Validation of accelerometry as a digital phenotyping measure of negative symptoms in schizophrenia.

Negative symptoms are commonly assessed via clinical rating scales; however, these measures have several inherent limitations that impact validity and utility for their use in clinical trials. Objective digital phenotyping measures that overcome some of these limitations are now available. The current study evaluated the validity of accelerometry (ACL), a passive digital phenotyping method that involves collecting data on the presence, vigor, and variability of movement. Outpatients with schizophrenia (SZ: n = 50) and demographically matched healthy controls (CN: n = 70) had ACL continuously recorded from a smartphone and smartband for 6 days. Active digital phenotyping assessments, including surveys related to activity context, were also collected via 8 daily surveys throughout the 6 day period. SZ participants had lower scores on phone ACL variables reflecting vigor and variability of movement compared to CN. ACL variables demonstrated convergent validity as indicated by significant correlations with active digital phenotyping self-reports of time spent in goal-directed activities and clinical ratings of negative symptoms. The discriminant validity of ACL was demonstrated by low correlations with clinical rating scale measures of positive, disorganized, and total symptoms. Collectively, findings suggest that ACL is a valid objective measure of negative symptoms that may complement traditional approaches to assessing the construct using clinical rating scales.

Digital phenotyping adherence, feasibility, and tolerability in outpatients with schizophrenia.

Digital phenotyping has potential for use as an objective and ecologically valid form of symptom assessment in clinical trials for schizophrenia. However, there are critical methodological factors that must be addressed before digital phenotyping can be used for this purpose. The current study evaluated levels of adherence, feasibility, and tolerability for active (i.e., signal and event contingent ecological momentary assessment surveys) and passive (i.e., geolocation, accelerometry, and ambulatory psychophysiology) digital phenotyping methods recorded from smartphone and smartband devices. Participants included outpatients diagnosed with schizophrenia (SZ: n = 54) and demographically matched healthy controls (CN: n = 55), who completed 6 days of digital phenotyping. Adherence was significantly lower in SZ than CN for active recordings, but not markedly different for passive recordings. Some forms of passive recordings had lower adherence (ambulatory psychophysiology) than others (accelerometry and geolocation). Active digital phenotyping adherence was predicted by higher psychosocial functioning, whereas passive digital phenotyping adherence was predicted by education, positive symptoms, negative symptoms, and psychosocial functioning in people with SZ. Both groups found digital phenotyping methods tolerable and feasibility was supported by low frequency of invalid responding, brief survey completion times, and similar impediments to study completion. Digital phenotyping methods can be completed by individuals with SZ with good adherence, feasibility, and tolerability. Recommendations are provided for using digital phenotyping methods in clinical trials for SZ.

The Latent Structure of Negative Symptoms in Individuals With Attenuated Psychosis Syndrome and Early Psychosis: Support for the 5 Consensus Domains.

Negative symptoms are prevalent in the prodromal and first-episode phases of psychosis and highly predictive of poor clinical outcomes (eg, liability for conversion and functioning). However, the latent structure of negative symptoms is unclear in the early phases of illness. Determining the latent structure of negative symptoms in early psychosis (EP) is of critical importance for early identification, prevention, and treatment efforts. In the current study, confirmatory factor analysis was used to evaluate latent structure in relation to 4 theoretically derived models: 1. a 1-factor model, 2. a 2-factor model with expression (EXP) and motivation and pleasure (MAP) factors, 3. a 5-factor model with separate factors for the 5 National Institute of Mental Health (NIMH) consensus development conference domains (blunted affect, alogia, anhedonia, avolition, and asociality), and 4. a hierarchical model with 2 second-order factors reflecting EXP and MAP, as well as 5 first-order factors reflecting the 5 consensus domains. Participants included 164 individuals at clinical high risk (CHR) who met the criteria for a prodromal syndrome and 377 EP patients who were rated on the Brief Negative Symptom Scale. Results indicated that the 1- and 2-factor models provided poor fit for the data. The 5-factor and hierarchical models provided excellent fit, with the 5-factor model outperforming the hierarchical model. These findings suggest that similar to the chronic phase of schizophrenia, the latent structure of negative symptom is best conceptualized in relation to the 5 consensus domains in the CHR and EP populations. Implications for early identification, prevention, and treatment are discussed.

Delay discounting in youth at clinical high-risk for psychosis and adults with schizophrenia.

BACKGROUND: Schizophrenia (SZ) is typically preceded by a prodromal (i.e. pre-illness) period characterized by attenuated positive symptoms and declining functional outcome. Negative symptoms are prominent among individuals at clinical high-risk (CHR) for psychosis (i.e. those with prodromal syndromes) and highly predictive of conversion to illness. Mechanisms underlying negative symptoms in the CHR population are unclear. Two studies were conducted to evaluate whether abnormalities in a reward processing mechanism thought to be core to negative symptoms in SZ, value representation, also exist in CHR individuals and whether they are associated with negative symptoms transphasically. METHODS: Study 1 included 33 individuals in the chronic phase of illness who have been diagnosed with schizophrenia or schizoaffective disorder (SZ) and 40 healthy controls (CN). Study 2 included 37 CHR participants and 45 CN. In both studies, participants completed the delay discounting (DD) task as a measure of value representation and the Brief Negative Symptom Scale was rated to measure negative symptoms. RESULTS: Results indicated that patients with SZ had steeper discounting rates than CN, indicating impairments in value representation. However, CHR participants were unimpaired on the DD task. In both studies, steeper discounting was associated with greater severity of negative symptoms. CONCLUSIONS: These findings suggest that deficits in value representation are associated with negative symptoms transphasically.

Geolocation as a Digital Phenotyping Measure of Negative Symptoms and Functional Outcome.

OBJECTIVE: Negative symptoms and functional outcome have traditionally been assessed using clinical rating scales, which rely on retrospective self-reports and have several inherent limitations that impact validity. These issues may be addressed with more objective digital phenotyping measures. In the current study, we evaluated the psychometric properties of a novel "passive" digital phenotyping method: geolocation. METHOD: Participants included outpatients with schizophrenia or schizoaffective disorder (SZ: n = 44), outpatients with bipolar disorder (BD: n =19), and demographically matched healthy controls (CN: n = 42) who completed 6 days of "active" digital phenotyping assessments (eg, surveys) while geolocation was recorded. RESULTS: Results indicated that SZ patients show less activity than CN and BD, particularly, in their travel from home. Geolocation variables demonstrated convergent validity by small to medium correlations with negative symptoms and functional outcome measured via clinical rating scales, as well as active digital phenotyping behavioral indices of avolition, asociality, and anhedonia. Discriminant validity was supported by low correlations with positive symptoms, depression, and anxiety. Reliability was supported by good internal consistency and moderate stability across days. CONCLUSIONS: These findings provide preliminary support for the reliability and validity of geolocation as an objective measure of negative symptoms and functional outcome. Geolocation offers enhanced precision and the ability to take a "big data" approach that facilitates sophisticated computational models. Near-continuous recordings and large numbers of samples may make geolocation a novel outcome measure for clinical trials due to enhanced power to detect treatment effects.

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

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.

Ambulatory digital phenotyping of blunted affect and alogia using objective facial and vocal analysis: Proof of concept.

Negative symptoms reflect one of the most debilitating aspects of one of the most debilitating diseases known to humankind. As yet, our treatments for negative symptoms are palliative at best and our understanding of their causes is relatively superficial. To address this, we are developing objective ambulatory tools for digitally phenotyping their severity which can be used outside the confines of the traditional clinical and research settings. The present study evaluated the feasibility, reliability and validity of ambulatory vocal acoustic and facial emotion expression analysis. Videos were provided by 25 patients with schizophrenia or schizoaffective disorder and 27 nonpsychiatric controls using inexpensive, non-invasive ambulatory recording methods. Controls provided 411 video recordings, and patients provided 377 video recordings; an average of 15.22 and 14.50 per participant per group respectively. The vast majority (over 80%) of these videos were usable for analysis. An empirically-supported, limited-feature vocal (7 features) and facial (3 features) set was examined. Within participants, these features varied considerably over time, but showed moderate to good test-retest reliability in many cases once contextual factors (e.g., activity involved in at the time of testing) were accounted for. Vocal and facial features showed statistically significant convergence with a "gold standard" negative symptom measure. Ambulatory vocal/facial features were more strongly associated with engagement in social or work activities in patients than negative symptom ratings. These data support the use of ambulatory vocal/facial analytic technologies for digital phenotyping of these negative symptoms.

Emotion regulation across the psychosis continuum.

Emotion regulation dysfunction is characteristic of psychotic disorders, but little is known about how the use of specific types of emotion regulation strategies differs across phases of psychotic illness. This information is vital for understanding factors contributing to psychosis vulnerability states and developing targeted treatments. Three studies were conducted to examine emotion regulation across phases of psychosis, which included (a) adolescent community members with psychotic-like experiences (PLEs; n = 262) and adolescents without PLEs (n = 1,226); (b) adolescents who met clinical high-risk criteria for a prodromal syndrome (n = 29) and healthy controls (n = 29); and (c) outpatients diagnosed with schizophrenia or schizoaffective disorder (SZ; n = 61) and healthy controls (n = 67). In each study, participants completed the Emotion Regulation Questionnaire and measures of psychiatric symptoms and functional outcome. The three psychosis groups did not differ from each other in reported use of suppression; however, there was evidence for a vulnerability-related, dose-dependent decrease in reappraisal. Across each sample, a lower use of reappraisal was associated with poorer clinical outcomes. Findings indicate that emotion regulation abnormalities occur across a continuum of psychosis vulnerability and represent important targets for intervention.

A meta-analysis of self-reported anticipatory and consummatory pleasure in the schizophrenia-spectrum.

OBJECTIVE: Recent conceptual frameworks propose anhedonia reflects abnormalities in the temporal dynamics of positive emotion in schizophrenia, characterized by intact consummatory and impaired anticipatory pleasure. A comprehensive meta-analysis can directly test this theory using self-report data. METHOD: A meta-analysis was performed on studies reporting Temporal Experience of Pleasure Scale (TEPS) data from healthy controls and schizophrenia or schizotypy groups. The TEPS was examined as it contains subscales to measure both consummatory and anticipatory pleasure separately. Statistical heterogeneity and study bias were examined. Meta-regressions evaluated moderators. RESULTS: 53 studies were retrieved (7,797 participants). Results revealed small effect sizes for comparisons of combined schizophrenia/schizotypy and control groups for both consummatory and anticipatory pleasure. Within-group comparisons of pleasure conditions were nonsignificant. The percentage of male schizophrenia/schizotypy participants significantly moderated anticipatory and consummatory pleasure for the combined sample and schizotypy alone; male participants were found to report reduced pleasure. There was only minor evidence of bias; sensitivity analysis confirmed result robustness. Exploratory outlier removal for schizophrenia within-group pleasure comparisons revealed a statistically significant difference between reported anticipatory and consummatory pleasure, with consummatory pleasure reduced relative to anticipatory (i.e., in the opposite direction of the majority of experimental research findings). CONCLUSIONS: These findings provided only modest support for the temporal dynamics of positive emotion conceptualization because they revealed no evidence for: 1) specific anticipatory pleasure deficits in schizophrenia-spectrum participants compared to controls; 2) significant reductions in anticipatory pleasure relative to consummatory pleasure in schizophrenia-spectrum participants.

Endogenous oxytocin levels are associated with impaired social cognition and neurocognition in schizophrenia.

Intranasal administration of the neuropeptide oxytocin (OT) has yielded inconsistent effects on social cognition and general cognition in individuals with schizophrenia (SZ). Few studies have examined whether endogenous peripheral OT levels are also associated with social and general cognition in SZ. The current study examined whether plasma OT levels are associated with performance on a higher-order social cognition measure (i.e., a task that requires inferential processes and knowledge not directly presented in social stimuli), as well as domains of general cognition. Participants included 30 individuals with SZ and 21 demographically matched healthy controls (CN). The MATRICS Consensus Cognitive Battery was administered to assess neuropsychological impairment in relation to 7 domains (processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving, and social cognition). Plasma OT levels were measured via radioimmunoassay. SZ had significantly lower endogenous OT levels and poorer MCCB performance on all 7 domains than CN. In CN and SZ, lower endogenous OT was associated with poorer social cognition. In SZ, lower endogenous OT was also associated with poorer processing speed and working memory. The significant association between OT and social cognition in both CN and SZ highlights the importance of endogenous OT levels as a biological predictor of social cognition, irrespective of clinical status. Significant associations between plasma OT and general neurocognition may reflect either an anxiolytic effect of plasma OT that results in better neurocognitive performance, or OT's action on dopamine and enhancement of dopamine tone that results in improved cognition.

A comprehensive review of psychophysiological applications for ecological momentary assessment in psychiatric populations.

Psychophysiological assessment is a core method used in psychopathology research that has led to important insights in relation to the etiology and maintenance of many disorders. However, laboratory psychophysiology has limited ecological validity. This limitation has resulted in the field moving toward ambulatory recordings of psychophysiology paired with ecological momentary assessment (EMA). This review uses the results of a comprehensive review of EMA psychophysiology studies to discuss applications, advantages, limitations, and future use of this methodology, including electrocardiography, blood pressure, electroencephalography, and more. Mobile psychophysiology has several advantages, including ecological validity, temporal precision, and concurrent evaluation of internally and externally generated contexts that influence physiological response. However, it is limited by the difficulty of conducting such studies and reduced experimental control. Future research using EMA psychophysiology should aim to record over longer periods, better integrate with everyday life, determine the utility of ecological momentary interventions based on psychophysiology, create guidelines for standardization, and aim to establish reliability and validity. EMA psychophysiology is a promising direction for the field and provides novel avenues for research and treatment of psychopathology, although methodological shortcomings must be addressed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Preliminary psychometric properties of the brief Negative Symptom Scale in youth at Clinical High-Risk for psychosis.

Preliminary psychometric properties of an adapted version of the Brief Negative Symptom Scale (BNSS) are reported in youth at Clinical High-Risk for psychosis (CHR). Participants included 29 CHR youth who met criteria for a prodromal syndrome on the Structured Interview for Prodromal Syndromes (SIPS). The adapted BNSS demonstrated excellent internal consistency, convergent validity, and discriminant validity, suggesting that the BNSS has utility for assessing negative symptoms in a CHR population.