Division of Schizophrenia Research Studies

Current Studies

  • Optical Coherence Tomography Pilot Investigation of Retinal Integrity in Schizophrenia
    Principal Investigator: Steven Silverstein, Ph.D.

    The purpose of this study is to determine whether thinning of the retina in people with schizophrenia can serve as a proxy for other important illness-related characteristics (e.g., loss of brain tissue, visual and cognitive impairments, duration of illness, and level of functioning). This is a pilot study whose purpose is to determine effect sizes so that, if predicted results are obtained, we can design an adequately powered study for a grant application. Our hypotheses are that retinal thinning will be related to: 1.) impairments in aspects of visual processing (e.g., contrast sensitivity, perceptual organization) whose origin in the eye vs. brain is currently unknown; 2.) reduced cognitive capacity; 3.) longer duration of illness; 4.) reduced levels of socio-vocational functioning. Recent OCT studies have also documented retinal and macular thinning in schizophrenia, with the only negative report to date having used an older, lower-resolution machine. Moreover, the extent of retinal thinning was found to correlate with duration of illness, suggesting that it may serve as a marker for progressive cortical tissue loss in schizophrenia.  In light of these findings, it has been suggested that retinal thinning may be a cause of the visual processing impairments found in schizophrenia; however, this hypothesis has never been tested. Finally, although retinal thinning has been associated with duration of illness in schizophrenia, and with level of functional disability in Parkinson’s Disease, the extent to which it can serve as a biomarker for functional disability in schizophrenia is not known.  We will evaluate the relationship between retinal thinning and socio-vocational functioning in patients diagnosed with schizophrenia using a standardized measure of functional outcome that we have used in other studies at Rutgers (including ongoing studies).

    Funding: Department Funded (UBHC-Division of Schizophrenia Research)

  • Project 1R01MH093439: Perceptual Organization as a Biomarker of Schizophrenia

    Principal Investigator: Steven Silverstein, Ph.D. and Thomas V. Papathomas, Ph.D.

    The NIMH MATRICS and CNTRICS initiatives have clarified the domains of cognitive functioning that are most relevant to treatment development targeting improved cognition and functioning in people with schizophrenia. These projects also identified specific tasks that are psychometrically sound and well validated in patient populations, and that, in the case of CNTRICS, have well understood neurophysiology. More recently, interest has increased in identifying tasks that meet these criteria and that are sensitive to treatment effects. Identification of such tasks is important for grounding our understanding of illness progression and recovery processes within a cognitive neuroscience framework. This information would also allow for cognitive neuroscience-based indicators of treatment responsiveness, and therefore for more targeted drug development efforts and early prediction of medication response. Promising candidates for this type of task are measures of perceptual organization. Selected tests of perceptual organization meet the criteria of psychometric soundness (including avoidance of generalized deficit confounds), validation in patient studies, and known neurophysiology, although evidence regarding treatment effects at this point comes from very limited data. We are now conducting the first study in which schizophrenia patients are followed-up from the acute to stabilization to stable phases of illness, to determine whether perceptual organization dysfunction normalizes over the course of recovery. We will also determine if perceptual organization indices are most relevant for an illness subtype characterized by poor premorbid functioning, poor prognosis, and disorganized symptoms - relationships suggested by past studies. In addition, we will examine the course of perceptual organization in a first-episode population, which has not been previously described. Some evidence suggests that perceptual organization is normal or exaggerated at first episode. We will clarify whether the impairment is present at first episode or whether it develops within 15 months after initial hospitalization. For patients who begin to demonstrate impairment during the follow-up period, we will determine with what clinical and functioning changes the emerging abnormality is associated. We will explore these issues using a follow-up design in which we will enroll first-episode and later-episode schizophrenia patients (and a healthy control group), test them at hospital admission and discharge, and then again every 3 months, over a 15-month period. We will also examine covariation between changes in perceptual organization and changes in symptoms and level of functioning. The proposed project is consistent with two objectives from the NIMH Strategic Plan: 1) Strategy 1.3: Identify and integrate biological markers (biomarkers) and behavioral indicators associated with mental disorders; and 2) Strategy 2.1: Define the developmental trajectories of mental disorders. This study will determine the extent to which performance-based indices from promising perceptual organization tasks serve as biomarkers of illness processes for schizophrenia in general, or for a severely disabled illness subtype.

    Funding: National Institute of Mental Health (NIMH)

  • Randomized Controlled Trial of Treatment for Internalized Stigma in Schizophrenia

    Principal Investigators: Philip Yanos, Ph.D. (John Jay) and Steven Silverstein, Ph.D.

    Groups of persons with schizophrenia will be given Narrative Enhancement/Cognitive Therapy (NECT), and outcomes will be compared relative to groups given established group therapies without stigma education. The aim of this research is to develop strategies that could improve self (internalized) stigma often experienced by individuals with serious mental illness. It is hoped that the results of this study will help future patients suffering from schizophrenia to experience some resolution of difficulties associated with self-esteem and perceived self-stigma issues. The results will also be useful for determining the efficacy of different therapy treatments.

    Funding: National Institute of Mental Health (NIMH)

  • 3/5 – Cognitive Neuroscience Task Reliability & Clinical Applications Consortium

    Principal Investigator: Steven Silverstein, Ph.D. and Deanna Barch, Ph.D. (Washington University, St. Louis)

    Traditional conceptualizations of disorders based on phenomenology are increasingly recognized as limited, but to date we have lacked a clear path toward a more valid approach. The Research Domain Criteria (RDoC) initiative has identified one such pathway – examination of behavioral endpoints linked to known neural systems forming the basis of core dimensions of psychopathology. This renewed project will provide new insights into the cognitive and emotional processes underlying core symptom dimensions in major mental illness and provides a new set of valid and reliable tools addressing the aims of RDoC and Objective 1.4 of the NIMH Strategic Plan: “Develop new ways of classifying disorders based on dimensions of observable behaviors and brain functions.” This work will also continue to facilitate assessing the impact of treatments focused on cognitive function and negative symptoms. This competitive renewal of the Cognitive Neuroscience Test Reliability and Clinical applications (CNTRaC) Consortium will optimize measures of six constructs from two core RDoC domains: Cognitive Systems (focus on working memory, WM) and Positive Valence Systems (focus on implicit and explicit positive and negative reinforcement learning and reversal learning). These are central constructs for understanding psychopathology, and we will use these measures to understand how deficits in these domains contribute to impairments across traditional diagnostic boundaries (i.e., schizophrenia (SZ), schizoaffective disorder (SZAD), bipolar disorder (BPD)). During the previous funding period we successfully developed and disseminated for public use (cntrics.ucdavis.edu) measures of three constructs identified by RDoC (Goal Maintenance in WM, Relational Encoding and Retrieval and Visual Integration [perception]) and highlighted in the NIMH CNTRICS initiative. This proposal utilizes the CNTRaC infrastructure and expertise to optimize measures of WM capacity, positive and negative reinforcement learning (implicit and explicit) and reversal learning, and then applies them together with previously validated measures to advance our understanding of core dimensions of psychopathology.

    Funding: National Institute of Mental Health (NIMH)

  • Developmental, Clinical, Cognitive, and Demographic Characteristics of Psychiatric Patients With a Serious Mental Illness and a Recent History of Violent Behavior

    Principal Investigator: Steven Silverstein, Ph.D.

    The overall purpose of this research is to help us understand better what factors are related to having had committed violence during a recent relapse of a psychiatric condition. In particular, we are interested in learning whether violent behavior can be understood as being related to a combination of factors such as development (e.g., a history of violent behavior during childhood and adolescence), symptoms (e.g., hallucinations, paranoid thoughts); cognition (e.g., problem solving skills), and demographics (e.g., age, gender, income, etc.) and if these characteristics can discriminate violent from nonviolent patients diagnosed with a psychotic disorder.  In addition, the study will determine which variables have the strongest relationships with violent behavior.  Although the study does not involve a longitudinal component, and does not attempt to predict future violence, it can be assumed, based on much past literature, that patients with a history of violent behavior are at highest risk for committing violent behavior in the future; therefore, the data from this study can inform efforts at risk assessment and identification of treatment targets for people with a psychotic disorder who are the highest risk of violence.

    Funding: Department Funded Pilot Study

  • Neural Mechanisms of Perceptual Organization Deficits Across the Schizo-bipolar Spectrum

    Principal Investigator: Brian Keane, Ph.D.

    "In this grant funded study, we employ functional neuroimaging to investigate the neural basis as to why people with schizophrenia are less able to create structure from fragmented or ambiguous visual information. The proposed research will also identify the neural mechanisms of perceptual organization in bipolar disorder . Finally, the proposed research will clarify the extent to which the neural and behavioral markers of perceptual organization impairment vary with dimensions that cut across the schizo-bipolar spectrum, so as to ultimately better identify individuals who are at risk or who respond better to treatment.”

    Funding: NIH Career Development Award (K01MH108783-01A1) to BPK

  • Prediction of Response to Attention Shaping with Laboratory Measures of Reinforcement Learning

    Principal Investigator: Steven Silverstein, Ph.D.

    This study is being done to see whether a method for teaching social skills to people with schizophrenia leads to more benefits for some people than others. This teaching method aims to increase people’s attention spans during group sessions, as a way to help people remember and learn the material that is being taught.  This is important because many people with schizophrenia have attention problems that limit how much they remember and learn from therapy groups that would otherwise be helpful to them.  We want to know if some people learn differently than others and if this affects how much you can improve your attention skills in this group.

    Funding: National Institute of Mental Health (NIMH)

  • Motion and Form Contributions to Biological Motion Deficits in Schizophrenia

    Principal Investigator: Brian Keane, Ph.D.

    Funding: Department Funded

  • An Effectiveness Study of Substance Abuse Prevention Services for Children with Conduct Disorders

    Principal Investigator: Steven Silverstein, Ph.D.

    The goal of the project is to provide children who are at elevated at-risk for the development of substance abuse issues and their families with a suite of interventions that target the individual and family-level factors that contribute to initiation of substance use and the development of substance use disorders. The purpose of the study is to evaluate the effectiveness of a novel combination of behavioral interventions for reducing the development of substance abuse disorders in youth at high risk for developing them. The interventions included in this project focus on social-emotional learning, cognitive enhancement, affect management (biofeedback), and family therapy.

    Funding: NJ Division of Mental Health and Addiction Services

Prior Studies

  • Project EPPS: Efficacy of Pregnenolone in Patients with Schizophrenia

    Principal Investigator: Adam Savitz and Site PI: Steven M. Silverstein, Ph.D.

    The specific aim of this study is to determine whether the FDA approved dietary supplement, pregnenolone, when taken with the prescribed medications for schizophrenia, improves negative symptoms and cognitive function. The hypothesis guiding this study proposes that pregnenolone, by improving negative symptoms and cognitive function, will produce a greater improvement in the quality of life of patients with schizophrenia than placebo. The primary objective of this study is to compare patients on pregnenolone to patients on a placebo, added to each patient's individual pharmaceutical treatment managed by their primary care physician and / or psychiatrist. Specifically, we expect that patients taking pregnenolone will show greater improvement in negative symptoms of schizophrenia, cognitive function, and quality of life, compared to patents receiving placebo. These will be measured with symptom interviews, computerized tests of cognitive function, and measures of quality of life. The secondary objective of this study is to determine whether pregnenolone is well tolerated in schizophrenia, and whether the side effects are minimal, compared to placebo. Tolerability of pregnenolone will be assessed with several established and well-validated measures of medication side-effects and adverse reactions.

    Funding: Stanley Medical Research Institute

  • Spatial Frequency Contributions to Contour Integration Deficits in Schizophrenia

    Principal Investigator: Brian Keane, Ph.D

    Contour integration (CI) refers to the ability to represent spatially segregated edges as a single continuous contour. Numerous studies suggest that people with schizophrenia (SZ) are impaired at contour integration, but the mechanisms, time-course, and clinical implications of the impairment are just beginning to be explored. To shed light on this issue, we conduct a two phase psychophysical investigation. In the first phase, we will satisfy NIMH Strategy 1.1, and clarify the neural mechanisms behind the deficit (Aim 1). Clinical CI studies to date have almost exclusively employed lower spatial frequency contour elements (< 7 cycles/deg), but converging evidence suggests that schizophrenia is characterized by magnocellular dysfunction and, correspondingly, impaired processing of lower spatial frequencies (< 8 cycles deg). To determine whether spatial frequency processing can account for CI deficits in SZ, a later-episode patient group and a matched healthy control group will perform 4 different tasks. The spatial frequency structure of the stimuli for each task will be varied to either include or not include low spatial frequencies. If CI deficits arise even with elements defined by high spatial frequencies, then impaired lateral interactions in early visual cortex would be evidenced as a core feature of schizophrenia. By contrast, if CI dysfunction arises only when lower spatial frequencies are available, then that would add to the growing evidence for magnocellular dysfunction in SZ, and would provide a new interpretation of results stemming from CI tasks. In the second data collection phase, we will satisfy NIMH Strategy 2.1 and examine the development of CI deficits from first-episode onward (Aim 2). Newly recruited subjects will be either healthy controls, first-episode patients, or later-episode patients. The tasks in this second phase will be the same as those that revealed between-group differences (p < 0.05) in the first phase. Importantly, this phase will provide the first data on whether CI deficits exist among people with schizophrenia who recently experienced their first psychotic episode. At the end of data collection, we will combine data across phases to make two determinations. First, we will assess if CI deficits' at either high or lower spatial frequencies' correlate with clinical variables such as: functional outcome, disorganized symptoms, positive/negative symptoms, and premorbid social functioning (Aim 3). Second, we will compare the four tasks on the basis of: between-group effect sizes, capacities to predict illness features, total duration, and drop-out rate (Aim 4). Evaluating the tasks in this way will guide future larger-scale studies aiming to further establish, explain, or make use of contour deficits in schizophrenia. In summary, the four aims achieved over two data collection phases will elucidate the neural mechanisms, time course, clinical correlates, and optimal measures of contour integration dysfunction in schizophrenia.

    Funding: F32MH094102 to BPK

  • Perception of Three-Dimensional Objects in Patients with Schizophrenia

    Principal Investigators: Steven Silverstein, Ph.D. and Thomas V. Papathomas, Ph.D.

    The specific aim of this study is to determine how patients with schizophrenia (SZ) perceive three-dimensional (3D) faces and objects differently from control subjects. The guiding hypothesis is that SZ patients emphasize the signals that come from their eyes and pay less attention to previous experiences and previous exposure to faces and objects.The study’s primary objective is to compare patients and non-clinical controls with the “hollow-mask illusion”, which is well known to demonstrate perceptual differences between the two groups. The second objective is to compare differences in the strength of the “reverse perspective illusion” between patients and controls; this illusion also exhibits reversal of depth, as does the hollow-mask illusion. The third major objective is to compare the two groups on their ability to use visual motion signals and stereo vision to influence the strength of the hollow-mask illusion. The final major objective is to compare the magnitude of the “hollow-mask inversion effect” (namely, the weakening of the illusion when the upright hollow mask is turned upside down) between patients and controls.

    Funding: Department Funded

  • Processing of Global Form in Faces and Letters in People with Schizophrenia

    Principal Investigators: Steven Silverstein, Ph.D. and Thomas V. Papathomas, Ph.D.

    The specific aim of this study is to further investigate perceptual organization impairment in schizophrenia patients using three well-validated measures.  Specifically, we are using two measures of perception that patients with BDD have performed abnormally on, indicating a perceptual organization impairment in that disorder.  The third task has been validated in healthy control and patients with frontal and temporal lobe lesions, both areas relevant to Schizophrenia and BDD.  The goal of this pilot study is to develop a preliminary conclusion as to whether schizophrenia and BDD can be viewed as being on a continuum of severity of perceptual organization impairment.  This is consistent with the NIMH Research Domain Criteria (RDoC) initiative, which aims to identify those core behavioral and biological processes that represent dimensions of functioning on which extremes represent mental illness.

    Funding: Department Funded

  • Project: Disorganization as a modifying influence in schizophrenia

    Principal Investigators: Keith Feigenson, Ph.D.

  • We are researching the implication that disorganization is not simply a symptom of schizophrenia, but a trait that varies in the general population and that may be a modifying influence on schizophrenia (i.e., if a person has schizophrenia and is high on disorganization then the clinical presentation is modified in the direction of extreme disorganization). Non-clinical study participants complete a battery of self-report personality inventories (i.e., measures of perceived need for structure), self-report cognitive inventories (e.g., measures of attention and memory failures, and cognitive slippage) and psychophysical tasks of perceptual organization. We hypothesize that individuals performing in the higher range on measures of disorganization will score more abnormally on psychophysical measures of perceptual organization. We are currently over halfway through data colletion (N=80) and data thus far confirm the study's hypothesis. In addition, with a grant from the Rutgers University Brain Imagine Center (RUBIC), we are examining this issue using functional connectivity data collected during performance of the perceptual organization tasks.

    Funding: Division of Schizophrenia Research Discretionary fund, RUBIC

  • Endophenotypes and Schizotypy: Comparing Covariance Matrices

    Principal Investigators: Mathew Roche

    This project sought to explore the similarity of the multivariate relationships between putative endophenotypes in samples of schizotypes recruited using different ascertainment methods. More specifically, we identified schizotypes using the psychometric and familial approaches and had them complete ratio scale-based assessments (cf. observer ratings) of sustained attention, working memory, subtle thought disorder, and working memory. We hypothesized that the two schizotypic groups would evidence similar patterns of relationships between performance on the endophenotypic tasks and that this pattern of relationships would distinguish them from non-schizotypic controls.

  • Genetic factors involved in a subtype of schizophrenia characterized by poor premorbid functioning, perceptual organization impairments, and disorganized symptoms.

    Principal Investigator: Jamie Joseph

    Visual perceptual deficits are a significant impairment in a subset of schizophrenia patients. Previous studies have shown that perceptual organization deficits, poor premorbid functioning, disorganization symptoms and reduced cognitive organization are associated with a subtype of patient having poorer long-term outcomes. However the relation of these phenotypes to the genetic etiology of schizophrenia is still unclear.

    The aim of this study is to determine whether genetic alterations implicated in glutamate and GABA neurocircuitry in schizophrenia are associated with cognitive and clinical features that have themselves been linked in past studies: poor premorbid social functioning, perceptual organization impairment, and disorganized symptoms. 

    In order to investigate this, we are using a combination of clinical assessments and a battery of perceptual organization tasks. We are also collecting saliva samples to classify patients based on specific genotypes. We are doing this by determining genotypes of 384 single nucleotide polymorphisms (SNPs), selected based on their association with glutamate/GABA circuitry, since deficits in perceptual organization are thought to be related to the glutamate/GABA dysregulation in schizophrenia. These SNPs have also previously shown positive association with clinical diagnosis and/or poor premorbid functioning in schizophrenia. 

    The results from this study will help us better understand the multiple demographic, clinical and perceptual variables that interact in schizophrenia and how these variables may be stratified in relation to the genetic liability of schizophrenia. The results from this study may be useful in developing future personalized treatments for a subtype of patient manifesting visual perceptual deficits that coincides with a specific demographic, clinical and/or psychosocial developmental course.

    Funding : American Psychological Foundation

  • Cognitive Behavioral Treatment of Post-Traumatic Stress Disorder in Seriously Mental Illness Clients

    Principal Investigator: Kim Mueser; Site PI: Steven Silverstein

    People with severe mental illnesses (SMI) such as major mood disorders and schizophrenia are at elevated risk for multiple traumatization over their lifetimes. As a result of trauma exposure in both childhood and adulthood, persons with SMI have high rates of posttraumatic stress disorder (PTSD), with most prevalence estimates of current PTSD between 29% and 43%, which is more than 10 times the general population rate. As in the general population, PTSD in people with SMI is associated with high levels of distress, disability, and increased service utilization, both medical and psychiatric. There is an urgent need for effective interventions that target PTSD and its consequences in this population in order to reduce the suffering associated with it and to improve the course of SMI. However, there are no evidence-based practices to effectively treat PTSD in the SMI population.

    To address this problem, we developed and standardized an individual 12-16 week cognitive-behavioral treatment (CBT) program, focused mainly on cognitive restructuring, for persons with SMI and PTSD. Based on the findings of a pilot study that showed feasibility and promising outcomes, we obtained NIMH R01 funding to conduct a randomized controlled trial (RCT) of the CBT program compared to treatment as usual (TAU) in people with SMI receiving public mental health services in New Hampshire and Vermont. Results of this trial confirmed the feasibility of the program, with high levels of client participation and retention in treatment. The intervention was clinically effective, with significantly greater improvements after treatment in PTSD symptoms for clients receiving CBT than TAU, as well as reduced severity of depression and other symptoms. Improvement was sustained at 3- and 6-month follow-ups. In order for this program to become an evidence-based practice, and one that can be broadly disseminated to and implemented by providers serving people with SMI, a number of crucial steps must be taken, including: 1) demonstrating treatment efficacy in urban, multi-ethnic populations (typical of clients with SMI in the U.S.); 2) proving that frontline providers can learn the program and implement it with fidelity; 3) assessing the impact of the program on functioning and well-being; and 4) evaluating the cost consequences to a behavioral health care service organization and potential impacts on local-area acute care services utilization associated with implementing the program. This study extends the research conducted in the initial R01 by addressing the following unique questions:

    Can frontline clinicians achieve the same effects with the CBT program as academically trained clinicians? In the initial R01 almost all CBT treatment was provided by Ph.D. level clinicians employed by Dartmouth Medical School, whereas in the proposed study all treatment will be provided by frontline, non-academic clinicians with masters level training.

    Will the CBT program be effective in a predominantly minority population? The SMI clients treated in our initial R01 was over 86% non-Hispanic White, whereas the majority of clients in the proposed study will be minorities (mainly African-American or Hispanic). Our pilot study of the CBT program in New Jersey suggests that it can be implemented successfully, and effectively, with minority clients with SMI and PTSD.

    Will the CBT program be effective for clients with psychotic disorders and PTSD? Only 15% of the original R01 sample had schizophrenia or schizoaffective disorder, while the rest had major mood disorders. In the proposed study, half of the clients will have schizophrenia-spectrum and half major mood disorders, allowing adequate power to test differential treatment effects by diagnosis.

    Will the CBT program be more effective than a briefer, standardized Psychoeducation program? Our initial R01 compared CBT with TAU, whereas the proposed research will compare CBT with a 3-session, pilot-tested, Psychoeducation program.

    What are the training, treatment, and other provider costs associated with delivery of the CBT program, and what are the potential cost-offsets, and broader quality of life and community functioning benefits of treating PTSD in the target population? These domains will be assessed in the proposed research.

    Funding: NIMH

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