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Scholarly Works (6 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2021)

Rationale: Childhood adversity is strongly associated with increased risk for psychosis. Despite clear evidence for an association between childhood trauma (CT) and psychosis, the biological mechanisms that mediate the relationship between CT and clinical outcomes in psychosis remain largely unknown. The aim of this study is to better understand associations between inflammation, CT, and clinical outcomes in subjects identified to be at clinical high risk for developing psychosis (CHR) and evaluate whether inflammation mediates the relationship between CT and clinical outcomes.

Design and Methods: Participants included 67 CHR subjects and 34 unaffected comparison subjects (UC; N = 101) ages 12-35 who participated in the North American Prodrome Longitudinal Study 2 (NAPLS2). Experience of CT was assessed using the Childhood Trauma and Abuse Scale. Severity of psychosis-risk symptoms was measured using the Structured Interview for Prodromal Syndromes (SIPS). Functioning was assessed using Global Assessment of Functioning (GAF) scale. Blood samples were analyzed using validated multiplex immunoassay. Group differences between UC and CHR in CT, functioning, psychosis risk symptom severity, and inflammation were evaluated using independent samples t-tests and Chi-squared tests. Two mediation models were tested to explore whether inflammation mediated the association between 1. total CT and GAF and 2. total CT and psychosis risk positive symptom severity.

Results: Compared to UC, CHR subjects demonstrated significantly higher incidence of total CT, greater severity of psychosis risk symptoms, and significantly lower global, role, and social functioning. Regression analyses revealed that total CT and a 15-Analyte Inflammatory Index uniquely predicted psychosis risk positive symptom severity (β = 0.24, t(65) = 1.9, p = 0.05) and GAF scores (β = -0.26, t(65) =-2.25, p = 0.03). Combined, these variables explained a significant proportion of variance in psychosis risk positive symptom severity (R2 = 0.122) and GAF (R2 = 0.151) scores.

Conclusions and Clinical Implications: The relationship between CT, increased psychosis-risk symptom severity, and decreased functioning was replicated in this study and results demonstrated novel associations between total CT, psychosis risk positive symptom severity, and GAF. This is the first study to demonstrate that CT and inflammation may have unique and additive effects on increased psychosis risk positive symptom severity and reduced global functioning in individuals at CHR for psychosis.

    Cover page: Does the Experience of Childhood Trauma Lead to a Pro-Inflammatory Phenotype in Youth at Clinical High Risk for Psychosis?
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2019)
    Background: Early psychosocial interventions targeting cognitive and functional outcomes in individuals at clinical high risk for psychosis are a research priority. An even greater need is the identification of effective interventions in underserved populations. Compensatory Cognitive Training (CCT) is a psychosocial intervention with demonstrated efficacy in chronic schizophrenia and first episode psychosis, but remains to be evaluated in pre-illness phases. The aim of this study was to describe the development and implementation of an ongoing pilot randomized controlled trial investigating the efficacy of group-based, manualized CCT, as compared to recreational therapy (RT), for Latino participants at clinical high risk for psychosis (CHR) in both the United States and Mexico. It is hypothesized that, in comparison to those receiving RT, participants receiving CCT will show significant improvements in neurocognitive performance and functional capacity (co-primary outcomes) and self-rated functioning and clinical symptoms (secondary outcomes). Methods: Latino CHR participants aged 12-30 years will be included in the study. Both CCT and RT will be delivered in either Spanish or English, depending on group preference. Additionally, all assessments will be administered in participants' preferred language. A comprehensive assessment of neurocognitive and functional performance and clinical symptomatology will be performed at baseline, mid-intervention (4 weeks, 8 weeks), post-intervention (12 weeks) and 3-month follow-up. The primary outcome measures are neurocognition and functional capacity, as assessed by the MATRICS (Measurement and Treatment Research in Cognition in Schizophrenia) Consensus Cognitive Battery and the University of California, San Diego Performance-Based Skills Assessment-Brief, respectively. Furthermore, secondary outcomes measures will be used to examine change in clinical symptoms and self-reported functioning in response to CCT versus RT. Discussion: The evaluation of a novel treatment such as CCT in CHR youth will provide empirical support for a low risk, comprehensive cognitive intervention that could have important implications for public health if it improves neurocognition and functioning.
      Cover page: Compensatory Cognitive Training for Latino Youth at Clinical High Risk for Psychosis: Study Protocol for a Randomized Controlled Trial.
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2020)

      Introduction

      Research examining the role of inflammation in psychosis has produced inconsistent results. Variables that influence inflammation, including antipsychotic medication, are inconsistently controlled across studies and variation of inflammatory analytes across stages of psychosis may also influence findings. The purpose of this study was to assess for evidence of immuno-inflammatory dysregulation across the stages of early psychosis. We examined a immuno-inflammatory analytes in subjects at clinical high risk (CHR) for developing a psychotic disorder, antipsychotic-naïve (-n) and antipsychotic treated (-a) subjects in their first episode of psychosis (FEP), and healthy control (HC) subjects.

      Methods

      A total of 11 subjects at CHR, 50 subjects within their FEP (40 FEP-n, 10 FEP-a), and 10 HC subjects were recruited from early psychosis programs in San Diego and Mexico City. Plasma was collected for biomarker assay.

      Results

      Immuno-inflammatory analytes significantly differed between groups: Interferon-gamma (IFN-γ), Interleukin-10 (IL-10), Eotaxin-1, Interferon Gamma-Induced Protein-10 (IP-10), Monocyte Chemotactic Protein-1 (MCP-1), Macrophage-Derived Chemokine (MDC), Macrophage Inflammatory Protein-1 beta (MIP-1β), Thymus and Activation Regulated Chemokine (TARC), and Brain Derived Neurotropic Factor (BDNF). Post-hoc analyses revealed an overall pattern of higher levels of IL-10, MCP-1, MIP-1β, TARC, and BDNF in CHR as compared to FEP-a, FEP-n, and HC subjects.

      Conclusions

      Results reveal a profile of immuno-inflammatory dysregulation in early stages of psychosis prior to psychotic conversion and treatment with antipsychotic medication. The CHR phase of early psychosis may represent a period of increased immuno-inflammatory activation, but due to limited sample size, these results deserve replication in a well characterized early psychosis population.
        Cover page: Immuno-inflammatory changes across phases of early psychosis: The impact of antipsychotic medication and stage of illness
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2022)
        Childhood trauma (CT) is associated with suicidal ideation and behaviors (SI/SB) in people with psychosis. The interpersonal psychological theory of suicide (IPTS) suggests that there are four factors that increase suicide risk: thwarted belongingness, perceived burdensomeness, acquired capacity for suicide, and hopelessness. The IPTS constructs and social cognitive biases are associated with SI/SB in psychotic disorders. However, the role of CT in IPTS constructs and social cognitive biases has not been examined in psychosis. In an outpatient community sample of persons with psychotic disorders (N = 96) assessed with the Childhood Trauma Questionnaire, the aims of this study were to a) evaluate rates of CT in this sample, b) determine the relationship between CT types and lifetime SI/SB, and c) explore the relationship between CT types, IPTS constructs, and social cognitive biases. All participants reported experiencing CT. Emotional abuse was associated with greater SI severity and higher rates of lifetime suicide attempts, as well as with greater perceived burdensomeness and more severe negative social cognitive biases. Other CT types were minimally associated with SI/SB or IPST constructs; hopelessness was not associated. Overall, negative interpersonal beliefs and social cognitive biases may explain how CT increases suicide risk in psychosis.
          Cover page: Childhood Trauma Associations With the Interpersonal Psychological Theory of Suicide and Social Cognitive Biases in Psychotic Disorders.
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2023)
          BACKGROUND: Disparities in physical and mental health among Black, Indigenous, and People of Color (BIPOC) are well-documented and mirrored in the Veteran population. Chronic stress due to racism and discrimination is one possible mechanism driving these negative health outcomes. The Race-Based Stress and Trauma Empowerment (RBSTE) group is a novel, manualized, health promotion intervention designed to address the direct and indirect impacts of racism among Veterans of Color. This paper describes the protocol of the first pilot randomized controlled trial (RCT) of RBSTE. This study will examine the feasibility, acceptability, and appropriateness of RBSTE compared to an active control (an adaptation of Present-Centered Therapy; PCT) in a Veterans Affairs (VA) healthcare setting. A secondary aim is to identify and optimize strategies for holistic evaluation. METHODS: Veterans of Color (N = 48) endorsing perceived discrimination and stress will be randomized to RBSTE or PCT; both groups will be delivered in 8 weekly, 90-min virtual group sessions. Outcomes will include measures of psychological distress, discrimination and ethnoracial identity, holistic wellness, and allostatic load. Measures will be administered at baseline and post-intervention. CONCLUSION: This study will inform future interventions targeting identity-based stressors and represents an important step in advancing equity for BIPOC in medicine and research. CLINICAL TRIAL REGISTRATION NUMBER: NCT05422638.
            Cover page: Mitigating the health effects of systemic racism: Evaluation of the Race-Based Stress and Trauma Empowerment intervention.
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2019)

            Objective

            Patients with schizophrenia have a high prevalence of metabolic disorders and cardiovascular mortality. It is possible that a vulnerability to metabolic abnormalities is associated with risk for psychosis, symptoms and functionality. In this study, we evaluate demographic information, cardiometabolic indices, symptoms and functioning in an antipsychotic free cohort at Clinical High Risk (CHR) for psychosis from the NAPLS Omega 3 fatty acid clinical trial.

            Method

            Subjects received physical exams and metabolic monitoring prior to randomization into the Omega 3 versus Placebo trial. Anthropometrical measures, vital signs, glucose, and lipids were assessed along with symptoms, functioning, dietary Omega 3 fatty acids, erythrocyte polyunsaturated fatty acid content and a measure of lipid peroxidation (TBARS, Thiobarbituric acid-reactive substances).

            Results

            The sample included 113 CHR subjects (42.1% female; 17.5% Latino) ages 12-29. The mean BMI was 24.3 with a trend toward higher BMI and a higher incidence of metabolic syndrome in Latino subjects; 36% of the sample was obese/overweight; 37.6% met criteria for prehypertension/hypertension; 4.2% met criteria for prediabetes/diabetes; 9.6% showed evidence of insulin resistance and 44.7% had dyslipidemia. The TBARS was elevated at 9.8 μM ± 6.1 (normal 1.86-3.94 μM). Metabolic parameters and a diet low in Omega 3 rich foods were significantly associated with prodromal symptoms and poor functioning.

            Conclusions

            CHR subjects show a high percentage of metabolic abnormalities prior to exposure to antipsychotic medication. These findings reinforce that early detection of metabolic disturbances and food insecurity is crucial since these factors are modifiable with the potential for significant gains in terms of quality of life, physical and mental health.
              Cover page: Metabolic abnormalities and low dietary Omega 3 are associated with symptom severity and worse functioning prior to the onset of psychosis: Findings from the North American Prodrome Longitudinal Studies Consortium.
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