Gregory P. Strauss

Dr. Strauss’ program of research examines the phenomenology, etiology, assessment, and treatment of negative symptoms in schizophrenia and youth at clinical high-risk for psychosis.

Negative symptoms are reductions in motivation, emotion, and behavior that are associated with a range of poor clinical outcomes. Unfortunately, interventions have proven ineffective at remediating negative symptoms. The identification of novel neurophysiological and psychological mechanisms that can serve as treatment targets for pharmacological and psychosocial treatments is therefore a significant need in our field, as is the development of new assessments that can measure the construct adequately. Research in the CAN Lab aims to address these needs in the field.

Phenomenology: 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 of negative symptoms. Beyond this threshold, negative symptom severity is predictive of individual differences in external correlates, such as cognitive impairment and functional outcome. However, negative symptoms are not unidimensional, as suggested by early factor analytic studies. Rather, negative symptoms are multi-dimensional and these dimensions have distinct pathophysiological and psychological mechanisms. Early work that we and others conducted on the factor structure of negative symptoms supported a two dimensional conceptualization, with dimensions reflecting diminished expression (EXP) and motivation and pleasure (MAP). However, using more advanced mathematical approaches, we have recently found that the construct is best considered in relation to 5 distinct domains (anhedonia, avolition, asociality, blunted affect, alogia). This 5 domain structure has been found across the 3 most contemporary measures (BNSS, CAINS, SANS), across multiple cultures and languages (e.g., English, Italian, Spanish, Chinese, Korean, Japanese), using multiple mathematical techniques (e.g., CFA, network analysis), and across chronic and clinical high-risk phases of illness. 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.

Etiology: 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. In recent years, 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. Most recently, we are evaluating environmental contributions to negative symptoms in relation to a bioecosystem theoretical framework (see Strauss, 2021: https://www.frontiersin.org/articles/10.3389/fpsyt.2021.655471/full).

Assessment: 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 scales resulted from this initiative. Dr. Strauss was co-developer of one of these scales along with Brian Kirkpatrick, the Brief Negative Symptom Scale (BNSS), and served as PI on multiple studies validating the scale. Our lab has also led efforts in translating the BNSS into other languages  and facilitating its primary intended use as an outcome measure in industry sponsored clinical trials. Most recently, Dr. Strauss and Dr. Vijay Mittal co-developed and validated a new scale for those at clinical high-risk for psychosis, the Negative Symptom Inventory-Psychosis Risk (NSI-PR). The measure is being modified and validated in a multi-site R01. Our lab has also begun developing and validating new digital phenotyping measures. This includes active (e.g., EMA surveys, videos, tasks) and passive (e.g., geolocation, accelerometry, ambient sound) negative symptom measurements taken from smart phones and smartbands (ambulatory psychophysiology, accelerometry). We are also exploring whether these tools hold promise as novel risk prediction and monitoring assessments for predicting conversion to a psychotic disorder among clinical high-risk youth.

Treatment: In collaboration with colleagues at multiple institutions, we 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 multiple clinical trials, oxytocin was not more effective than placebo, and we recently extended this work by demonstrating that combining oxytocin with psychosocial treatment had no added benefit over psychosocial treatment alone. We have partnered with pharmaceutical companies to investigate the efficacy of pharmacological agents for negative symptoms, testing differential efficacy for negative symptom domains. Using a network analytic approach, we recently found that avolition may be the most central symptom to target to produce global improvements in the entire negative symptom construct. Currently, we are exploring the efficacy of a novel app-based cognitive training intervention for improving emotion regulation abnormalities in an R33 grant from NIMH. 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.

Research Methods:

Primary/Used for Several years: Electroencephalography (EEG), eye tracking, pupillometry, digital phenotyping/ecological momentary assessment

Secondary/Newer: Functional Magnetic Resonance Imaging (fMRI), peripheral psychophysiology (electrodermal activity, electrocardiography), blood and saliva draws for biomarkers (e.g., cytokines, cortisol, oxytocin), computational modeling 

Lab Website:

Clinical Affective Neuroscience Laboratory (CAN Lab): https://ugacanlab.com