Background: Schizophrenia is a severe and chronic medical condition, characterized by positive an... more Background: Schizophrenia is a severe and chronic medical condition, characterized by positive and negative symptoms, as well as pervasive social cognitive deficits. Despite the functional significance of the social cognition deficits affecting many aspects of daily living, such as social relationships, occupational status, and independent living, there is still no effective treatment option for these deficits, which is applied as standard of care. To address this need, we developed a novel, internet-based training program that targets social cognition deficits in schizophrenia (SocialVille). Preliminary studies demonstrate the feasibility and initial efficacy of Socialville in schizophrenia patients . The purpose of the current trial (referred to as the TReatment of Social cognition in Schizophrenia Trial or TRuSST) is to compare SocialVille to an active control training condition, include a larger sample of patients, and assess both social cognitive functioning, and functional outcomes. Methods/Design: We will employ a multi-site, longitudinal, blinded, randomized controlled trial (RCT) design with a target sample of 128 patients with schizophrenia. Patients will perform, at their home or in clinic, 40 sessions of either the SocialVille training program or an active control computer game condition. Each session will last for 40-45 minutes/day, performed 3-5 days a week, over 10-12 weeks, totaling to 30 hours of training. Patients will be assessed on a battery of social cognitive, social functioning and functional outcomes immediately before training, mid-way through training (after 20 training sessions) and at the completion of the 40 training sessions. Discussion: The strengths of this protocol are that it tests an innovative, internet-based treatment that targets fundamental social cognitive deficits in schizophrenia, employs a highly sensitive and extensive battery of functional outcome measures, and incorporates a large sample size in an RCT design.
The goal of this study was to determine if family burden experienced by the families of individua... more The goal of this study was to determine if family burden experienced by the families of individuals with a recent-onset of schizophrenia is associated with whether the individual is able to work or attend school during the first year of treatment. Forty-one participants with a recent first episode of schizophrenia and their families enrolled in two NIMH-funded protocols through the UCLA Aftercare Research Program completed a measure of family burden at baseline. Amount of work during this time was also recorded. Baseline family burden was associated with work status (no work, part-time work, or full-time work) at both the six-month, r = -0.321, p = .04, and one-year time point, r = -0.47, p = .002. Family burden was also associated with hours participated in work/school hours at the six-month time point, r = -0.390, p = .012, and at the one-year time point, r = -0.492, p = .01. Further exploration into the family burden measure shows that family perceived limited opportunities resulting from the individual's psychiatric disorder was associated with worse functional outcome at all three time points beyond psychiatric symptoms and baseline functioning. Missed opportunities due to a family member's illness may reduce the level of support provided to the individual and thus impact their psychosocial functioning. Our findings suggest that this dimension of family burden is highlighting the importance of and need for more balanced family support to boost functional outcome.
Background: Early-stage visual processing deficits are evident in chronic schizophrenia. Consiste... more Background: Early-stage visual processing deficits are evident in chronic schizophrenia. Consistent with a cascade model of information processing, whereby early perceptual processes have downstream effects on higher-order cognition, impaired visual processing is associated with deficits in social cognition in this clinical population. However, the nature of this relationship in the early phase of illness is unknown. Here, we present data from a study of early visual processing and social cognitive performance in recent-onset schizophrenia (ROSz). Method: Thirty-two people with ROSz and 20 healthy controls (HC) completed a visual backward masking task using stimuli of real world objects (Object Masking) to assess early-stage (i.e., 0-125 ms post-stimulus onset) visual processing. Subjects also completed two tasks of social cognition, one assessing relatively low-level processes of emotion identification (Emotion Biological Motion, EmoBio), and another assessing more complex, higher-order theory of mind abilities (The Awareness of Social Inference Test, TASIT). Group differences were tested with repeated measures ANOVAs and t-tests. Bivariate correlations and linear regressions tested the strength of associations between early-stage visual processing and social cognitive performance in ROSz. Results: For Object Masking, the mask interfered with object identification over a longer interval for ROSz than for HC [F (3.19, 159.35) = 8.51, p < 0.001]. ROSz were less accurate on the EmoBio task [t (50) = -3.36, p = 0.001] and on the TASIT compared to HC [F (1, 50) = 38.37, p < 0.001]. For the TASIT ROSz were disproportionately impaired on items assessing sarcasm detection [F (1, 50) = 4.30, p = 0.04]. In ROSz, better Object Masking performance was associated with better social cognitive performance [r EmoBio = 0.45, p < 0.01; r TASIT = 0.41, p < 0.02]. Regression analyses did not provide significant support for low-level social cognition mediating the relationship between visual processing and high-level social cognition. Early-stage visual processing, low-level social cognition, and high-level social cognition were all significantly impaired in ROSz. Early-stage visual processing was
The current management of patients with primary psychosis worldwide is often remarkably stereotyp... more The current management of patients with primary psychosis worldwide is often remarkably stereotyped. In almost all cases an antipsychotic medica tion is prescribed, with secondgeneration antipsychotics usually preferred to firstgeneration ones. Cognitive behavioral therapy is rarely used in the vast majority of countries, although there is evidence to support its efficacy. Psychosocial interventions are often provided, especially in chronic cases, but those applied are frequently not validated by research. Evidencebased family interventions and supported employment programs are seldom implemented in ordinary practice. Although the notion that patients with primary psychosis are at increased risk for cardiovascular diseases and diabetes mellitus is widely shared, it is not frequent that appropriate measures be implemented to address this problem. The view that the management of the patient with primary psychosis should be personalized is endorsed by the vast majority of clinicians, but this personalization is lacking or inadequate in most clinical contexts. Although many mental health services would declare themselves "recoveryoriented", it is not common that a focus on empowerment, identity, meaning and resilience is ensured in ordinary practice. The present paper aims to address this situation. It describes systematically the salient domains that should be considered in the characterization of the individual patient with primary psychosis aimed at personalization of management. These include positive and negative symptom dimensions, other psychopathological compo nents, onset and course, neurocognition and social cognition, neurodevelopmental indicators; social functioning, quality of life and unmet needs; clinical staging, antecedent and concomitant psychiatric conditions, physical comorbidities, family history, history of obstetric complications, early and recent environmental exposures, protective factors and resilience, and internalized stigma. For each domain, simple assessment instruments are identified that could be considered for use in clinical practice and included in standardized decision tools. A management of primary psychosis is encouraged which takes into account all the available treatment modalities whose efficacy is supported by research evidence, selects and modulates them in the individual patient on the basis of the clinical characterization, addresses the patient's needs in terms of employment, housing, selfcare, social relationships and education, and offers a focus on identity, meaning and resilience.
Background-Although many studies have assessed cognitive functioning in first-episode schizophren... more Background-Although many studies have assessed cognitive functioning in first-episode schizophrenia (FESz), the pattern and severity of impairment across cognitive domains remains unclear. Moreover, few studies have directly compared the pattern of cognitive performance between FESz and chronic schizophrenia (CSz). In this study we examined the cognitive
Studies indicate that people with schizophrenia experience deficits in their ability to accuratel... more Studies indicate that people with schizophrenia experience deficits in their ability to accurately detect emotions, both through facial expressions and voice intonation (i.e., prosody), and that functioning and symptoms are associated with these deficits. This study aimed to examine how facial emotion and affective prosody recognition are related to functioning and symptoms in a first-episode schizophrenia sample. Further, in light of research suggesting variable emotion-specific performance in people with schizophrenia, this study explored emotionspecific performance. Participants were 49 people with a recent first episode of schizophrenia taking part in a larger RCT. Results revealed that affective prosody recognition was significantly correlated with both role and social functioning. Regarding associations with psychiatric symptoms, facial emotion recognition was significantly, negatively associated with all three positive symptom scales, whereas affective prosody recognition was significantly, negatively associated with disorganization only. Emotion-specific analyses revealed that for affective prosody, participants were most accurate in recognizing anger and least accurate for disgust. For facial emotion recognition, participants were most accurate in recognizing happiness and least accurate for fear. Taken together, results suggest that affective prosody recognition is important for social and role functioning in people with first-episode schizophrenia. Results also suggest that this group may struggle more to identify negative emotions, though additional work is needed to clarify this pattern in affective prosody and determine real-world impact on social interactions.
The goal of this study was to determine if family burden experienced by the families of individua... more The goal of this study was to determine if family burden experienced by the families of individuals with a recent-onset of schizophrenia is associated with whether the individual is able to work or attend school during the first year of treatment. Forty-one participants with a recent first episode of schizophrenia and their families enrolled in two NIMH-funded protocols through the UCLA Aftercare Research Program completed a measure of family burden at baseline. Amount of work during this time was also recorded. Baseline family burden was associated with work status (no work, part-time work, or full-time work) at both the six-month, r = -0.321, p = .04, and one-year time point, r = -0.47, p = .002. Family burden was also associated with hours participated in work/school hours at the six-month time point, r = -0.390, p = .012, and at the one-year time point, r = -0.492, p = .01. Further exploration into the family burden measure shows that family perceived limited opportunities resulting from the individual's psychiatric disorder was associated with worse functional outcome at all three time points beyond psychiatric symptoms and baseline functioning. Missed opportunities due to a family member's illness may reduce the level of support provided to the individual and thus impact their psychosocial functioning. Our findings suggest that this dimension of family burden is highlighting the importance of and need for more balanced family support to boost functional outcome.
Studies demonstrate that dynamic assessment (i.e., learning potential) improves the prediction of... more Studies demonstrate that dynamic assessment (i.e., learning potential) improves the prediction of response to rehabilitation over static measures in individuals with schizophrenia. Learning potential is most commonly assessed using neuropsychological tests under a test-train-test paradigm to examine change in performance. Novel learning potential approaches using social cognitive tasks may have added value, particularly for the prediction of social functioning, but this area is unexplored. The present study is the first to investigate whether patients with schizophrenia demonstrate social cognitive learning potential across phase of illness. This study included 43 participants at clinical high risk (CHR), 63 first-episode, and 36 chronic schizophrenia patients. Assessment of learning potential involved test-train-test versions of the Wisconsin Card Sorting Test (non-social cognitive learning potential) and the Facial Emotion Identification Test (social cognitive learning potential)....
Cognitive training (CT) and aerobic exercise have separately shown promise for improving cognitiv... more Cognitive training (CT) and aerobic exercise have separately shown promise for improving cognitive deficits in schizophrenia. Aerobic exercise releases brain-derived neurotrophic factor, which promotes synaptic plasticity and neurogenesis. Thus, aerobic exercise provides a neurotrophic platform for neuroplasticity-based CT. The combination of aerobic exercise and CT may yield more robust effects than CT alone, particularly in the initial course of schizophrenia. In a pilot study, 7 patients with a recent onset of schizophrenia were assigned to Cognitive Training & Exercise (CT&E) and 9 to CT alone for a 10-week period. Posit Science programs were used for CT. Neurocognitive training focused on tuning neural circuits related to perceptual processing and verbal learning and memory. Social cognitive training used the same learning principles with social and affective stimuli. Both groups participated in these training sessions 2d/wk, 2h/d. The CT&E group also participated in an aerobic...
Long-acting, injectable, second-generation antipsychotic medication has tremendous potential to b... more Long-acting, injectable, second-generation antipsychotic medication has tremendous potential to bring clinical stability to persons with schizophrenia. However, long-acting medications are rarely used following a first episode of schizophrenia. OBJECTIVE To compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia. A randomized clinical trial performed at a university-based research clinic, between 2005 and 2012. Eighty-six patients with recent onset of schizophrenia were randomized to receive long-acting injectable risperidone or oral risperidone. Half of each group was simultaneously randomized to receive cognitive remediation to improve cognitive functioning or healthy-behaviors training to improve lifestyle habits and well-being. An intent-to-treat analysis was performed between October 4, 2012, and November 12, 2014. MAIN OUTCOMES AND MEASURES Psychotic relapse and control of breakthrough psychotic symptoms. Of the 86 patients randomized, 3 refused treatment in the long-acting injectable risperidone group. The psychotic exacerbation and/or relapse rate was lower for the long-acting risperidone group compared with the oral group (5% vs 33%; χ 2 1 = 11.1; P < .001; relative risk reduction, 84.7%). Long-acting injectable risperidone better controlled mean levels of hallucinations and delusions throughout follow-up (β = -0.30; t 68 = -2.6, P = .01). The cognitive remediation and healthy-behaviors training groups did not differ significantly regarding psychotic relapse, psychotic symptom control, or hospitalization rates, and there were no significant interactions between the 2 medications and the 2 psychosocial treatments. Discontinuations owing to inadequate clinical response were more common in the oral group than in the long-acting risperidone group (χ 2 1 = 6.1; P = .01). Adherence to oral risperidone did not appear to differ before randomization but was better for the long-acting risperidone group compared with the oral group (t 80 = 5.3; P < .001). Medication adherence was associated with prevention of exacerbation and/or relapse (χ 2 1 =11.1; P = .003) and control of breakthrough psychotic symptoms (β = 0.2; t 79 = 2.1; P = .04). The use of long-acting injectable risperidone after a first episode of schizophrenia has notable advantages for clinical outcomes. The key clinical advantages are apparently owing to the more consistent administration of the long-acting injectable. Such formulations should be offered earlier in the course of illness.
American journal of psychiatric rehabilitation, 2014
It is clear that people with schizophrenia typically have cognitive problems in multiple domains ... more It is clear that people with schizophrenia typically have cognitive problems in multiple domains as part of their illness. The cognitive deficits are among the main contributors to limitations in their everyday functioning, including their work recovery. Cognitive remediation has been applied successfully to help people with long-term, persistent schizophrenia to improve their cognitive functioning, but it is only beginning to be applied with individuals who have recently had a first episode of psychosis. Several different approaches to cognitive training have been developed. Some approaches emphasize extensive systematic practice with lower-level cognitive processes and building toward higher-level processes ("bottom-up"), while others emphasize greater focus on high-level cognitive processes that normally integrate and organize lower-level processes ("top-down"). Each approach has advantages and disadvantages for a disorder like schizophrenia, with its multiple...
Background-Factor analytic studies have shown that in schizophrenia patients, disorganization (co... more Background-Factor analytic studies have shown that in schizophrenia patients, disorganization (conceptual disorganization, bizarre behavior) is a separate dimension from other types of positive symptoms such as reality distortion (delusions and hallucinations). Although some studies have found that disorganization is more strongly linked to neurocognitive deficits and poor functional outcomes than reality distortion, the findings are not always consistent. Methods-A meta-analysis of 104 studies (combined n = 8,015) was conducted to determine the magnitude of the relationship between neurocognition and disorganization as compared to reality distortion. Additional analyses were conducted to determine whether the strength of these relationships differed depending on the neurocognitive domain under investigation. Results-The relationship between reality distortion and neurocognition was weak (r = -.04; p=. 03) as compared to the moderate association between disorganization and neurocognition (r = -. 23; p <.01). In each of the six neurocognitive domains that were examined, disorganization was more strongly related to neurocognition (r's range from -.20 to -.26) than to reality distortion (r's range from .01 to -.12). Conclusions-The effect size of the relationship between neurocognition and disorganization was significantly larger than the effect size of the relationship between neurocognition and reality
Objective-To explore the extent to which initial severity of positive or negative symptoms in pat... more Objective-To explore the extent to which initial severity of positive or negative symptoms in patients with recent-onset schizophrenia is related to medication nonadherence during the first outpatient year. Methods-The study involved 64 first-episode schizophrenia patients treated with the secondgeneration oral antipsychotic medication, risperidone, for 12 months. Symptoms were evaluated using the SANS and SAPS completed every 3 months. Pearson correlations between medication adherence and symptoms were examined over each 3-month interval during 12 months of followthrough treatment. Possible causality was inferred from cross-lagged panel analyses. Results-As expected, higher levels of adherence with antipsychotic medication were generally associated with lower levels of concurrent reality distortion (mean of SAPS delusions and hallucinations). Greater adherence during the 3-month baseline interval was generally associated with lower levels of avolition-apathy as well as alogia throughout the first outpatient year. However, medication adherence was not significantly associated with decreases in avolition-
Background-In schizophrenia patients, one of the most commonly studied deficits of social cogniti... more Background-In schizophrenia patients, one of the most commonly studied deficits of social cognition is emotion processing (EP), which has documented links to facial recognition (FR). But, how are deficits in facial recognition linked to emotion processing deficits? Can neurocognitive and symptom correlates of FR and EP help differentiate the unique contribution of FR to the domain of social cognition? Methods-A meta-analysis of 102 studies (combined n = 4826) in schizophrenia patients was conducted to determine the magnitude and pattern of relationships between facial recognition, emotion processing, neurocognition, and type of symptom. Results-Meta-analytic results indicated that facial recognition and emotion processing are strongly interrelated (r = .51). In addition, the relationship between FR and EP through voice prosody (r = .58) is as strong as the relationship between FR and EP based on facial stimuli (r = . 53). Further, the relationship between emotion recognition, neurocognition, and symptoms is independent of the emotion processing modality -facial stimuli and voice prosody. Discussion-The association between FR and EP that occurs through voice prosody suggests that FR is a fundamental cognitive process. The observed links between FR and EP might be due to bottom-up associations between neurocognition and EP, and not simply because most emotion recognition tasks use visual facial stimuli. In addition, links with symptoms, especially negative symptoms and disorganization, suggest possible symptom mechanisms that contribute to FR and EP deficits.
The Psychosis Proneness Scales developed by the Chapmans and colleagues are widely used to identi... more The Psychosis Proneness Scales developed by the Chapmans and colleagues are widely used to identify nonpatient individuals who are hypothesized to possess heightened vulnerability to schizophrenia and related psychopathology. Yet surprisingly little is known about whether schizophrenia patients themselves show abnormalities on these scales across different clinical states, as would be expected for vulnerability indicators. Scores on four of the Psychosis Proneness Scales were evaluated at three assessment points over a 15-month period in healthy controls (n = 54) and in recent-onset schizophrenia patients (n = 72) who experienced symptom fluctuations across assessments. Patients showed steady elevations on the Physical Anhedonia Scale across time and clinical state, consistent with a stable vulnerability indicator. Patients had higher scores on the Perceptual Aberration and Magical Ideation Scales than controls throughout the followup period but scores also changed across clinical states, consistent with a mediating vulnerability indicator. Patients had higher scores on the Impulsive Non-Conformity Scale than controls only during a psychotic state, reflecting an episode indicator. The longitudinal characteristics of these scales in people who are actually diagnosed with schizophrenia provide key evidence for the validity of three commonly used psychometric indicators of vulnerability to psychosis.
Context-Imaging and post-mortem studies provide converging evidence that subjects with schizophre... more Context-Imaging and post-mortem studies provide converging evidence that subjects with schizophrenia (SZ) have a dysregulated trajectory of frontal lobe myelination. Prior MRI studies suggested that early in treatment of SZ, antipsychotic medications initially increase frontal lobe white matter (WM) volume, which subsequently declines prematurely in chronic stages of the
Background-Although in the early course of schizophrenia relapse prevention is of paramount impor... more Background-Although in the early course of schizophrenia relapse prevention is of paramount importance, there is an increasing emphasis on establishing and maintaining sustained periods of symptom remission. Recovery in the early course of illness is also possible, although the rates of recovery are lower than for symptom remission. Symptom remission and recovery rates vary considerably across recent-onset schizophrenia studies because of lack of consistency in treatment interventions and in applying operational outcome criteria. Method-Patients who were within two years of their first psychotic episode (N=77) who were treated with continuous antipsychotic medication in conjunction with psychosocial interventions (without targeted work rehabilitation) were assessed during the first outpatient year after hospital discharge. Published operational criteria were used to classify symptom remission and recovery.
Visual masking deficit in schizophrenia has been suggested to be a potential vulnerability marker... more Visual masking deficit in schizophrenia has been suggested to be a potential vulnerability marker for schizophrenia. An important characteristic of a vulnerability marker is stability over time, but relatively little is known about the longitudinal course of masking performance of schizophrenia patients. In this study, we examined the stability of visual masking performance in recent-onset schizophrenia patients over an 18-month period. We administered both forward and backward masking trials with multiple stimulus onset asynchronies for four masking conditions at three time points (baseline, 6-month, and 18-month). Recent-onset schizophrenia patients showed stable masking performance for both forward and backward conditions over a period of 18 months. Furthermore, the stable performance was observed across all four masking conditions. The findings of this study provide further support for the view that visual masking deficits reflect a possible vulnerability marker for schizophrenia.
Background: Cognitive deficits are core features of schizophrenia that have been associated relia... more Background: Cognitive deficits are core features of schizophrenia that have been associated reliably with functional outcomes and now are a focus of treatment research. New rating scales are needed to complement current psychometric testing procedures, both to enable wider clinical use, and to serve as endpoints in clinical trials. Methods: Subjects were 35 schizophrenia patient-and-caregiver pairs recruited from the UCLA and West Los Angeles VA Outpatient Psychiatry Departments. Participants were assessed with the Clinical Global Impression of Cognition in Schizophrenia (CGI-CogS), an interview-based rating scale of cognitive functioning, on 3 occasions (baseline, 1 month, and 3 months). A computerized neurocognitive battery (Cogtest), an assessment of functioning, and symptom measures were administered at two occasions (baseline and one month). Results: The CGI-CogS ratings generally showed a high level of internal consistency (Cronbach's alpha = .69 to .96), adequate levels of inter-rater reliability (ICC's = .71 to .80), and high test-retest stability (ICC's = .92 to .95). Correlations of caregiver and rater global (but not "patient only rating") CGI-CogS ratings with neurocognitive performance were in the moderate range (r's = -.27 to -.48), while most of the correlations with functional outcome were moderate to high (r's = -.41 to -.72). In fact, the CGI-CogS ratings were significantly more correlated with Social Functioning than were objective neurocognitive test scores (p = .02) and showed a trend in the same direction for predicting Instrumental Functioning (p = .06). We found moderate correlations between CGI-CogS global ratings and PANSS positive (r's = .36 to .49) and SANS negative symptoms (r = .41 to .61), but not with BPRS depression (r's = .11 to .13). Conclusions: An interview-based measure of cognition demonstrated high internal consistency, good inter-rater reliability, and high test-retest reliability. Caregiver ratings appear to add important clinical information over patient-only ratings. The CGI-CogS showed moderate validity with respect to neurocognitive performance and functional outcome, and correlations of CGI-CogS with functional outcomes were stronger than correlations of objective neurocognitive performance with functional outcomes. The CGI-CogS appears to offer a reliable and valid method for clinical rating of cognitive deficits and their impact on everyday functioning in schizophrenia.
Background-Neurocognitive functioning in schizophrenia has received considerable attention becaus... more Background-Neurocognitive functioning in schizophrenia has received considerable attention because of its robust prediction of functional outcome. Psychiatric symptoms, in particular negative symptoms, have also been shown to predict functional outcome, but have garnered much less attention. The high degree of intercorrelation among all of these variables leaves unclear whether neurocognition has a direct effect on functional outcome or whether that relationship to functional outcome is partially mediated by symptoms. Methods-A meta-analysis of 73 published English language studies (total n = 6519) was conducted to determine the magnitude of the relationship between neurocognition and symptoms, and between symptoms and functional outcome. A model was tested in which symptoms mediate the relationship between neurocognition and functional outcome. Functional outcome involved measures of social relationships, school and work functioning, and laboratory assessments of social skill. Results-Although negative symptoms were found to be significantly related to neurocognitive functioning (p < .01) positive symptoms were not (p = .97). The relationship was moderate for negative symptoms (r=-.24, n = 4757, 53 studies), but positive symptoms were not at all related to neurocogniton (r = .00, n= 1297, 25 studies). Negative symptoms were significantly correlated with ☆ The findings from this meta-analysis were presented in part at the 10th bi-annual meeting of the International Congress on Schizophrenia
Background: Schizophrenia is a severe and chronic medical condition, characterized by positive an... more Background: Schizophrenia is a severe and chronic medical condition, characterized by positive and negative symptoms, as well as pervasive social cognitive deficits. Despite the functional significance of the social cognition deficits affecting many aspects of daily living, such as social relationships, occupational status, and independent living, there is still no effective treatment option for these deficits, which is applied as standard of care. To address this need, we developed a novel, internet-based training program that targets social cognition deficits in schizophrenia (SocialVille). Preliminary studies demonstrate the feasibility and initial efficacy of Socialville in schizophrenia patients . The purpose of the current trial (referred to as the TReatment of Social cognition in Schizophrenia Trial or TRuSST) is to compare SocialVille to an active control training condition, include a larger sample of patients, and assess both social cognitive functioning, and functional outcomes. Methods/Design: We will employ a multi-site, longitudinal, blinded, randomized controlled trial (RCT) design with a target sample of 128 patients with schizophrenia. Patients will perform, at their home or in clinic, 40 sessions of either the SocialVille training program or an active control computer game condition. Each session will last for 40-45 minutes/day, performed 3-5 days a week, over 10-12 weeks, totaling to 30 hours of training. Patients will be assessed on a battery of social cognitive, social functioning and functional outcomes immediately before training, mid-way through training (after 20 training sessions) and at the completion of the 40 training sessions. Discussion: The strengths of this protocol are that it tests an innovative, internet-based treatment that targets fundamental social cognitive deficits in schizophrenia, employs a highly sensitive and extensive battery of functional outcome measures, and incorporates a large sample size in an RCT design.
The goal of this study was to determine if family burden experienced by the families of individua... more The goal of this study was to determine if family burden experienced by the families of individuals with a recent-onset of schizophrenia is associated with whether the individual is able to work or attend school during the first year of treatment. Forty-one participants with a recent first episode of schizophrenia and their families enrolled in two NIMH-funded protocols through the UCLA Aftercare Research Program completed a measure of family burden at baseline. Amount of work during this time was also recorded. Baseline family burden was associated with work status (no work, part-time work, or full-time work) at both the six-month, r = -0.321, p = .04, and one-year time point, r = -0.47, p = .002. Family burden was also associated with hours participated in work/school hours at the six-month time point, r = -0.390, p = .012, and at the one-year time point, r = -0.492, p = .01. Further exploration into the family burden measure shows that family perceived limited opportunities resulting from the individual's psychiatric disorder was associated with worse functional outcome at all three time points beyond psychiatric symptoms and baseline functioning. Missed opportunities due to a family member's illness may reduce the level of support provided to the individual and thus impact their psychosocial functioning. Our findings suggest that this dimension of family burden is highlighting the importance of and need for more balanced family support to boost functional outcome.
Background: Early-stage visual processing deficits are evident in chronic schizophrenia. Consiste... more Background: Early-stage visual processing deficits are evident in chronic schizophrenia. Consistent with a cascade model of information processing, whereby early perceptual processes have downstream effects on higher-order cognition, impaired visual processing is associated with deficits in social cognition in this clinical population. However, the nature of this relationship in the early phase of illness is unknown. Here, we present data from a study of early visual processing and social cognitive performance in recent-onset schizophrenia (ROSz). Method: Thirty-two people with ROSz and 20 healthy controls (HC) completed a visual backward masking task using stimuli of real world objects (Object Masking) to assess early-stage (i.e., 0-125 ms post-stimulus onset) visual processing. Subjects also completed two tasks of social cognition, one assessing relatively low-level processes of emotion identification (Emotion Biological Motion, EmoBio), and another assessing more complex, higher-order theory of mind abilities (The Awareness of Social Inference Test, TASIT). Group differences were tested with repeated measures ANOVAs and t-tests. Bivariate correlations and linear regressions tested the strength of associations between early-stage visual processing and social cognitive performance in ROSz. Results: For Object Masking, the mask interfered with object identification over a longer interval for ROSz than for HC [F (3.19, 159.35) = 8.51, p < 0.001]. ROSz were less accurate on the EmoBio task [t (50) = -3.36, p = 0.001] and on the TASIT compared to HC [F (1, 50) = 38.37, p < 0.001]. For the TASIT ROSz were disproportionately impaired on items assessing sarcasm detection [F (1, 50) = 4.30, p = 0.04]. In ROSz, better Object Masking performance was associated with better social cognitive performance [r EmoBio = 0.45, p < 0.01; r TASIT = 0.41, p < 0.02]. Regression analyses did not provide significant support for low-level social cognition mediating the relationship between visual processing and high-level social cognition. Early-stage visual processing, low-level social cognition, and high-level social cognition were all significantly impaired in ROSz. Early-stage visual processing was
The current management of patients with primary psychosis worldwide is often remarkably stereotyp... more The current management of patients with primary psychosis worldwide is often remarkably stereotyped. In almost all cases an antipsychotic medica tion is prescribed, with secondgeneration antipsychotics usually preferred to firstgeneration ones. Cognitive behavioral therapy is rarely used in the vast majority of countries, although there is evidence to support its efficacy. Psychosocial interventions are often provided, especially in chronic cases, but those applied are frequently not validated by research. Evidencebased family interventions and supported employment programs are seldom implemented in ordinary practice. Although the notion that patients with primary psychosis are at increased risk for cardiovascular diseases and diabetes mellitus is widely shared, it is not frequent that appropriate measures be implemented to address this problem. The view that the management of the patient with primary psychosis should be personalized is endorsed by the vast majority of clinicians, but this personalization is lacking or inadequate in most clinical contexts. Although many mental health services would declare themselves "recoveryoriented", it is not common that a focus on empowerment, identity, meaning and resilience is ensured in ordinary practice. The present paper aims to address this situation. It describes systematically the salient domains that should be considered in the characterization of the individual patient with primary psychosis aimed at personalization of management. These include positive and negative symptom dimensions, other psychopathological compo nents, onset and course, neurocognition and social cognition, neurodevelopmental indicators; social functioning, quality of life and unmet needs; clinical staging, antecedent and concomitant psychiatric conditions, physical comorbidities, family history, history of obstetric complications, early and recent environmental exposures, protective factors and resilience, and internalized stigma. For each domain, simple assessment instruments are identified that could be considered for use in clinical practice and included in standardized decision tools. A management of primary psychosis is encouraged which takes into account all the available treatment modalities whose efficacy is supported by research evidence, selects and modulates them in the individual patient on the basis of the clinical characterization, addresses the patient's needs in terms of employment, housing, selfcare, social relationships and education, and offers a focus on identity, meaning and resilience.
Background-Although many studies have assessed cognitive functioning in first-episode schizophren... more Background-Although many studies have assessed cognitive functioning in first-episode schizophrenia (FESz), the pattern and severity of impairment across cognitive domains remains unclear. Moreover, few studies have directly compared the pattern of cognitive performance between FESz and chronic schizophrenia (CSz). In this study we examined the cognitive
Studies indicate that people with schizophrenia experience deficits in their ability to accuratel... more Studies indicate that people with schizophrenia experience deficits in their ability to accurately detect emotions, both through facial expressions and voice intonation (i.e., prosody), and that functioning and symptoms are associated with these deficits. This study aimed to examine how facial emotion and affective prosody recognition are related to functioning and symptoms in a first-episode schizophrenia sample. Further, in light of research suggesting variable emotion-specific performance in people with schizophrenia, this study explored emotionspecific performance. Participants were 49 people with a recent first episode of schizophrenia taking part in a larger RCT. Results revealed that affective prosody recognition was significantly correlated with both role and social functioning. Regarding associations with psychiatric symptoms, facial emotion recognition was significantly, negatively associated with all three positive symptom scales, whereas affective prosody recognition was significantly, negatively associated with disorganization only. Emotion-specific analyses revealed that for affective prosody, participants were most accurate in recognizing anger and least accurate for disgust. For facial emotion recognition, participants were most accurate in recognizing happiness and least accurate for fear. Taken together, results suggest that affective prosody recognition is important for social and role functioning in people with first-episode schizophrenia. Results also suggest that this group may struggle more to identify negative emotions, though additional work is needed to clarify this pattern in affective prosody and determine real-world impact on social interactions.
The goal of this study was to determine if family burden experienced by the families of individua... more The goal of this study was to determine if family burden experienced by the families of individuals with a recent-onset of schizophrenia is associated with whether the individual is able to work or attend school during the first year of treatment. Forty-one participants with a recent first episode of schizophrenia and their families enrolled in two NIMH-funded protocols through the UCLA Aftercare Research Program completed a measure of family burden at baseline. Amount of work during this time was also recorded. Baseline family burden was associated with work status (no work, part-time work, or full-time work) at both the six-month, r = -0.321, p = .04, and one-year time point, r = -0.47, p = .002. Family burden was also associated with hours participated in work/school hours at the six-month time point, r = -0.390, p = .012, and at the one-year time point, r = -0.492, p = .01. Further exploration into the family burden measure shows that family perceived limited opportunities resulting from the individual's psychiatric disorder was associated with worse functional outcome at all three time points beyond psychiatric symptoms and baseline functioning. Missed opportunities due to a family member's illness may reduce the level of support provided to the individual and thus impact their psychosocial functioning. Our findings suggest that this dimension of family burden is highlighting the importance of and need for more balanced family support to boost functional outcome.
Studies demonstrate that dynamic assessment (i.e., learning potential) improves the prediction of... more Studies demonstrate that dynamic assessment (i.e., learning potential) improves the prediction of response to rehabilitation over static measures in individuals with schizophrenia. Learning potential is most commonly assessed using neuropsychological tests under a test-train-test paradigm to examine change in performance. Novel learning potential approaches using social cognitive tasks may have added value, particularly for the prediction of social functioning, but this area is unexplored. The present study is the first to investigate whether patients with schizophrenia demonstrate social cognitive learning potential across phase of illness. This study included 43 participants at clinical high risk (CHR), 63 first-episode, and 36 chronic schizophrenia patients. Assessment of learning potential involved test-train-test versions of the Wisconsin Card Sorting Test (non-social cognitive learning potential) and the Facial Emotion Identification Test (social cognitive learning potential)....
Cognitive training (CT) and aerobic exercise have separately shown promise for improving cognitiv... more Cognitive training (CT) and aerobic exercise have separately shown promise for improving cognitive deficits in schizophrenia. Aerobic exercise releases brain-derived neurotrophic factor, which promotes synaptic plasticity and neurogenesis. Thus, aerobic exercise provides a neurotrophic platform for neuroplasticity-based CT. The combination of aerobic exercise and CT may yield more robust effects than CT alone, particularly in the initial course of schizophrenia. In a pilot study, 7 patients with a recent onset of schizophrenia were assigned to Cognitive Training & Exercise (CT&E) and 9 to CT alone for a 10-week period. Posit Science programs were used for CT. Neurocognitive training focused on tuning neural circuits related to perceptual processing and verbal learning and memory. Social cognitive training used the same learning principles with social and affective stimuli. Both groups participated in these training sessions 2d/wk, 2h/d. The CT&E group also participated in an aerobic...
Long-acting, injectable, second-generation antipsychotic medication has tremendous potential to b... more Long-acting, injectable, second-generation antipsychotic medication has tremendous potential to bring clinical stability to persons with schizophrenia. However, long-acting medications are rarely used following a first episode of schizophrenia. OBJECTIVE To compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia. A randomized clinical trial performed at a university-based research clinic, between 2005 and 2012. Eighty-six patients with recent onset of schizophrenia were randomized to receive long-acting injectable risperidone or oral risperidone. Half of each group was simultaneously randomized to receive cognitive remediation to improve cognitive functioning or healthy-behaviors training to improve lifestyle habits and well-being. An intent-to-treat analysis was performed between October 4, 2012, and November 12, 2014. MAIN OUTCOMES AND MEASURES Psychotic relapse and control of breakthrough psychotic symptoms. Of the 86 patients randomized, 3 refused treatment in the long-acting injectable risperidone group. The psychotic exacerbation and/or relapse rate was lower for the long-acting risperidone group compared with the oral group (5% vs 33%; χ 2 1 = 11.1; P < .001; relative risk reduction, 84.7%). Long-acting injectable risperidone better controlled mean levels of hallucinations and delusions throughout follow-up (β = -0.30; t 68 = -2.6, P = .01). The cognitive remediation and healthy-behaviors training groups did not differ significantly regarding psychotic relapse, psychotic symptom control, or hospitalization rates, and there were no significant interactions between the 2 medications and the 2 psychosocial treatments. Discontinuations owing to inadequate clinical response were more common in the oral group than in the long-acting risperidone group (χ 2 1 = 6.1; P = .01). Adherence to oral risperidone did not appear to differ before randomization but was better for the long-acting risperidone group compared with the oral group (t 80 = 5.3; P < .001). Medication adherence was associated with prevention of exacerbation and/or relapse (χ 2 1 =11.1; P = .003) and control of breakthrough psychotic symptoms (β = 0.2; t 79 = 2.1; P = .04). The use of long-acting injectable risperidone after a first episode of schizophrenia has notable advantages for clinical outcomes. The key clinical advantages are apparently owing to the more consistent administration of the long-acting injectable. Such formulations should be offered earlier in the course of illness.
American journal of psychiatric rehabilitation, 2014
It is clear that people with schizophrenia typically have cognitive problems in multiple domains ... more It is clear that people with schizophrenia typically have cognitive problems in multiple domains as part of their illness. The cognitive deficits are among the main contributors to limitations in their everyday functioning, including their work recovery. Cognitive remediation has been applied successfully to help people with long-term, persistent schizophrenia to improve their cognitive functioning, but it is only beginning to be applied with individuals who have recently had a first episode of psychosis. Several different approaches to cognitive training have been developed. Some approaches emphasize extensive systematic practice with lower-level cognitive processes and building toward higher-level processes ("bottom-up"), while others emphasize greater focus on high-level cognitive processes that normally integrate and organize lower-level processes ("top-down"). Each approach has advantages and disadvantages for a disorder like schizophrenia, with its multiple...
Background-Factor analytic studies have shown that in schizophrenia patients, disorganization (co... more Background-Factor analytic studies have shown that in schizophrenia patients, disorganization (conceptual disorganization, bizarre behavior) is a separate dimension from other types of positive symptoms such as reality distortion (delusions and hallucinations). Although some studies have found that disorganization is more strongly linked to neurocognitive deficits and poor functional outcomes than reality distortion, the findings are not always consistent. Methods-A meta-analysis of 104 studies (combined n = 8,015) was conducted to determine the magnitude of the relationship between neurocognition and disorganization as compared to reality distortion. Additional analyses were conducted to determine whether the strength of these relationships differed depending on the neurocognitive domain under investigation. Results-The relationship between reality distortion and neurocognition was weak (r = -.04; p=. 03) as compared to the moderate association between disorganization and neurocognition (r = -. 23; p <.01). In each of the six neurocognitive domains that were examined, disorganization was more strongly related to neurocognition (r's range from -.20 to -.26) than to reality distortion (r's range from .01 to -.12). Conclusions-The effect size of the relationship between neurocognition and disorganization was significantly larger than the effect size of the relationship between neurocognition and reality
Objective-To explore the extent to which initial severity of positive or negative symptoms in pat... more Objective-To explore the extent to which initial severity of positive or negative symptoms in patients with recent-onset schizophrenia is related to medication nonadherence during the first outpatient year. Methods-The study involved 64 first-episode schizophrenia patients treated with the secondgeneration oral antipsychotic medication, risperidone, for 12 months. Symptoms were evaluated using the SANS and SAPS completed every 3 months. Pearson correlations between medication adherence and symptoms were examined over each 3-month interval during 12 months of followthrough treatment. Possible causality was inferred from cross-lagged panel analyses. Results-As expected, higher levels of adherence with antipsychotic medication were generally associated with lower levels of concurrent reality distortion (mean of SAPS delusions and hallucinations). Greater adherence during the 3-month baseline interval was generally associated with lower levels of avolition-apathy as well as alogia throughout the first outpatient year. However, medication adherence was not significantly associated with decreases in avolition-
Background-In schizophrenia patients, one of the most commonly studied deficits of social cogniti... more Background-In schizophrenia patients, one of the most commonly studied deficits of social cognition is emotion processing (EP), which has documented links to facial recognition (FR). But, how are deficits in facial recognition linked to emotion processing deficits? Can neurocognitive and symptom correlates of FR and EP help differentiate the unique contribution of FR to the domain of social cognition? Methods-A meta-analysis of 102 studies (combined n = 4826) in schizophrenia patients was conducted to determine the magnitude and pattern of relationships between facial recognition, emotion processing, neurocognition, and type of symptom. Results-Meta-analytic results indicated that facial recognition and emotion processing are strongly interrelated (r = .51). In addition, the relationship between FR and EP through voice prosody (r = .58) is as strong as the relationship between FR and EP based on facial stimuli (r = . 53). Further, the relationship between emotion recognition, neurocognition, and symptoms is independent of the emotion processing modality -facial stimuli and voice prosody. Discussion-The association between FR and EP that occurs through voice prosody suggests that FR is a fundamental cognitive process. The observed links between FR and EP might be due to bottom-up associations between neurocognition and EP, and not simply because most emotion recognition tasks use visual facial stimuli. In addition, links with symptoms, especially negative symptoms and disorganization, suggest possible symptom mechanisms that contribute to FR and EP deficits.
The Psychosis Proneness Scales developed by the Chapmans and colleagues are widely used to identi... more The Psychosis Proneness Scales developed by the Chapmans and colleagues are widely used to identify nonpatient individuals who are hypothesized to possess heightened vulnerability to schizophrenia and related psychopathology. Yet surprisingly little is known about whether schizophrenia patients themselves show abnormalities on these scales across different clinical states, as would be expected for vulnerability indicators. Scores on four of the Psychosis Proneness Scales were evaluated at three assessment points over a 15-month period in healthy controls (n = 54) and in recent-onset schizophrenia patients (n = 72) who experienced symptom fluctuations across assessments. Patients showed steady elevations on the Physical Anhedonia Scale across time and clinical state, consistent with a stable vulnerability indicator. Patients had higher scores on the Perceptual Aberration and Magical Ideation Scales than controls throughout the followup period but scores also changed across clinical states, consistent with a mediating vulnerability indicator. Patients had higher scores on the Impulsive Non-Conformity Scale than controls only during a psychotic state, reflecting an episode indicator. The longitudinal characteristics of these scales in people who are actually diagnosed with schizophrenia provide key evidence for the validity of three commonly used psychometric indicators of vulnerability to psychosis.
Context-Imaging and post-mortem studies provide converging evidence that subjects with schizophre... more Context-Imaging and post-mortem studies provide converging evidence that subjects with schizophrenia (SZ) have a dysregulated trajectory of frontal lobe myelination. Prior MRI studies suggested that early in treatment of SZ, antipsychotic medications initially increase frontal lobe white matter (WM) volume, which subsequently declines prematurely in chronic stages of the
Background-Although in the early course of schizophrenia relapse prevention is of paramount impor... more Background-Although in the early course of schizophrenia relapse prevention is of paramount importance, there is an increasing emphasis on establishing and maintaining sustained periods of symptom remission. Recovery in the early course of illness is also possible, although the rates of recovery are lower than for symptom remission. Symptom remission and recovery rates vary considerably across recent-onset schizophrenia studies because of lack of consistency in treatment interventions and in applying operational outcome criteria. Method-Patients who were within two years of their first psychotic episode (N=77) who were treated with continuous antipsychotic medication in conjunction with psychosocial interventions (without targeted work rehabilitation) were assessed during the first outpatient year after hospital discharge. Published operational criteria were used to classify symptom remission and recovery.
Visual masking deficit in schizophrenia has been suggested to be a potential vulnerability marker... more Visual masking deficit in schizophrenia has been suggested to be a potential vulnerability marker for schizophrenia. An important characteristic of a vulnerability marker is stability over time, but relatively little is known about the longitudinal course of masking performance of schizophrenia patients. In this study, we examined the stability of visual masking performance in recent-onset schizophrenia patients over an 18-month period. We administered both forward and backward masking trials with multiple stimulus onset asynchronies for four masking conditions at three time points (baseline, 6-month, and 18-month). Recent-onset schizophrenia patients showed stable masking performance for both forward and backward conditions over a period of 18 months. Furthermore, the stable performance was observed across all four masking conditions. The findings of this study provide further support for the view that visual masking deficits reflect a possible vulnerability marker for schizophrenia.
Background: Cognitive deficits are core features of schizophrenia that have been associated relia... more Background: Cognitive deficits are core features of schizophrenia that have been associated reliably with functional outcomes and now are a focus of treatment research. New rating scales are needed to complement current psychometric testing procedures, both to enable wider clinical use, and to serve as endpoints in clinical trials. Methods: Subjects were 35 schizophrenia patient-and-caregiver pairs recruited from the UCLA and West Los Angeles VA Outpatient Psychiatry Departments. Participants were assessed with the Clinical Global Impression of Cognition in Schizophrenia (CGI-CogS), an interview-based rating scale of cognitive functioning, on 3 occasions (baseline, 1 month, and 3 months). A computerized neurocognitive battery (Cogtest), an assessment of functioning, and symptom measures were administered at two occasions (baseline and one month). Results: The CGI-CogS ratings generally showed a high level of internal consistency (Cronbach's alpha = .69 to .96), adequate levels of inter-rater reliability (ICC's = .71 to .80), and high test-retest stability (ICC's = .92 to .95). Correlations of caregiver and rater global (but not "patient only rating") CGI-CogS ratings with neurocognitive performance were in the moderate range (r's = -.27 to -.48), while most of the correlations with functional outcome were moderate to high (r's = -.41 to -.72). In fact, the CGI-CogS ratings were significantly more correlated with Social Functioning than were objective neurocognitive test scores (p = .02) and showed a trend in the same direction for predicting Instrumental Functioning (p = .06). We found moderate correlations between CGI-CogS global ratings and PANSS positive (r's = .36 to .49) and SANS negative symptoms (r = .41 to .61), but not with BPRS depression (r's = .11 to .13). Conclusions: An interview-based measure of cognition demonstrated high internal consistency, good inter-rater reliability, and high test-retest reliability. Caregiver ratings appear to add important clinical information over patient-only ratings. The CGI-CogS showed moderate validity with respect to neurocognitive performance and functional outcome, and correlations of CGI-CogS with functional outcomes were stronger than correlations of objective neurocognitive performance with functional outcomes. The CGI-CogS appears to offer a reliable and valid method for clinical rating of cognitive deficits and their impact on everyday functioning in schizophrenia.
Background-Neurocognitive functioning in schizophrenia has received considerable attention becaus... more Background-Neurocognitive functioning in schizophrenia has received considerable attention because of its robust prediction of functional outcome. Psychiatric symptoms, in particular negative symptoms, have also been shown to predict functional outcome, but have garnered much less attention. The high degree of intercorrelation among all of these variables leaves unclear whether neurocognition has a direct effect on functional outcome or whether that relationship to functional outcome is partially mediated by symptoms. Methods-A meta-analysis of 73 published English language studies (total n = 6519) was conducted to determine the magnitude of the relationship between neurocognition and symptoms, and between symptoms and functional outcome. A model was tested in which symptoms mediate the relationship between neurocognition and functional outcome. Functional outcome involved measures of social relationships, school and work functioning, and laboratory assessments of social skill. Results-Although negative symptoms were found to be significantly related to neurocognitive functioning (p < .01) positive symptoms were not (p = .97). The relationship was moderate for negative symptoms (r=-.24, n = 4757, 53 studies), but positive symptoms were not at all related to neurocogniton (r = .00, n= 1297, 25 studies). Negative symptoms were significantly correlated with ☆ The findings from this meta-analysis were presented in part at the 10th bi-annual meeting of the International Congress on Schizophrenia
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