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Open Access Publications from the University of California

Scholarly Works (10 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2016)

The neural substrate of interactions of working memory (WM) with socio-emotional processing is poorly understood in schizophrenia. This study builds on published papers using a delayed match to sample design to study the interaction of WM load with type of distracter (socially relevant faces vs. socially irrelevant geometric designs [FvG]) presented briefly during the WM maintenance period. Based on previously published findings, we hypothesize: (1) The FvG difference in brain activity in the dorsolateral prefrontal cortex (DLPFC) in the task maintenance period will be largest at the highest WM load. (2) Among schizophrenia/ schizoaffective patients and healthy controls the magnitude of the face vs. geometric design (FvG) contrast in brain activity in the amygdala during the task maintenance period will follow a quadratic pattern across WM load when averaged over face type. (3) Among schizophrenia patients, the magnitude of the FvG contrast in brain activity in the amygdala and DLPFC at the greatest WM load will be correlated with negative symptoms.

Individuals between the ages of 18-55 diagnosed with schizophrenia/schizoaffective disorder (N = 12) and non-psychiatric controls (N = 20) matched with the patients on age, gender, paternal education and paternal socioeconomic status underwent structural and functional magnetic resonance imaging (fMRI). To assess the effect of implicit socioemotional modulation on brain activity during WM, the effect of facial distraction on brain activation was assessed for WM of pseudowords at three syllable loads (1, 2, and 3) across several face valence types and contrasted with the effect of a geometric distracter.

Results: Although patients performed significantly above chance, they were less accurate than controls with no difference in response latency. When the FvG contrast was tested for response latency, we observed a significant quadratic effect of WM load in healthy controls (F[1,19] = 6.108, p = .023, η2 = .24) but a linear effect among patients (F[1,10] = 4.012, p = .073, η2 = .29). Similar patterns were found for response accuracy but were not statistically significant. With regard to neural activity, we found a significant bilateral linear trend of percent signal change on WM load for the FvG contrast in the DLPFC (F[1,19] = 5.818, p = .026, MSE = .077, η2 = .23). among controls, with brain activation to faces greater than activation to designs only at the highest WM load. In the amygdala we observed a significant bilateral quadratic effect of percent signal change on WM load for the FvG contrast in the control group (F[1,19] = 10.423, p = .004, MSE = .121, η2 = .35). We observed a significant difference in neural activation patterns in patients compared to controls in the DLPFC and the amygdala. Specifically, in patients, we observed a quadratic instead of a linear trend in the DLPFC but only in the right hemisphere (hemisphere x quadratic: F[1,11] = 9.362, p = .011, η2 = .40). In the amygdala, the patients displayed a quadratic trend also only in the right hemisphere, (hemisphere x quadratic: F[1,11] = 10.442 p = .008, η2 = .49). In neither controls nor patients did individual differences in the quadratic effect of brain activity in the amygdala correlate with the quadratic effect in response time or accuracy. Although the correlation between the magnitude of the quadratic trend in the right amygdala at the highest WM load with general psychopathology was moderately large in patients, neither this effect nor any other brain activation effects were significantly correlated with psychopathology.

Confirming hypothesis one, controls showed the largest difference in brain activity of the FvG contrast in the DLPFC during the maintenance period at the highest WM load. However, in patients we saw significantly decreased percent signal change in DLPFC at the highest WM load on the FvG contrast in the maintenance period. For hypothesis two we observed a quadratic pattern of WM load on the FvG contrast in the maintenance period for both controls and patients, although this effect was only present in the right hemisphere of patients. Furthermore, contrary to hypothesis 3 we did not observe significant correlations between symptom severity and the magnitude of the FvG contrast in brain activity in the amygdala and DLPFC at the greatest WM load. These results suggest a separate process of social-discrimination is taking place in controls. However, this process appears to be impaired in individuals with schizophrenia. This disruption may be due to poor integration of different brain areas and interhemispheric communication.

    Cover page: Implicit socioemotional modulation of working memory brain activity in schizophrenia
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2019)
    Bullying is an adverse childhood experience that is more common among youth with special needs and is associated with increased psychopathology throughout the lifespan. Individuals with chromosome 22q11.2 deletion syndrome (22q) represent one group of special needs youth who are at increased risk for bullying due to co-occurring genetically-mediated developmental, physical, and learning difficulties. Furthermore, individuals with 22q are at increased risk for developing psychotic disorders such as schizophrenia. However, there is a paucity of research exploring the impact of bullying on individuals with 22q and the possible impact this has on risk for psychosis in this population. To explore this relationship using existing research the goals of the review are: (i) to explore the nature of bullying among youth with special needs, and (ii) to discuss its potential role as a specific risk factor in the development of adverse outcomes, including psychosis symptoms. We reviewed the relationship between bullying and its short and long-term effects on the cognitive, social, and developmental functioning of typically developing individuals and those with special needs. We propose an interactive relationship between trauma, stress, and increased psychosis risk among youth with 22q with a history of bullying. The early childhood experience of trauma in the form of bullying promotes an altered developmental trajectory that may elevate the risk for maladaptive functioning and subsequent psychotic disorders, particularly in youth with genetic vulnerabilities. Therefore, we conclude the experience of bullying among individuals with 22q should be more closely examined.
      Cover page: Bullying and psychosis: The impact of chronic traumatic stress on psychosis risk in 22q11.2 deletion syndrome - a uniquely vulnerable population.
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2019)
      Bullying is an adverse childhood experience that is more common among youth with special needs and is associated with increased psychopathology throughout the lifespan. Individuals with chromosome 22q11.2 deletion syndrome (22q) represent one group of special needs youth who are at increased risk for bullying due to co-occurring genetically-mediated developmental, physical, and learning difficulties. Furthermore, individuals with 22q are at increased risk for developing psychotic disorders such as schizophrenia. However, there is a paucity of research exploring the impact of bullying on individuals with 22q and the possible impact this has on risk for psychosis in this population. To explore this relationship using existing research the goals of the review are: (i) to explore the nature of bullying among youth with special needs, and (ii) to discuss its potential role as a specific risk factor in the development of adverse outcomes, including psychosis symptoms. We reviewed the relationship between bullying and its short and long-term effects on the cognitive, social, and developmental functioning of typically developing individuals and those with special needs. We propose an interactive relationship between trauma, stress, and increased psychosis risk among youth with 22q with a history of bullying. The early childhood experience of trauma in the form of bullying promotes an altered developmental trajectory that may elevate the risk for maladaptive functioning and subsequent psychotic disorders, particularly in youth with genetic vulnerabilities. Therefore, we conclude the experience of bullying among individuals with 22q should be more closely examined.
        Cover page: Bullying and psychosis: The impact of chronic traumatic stress on psychosis risk in 22q11.2 deletion syndrome - a uniquely vulnerable population
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2014)
        This study investigated implicit socioemotional modulation of working memory (WM) in the context of symptom severity and functional status in individuals with psychosis (N = 21). A delayed match-to-sample task was modified wherein task-irrelevant facial distracters were presented early and briefly during the rehearsal of pseudoword memoranda that varied incrementally in load size (1, 2, or 3 syllables). Facial distracters displayed happy, sad, or emotionally neutral expressions. Implicit socioemotional modulation of WM was indexed by subtracting task accuracy on nonfacial geometrical distraction trials from facial distraction trials. Results indicated that the amount of implicit socioemotional modulation of high WM load accuracy was significantly associated with negative symptoms (r = 0.63, P < 0.01), role functioning (r = -0.50, P < 0.05), social functioning (r = -0.55, P < 0.01), and global assessment of functioning (r = -0.53, P < 0.05). Specifically, greater attentional distraction of high WM load was associated with less severe symptoms and functional impairment. This study demonstrates the importance of the WM-socioemotional interface in influencing clinical and psychosocial functional status in psychosis.
          Cover page: Not All Distraction Is Bad: Working Memory Vulnerability to Implicit Socioemotional Distraction Correlates with Negative Symptoms and Functional Impairment in Psychosis
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2020)
          Behavioral components of chromosome 22q11.2 deletion syndrome (22q), caused by the most common human microdeletion, include cognitive and adaptive functioning impairments, heightened anxiety, and an elevated risk of schizophrenia. We investigated how interactions between executive function and the largely overlooked factor of emotion regulation might relate to the incidence of symptoms of psychotic thinking in youth with 22q. We measured neural activity with event-related potentials (ERPs) in variants of an inhibitory function (Go/No-Go) experimental paradigm that presented affective or non-affective stimuli. The study replicated inhibition impairments in the 22q group that were amplified in the presence of stimuli with negative, more than positive affective salience. Importantly, the anterior N2 conflict monitoring ERP significantly increased when youth with 22q viewed angry and happy facial expressions, unlike the typically developing participants. This suggests that youth with 22q may require greater conflict monitoring resources when controlling their behavior in response to highly salient social signals. This evidence of both behavioral and neurophysiological differences in affectively influenced inhibitory function suggests that frequently anxious youth with 22q may struggle more with cognitive control in emotionally charged social settings, which could influence their risk of developing symptoms of psychosis.
            Cover page: Neural and behavioral measures suggest that cognitive and affective functioning interactions mediate risk for psychosis‐proneness symptoms in youth with chromosome 22q11.2 deletion syndrome
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2019)
            Psychosis is conceptualized in a neurodevelopmental vulnerability-stress framework, and childhood trauma is one environmental factor that can lead to psychotic symptoms and the development of psychotic disorders. Higher rates of trauma are associated with higher psychosis risk and greater symptom frequency and severity, resulting in increased hospitalization rates and demand on outpatient primary care and mental health services. Despite an estimated 70% of individuals in the early stages of psychosis reporting a history of experiencing traumatic events, trauma effects (post-traumatic anxiety or depressive symptoms) are often overlooked in psychosis treatment and current interventions typically do not target commonly comorbid post-traumatic stress symptoms. We presented a protocol for Trauma-Integrated Cognitive Behavioral Therapy for Psychosis (TI-CBTp), an approach to treating post-traumatic stress symptoms in the context of early psychosis care. We provided a brief summary of TI-CBTp as implemented in the context of Coordinated Specialty Care and presented preliminary data supporting the use of TI-CBTp in early psychosis care. The preliminary results suggest that individuals with comorbid psychosis and post-traumatic stress symptoms can be appropriately and safely treated using TI-CBTp within Coordinated Specialty Care.
              Cover page: Uncharted Waters: Treating Trauma Symptoms in the Context of Early Psychosis.
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2020)
              Behavioral components of chromosome 22q11.2 deletion syndrome (22q), caused by the most common human microdeletion, include cognitive and adaptive functioning impairments, heightened anxiety, and an elevated risk of schizophrenia. We investigated how interactions between executive function and the largely overlooked factor of emotion regulation might relate to the incidence of symptoms of psychotic thinking in youth with 22q. We measured neural activity with event-related potentials (ERPs) in variants of an inhibitory function (Go/No-Go) experimental paradigm that presented affective or non-affective stimuli. The study replicated inhibition impairments in the 22q group that were amplified in the presence of stimuli with negative, more than positive affective salience. Importantly, the anterior N2 conflict monitoring ERP significantly increased when youth with 22q viewed angry and happy facial expressions, unlike the typically developing participants. This suggests that youth with 22q may require greater conflict monitoring resources when controlling their behavior in response to highly salient social signals. This evidence of both behavioral and neurophysiological differences in affectively influenced inhibitory function suggests that frequently anxious youth with 22q may struggle more with cognitive control in emotionally charged social settings, which could influence their risk of developing symptoms of psychosis.
                Cover page: Neural and behavioral measures suggest that cognitive and affective functioning interactions mediate risk for psychosis‐proneness symptoms in youth with chromosome 22q11.2 deletion syndrome
                • Article
                • Peer Reviewed
                UC Davis Previously Published Works (2024)
                Screening for psychosis spectrum disorders in primary care could improve early identification and reduce the duration of untreated psychosis. However, the accuracy of psychosis screening in this setting is unknown. To address this, we conducted a diagnostic accuracy study of screening for psychosis spectrum disorders in eight behavioral health services integrated into primary care clinics. Patients attending an integrated behavioral health appointment at their primary care clinic completed the Prodromal Questionnaire - Brief (PQ-B) immediately prior to their intake assessment. This was compared to a diagnostic phone interview based on the Structured Interview for Psychosis Risk Syndromes (SIPS). In total, 145 participants completed all study procedures, of which 100 screened positive and 45 negative at a provisional PQ-B threshold of ≥20. The PQ-B was moderately accurate at differentiating psychosis spectrum from no psychosis spectrum disorders; a PQ-B distress score of ≥27 had a sensitivity and specificity of 71.2 % and 57.0 % respectively. In total, 66 individuals (45.5 %) met criteria for a psychosis spectrum disorder and 24 (16.7 %) were diagnosed with full psychosis, indicating a high prevalence of psychosis in the sample. Overall, screening for psychosis spectrum disorders in an IBH primary care setting identified a relatively high number of individuals and may identify people that would otherwise be missed. The PQ-B performed slightly less well than in population-based screening in community mental health settings. However, the findings suggest this may represent an effective way to streamline the pathway between specialty early psychosis programs and primary care clinics for those in need.
                  Cover page: The diagnostic accuracy of screening for psychosis spectrum disorders in behavioral health clinics integrated into primary care
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2021)
                  The authors examine U.S.-based evidence that connects characteristics of the social environment with outcomes across the psychosis continuum, from psychotic experiences to schizophrenia. The notion that inequitable social and economic systems of society significantly influence psychosis risk through proxies, such as racial minority and immigrant statuses, has been studied more extensively in European countries. While there are existing international reviews of social determinants of psychosis, none to the authors' knowledge focus on factors in the U.S. context specifically-an omission that leaves domestic treatment development and prevention efforts incomplete and underinformed. In this review, the authors first describe how a legacy of structural racism in the United States has shaped the social gradient, highlighting consequential racial inequities in environmental conditions. The authors offer a hypothesized model linking structural racism with psychosis risk through interwoven intermediary factors based on existing theoretical models and a review of the literature. Neighborhood factors, cumulative trauma and stress, and prenatal and perinatal complications were three key areas selected for review because they reflect social and environmental conditions that may affect psychosis risk through a common pathway shaped by structural racism. The authors describe evidence showing that Black and Latino people in the United States suffer disproportionately from risk factors within these three key areas, in large part as a result of racial discrimination and social disadvantage. This broad focus on individual and community factors is intended to provide a consolidated space to review this growing body of research and to guide continued inquiries into social determinants of psychosis in U.S. contexts.
                    Cover page: From Womb to Neighborhood: A Racial Analysis of Social Determinants of Psychosis in the United States
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2023)

                    Importance

                    Reducing the duration of untreated psychosis (DUP) is essential to improving outcomes for people with first-episode psychosis (FEP). Current US approaches are insufficient to reduce DUP to international standards of less than 90 days.

                    Objective

                    To determine whether population-based electronic screening in addition to standard targeted clinician education increases early detection of psychosis and decreases DUP, compared with clinician education alone.

                    Design, setting, and participants

                    This cluster randomized clinical trial included individuals aged 12 to 30 years presenting for services between March 2015 and September 2017 at participating sites that included community mental health clinics and school support and special education services. Eligible participants were referred to the Early Diagnosis and Preventative Treatment (EDAPT) Clinic. Data analyses were performed in September and October 2019 for the primary and secondary analyses, with the exploratory subgroup analyses completed in May 2021.

                    Interventions

                    All sites in both groups received targeted education about early psychosis for health care professionals. In the active screening group, clients also completed the Prodromal Questionnaire-Brief using tablets at intake; referrals were based on those scores and clinical judgment. In the group receiving treatment as usual (TAU), referrals were based on clinical judgment alone.

                    Main outcomes and measures

                    Primary outcomes included DUP, defined as the period from full psychosis onset to the date of the EDAPT diagnostic telephone interview, and the number of individuals identified with FEP or a psychosis spectrum disorder. Exploratory analyses examined differences by site type, completion rates between conditions, and days from service entry to telephone interview.

                    Results

                    Twenty-four sites agreed to participate, and 12 sites were randomized to either the active screening or TAU group. However, only 10 community clinics and 4 school sites were able to fully implement population screening and were included in the final analysis. The total potentially eligible population size within each study group was similar, with 2432 individuals entering at active screening group sites and 2455 at TAU group sites. A total of 303 diagnostic telephone interviews were completed (178 [58.7%] female individuals; mean [SD] age, 17.09 years [4.57]). Active screening sites reported a significantly higher detection rate of psychosis spectrum disorders (136 cases [5.6%], relative to 65 [2.6%]; P < .001) and referred a higher proportion of individuals with FEP and DUP less than 90 days (13 cases, relative to 4; odds ratio, 0.30; 95% CI, 0.10-0.93; P = .03). There was no difference in mean (SD) DUP between groups (active screening group, 239.0 days [207.4]; TAU group 262.3 days [170.2]).

                    Conclusions and relevance

                    In this cluster trial, population-based technology-enhanced screening across community settings detected more than twice as many individuals with psychosis spectrum disorders compared with clinical judgment alone but did not reduce DUP. Screening could identify people undetected in US mental health services. Significant DUP reduction may require interventions to reduce time to the first mental health contact.

                    Trial registration

                    ClinicalTrials.gov Identifier: NCT02841956.
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