Research

Phenomenology of Negative Symptoms

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 Our research on phenomenology has focused on determining: 1) whether  negative symptoms are best conceptualized as a categorical, dimensional,  or hybrid construct; 2) how many domains are part of the negative  symptom construct. Our findings indicate that negative symptoms are a  hybrid dimensional-categorical construct, such that people with  schizophrenia differ in kind above a certain symptom threshold that is  predictive of individual differences in the severity of several external  correlates. Early work that we and others conducted on the factor  structure of negative symptoms supported a two dimensional  conceptualization. However, most recently, we have found that the  construct is best considered in relation to 5 domains (anhedonia,  avolition, asociality, blunted affect, alogia); this finding has been  replicated using multiple mathematical techniques (e.g., CFA and network analysis), using multiple scales (BNSS, CAINS, SANS), and across multiple cultures, suggesting that the 5 domain conceptualization  is robust. Recently, we have been examining whether these 5 domains have  distinct pathophysiological mechanisms and clinical correlates to  determine whether a change is needed for DSM-5 negative symptom  diagnostic criteria and whether the 5 domains reflect distinct treatment  targets. 

Assessment of Negative Symptoms

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 The development of next-generation negative symptom  assessments has been another key focus of research in the CAN Lab. In  2005, NIMH held a consensus development conference on negative symptoms.  A key conclusion of this meeting was that new rating scales were needed  to increase chances of observing treatment effects. Two second generation negative symptom rating scales resulted  from this initiative. Dr. Strauss was co-developer of one of these  scales, the Brief Negative Symptom Scale (BNSS), and served as PI on  multiple studies validating the scale. Dr Strauss has also led efforts  in translating the BNSS into over a dozen languages  and facilitating  its primary intended use as an outcome measure in industry sponsored  clinical trials. Most recently, he co-developed and validated a new  scale for those at high-risk, the Prodromal Inventory for Negative  Symptoms, which is being examined in an R01 from NIMH. He has also begun developing and validating novel digital phenotyping measures of negative  symptoms that likely reflect the third generation of negative symptom  assessment (e.g., geolocation, accelerometry, ambient sound, measures of facial and vocal affect recorded from ambulatory videos). We are pioneering novel "big data" analytic approaches to  analyzing these novel mobile technology based negative symptom  assessments and working to develop a standardized app and norms for the  general population and individuals with schizophrenia.   

Pathophysiology of Negative Symptoms

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 The primary focus of our research is on identifying  mechanisms underlying negative symptoms. Our initial studies examined  the most straightforward explanation for avolitional symptoms in  schizophrenia- that patients fail to engage in activities because they  do not find them rewarding; however, this hypothesis was not supported  because subjective and neurophysiological response to rewarding stimuli  is intact in schizophrenia. This finding lead us to explore why  apparently normal hedonic responses do not translate into goal-directed  behavior in schizophrenia. We have demonstrated that abnormalities in  several aspects of reward processing (e.g., reinforcement learning,  effort-cost computation, value representation, uncertainty-driven  exploration) that are driven by aberrant cortico-striatal interactions  may prevent intact hedonic responses from influencing decision-making  processes that are needed to initiate motivated behavior. We have also  demonstrated that avolition is associated with dysfunctional  cognition-emotion interactions (e.g., memory, attention), emotion  regulation abnormalities, social cognition impairments, a reduction in  the positivity offset, and anhedonic beliefs. Most recently, we have  expanded our work on the etiology of negative symptoms into the  psychosis prodrome, where we have found that reward processing deficits  predict the severity of negative symptoms in at-risk youth. However, due  to the greater propensity for depression in this phase of illness,  hedonic deficits play a greater role in negative symptoms in the  prodrome than in schizophrenia, propagating forward and creating  deficits in other aspects of reward processing that also occur in  schizophrenia. We are currently conducting longitudinal studies to  determine which reward processing mechanisms associated with negative  symptoms predict the emergence of psychotic disorders versus other  conditions (e.g., depression) in youth at clinical high-risk for  psychosis. 

Treatment of Negative Symptoms

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 In collaboration with colleagues in psychiatry, I have conducted clinical trials examining the  efficacy of pharmacological treatments for negative symptoms. Based on  our studies showing a role for endogenous oxytocin in social cognition  deficits and negative symptoms, we examined the efficacy of oxytocin as a  treatment for asociality. In two trials, oxytocin was not more  effective than placebo, and we recently extended this work by  demonstrating that combining oxytocin with psychosocial treatment has no  added benefit over psychosocial treatment alone. Most  recently, we are exploring the efficacy of a novel app-based cognitive  training intervention for improving emotion regulation abnormalities via  a direct mechanistic effect on the prefrontal cortex. We are examining  whether increased prefrontal activation leads to better emotion  regulation, and whether this translates into reductions in negative  symptoms, positive symptoms, and improved functional outcome. 

Our Methods

Electroencephalography (EEG)

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We use EEG to examine the time-course of neural activity in relation to various emotional and cognitive processes. EEG involves recording electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within neurons. In our studies, we have primarily been interested in Event Related Potentials (ERPs), which are averaged EEG responses that are time-locked to stimuli in an experiment. For example, we have examined time-locked response to pleasant, unpleasant, and neutral images to explore the time-course of affective response in people with schizophrenia compared to controls. Our EEG studies are conducted within our laboratory in the Psychology Department. We have two 64-channel Brain Vision ActiChamp Systems. We have been using EEG/ERPs since 2010.

Eye Tracking

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We use eye-tracking to measure the role of visual attention in various cognitive and emotional processes. We do this by measuring point of gaze or motion of the eyes relative to the head and a stimulus presented on the computer screen using an eye-tracker. The eye-tracker monitors the position of the pupil, pupil size, and corneal reflection as a participant views images on the screen. We have used eye-tracking to explore individual components of attention and how they interact with emotional vs. neutral stimuli in people with schizophrenia and controls. We are also interested in how pupil dilation is impacted by various manipulations of emotion and cognitive load. Our lab has two SR Research Eyelink 1000 systems that are used to measure attentional allocation and pupil dilation. This desktop mounted system allows for a remote and headfree evaluation of eye-movements at a very high sampling rate. We also interface EEG/ERPs and eye-tracking in the lab and fMRI and eye tracking at the BIRC.  We have been using eye tracking since 2004.

Functional Magnetic Ressonance Imaging (fMRI)

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Our fMRI studies are conducted at UGA's Biomedical Imaging Research Center (BIRC): https://birc.uga.edu/. The BIRC houses a state-of-the-art, General Electric 16-channel fixed-site Signa HDx 3.0 Tesla Magnetic Resonance Imaging (MRI) magnet. The magnet makes available multiple magnetic resonance imaging techniques including magnetic resonance imaging for structural tissue imaging (MRI), functional neuroimaging (fMRI) for studies of brain activation in real time, magnetic resonance spectroscopy (MRS) for the study of chemical changes in the brain, and magnetic resonance angiography (MRA) for the study of vascular changes throughout the system. Multinuclear spectroscopy (MNS) is available for enhanced spectroscopic studies and includes phosphorous-31.  We have been using fMRI since 2019.

Psychophysiology

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We use the wireless Bionomadix recording system from Biopac to examine facial electromyography, respiration, heart rate, and skin conductance. These psychophysiological measures allow us to explore the timecourse of psychophysiological response in relation to emotional reactivity and emotion regulation tasks, as well as the coherence between subjective, neural, and peripheral psychophysiological response when used in conjunction with our other measures. We use the wireless bionomadix system in our studies involving social interaction, as well as more traditional computerized laboratory paradigms examining emotion.  We have been using peripheral psychophysiology since 2013.

Digital Phenotyping

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We use digital phenotyping to explore symptoms and their mechanisms as they occur in everyday life. Participants are asked to carry a smart phone and wear a digital band that collects psychophysiology for several days in the context of everyday life. Participants report their current activities, as well as their emotional experience during those activities at several points throughout the day. The internal sensors of the phone also passively collect objective data related to behavior via measurements of accelerometry, geolocation, and ambient sound. Participants also record brief videos on the cell phone that are later submitted to automated algorithms for processing facial and vocal affect. We are using these digital phenotyping methods to explore hypotheses related to negative symptoms, as well as the reliability and validity of active and passive data collection methods as third-generation negative symptom measures. We have been using digital phenotyping since 2015.

Blood Draw/Saliva

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We obtain salivary and blood samples to test hypotheses related to neuroendocrine (e.g., cortisol) and immune (cytokines) function in relation to task performance. Salivary samples are obtained and stored in a -40 freezer located in our lab in the Psychology building. Blood samples are obtained and stored at the Clinical Translational Research Unit on the UGA Medical School campus. We have been gathering saliva/blood draws since 2010.  

Grant Funding

National Institute of Mental Health

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National Science Foundation

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Brain & Behavior Research Foundation

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American Psychological Foundation

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VA MIRECC

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UGA Internal

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ACTIVE 

  

  

1. R21-MH119438 (PI GP Strauss)   09/01/2019-08/31/2021 

NIMH   $415,250

Mechanisms Underlying Emotion Regulation Abnormalities in Youth at Clinical High-Risk for Psychosis 

Role: PI


2. R01-MH116039 (PI GP Strauss)   03/01/2019-11/30/2023

NIMH  $2,969,883

Prodromal Inventory for Negative Symptoms (PINS): A Development and Validation Study  

This grant develops and validates novel methods for assessing negative symptoms in youth at clinical high-risk for psychosis to enhance risk prediction algorithms 

Role: PI  


3. R21- MH112925  (PI GP Strauss)   04/01/2017- 03/31/2020 

NIMH   $417,456  

Modeling anhedonia in schizophrenia: A stochastic dynamical systems approach 

This grant applies mathematical models to ecological momentary assessment data to test novel theories about anhedonia reflecting abnormalities in the temporal dynamics of emotion in schizophrenia. 

Role: PI   


4.   NARSAD Young Investigator Grant (PI GP Strauss)  01/15/2019-01/15/2021

Brain & Behavior Research Foundation  $70,000

Neurocomputational models of psychosis risk

This grant uses computational modeling approaches to examine mechanisms underlying positive and negative symptoms involved with conversion to a psychotic disorder in youth at clinical high-risk for psychosis.

Role: PI


5. University of Georgia (PI GP Strauss) 8/1/2019-5/30/2020 

Clinical Translational Research Unit Pilot Grant  $40,000

Mechanisms of amotivation in youth at clinical high-risk for psychosis 

This grant uses fMRI to examine neural circuitry involved with reward processing mechanisms underlying avolition in youth at clinical high-risk for psychosis. 

Role: PI 



COMPLETED

  

1. University of Georgia (PI GP Strauss) 10/15/2017-6/30/2019 

Clinical Translational Research Unit Pilot Grant  $25,200 

The Effects of Inflammation on Neurocomputationally Derived Reinforcement Learning Profiles in Schizophrenia 

This grant examines whether cytokines predict computationally derived measures of reinforcement learning in schizophrenia to index the contributions of inflammation to negative symptoms. 

Role: PI 


2. University of Georgia (PI GP Strauss)  11/01/2017-06/30/2017

Owens Institute for Behavioral Research Pilot Grant   $10,000

Neurocomputational Models of Reinforcement Learning in Youth at Clinical High-Risk for Psychosis

The study examines a computational neuroscience framework for understanding delusions and avolition in youth at clinical high-risk for psychosis using computational models of reinforcement learning.

Role: PI


3. NSF Graduate Research Fellowship (PI: KH Frost)   08/31/2015-08/30/2018

National Science Foundation  $105,600

The Effects of Acute Social Stress on Reward Processing in Humans

This mentored grant examines sex differences in the effects of acute social stress on reward processing in humans, including implicit reinforcement learning, prediction error signaling, value representation, reward anticipation, reward consummation, effort-cost computation, and action selection.

Role: Mentor


4. R34-MH100362 (PI: RW Buchanan)  3/31/13 – 3/31/2016  

NIMH    $690,750

Combined Oxytocin and CBSST for Social Function in People with Schizophrenia

The study examines the efficacy of oxytocin combined with cognitive behavior therapy social skills training (CBSST) at improving social outcome in people with schizophrenia.

Role: Co-Investigator


5. Wechsler Early Career Grant for Innovative Work in Cognition 10/01/2015-2/30/2017

American Psychological Foundation (APF)   $25,000

A Cognitive Neuroscience Account of Low Cognitive Effort in Schizophrenia

This grant explores a novel account of low effort in schizophrenia as resulting from failure to detect cognitive demands and adjust effort levels accordingly to maximize cognitive performance.

Role: PI


6. Interdisciplinary Collaborative Grant  (PI: GP Strauss)  05/01/2015 – 12/30/2016

State University of New York  $10,000

Using Network Analysis to Explore the Temporal Dynamics of Emotion in Schizophrenia. 

This study uses network analysis to Ecological Momentary Assessment data in people with schizophrenia to determine whether anhedonia reflects abnormal temporal dynamics of emotional experience.

Role: PI


7. Transdisciplinary Areas of Excellence Grant (PI: GP Strauss) 05/01/2015-12/30/2016

State University of New York  $20,000

Predicting Conversion to Psychosis in At-Risk Youth: The Role of Stress-Inflammation Interactions. 

The study examines whether biomarkers of stress and inflammation following an acute social stressor predict symptoms of attenuated psychosis and conversion to a psychotic disorder in at-risk youth.

Role: PI


8. K23-MH092530 (PI: GP Strauss)   09/08/10 – 09/30/2015  

NIMH    $796,699

Motivated Attention and Avolition in Individuals with Schizophrenia 

The study examines early emotion processing abnormalities in schizophrenia, and attempts to identify precise cognitive mechanisms that contribute to abnormal attention-emotion interactions in schizophrenia. Career development activities include training in Event Related Potential and Eye-Tracking technology, as well as the theoretical basis of cognitive/affective neuroscience.

Role: PI


9. Department of Veterans Affairs (PI: GP Strauss)   10/01/2011 –09/30/2013 

MIRECC VISN 5   $50,000

Oxytocin and Social Cognition in Schizophrenia

The study examined the role of the oxytocin receptor gene and plasma oxytocin levels in deficits in social cognition, emotional experience, emotion perception, and emotional memory in people with schizophrenia.

Role: PI


10. Department of Veterans Affairs (PI: GP Strauss)   10/01/2012 –09/30/2013 

MIRECC VISN 5    $25,000

A Study of Subjective Emotional Experience and Emotion Regulation in Schizophrenia using an Experience Sampling Approach

The study used experience sampling methodology to examine differences in prospective, retrospective, and in-the-moment reports of positive and negative emotion in people with schizophrenia and healthy controls, as well as the effectiveness of various emotion regulation strategies in the context of every-day life.

Role: PI


11. Department of Veterans Affairs (PI: GP Strauss)   10/01/2010 –09/30/2011 

MIRECC VISN 5   $25,000

Cognitive Behavioral Social Skills Training to Enhance Consumer Recovery in 

Schizophrenia

The study examined the efficacy of Cognitive Behavioral Social Skills Therapy enhanced with new techniques that foster optimism, hope, mastery, empowerment, and self-esteem for consumer-oriented recovery in schizophrenia.

Role: PI


12. T32-MH067533 (PI : WT Carpenter)   07/01/2010-06/30/2015 

 NIMH       $106,515

Multidisciplinary Schizophrenia Research Training 

The major goals of the project are to provide young investigators with research training in 

schizophrenia research to facilitate their goals of becoming an independent investigator.

Role: Co-Investigator


13. P50-MH082999 (PI: WT Carpenter) 09/01/08- 08/31/12  

 NIMH   $9,708,330

 MPRC Centers for Intervention Development and Applied Research (CIDAR)

This application proposes to establish a Center for Intervention Development and Applied Research (CIDAR) in response to PAR-05-039. Its focus will be to advance drug discovery using innovative evaluation platforms and testing drugs with novel molecular targets to address negative symptoms and cognitive impairments in schizophrenia.

Role: Co-Investigator


Measures

Brief Negative Symptom Scale (BNSS)

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The BNSS is a 13-item psychiatric rating scale designed to assess the negative symptoms of schizophrenia. The scale is rated after completing a 15-minute interview. The BNSS includes a brief but comprehensive 9 page manual, a workbook to be used when conducting the clinical interview, and a scoresheet. In multiple psychometric studies, the BNSS has demonstrated excellent inter-rater agreement, internal-consistency, test-retest reliability, convergent validity, and discriminant validity. It produces a 5 factor solution for the domains of anhedonia, avolition, asocality, restricted affect, alogia. The BNSS has been, or is currently in the process of being translated into several languages, including: Spanish, Italian, German, Cantonese, French, Korean, and Turkish. Individuals interested in obtaining BNSS materials and publications can visit our Resources page. Commercial entities wishing to use the BNSS in clinical trials can contact Prophase, which offers professional BNSS training that was developed in consultation with the test developers. Drs. Strauss and Kirkpatrick receive royalties and consultation fees from Prophase LLC in connection with commercial use of the BNSS and other professional activities. Individual researchers/research groups may use the BNSS free of charge and obtain training materials by contacting Dr. Strauss gstrauss@uga.edu or Dr. Kirkpatrick bkirkpatrick@unr.edu 

Prodromal Inventory of Negative Symptoms (PINS)

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 The PINS is a new measure being developed via a multi-site collaborative R01 from NIMH as part of the Georgia and Illinois Negative Symptom Study (GAINS). The study is conducted in the laboratories of Dr. Gregory Strauss at UGA, Dr. Vijay Mittal at Northwestern, and Dr. Elaine Walker at Emory University. It is a clinical rating scale designed to assess negative symptoms in the prodromal phase of illness specifically. The measure is currently undergoing revision as part of an iterative data-driven process intended to produce a finalized briefer scale. To obtain the latest version please email Dr. Strauss gstrauss@uga.edu or Dr. Mittal: vijay.mittal@northwestern.edu

Digital Phenotyping

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We are developing and validating a number of novel digital phenotyping methods for assessing psychiatric symptoms. These involve active methods (e.g., daily surveys, cognitive tests, videos) completed by the participant on the phone, as well as passive methods that involve unobtrusively recording objective emasures of symptoms via the internal sensors of the phone (e.g., geolocation, accelerometry, ambient sound). Contact Dr. Strauss at gstrauss@uga.edu for details.

CAN Lab Newsletter- 2018

Can Lab Newsletter 2018 (pdf)

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