Schizophrenia Center Publications

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Nuechterlein KH(1), Ventura J, Subotnik KL, Bartzokis G. The early longitudinal course of cognitive deficits in schizophrenia. 1. J Clin Psychiatry. 2014;75 Suppl 2:25-9. doi: 10.4088/JCP.13065.su1.06.

2014, July 16 - 15:24
Cognitive impairment is a core feature of schizophrenia. However, the longitudinal course and pattern of this impairment, and its relationship to functional outcome, are not fully understood. Among the likely factors in the persistence of cognitive deficits in schizophrenia are brain tissue changes over time, which in turn appear to be related to antipsychotic medication adherence. Cognitive deficits are viewed as a core feature of schizophrenia primarily because cognitive deficits clearly exist before the onset of psychosis and can predict illness onset among those at high risk of developing the illness. Additionally, these deficits often persist during symptomatic remissions in patients and are relatively stable across time both in patients and in individuals at risk for schizophrenia. Despite clear evidence that cognitive impairment can predict functional outcome in chronic schizophrenia, results of studies examining this relationship in the early phase of psychosis have been mixed. Recent data, however, strongly suggest that interventions targeting early cognitive deficits may be crucial to the prevention of chronic disability and thus should be a prominent target for therapy. Finally, it is vital to keep schizophrenia patients consistently on their antipsychotic medications. A novel method of examining intracortical myelin volume indicated that the choice of antipsychotic treatment had a differential impact on frontal myelination. These data suggest that long-acting injectable antipsychotic medication may prevent patients from declining further through a combination of better adherence and pharmacokinetics.

Tsai KH(1), López S, Marvin S, Zinberg J, Cannon TD, O'Brien M, Bearden CE. Perceptions of family criticism and warmth and their link to symptom expression in racially/ethnically diverse adolescents and young adults at clinical high risk for psychosis. 1.

2014, July 16 - 15:24
AIM: Little is known about the role of expressed emotion (EE) in early symptom expression in individuals at clinical high risk (CHR) for psychosis. In patients with established schizophrenia, the effects of EE on clinical outcomes have purportedly varied across racial/ethnic groups, but this has not yet been investigated among CHR patients. Furthermore, studies have traditionally focused upon caregiver levels of EE via interview-based ratings, whereas the literature on patient perceptions of caregiver EE on psychosis symptoms is relatively limited. METHODS: Linear regression models were conducted to examine the impact of criticism and perceived warmth in the family environment, from the CHR patient's perspective, on positive and negative symptom expression in non-Latino white (NLW; n?=?38) and Latino (n?=?11) adolescents and young adults at CHR for developing psychosis. RESULTS: Analyses examining the sample as a whole demonstrated that perceived levels of maternal criticism were negatively associated with negative CHR symptomatology. Additional analyses indicated that race/ethnicity moderated the relationship between criticism/warmth and clinical symptomatology. We found evidence of a contrasting role of patient perceived criticism and warmth depending upon the patient's race/ethnicity. CONCLUSION: Family processes shown to impact the course of schizophrenia among NLWs may function differently among Latino than NLW patients. These findings have important implications for the development of culturally appropriate interventions and may aid efforts to improve the effectiveness of mental health services for diverse adolescents and young adults at CHR for psychosis. Given the small sample size of this study, analyses should be replicated in a larger study before more definitive conclusions can be made.

Ventura J(1), Subotnik KL, Ered A, Gretchen-Doorly D, Hellemann GS, Vaskinn A, Nuechterlein KH. The Relationship of Attitudinal Beliefs to Negative Symptoms, Neurocognition, and Daily Functioning in Recent-Onset Schizophrenia. 1. Schizophr Bull. 2014 Feb

2014, July 16 - 15:24
Background: In the early course of schizophrenia, premorbid functioning, negative symptoms, and neurocognition have been robustly associated with several domains of daily functioning. Research with chronic schizophrenia patients suggests that attitudinal beliefs may influence daily functioning. However, these relationships have not been examined in recent-onset schizophrenia patients. Methods: The sample consisted of recent-onset schizophrenia outpatients (n = 71) who were on average 21.7 (SD = 3.3) years old, had 12.5 (SD = 1.8) years of education, and 5.9 (SD = 6.3) months since psychosis onset. Patients were assessed for premorbid adjustment, positive and negative symptoms, neurocognition, attitudinal beliefs, and daily functioning. Normal controls (n = 20) were screened for psychopathology and demographically matched to the patients. Results: Comparisons indicated that recent-onset patients had higher levels of dysfunctional attitudes and lower self-efficacy compared to healthy controls (t = 3.35, P andlt; .01; t = -4.1, P andlt; .01, respectively). Dysfunctional attitudes (r = -.34) and self-efficacy (r = .36) were significantly correlated with daily functioning. Negative symptoms were found to mediate the relationship between self-efficacy and daily functioning (Sobel test, P andlt; .01), as well as between dysfunctional attitudes and daily functioning (Sobel test, P andlt; .05). Neurocognition was a significant mediator of the relationship between self-efficacy and daily functioning (Sobel test, P andlt; .05). Discussion: Early course schizophrenia patients have significantly more dysfunctional attitudes and lower self-efficacy than healthy subjects. Both self-efficacy and dysfunctional attitudes partially contribute to negative symptoms, which in turn influence daily functioning. In addition, self-efficacy partially contributes to neurocognition, which in turn influences daily functioning.

Jalbrzikowski M, Krasileva KE, Marvin S, Zinberg J, Andaya A, Bachman P, Cannon TD, Bearden CE. Reciprocal social behavior in youths with psychotic illness and those at clinical high risk. 1. Dev Psychopathol. 2013 Nov;25(4 Pt 1):1187-97. doi: 10.1017/S09

2014, July 16 - 15:24
Youths at clinical high risk (CHR) for psychosis typically exhibit significant social dysfunction. However, the specific social behaviors associated with psychosis risk have not been well characterized. We administer the Social Responsiveness Scale (SRS), a measure of autistic traits that examines reciprocal social behavior, to the parents of 117 adolescents (61 CHR individuals, 20 age-matched adolescents with a psychotic disorder [AOP], and 36 healthy controls) participating in a longitudinal study of psychosis risk. AOP and CHR individuals have significantly elevated SRS scores relative to healthy controls, indicating more severe social deficits. Mean scores for AOP and CHR youths are typical of scores obtained in individuals with high functioning autism (Constantino andamp; Gruber, 2005). SRS scores are significantly associated with concurrent real-world social functioning in both clinical groups. Finally, baseline SRS scores significantly predict social functioning at follow-up (an average of 7.2 months later) in CHR individuals, over and above baseline social functioning measures (p andlt; .009). These findings provide novel information regarding impairments in domains critical for adolescent social development, because CHR individuals and those with overt psychosis show marked deficits in reciprocal social behavior. Further, the SRS predicts subsequent real-world social functioning in CHR youth, suggesting that this measure may be useful for identifying targets of treatment in psychosocial interventions.

Ventura J, Wood RC, Jimenez AM, Hellemann GS. Neurocognition and symptoms identify links between facial recognition and emotion processing in schizophrenia: Meta-analytic findings. 1. Schizophr Res. 2013 Nov 20. pii: S0920-9964(13)00561-6. doi: 10.1016/j.

2014, July 16 - 15:24
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.

Karlsgodt KH, van Erp TG, Bearden CE, Cannon TD. Altered relationships between age and functional brain activation in adolescents at clinical high risk for psychosis. 1. Psychiatry Res. 2013 Oct 18. pii: S0925-4927(13)00217-5. doi: 10.1016/j.pscychresns.

2014, July 16 - 15:24
Schizophrenia is considered a neurodevelopmental disorder, but whether the adolescent period, proximal to onset, is associated with aberrant development in individuals at clinical high risk (CHR) for psychosis is incompletely understood. While abnormal gray and white matter development has been observed, alterations in functional neuroimaging (fMRI) parameters during adolescence as related to conversion to psychosis have not yet been investigated. Twenty CHR individuals and 19 typically developing controls (TDC), (ages 14-21), were recruited from the Center for Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Participants performed a Sternberg-style verbal working memory (WMem) task during fMRI and data were analyzed using a cross-sectional design to test the hypothesis that there is a deviant developmental trajectory in WMem associated neural circuitry in those at risk for psychosis. Eight of the CHR adolescents converted to psychosis within 2 years of initial assessment. A voxel-wise regression examining the relationship between age and activation revealed a significant group-by-age interaction. TDC showed a negative association between age and functional activation in the WMem circuitry while CHR adolescents showed a positive association. Moreover, CHR patients who later converted to overt psychosis showed a distinct pattern of abnormal age-associated activation in the frontal cortex relative to controls, while non-converters showed a more diffuse posterior pattern. Finding that age related variation in baseline patterns of neural activity differentiate individuals who subsequently convert to psychosis from healthy subjects suggests that these differences are likely to be clinically relevant.

Golembo-Smith S, Bachman P, Senturk D, Cannon TD, Bearden CE. Youth-caregiver Agreement on Clinical High-risk Symptoms of Psychosis. 1. J Abnorm Child Psychol. 2013 Oct 4. [Epub ahead of print]

2014, July 16 - 15:24
Early identification of individuals who will go on to develop schizophrenia is a difficult endeavor. The variety of symptoms experienced by clinical high-risk youth make it difficult to identify who will eventually develop schizophrenia in the future. Efforts are being made, therefore, to more accurately identify at-risk individuals and factors that predict conversion to psychosis. As in most assessments of children and adolescents, however, both youth and parental report of symptomatology and resulting dysfunction are important to assess. The goals of the current study were to assess the extent of cross-informant agreement on the Structured Interview for Prodromal Symptoms (SIPS), a widely-used tool employed to determine clinical high-risk status. A total of 84 youth-caregiver pairs participated. Youth and caregiver raters displayed moderate overall agreement on SIPS-rated symptoms. Both youth and caregiver ratings of youth symptomatology contributed significantly to predicting conversion to psychosis. In addition, youth age and quality of youth-caregiver relationships appear to be related to cross-informant symptom ratings. Despite differences on individual SIPS domains, the majority of dyads agreed on youth clinical high-risk status. Results highlight the potential clinical utility of using caregiver informants to determine youth psychosis risk.

Woods SW, Addington J, Bearden CE, Cadenhead KS, Cannon TD, Cornblatt BA, Mathalon DH, Perkins DO, Seidman LJ, Tsuang MT, Walker EF, McGlashan TH. Psychotropic medication use in youth at high risk for psychosis: Comparison of baseline data from two resear

2014, July 16 - 15:24
BACKGROUND: Antipsychotic medication use rates have generally been rising among youth with psychiatric disorders, but little is known about use rates of antipsychotics or other psychotropic medications in patients at high risk for psychosis. METHOD: Baseline psychotropic medication use rates were compared in two research cohorts of patients at high risk for psychosis that enrolled between 1998-2005 (n=391) and 2008-2011 (n=346). Treatment durations and antipsychotic doses were described for cohort 2. RESULTS: Median age was 17years in cohort 1 and 18years in cohort 2. The rate of prescription of any psychotropic at baseline was roughly 40% for each cohort. Antipsychotic prescription rates were 24% among sites that permitted baseline antipsychotic use in cohort 1 and 18% in the cohort 2; the decline did not quite reach statistical significance (p=0.064). In cohort 2 the mean±SD baseline chlorpromazine-equivalent dose was 121±108mg/d, and lifetime duration of antipsychotic treatment was 3.8±5.9months. DISCUSSION: Although the rate of antipsychotic prescription among high-risk youth may have fallen slightly, the nearly one-in-five rate in the second cohort still constitutes a significant exposure. Mitigating factors were that doses and durations of treatment were low. As for other nonpsychotic conditions, it is incumbent on our field to develop alternative treatments for high-risk patients and to generate additional evidence for or against the efficacy of antipsychotics to help define their appropriate role if alternative treatments fail.

Zanello A, Berthoud L, Ventura J, Merlo MC. The Brief Psychiatric Rating Scale (version 4.0) factorial structure and its sensitivity in the treatment of outpatients with unipolar depression. 1. Psychiatry Res. 2013 Jul 26. pii: S0165-1781(13)00376-4. doi:

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The 24-item Brief Psychiatric Rating Scale (version 4.0) enables the rater to measure psychopathology severity. Still, little is known about the BPRS's reliability and validity outside of the psychosis spectrum. The aim of this study was to examine the factorial structure and sensitivity to change of the BPRS in patients with unipolar depression. Two hundred and forty outpatients with unipolar depression were administered the 24-item BPRS. Assessments were conducted at intake and at post-treatment in a Crisis Intervention Centre. An exploratory factor analysis of the 24-item BPRS produced a six-factor solution labelled "Mood disturbance", "Reality distortion", "Activation", "Apathy", "Disorganization", and "Somatization". The reduction of the total BPRS score and dimensional scores, except for "Activation", indicates that the 24-item BPRS is sensitive to change as shown in patients that appeared to have benefited from crisis treatment. The findings suggest that the 24-item BPRS could be a useful instrument to measure symptom severity and change in symptom status in outpatients presenting with unipolar depression.

Allott KA, Turner LR, Chinnery GL, Killackey EJ, Nuechterlein KH. Managing disclosure following recent-onset psychosis: utilizing the Individual Placement and Support model. 1. Early Interv Psychiatry. 2013 Jan 24. doi: 10.1111/eip.12030. [Epub ahead of p

2014, July 16 - 15:24
AIMS: Individual Placement and Support is the most defined and evidence-based approach to supported employment for severe mental illness, including recent-onset psychosis. However, there is limited evidence or detailed guidelines informing the management of mental illness disclosure to educators or employers when delivering Individual Placement and Support. In this paper, we describe the initial disclosure preferences of young people with recent-onset psychosis enrolled in Individual Placement and Support and provide guidance for managing disclosure when delivering Individual Placement and Support with this population. METHODS: Drawing from sites in Melbourne, Australia and Los Angeles, USA, clients' initial disclosure preferences were examined. We describe approaches to providing IndividualPlacement and Support when no disclosure is permitted compared withwhen disclosure is permitted, including two illustrative case vignettes. RESULTS: No disclosure of mental illness or disability was requested by 54-59% of clients; 41-46% of clients permitted partial or complete disclosure. The 'no disclosure' scenario required the Individual Placement and Support worker to provide support 'behind the scenes', whereas when disclosure was permitted, the Individual Placement and Support worker could have contact with instructors/employers and work 'on the front lines'. The case vignettes illustrate how both approaches can lead to successful vocational outcomes. CONCLUSIONS: We found that Individual Placement and Support can be provided in an educative, flexible, creative and collaborative manner according to client disclosure preferences. We suggest that disclosure preferences do not prevent successful vocational outcomes, although this supposition requires empirical investigation.

Bartzokis G, Lu PH, Raven EP, Amar CP, Detore NR, Couvrette AJ, Mintz J, Ventura J, Casaus LR, Luo JS, Subotnik KL, Nuechterlein KH. Impact on intracortical myelination trajectory of long acting injection versus oral risperidone in first-episode schizoph

2014, July 16 - 15:24
CONTEXT: Imaging and post-mortem studies suggest that frontal lobe intracortical myelination is dysregulated in schizophrenia (SZ). Prior MRI studies suggested that early in the treatment of SZ, antipsychotic medications initially increase frontal lobe intracortical myelin (ICM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of ICM decline in chronic SZ is due to medication non-adherence or pharmacokinetics, it may be modifiable by long acting injection (LAI) formulations. OBJECTIVES: Assess the effect of risperidone formulation on the ICM trajectory during a six-month randomized trial of LAI (RLAI) versus oral (RisO) in first-episode SZ subjects. DESIGN: Two groups of SZ subjects (RLAI, N=9; and RisO, N=13) matched on pre-randomization oral medication exposure were prospectively examined at baseline and 6 months later, along with 12 healthy controls (HCs). Frontal lobe ICM volume was assessed using inversion recovery (IR) and proton density (PD) MRI images. Medication adherence was tracked. MAIN OUTCOME MEASURE: ICM volume change scores were adjusted for the change in the HCs. RESULTS: ICM volume increased significantly (p=.005) in RLAI and non-significantly (p=.39) in the RisO groups compared with that of the healthy controls. A differential between-group treatment effect was at a trend level (p=.093). SZ subjects receiving RLAI had better medication adherence and more ICM increases (chi-square pandlt;.05). CONCLUSIONS: The results suggest that RLAI may promote ICM development in first-episode SZ patients. Better adherence and/or pharmacokinetics provided by LAI may modify the ICM trajectory. In vivo MRI myelination measures can help clarify pharmacotherapeutic mechanisms of action.

Gretchen-Doorly D, Kite RE, Subotnik KL, Detore NR, Ventura J, Kurtz AS, Nuechterlein KH. Cardiorespiratory endurance, muscular flexibility and strength in first-episode schizophrenia patients: use of a standardized fitness assessment. 1. Early Interv Psy

2014, July 16 - 15:24
AIM: This study determined the fitness status and examined potential correlates of fitness in first-episode schizophrenia patients using a standardized fitness test protocol. METHODS: A certified fitness instructor administered the Young Men's Christian Association (YMCA) fitness test to 70 recent-onset schizophrenia participants within 3 months of entry into the study. RESULTS: Percentile ranks of scores on muscular strength and endurance, muscular flexibility and cardiorespiratory fitness in our sample were all below the 50th percentile when compared with national norms in the United States. As expected, patients with a higher body mass index and those who smoked had poorer cardiorespiratory fitness. A non-significant trend indicated that patients with a longer duration of illness had worse cardiorespiratory fitness. Exposure to antipsychotic medication was unrelated to cardiorespiratory fitness. CONCLUSION: Results suggest that physical fitness is impaired and might decline over time in first-episode schizophrenia patients, but this needs to be confirmed in a longitudinal study.

Jalbrzikowski M, Sugar CA, Zinberg J, Bachman P, Cannon TD, Bearden CE. Coping styles of individuals at clinical high risk for developing psychosis. 1. Early Interv Psychiatry. 2012 Nov 19. doi: 10.1111/eip.12005. [Epub ahead of print]

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AIM: There is a wealth of evidence suggesting that patients with schizophrenia tend to respond to life stressors using less effective coping skills, which are in turn related to poor outcome. However, the contribution of coping strategies to outcome in youth at clinical high risk (CHR) for developing psychosis has not been investigated. METHODS: This longitudinal study followed CHR youth over a 12-month period, using the Brief COPE questionnaire. CHR subjects (n?=?88) were compared at baseline with a healthy control sample (n?=?53), and then mixed models were used to explore the relationship of coping strategies to clinical and psychosocial outcomes in CHR subjects over time (n?=?102). RESULTS: Cross-sectional analyses revealed that, in comparison with healthy controls, CHR youth reported using more maladaptive coping strategies (P?andlt;?0.001) and fewer adaptive coping strategies (P?andlt;?0.01). Longitudinal analyses within the CHR group showed significant decreases in maladaptive coping and symptom severity over time, with corresponding improvements in social and role functioning. Adaptive coping was associated with better concurrent social functioning and less severe symptomatology (both P?andlt;?0.001). Over time, more maladaptive coping was associated with more severe positive and negative symptoms (both P?andlt;?0.005). CONCLUSIONS: Youth at risk for psychosis report using fewer adaptive and more maladaptive coping strategies relative to healthy controls. Over 1-year follow-up, more adaptive coping styles are associated with less severe clinical symptomatology and better social functioning. These findings suggest that teaching adaptive coping styles may be an important target for intervention in youth at high risk for psychosis.

Mittal VA, Willhite R, Daley M, Bearden CE, Niendam T, Ellman LM, Cannon TD. Obstetric complications and risk for conversion to psychosis among individuals at high clinical risk. 1. Early Interv Psychiatry. 2009 Aug;3(3):226-30. doi: 10.1111/j.1751-7893.2

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AIM: Examining risk factors among high-risk populations stands to inform treatment and to elucidate our understanding of the pathophysiology of schizophrenia. Despite substantial evidence implicating the incidence of obstetric complications (OCs) as a risk factor for schizophrenia, little is known about the relationship between OCs and risk for conversion among high-risk individuals. METHODS: We prospectively followed individuals at high risk for developing psychotic disorders for a two-year period to determine if a history of OCs is associated with conversion. RESULTS: Individuals who converted to psychosis had significantly more OCs when compared to non-converting participants; a history of OCs was associated with increased odds of conversion (odds ratio = 4.90, confidence interval :1.04/22.20). OCs were positively associated with prodromal symptomatology. CONCLUSIONS: To date, this report represents the first empirical evidence suggesting that OCs confer increased risk of conversion to psychosis. It is possible that OCs interact with brain maturational processes in the pathophysiology of schizophrenia and can serve as a risk marker.

Moran ZD, Williams TJ, Bachman P, Nuechterlein KH, Subotnik KL, Yee CM. Spectral decomposition of P50 suppression in schizophrenia during concurrent visual processing. 1. Schizophr Res. 2012 Sep;140(1-3):237-42. doi: 10.1016/j.schres.2012.07.002. Epub 20

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Reduced suppression of the auditory P50 event-related potential has long been associated with schizophrenia, but the mechanisms associated with the generation and suppression of the P50 are not well understood. Recent investigations have used spectral decomposition of the electroencephalograph (EEG) signal to gain additional insight into the ongoing electrophysiological activity that may be reflected by the P50 suppression deficit. The present investigation extended this line of study by examining how both a traditional measure of sensory gating and the ongoing EEG from which it is extracted might be modified by the presence of concurrent visual stimulation - perhaps better characterizing gating deficits as they occur in a real-world, complex sensory environment. The EEG was obtained from 18 patients with schizophrenia and 17 healthy control subjects during the P50 suppression paradigm and while identical auditory paired-stimuli were presented concurrently with affectively neutral pictures. Consistent with prior research, schizophrenia patients differed from healthy subjects in gating of power in the theta range; theta activity also was modulated by visual stimulation. In addition, schizophrenia patients showed intact gating but overall increased power in the gamma range, consistent with a model of NMDA receptor dysfunction in the disorder. These results are in line with a model of schizophrenia in which impairments in neural synchrony are related to sensory demands and the processing of multimodal information.

Niendam TA, Jalbrzikowski M, Bearden CE. Exploring predictors of outcome in the psychosis prodrome: implications for early identification and intervention. 1. Neuropsychol Rev. 2009 Sep;19(3):280-93. Epub 2009 Jul 14.

2014, July 16 - 15:24
Functional disability is a key component of many psychiatric illnesses, particularly schizophrenia. Impairments in social and role functioning are linked to cognitive deficits, a core feature of psychosis. Retrospective analyses demonstrate that substantial functional decline precedes the onset of psychosis. Recent investigations reveal that individuals at clinical-high-risk (CHR) for psychosis show impairments in social relationships, work/school functioning and daily living skills. CHR youth also demonstrate a pattern of impairment across a range of cognitive domains, including social cognition, which is qualitatively similar to that of individuals with schizophrenia. While many studies have sought to elucidate predictors of clinical deterioration, specifically the development of schizophrenia, in such CHR samples, few have investigated factors relevant to psychosocial outcome. This review integrates recent findings regarding cognitive and social-cognitive predictors of outcome in CHR individuals, and proposes potential directions for future research that will contribute to targeted interventions and improved outcome for at-risk youth.