Social Cognition Psychometric Evaluation (SCOPE) for Early Psychosis

ABSTRACT Kelsey A. Ludwig: Social Cognition Psychometric Evaluation (SCOPE) for Early Psychosis (Under the direction of Dr. David L. Penn) Social cognition is an important outcome in schizophrenia research. Unfortunately, there has been a lack of consensus regarding which measures of social cognition best capture this domain of functioning. The Social Cognition Psychometric Evaluation (SCOPE) study was developed to address the need for a battery of measures that have sound psychometric properties and can be implemented in clinical trials for individuals with chronic schizophrenia. The current study expands upon the SCOPE study by examining the psychometric properties of the eight candidate measures administered to individuals early in the course of psychosis. Thirty-eight stable outpatients with first episode psychosis (FEP) and thirty-nine healthy controls completed the battery at baseline and one-month follow-up assessments. The SCOPE battery was evaluated on a collection of psychometric properties, including: (1) Reliability – including test-retest and internal consistency, (2) Between group differences – including direct comparisons between first episode patients, the chronic schizophrenia sample from SCOPE, and both demographically-matched control groups, (3) Utility as a repeated measure, (4) Convergent and discriminant validity, (5) Relationship to social and occupational functioning, (6) Incremental validity – variance in functioning beyond neurocognition, and (7) Feasibility – including practicality of administration and tolerability. Social cognition accounted for substantially more variance in functional outcome than neurocognition. Participants with FEP outperformed chronic schizophrenia patients on the majority of candidate measures of social cognition. Only one measure, the Hinting task, displayed adequate psychometric properties to be recommended for use in clinical research with first episode psychosis. The remaining candidate measures would require modifications before implementation or cannot be recommended for use in clinical research with first episode psychosis.Master of Art

Why Loneliness Matters in Psychosis: A Comprehensive and Integrative Approach to Research and Intervention

Aim: We used an integrative approach to examine the experience and impact of lonely feelings among persons diagnosed with a psychotic disorder. Study 1 evaluated relationships between loneliness and social cognition and functioning in a large sample of persons with schizophrenia or schizoaffective disorder. Study 2 assessed the impact of active engagement in an online social media platform specifically designed for individuals with first episode psychosis on loneliness severity and perceived social support. Study 3 examined which aspects of living with psychosis were associated with perceptions of loneliness, including symptomatology, perceptions of extant social relationships, and disruptions in school or work, among others. Methods: As part of Study 1, seventy-four stable outpatients with SSDs and 58 healthy controls completed the UCLA Loneliness Scale in addition to the standard Social Cognition Psychometric Evaluation (SCOPE) battery. For Study 2, twenty-six participants recruited from three first episode coordinated specialty care clinics in North Carolina were provided access to the moderated Horyzons platform for 12 weeks. During the intervention period, participants were encouraged to access therapeutic content and social components embedded within the site. Study 3 involved the implementation of semi-structured, qualitative interviews focused on experiences of loneliness with sixteen participants diagnosed with schizophrenia or schizoaffective disorder. During the interview, participants were asked to comment on current activities and social relationships, including their perceptions of the quantity, quality and types of relationships central to their social network. Results: Findings from Study 1 support prior research indicating persons diagnosed with a psychotic disorder experience greater levels of loneliness than normative groups. However, the results also indicate that self-reported loneliness is not associated with social cognitive abilities or functional outcome in psychosis. Regression analyses indicate that roughly half the variance in loneliness endorsed by persons with SSDs is accounted for by clinical variables, with loneliness most strongly associated with guilt and self-esteem. Results from Study 2 indicated that Horyzons was both feasible and very well tolerated, with a 92.3% retention rate and 79.2% of participants actively engaged in the platform. Preliminary results with engaged participants showed the greatest improvements in psychosis-related symptoms, followed by self-reported experience of negative emotions, depressive symptoms, and loneliness. Analyses revealed four key themes related to loneliness across participants involved in Study 3. Namely, participants reported that aspects of the physical environment (e.g., financial limitations), social context (e.g., lacking a romantic partner), and psychological functioning (e.g., psychotic and low mood symptoms) facilitated or exacerbated lonely feelings. Participants also commented on coping strategies employed to manage loneliness and provided suggestions for possible interventions. Conclusion: Taken together, these studies highlight the importance of cognition as it relates to loneliness. In particular, lonely feelings may be closely linked to the following cognitive processes: attention, perception, interpretation, attributions, and memory. Issues with measurement also arose as a central theme related to our understanding of loneliness in psychotic disorders. On their own, findings across the three studies of this dissertation may facilitate the identification of individuals who may be most at risk of intense loneliness. They may also help researchers identify specific target areas of treatment and inform the development of individualized treatment plans for persons with psychosis experiencing exacerbated lonely feelings.Doctor of Philosoph

Intact implicit processing of facial threat cues in schizophrenia

An emerging body of research suggests that people with schizophrenia retain the ability to implicitly perceive facial affect, despite well-documented difficulty explicitly identifying emotional expressions. It remains unclear, however, whether such functional implicit processing extends beyond emotion to other socially relevant facial cues. Here, we constructed two novel versions of the Affect Misattribution Procedure, a paradigm in which affective responses to primes are projected onto neutral targets. The first version included three face primes previously validated to elicit varying inferences of threat from healthy individuals via emotion-independent structural modification (e.g., nose and eye size). The second version included the threat-relevant emotional primes of angry, neutral, and happy faces. Data from 126 participants with schizophrenia and 84 healthy controls revealed that although performing more poorly on an assessment of explicit emotion recognition, patients showed normative implicit threat processing for both non-emotional and emotional facial cues. Collectively, these results support recent hypotheses postulating that the initial perception of salient facial information remains intact in schizophrenia, but that deficits arise at subsequent stages of contextual integration and appraisal. Such a breakdown in the stream of face processing has important implications for mechanistic models of social cognitive impairment in schizophrenia and treatment strategies aiming to improve functional outcome

User experiences of an American-adapted moderated online social media platform for first-episode psychosis: Qualitative analysis

Objectives The current study sought to qualitatively characterize the experiences of American users in a recent open trial of the Horyzons digital platform. Methods In total, 20 users on Horyzons USA completed semistructured interviews 12 weeks after their orientation to the platform and addressed questions related to (1) the platform, (2) their online therapist, and (3) the peer workers and community space. A hybrid inductive-deductive coding strategy was used to conduct a thematic analysis of the data (NCT04673851). Results The authors identified seven prominent themes that mapped onto the three components of self-determination theory. Features of the platform itself as well as inter- and intra-personal factors supported the autonomous use of Horyzons. Users also reflected that their perceived competence in social settings and in managing mental health was increased by the familiarity, privacy, and perceived safety of the platform and an emphasis on personalized therapeutic content. The behaviors or traits of online therapists as perceived by users and regular contact with peers and peer support specialists satisfied users’ need for relatedness and promoted confidence in social settings. Users also described aspects of Horyzons USA that challenged their satisfaction of autonomy, competence, and relatedness, highlighting potential areas for future iterations of the platform's content and interface. Conclusions Horyzons USA is a promising digital tool that provides young adults with psychosis with the means to access tailored therapy material on demand and a supportive digital community to aid in the recovery process

Genetic differences in the aryl hydrocarbon receptor and CYP1A2 affect sensitivity to developmental polychlorinated biphenyl exposure in mice: relevance to studies of human neurological disorders

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that remain a human health concern with newly discovered sources of contamination and ongoing bioaccumulation and biomagnification. Children exposed during early brain development are at highest risk of neurological deficits, but highly exposed adults reportedly have an increased risk of Parkinson\u27s disease. Our previous studies found allelic differences in the aryl hydrocarbon receptor and cytochrome P450 1A2 (CYP1A2) affect sensitivity to developmental PCB exposure, resulting in cognitive deficits and motor dysfunction. High-affinity Ahr b Cyp1a2(-/-) mice were most sensitive compared with poor-affinity Ahr d Cyp1a2(-/-) and wild-type Ahr b Cyp1a2(+/+) mice. Our follow-up studies assessed biochemical, histological, and gene expression changes to identify the brain regions and pathways affected. We also measured PCB and metabolite levels in tissues to determine if genotype altered toxicokinetics. We found evidence of AHR-mediated toxicity with reduced thymus and spleen weights and significantly reduced thyroxine at P14 in PCB-exposed pups. In the brain, the greatest changes were seen in the cerebellum where a foliation defect was over-represented in Cyp1a2(-/-) mice. In contrast, we found no difference in tyrosine hydroxylase immunostaining in the striatum. Gene expression patterns varied across the three genotypes, but there was clear evidence of AHR activation. Distribution of parent PCB congeners also varied by genotype with strikingly high levels of PCB 77 in poor-affinity Ahr d Cyp1a2(-/-) while Ahr b Cyp1a2(+/+) mice effectively sequestered coplanar PCBs in the liver. Together, our data suggest that the AHR pathway plays a role in developmental PCB neurotoxicity, but we found little evidence that developmental exposure is a risk factor for Parkinson\u27s disease

Constraints on the timing and conditions of high-grade metamorphism, charnockite formation and fluid-rock interaction in the Trivandrum Block, southern India

Incipient charnockites have been widely used as evidence for the infiltration of CO2-rich fluids driving dehydration of the lower crust. Rocks exposed at Kakkod quarry in the Trivandrum Block of southern India allow for a thorough investigation of the metamorphic evolution by preserving not only orthopyroxene-bearing charnockite patches in a host garnet-biotite felsic gneiss, but also layers of garnet-sillimanite metapelite gneiss. Thermodynamic phase equilibria modelling of all three bulk compositions indicates consistent peak-metamorphic conditions of 830-925 °C and 6-9 kbar with retrograde evolution involving suprasolidus decompression at high temperature. These models suggest that orthopyroxene was most likely stabilized close to the metamorphic peak as a result of small compositional heterogeneities in the host garnet-biotite gneiss. There is insufficient evidence to determine whether the heterogeneities were inherited from the protolith or introduced during syn-metamorphic fluid flow. U-Pb geochronology of monazite and zircon from all three rock types constrains the peak of metamorphism and orthopyroxene growth to have occurred between the onset of high-grade metamorphism at c. 590 Ma and the onset of melt crystallization at c. 540 Ma. The majority of metamorphic zircon growth occurred during protracted melt crystallization between c. 540 and 510 Ma. Melt crystallization was followed by the influx of aqueous, alkali-rich fluids likely derived from melts crystallizing at depth. This late fluid flow led to retrogression of orthopyroxene, the observed outcrop pattern and to the textural and isotopic modification of monazite grains at c. 525-490 Ma

Type 2 diabetes in adolescents and young adults

The prevalence of type 2 diabetes in adolescents and young adults is dramatically increasing. Similar to older-onset type 2 diabetes, the major predisposing risk factors are obesity, family history, and sedentary lifestyle. Onset of diabetes at a younger age (defined here as up to age 40 years) is associated with longer disease exposure and increased risk for chronic complications. Young-onset type 2 diabetes also affects more individuals of working age, accentuating the adverse societal effects of the disease. Furthermore, evidence is accumulating that young-onset type 2 diabetes has a more aggressive disease phenotype, leading to premature development of complications, with adverse effects on quality of life and unfavourable effects on long-term outcomes, raising the possibility of a future public health catastrophe. In this Review, we describe the epidemiology and existing knowledge regarding pathophysiology, risk factors, complications, and management of type 2 diabetes in adolescents and young adults