT03886779.
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http://dx.doi.org/10.1007/s40123-019-00215-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858409PMC
December 2019