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class="c-scholworks__tag-list"><li class="c-scholworks__tag-article">Article</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/7kp468h0"><div class="c-clientmarkup">Cognitive-Behavioral Social Skills Training: Outcome of a Randomized Controlled Trial for Youth at Risk of Psychosis.</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3ACornblatt%2C%20Barbara">Cornblatt, Barbara</a>; </li><li><a href="/search/?q=author%3AHolden%2C%20Jason">Holden, Jason</a>; </li><li><a href="/search/?q=author%3AGranholm%2C%20Eric">Granholm, Eric</a>; </li><li><a href="/search/?q=author%3AAddington%2C%20Jean">Addington, Jean</a>; </li><li><a href="/search/?q=author%3ALiu%2C%20Lu">Liu, Lu</a>; </li><li><a href="/search/?q=author%3ABraun%2C%20Amy">Braun, Amy</a>; </li><li><a href="/search/?q=author%3ABrummitt%2C%20Kali">Brummitt, Kali</a>; </li><li class="c-authorlist__end"><a href="/search/?q=author%3ACadenhead%2C%20Kristin">Cadenhead, Kristin</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/ucsd_postprints">UC San Diego Previously Published Works</a> (<!-- -->2023<!-- -->)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup">AIM: Difficulties in social functioning have been observed in youth at clinical high-risk (CHR) of psychosis even in those who do not go on to develop a psychotic illness. Few treatment studies have attempted to improve social functioning in this population. The aim of this study was to conduct a randomized trial comparing the effects of Cognitive-Behavioral Social Skills Training (CBSST) with a supportive therapy (ST). METHODS: Both CBSST and ST were weekly group therapies, delivered over 18 weeks. This was a 2-arm trial with single-blinded ratings and intention-to-treat analyses. Assessments occurred at baseline, end-of-treatment, and 12 months after the baseline assessment. The primary outcome was social and role functioning and defeatist performance attitudes were the secondary outcome. Attenuated positive and negative symptoms, anxiety, depression, self-efficacy, and beliefs about self and others were examined as exploratory outcomes. RESULTS: There were no significant differences between the 2 groups at baseline or either of the 2 follow-ups. However, at follow-ups, in each group there were significant improvements in clinical symptoms. These could not be attributed to group treatment since there was no control or wait-list group. CONCLUSIONS: Since poor social functioning is one of the most observed difficulties in CHR individuals, and a decline in social functioning may be a significant predictor of later transition to psychosis, future work will be needed to find effective treatments for this decline in functioning for CHR youth.</div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/7kp468h0"><img src="/cms-assets/2e89a78009d186425611d3cb86a26e58ae7b30acf423bb295f2303a903743f3b" alt="Cover page: Cognitive-Behavioral Social Skills Training: Outcome of a Randomized Controlled Trial for Youth at Risk of Psychosis."/></a></div></section><section class="c-scholworks"><div class="c-scholworks__main-column"><ul class="c-scholworks__tag-list"><li class="c-scholworks__tag-article">Article</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/23r3p0mp"><div class="c-clientmarkup">Cognitive-Behavioural Social Skills Training: Mediation of Treatment Outcomes in a Randomized Controlled Trial for Youth at Risk of Psychosis: Lentraînement aux compétences sociales cognitivo-comportementales : variables médiatrices des résultats thérapeutiques dans le cadre dun essai clinique randomisé pour les jeunes présentant un risque de psychose.</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3ADevoe%2C%20Daniel">Devoe, Daniel</a>; </li><li><a href="/search/?q=author%3ALiu%2C%20Lu">Liu, Lu</a>; </li><li><a href="/search/?q=author%3ABraun%2C%20Amy">Braun, Amy</a>; </li><li><a href="/search/?q=author%3ACadenhead%2C%20Kristin">Cadenhead, Kristin</a>; </li><li><a href="/search/?q=author%3ACornblatt%2C%20Barbara">Cornblatt, Barbara</a>; </li><li><a href="/search/?q=author%3AGranholm%2C%20Eric">Granholm, Eric</a>; </li><li class="c-authorlist__end"><a href="/search/?q=author%3AAddington%2C%20Jean">Addington, Jean</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/ucsd_postprints">UC San Diego Previously Published Works</a> (<!-- -->2024<!-- -->)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup">OBJECTIVES: Currently, there are no effective treatments for functional outcomes (i.e., role and social) and negative symptoms for youth at clinical high-risk (CHR) for psychosis. Investigations into possible mechanisms that may contribute to the improvement of functioning and negative symptoms are needed in CHR research to help inform psychosocial treatments. The present study examined whether functioning and negative symptoms were mediated by asocial beliefs, defeatist beliefs, self-efficacy, maladaptive schemas, anxiety, depression, social cognition, or attenuated psychotic symptoms (APS) in a large clinical trial. METHODS: CHR participants (n = 203; 104 females; 99 males) were recruited as part of a three-site randomized control trial comparing group cognitive-behavioural social skills training (CBSST) versus a supportive therapy group. Mediation analyses were conducted to test the relationships between treatment group, mediators (asocial beliefs, defeatist beliefs, self-efficacy, maladaptive schemas, anxiety, depression, social cognition, and APS), and outcome (social and role functioning, and negative symptoms). The mediation analyses employed conditional process path analysis via ordinary least squares regression. RESULTS: At the end of treatment, but not 12-month follow-up, more severe APS were found to mediate the impact of treatment on negative symptoms, and social and role functioning. The greater the severity of APS, the less likely that CBSST would result in improvement in negative symptoms and social and role functioning. Many of the other variables showed significant associations with social (less for role) functioning and negative symptoms but did not mediate the effect of treatment on these outcomes at the end of treatment or 12-month follow-up. CONCLUSIONS: There were no significant mediators except for APS at the end of treatment. Since more severe APS may result in participants being unable to fully participate in therapy and thus limit their gains, clinical implications may include offering some individual therapy to prepare these young people to benefit from the group treatment.</div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/23r3p0mp"><img src="/cms-assets/52266e39e5452cd26b38f15e1699fc684261f517c5c5ccc1b61249127d187299" alt="Cover page: Cognitive-Behavioural Social Skills Training: Mediation of Treatment Outcomes in a Randomized Controlled Trial for Youth at Risk of Psychosis: Lentraînement aux compétences sociales cognitivo-comportementales : variables médiatrices des résultats thérapeutiques dans le cadre dun essai clinique randomisé pour les jeunes présentant un risque de psychose."/></a></div></section><section class="c-scholworks"><div class="c-scholworks__main-column"><ul class="c-scholworks__tag-list"><li class="c-scholworks__tag-article">Article</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/85g271k0"><div class="c-clientmarkup">39.1 DNA METHYLATION OF IMMUNE CELLS IN PERSONS AT CLINICAL HIGH RISK FOR PSYCHOSIS</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3APerkins%2C%20Diana">Perkins, Diana</a>; </li><li><a href="/search/?q=author%3AClark%2C%20Jeffries">Clark, Jeffries</a>; </li><li><a href="/search/?q=author%3AAddington%2C%20Jean">Addington, Jean</a>; </li><li><a href="/search/?q=author%3ABeardon%2C%20Carrie">Beardon, Carrie</a>; </li><li><a href="/search/?q=author%3ACadenhead%2C%20Kristin">Cadenhead, Kristin</a>; </li><li><a href="/search/?q=author%3ACannon%2C%20Tyrone">Cannon, Tyrone</a>; </li><li><a href="/search/?q=author%3ACornblatt%2C%20Barbara">Cornblatt, Barbara</a>; </li><li><a href="/search/?q=author%3AMathalon%2C%20Daniel">Mathalon, Daniel</a>; </li><li><a href="/search/?q=author%3AMcGlashan%2C%20Thomas">McGlashan, Thomas</a>; </li><li><a href="/search/?q=author%3ASeidman%2C%20Larry">Seidman, Larry</a>; </li><li><a href="/search/?q=author%3ATsuang%2C%20Ming">Tsuang, Ming</a>; </li><li><a href="/search/?q=author%3AWalker%2C%20Elaine">Walker, Elaine</a>; </li><li class="c-authorlist__end"><a href="/search/?q=author%3AWoods%2C%20Scott">Woods, Scott</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/ucsd_postprints">UC San Diego Previously Published Works</a> (<!-- -->2018<!-- -->)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup">Abstract <h3>Background</h3> A dysregulated immune system is implicated in the development of psychotic disorders. Persons with schizophrenia have altered levels of circulating immune cell signaling molecules (cytokines), and elevation of specific cytokines predict conversion to psychosis in persons at clinical high risk. Whether these peripheral signals are a causal or a secondary phenomenon is unclear. But, subpopulations of circulating immune cells do regulate the brain from meningeal and perivascular locations influencing cognition, mood, and behavior, and thus may be relevant to schizophrenia vulnerability. Hematopoietic stem cells in the bone marrow differentiate into cascading subtypes depending on signals from other organs, especially the brain. For example, a monocyte subpopulation emerges with repeated social defeat that establish the persistence of anxiety-like behaviors; blocking their release or inhibiting their attachment to brain vascular endothelium prevents the emergence of anxiety-like behaviors. In humans, a similar monocyte subpopulation is associated with social isolation and other adversities including low SES, chronic stress, and bereavement. <h3>Methods</h3> The North American Prodrome Longitudinal Study (NAPLS2) is an eight-site observational study of predictors and mechanisms of conversion to psychosis The full cohort includes 763 at clinical high risk (CHR) based on the Criteria of Prodromal State (COPS) and 279 demographically similar unaffected comparison (UC) subjects. Methylation of whole blood DNA collected in PAXgene tubes at baseline was analyzed with the Illumina 450k array in a subgroup of 59 subjects who converted to psychosis (CHR-C), 84 CHR subjects followed for 2 years who did not develop psychosis (CHR-NC) and 67 unaffected subjects (UC). Our analyses focused on methylation of promoter regions of genes, associated with gene expression. Classifier construction used Coarse Approximation Linear Function (CALF) with bootstrapping of 1000 random 80% subsets with replacement to determine statistical likelihood. <h3>Results</h3> We found highly overlapping sets of differentially methylated promoter regions in CHR-C subjects compared to CHR-NC and to UC subjects. A set of 10 markers correctly classified CHR-C and CHR-NC subjects with high accuracy (AUC=0.94, 95% CI 0.89–0.98). Included was SIRT1, a gene that is upregulated with HSV reactivation. <h3>Discussion</h3> Circulating immune cells excerpt powerful influences on mood, cognition and behavior. An obvious example is the experience of most human with “sickness syndrome”, characterized by apathy, avolition, and withdrawal, and triggered by immune-cell-released cytokines producing an adaptive, resource conserving, behavioral response. While at an early stage, our findings further implicate immune system dysregulation as a mechanism in the development of psychosis.</div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/85g271k0"><img src="/cms-assets/c1a89740f2be8244d329319dacf0a575e667c9389e3af373246e3e12cef8f5c8" alt="Cover page: 39.1 DNA METHYLATION OF IMMUNE CELLS IN PERSONS AT CLINICAL HIGH RISK FOR PSYCHOSIS"/></a></div></section><section class="c-scholworks"><div class="c-scholworks__main-column"><ul class="c-scholworks__tag-list"><li class="c-scholworks__tag-article">Article</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/5666t6qw"><div class="c-clientmarkup">SU127. Negative Symptoms in Youth at Clinical High Risk of Psychosis</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3ADevoe%2C%20Daniel">Devoe, Daniel</a>; </li><li><a href="/search/?q=author%3ACadenhead%2C%20Kristen">Cadenhead, Kristen</a>; </li><li><a href="/search/?q=author%3ACannon%2C%20Tyrone">Cannon, Tyrone</a>; </li><li><a href="/search/?q=author%3ACornblatt%2C%20Barbara">Cornblatt, Barbara</a>; </li><li><a href="/search/?q=author%3AMcGlashan%2C%20Tom">McGlashan, Tom</a>; </li><li><a href="/search/?q=author%3APerkins%2C%20Diana">Perkins, Diana</a>; </li><li><a href="/search/?q=author%3ASeidman%2C%20Larry%20J">Seidman, Larry J</a>; </li><li><a href="/search/?q=author%3ATsuang%2C%20Ming">Tsuang, Ming</a>; </li><li><a href="/search/?q=author%3AWalker%2C%20Elaine">Walker, Elaine</a>; </li><li><a href="/search/?q=author%3AWoods%2C%20Scott">Woods, Scott</a>; </li><li><a href="/search/?q=author%3ABearden%2C%20Carrie">Bearden, Carrie</a>; </li><li><a href="/search/?q=author%3AMathalon%2C%20Daniel">Mathalon, Daniel</a>; </li><li class="c-authorlist__end"><a href="/search/?q=author%3AAddington%2C%20Jean">Addington, Jean</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/ucsd_postprints">UC San Diego Previously Published Works</a> (<!-- -->2017<!-- -->)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup">Abstract Background: Longitudinal studies examining youth at clinical high risk (CHR) of psychosis have predominantly focused on positive symptoms. However, youth at CHR often demonstrate persistent and significant negative symptoms, which have been reported to be predictive of conversion to psychosis. The goal of this study was to examine negative symptoms over time in youth at CHR of psychosis and compare baseline negative symptoms in those who convert to psychosis with those who did not convert. Methods: Youth at CHR (N = 764) were recruited for the North American Prodrome Longitudinal Study (NAPLS 2) at 8 sites across North America. Negative symptoms were rated on the Scale of Prodromal Symptoms (SOPS) at baseline, 6, 12, 18, and 24 months. Difference in prevalence of negative symptoms was assessed using Z test and change in negative symptom severity over time was assessed using repeated measures analysis of variance ANOVA. Wilcoxon rank sum test and 2-sample t test were utilized to compare baseline negative symptoms in converters vs nonconverters. Results: The mean total negative symptom score at baseline was 11.90 (SD = 9.80). A majority of participants (84.57%) had at least one negative symptom rated ≥3 at baseline. Negative symptom severity significantly decreased over time compared to baseline measures. Eighty-six participants converted in total. In participants with at least one negative symptom of moderate severity or above (N ≥ 3), nonconverters had lower severity ratings on expression of emotion (M = 1.49, SD = 1.47 vs M = 1.94, SD = 1.64, P = .02) and ideational richness (M = 1.23, SD = 1.37 vs M = 1.60, SD = 1.35, P = .04) compared to converters at baseline. In participants who completed 24 months of assessment and had negative symptom severity of moderate severity or above (N ≥ 3), nonconverters had significantly better expression of emotion (M = 1.40, SD = 1.51) compared to converters (M = 1.79, SD = 1.63, P = .03). Conclusion: First, this study demonstrated that the majority of youth at CHR have moderate to severe negative symptoms at baseline. Second, both decreased expression of emotion and decreased ideational richness was significantly more severe in participants who converted and may be indicative of later conversion to psychosis. Thus, early and persistent higher negative symptom scores may represent subsequent risk of conversion to psychosis.</div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/5666t6qw"><img src="/cms-assets/4f75c4f2a44c9ede1a107b6e4d80f3a743cf5fc75d85f50da3598a9ef7e70728" alt="Cover page: SU127. Negative Symptoms in Youth at Clinical High Risk of Psychosis"/></a></div></section><section class="c-scholworks"><div class="c-scholworks__main-column"><ul class="c-scholworks__tag-list"><li class="c-scholworks__tag-article">Article</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/5jd2p259"><div class="c-clientmarkup">23. Omega-3 Fatty Acid Versus Placebo in a Clinical High-Risk Sample From the North American Prodrome Longitudinal Studies (NAPLS) Consortium</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3ACadenhead%2C%20Kristin">Cadenhead, Kristin</a>; </li><li><a href="/search/?q=author%3AAddington%2C%20Jean">Addington, Jean</a>; </li><li><a href="/search/?q=author%3ACannon%2C%20Tyrone">Cannon, Tyrone</a>; </li><li><a href="/search/?q=author%3ACornblatt%2C%20Barbara">Cornblatt, Barbara</a>; </li><li><a href="/search/?q=author%3AMathalon%2C%20Daniel">Mathalon, Daniel</a>; </li><li><a href="/search/?q=author%3AMcGlashan%2C%20Tom">McGlashan, Tom</a>; </li><li><a href="/search/?q=author%3APerkins%2C%20Diana">Perkins, Diana</a>; </li><li><a href="/search/?q=author%3ASeidman%2C%20Larry%20J">Seidman, Larry J</a>; </li><li><a href="/search/?q=author%3ATsuang%2C%20Ming">Tsuang, Ming</a>; </li><li><a href="/search/?q=author%3AWalker%2C%20Elaine">Walker, Elaine</a>; </li><li class="c-authorlist__end"><a href="/search/?q=author%3AWoods%2C%20Scott">Woods, Scott</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/ucsd_postprints">UC San Diego Previously Published Works</a> (<!-- -->2017<!-- -->)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup">Abstract Background: Omega-3 Fatty Acids (FAs), EPA (eicosapentaenoic acid) and DHA (Docosahexaenoic acid), are essential for normal brain development and may also have neuroprotective properties. Dietary supplementation of EPA and DHA has beneficial effects in medical illnesses as well as depression, bipolar disorder, and dementia. Abnormal FA metabolism may play a role in the etiology of psychiatric illness. Studies of erythrocytes and skin fibroblasts have shown reduced levels of FAs and phospholipids in schizophrenia. Studies of Omega-3FA supplementation in schizophrenia have been mixed. Amminger et al performed a randomized, double-blind, placebo-controlled trial in 81 subjects with prodromal symptoms of psychosis. The treatment consisted of 1.2g/day of Omega-3FAs (700 mg EPA, 480 mg DHA). After 12 weeks, 2 (4.9%) of 41 individuals in the Omega-3FA group and 11 of 40 (27.5%) in the placebo group converted to a psychotic disorder. Omega-3FAs also significantly reduced symptoms and improved functioning. The Aims of the current study were to replicate the Amminger study in Clinical High Risk (CHR) subjects from the NAPLS consortium. Methods: This was a 24-week, randomized, double-blind, placebo, fixed dose-controlled study of Omega-3FA versus placebo in 127 CHR subjects. The Omega-3FA compound contained a 2:1 proportion of EPA to DHA. The total dose was 740 mg of EPA and 400 mg of DHA. Baseline diet characterization was assessed using a systematic checklist that includes Omega-3FA foods. In addition, fasting erythrocyte FA composition was assessed. Results: Of the 127 CHR subjects recruited into the trial, 118 completed baseline assessment, and 70 (59%) completed the 6-month trial. Seven (10% Kaplan-Meier) subjects converted to psychosis during the 24 months. The rate of psychotic conversion did not differ in the Omega-3FA (13%) versus Placebo (8%) samples. Conversion to psychosis was predicted by low Omega-3FA rich foods in the diet (Wald Statistic = 4.96, P < .05). Although there were significant improvements in symptom and functioning over time in Mixed Model analyses, there were no significant group or Group × Time interaction effects. Conclusion: The rate of conversion to psychosis in the present sample was lower than is typically observed in an at-risk population. Given the study attrition and low rate of conversion to psychosis, the trial was underpowered to replicate the conversion effect in the Amminger et al.’s study. Despite the overall improvement in symptoms and functioning over time in all subjects, there was no clear evidence of a differential effect in the sample on Omega-3FA vs Placebo. Further work is needed to better tease out the role of diet and Omega-3FA in mental illness. The finding of a significant association between baseline diet low in Omega-3FA rich foods and later conversion to psychosis raises the question of whether it is possible to influence both physical and mental health with lifestyle choices including diet.</div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/5jd2p259"><img src="/cms-assets/0d42bcaf8ad048fd0ee8123a8d5b3da501aedef669a69070369b824d8ac3e8d9" alt="Cover page: 23. Omega-3 Fatty Acid Versus Placebo in a Clinical High-Risk Sample From the North American Prodrome Longitudinal Studies (NAPLS) Consortium"/></a></div></section><section class="c-scholworks"><div class="c-scholworks__main-column"><ul class="c-scholworks__tag-list"><li class="c-scholworks__tag-article">Article</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/53534296"><div class="c-clientmarkup">24.2 NEUROCOGNITIVE PROFILES IN THE PRODROME TO PSYCHOSIS IN NAPLS-1</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3AVelthorst%2C%20Eva">Velthorst, Eva</a>; </li><li><a href="/search/?q=author%3ABearden%2C%20Carrie">Bearden, Carrie</a>; </li><li><a href="/search/?q=author%3AMeyer%2C%20Eric">Meyer, Eric</a>; </li><li><a href="/search/?q=author%3AGiuliano%2C%20Anthony">Giuliano, Anthony</a>; </li><li><a href="/search/?q=author%3AAddington%2C%20Jean">Addington, Jean</a>; </li><li><a href="/search/?q=author%3ACadenhead%2C%20Kristin">Cadenhead, Kristin</a>; </li><li><a href="/search/?q=author%3ACannon%2C%20Tyrone">Cannon, Tyrone</a>; </li><li><a href="/search/?q=author%3ACornblatt%2C%20Barbara">Cornblatt, Barbara</a>; </li><li><a href="/search/?q=author%3AMcglashan%2C%20Thomas">Mcglashan, Thomas</a>; </li><li><a href="/search/?q=author%3APerkins%2C%20Diana">Perkins, Diana</a>; </li><li><a href="/search/?q=author%3ATsuang%2C%20Ming">Tsuang, Ming</a>; </li><li><a href="/search/?q=author%3AWalker%2C%20Elaine">Walker, Elaine</a>; </li><li><a href="/search/?q=author%3AWoods%2C%20Scott">Woods, Scott</a>; </li><li class="c-authorlist__end"><a href="/search/?q=author%3ASeidman%2C%20Larry">Seidman, Larry</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/ucsd_postprints">UC San Diego Previously Published Works</a> (<!-- -->2018<!-- -->)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup">Abstract <h3>Background</h3> The vast majority of studies of neuropsychological (NP) functioning in Clinical High Risk (CHR) cohorts have examined group averages, possibly concealing a range of subgroups ranging from very impaired to high functioning. Our objective was to assess NP profiles and to explore associations with conversion to psychosis, functional and diagnostic outcome. <h3>Methods</h3> Data were acquired from 324 participants (mean age 18.4) in the first phase of the North American Prodrome Longitudinal Study (NAPLS-1), a multi-site consortium following individuals for up to 2½ years. We applied Ward’s method for hierarchical clustering data to 8 baseline neurocognitive measures, in 166 CHR individuals, 49 non-CHR youth with a family history of psychosis, and 109 healthy controls. We tested whether cluster membership was associated with conversion to psychosis, social and role functioning, and follow-up diagnosis. Analyses were repeated after data were clustered based on independently developed clinical decision rules. <h3>Results</h3> Four neurocognitive clusters were identified: Significantly Impaired (n=33); Mildly Impaired (n=82); Normal (n=145) and High (n=64). The Significantly Impaired subgroup demonstrated the largest deviations on processing speed and memory tasks and had a conversion rate of 58%, a 40% chance of developing a schizophrenia spectrum diagnosis (compared to 24.4% in the Mildly Impaired, and 10.3% in the other two groups combined), and significantly worse functioning at baseline and 12-months. Data clustered using clinical decision rules yielded similar results, pointing to high convergent validity. <h3>Discussion</h3> Despite extensive neuropsychological investigations within CHR cohorts, this is one of the first studies to investigate NP clustering profiles as a contributor to heterogeneity in outcome. Our results indicate that the four NP profiles vary substantially in their outcome, underscoring the relevance of cognitive functioning in the prediction of illness progression. Our findings tentatively suggest that individualized cognitive profiling should be explored in clinical settings.</div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/53534296"><img src="/cms-assets/657a3125df11cbcd556b3cf3a95485228ac64c40f2e47acd76e6f7fad3d1c789" alt="Cover page: 24.2 NEUROCOGNITIVE PROFILES IN THE PRODROME TO PSYCHOSIS IN NAPLS-1"/></a></div></section><section class="c-scholworks"><div class="c-scholworks__main-column"><ul class="c-scholworks__tag-list"><li class="c-scholworks__tag-article">Article</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/0t23x1cq"><div class="c-clientmarkup">59.4 Networks of Blood Analytes are Collectively Informative of Risk of Conversion to Schizophrenia</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3AJeffries%2C%20Clark">Jeffries, Clark</a>; </li><li><a href="/search/?q=author%3APerkins%2C%20Diana">Perkins, Diana</a>; </li><li><a href="/search/?q=author%3AAddington%2C%20Jean">Addington, Jean</a>; </li><li><a href="/search/?q=author%3ABearden%2C%20Carrie">Bearden, Carrie</a>; </li><li><a href="/search/?q=author%3ACadenhead%2C%20Kristen">Cadenhead, Kristen</a>; </li><li><a href="/search/?q=author%3ACannon%2C%20Tyrone">Cannon, Tyrone</a>; </li><li><a href="/search/?q=author%3ACornblatt%2C%20Barbara">Cornblatt, Barbara</a>; </li><li><a href="/search/?q=author%3AMathalon%2C%20Daniel">Mathalon, Daniel</a>; </li><li><a href="/search/?q=author%3AMcGlashan%2C%20Tom">McGlashan, Tom</a>; </li><li><a href="/search/?q=author%3ASeidman%2C%20Larry%20J">Seidman, Larry J</a>; </li><li><a href="/search/?q=author%3ATsuang%2C%20Ming">Tsuang, Ming</a>; </li><li><a href="/search/?q=author%3AWalker%2C%20Elaine">Walker, Elaine</a>; </li><li class="c-authorlist__end"><a href="/search/?q=author%3AWoods%2C%20Scott">Woods, Scott</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/ucsd_postprints">UC San Diego Previously Published Works</a> (<!-- -->2017<!-- -->)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup">Abstract Background: The presence and severity of attenuated-psychosis symptoms define a clinical high risk (CHR) population at elevated risk for psychotic disorders. The NAPLS project is a prospective study of mechanisms contributing to psychosis vulnerability in persons at CHR. Here we investigated a hypothesized role for the highly-integrated immune and redox systems in the development of psychosis. Methods: We examined expression of 143 plasma analytes from a subgroup of the NAPLS2 cohort, including 32 CHR with subsequent psychosis conversion, 40 CHR followed for 2 years without psychosis, and 35 unaffected subjects. We used a Luminex platform with analytes chosen to reflect immune, redox, hormonal, and metabolic system status, including many analytes previously associated with schizophrenia and psychosis risk. We applied correlation network analysis to discover potentially co-regulated networks associated with later development of psychosis. Results: Several robust (r > .75) and highly significant (P < .0001 after correction for multiple testing) correlation networks were found in all groups, including a network involving IL3, IL5, IL7, and IL13, and a network involving CCL5, BDNF, TSH, and PDGF. There were significantly fewer nodes in CHR-converters compared with CHR-nonconverters and unaffected subjects. In unaffected subjects, plasminogen activator inhibitor-1 (PAI-1) was highly correlated with matrix metallopeptidases (MMP) 7, 9 and 10 and CD40LG, this network was absent in CHR subjects, and in CHR-converters PAI-1 was robustly and significantly correlated with TIMP1, CCL13, and TIMP1. Conclusion: A pattern of robust and highly significant correlation networks in plasma analytes suggests shared regulatory mechanisms for the inter-correlated analytes. The lower number of correlated analytes in CHR subjects who converted to psychosis suggest a shift in regulation, as does the change in the correlation network involving PAI-1. PAI-1 is of interest given studies linking schizophrenia with reduced tissue plasminogen activator (tPA) and increases in negative regulators of tPA, including activation of both PAI-1and TIMP1 with oxidative stress. In addition, a recent study links toxoplasmosis infection and schizophrenia risk to a pathway involving PAI-1 and TIMP1. Patricio O’Donnell, Pfizer Inc.</div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/0t23x1cq"><img src="/cms-assets/d7f57468db9e0db827d0c1e60b1022a1c2a6b060ce52f3cb5f499b566cb43147" alt="Cover page: 59.4 Networks of Blood Analytes are Collectively Informative of Risk of Conversion to Schizophrenia"/></a></div></section><section class="c-scholworks"><div class="c-scholworks__main-column"><ul class="c-scholworks__tag-list"><li class="c-scholworks__tag-article">Article</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/8j42s24m"><div class="c-clientmarkup">Sex- and Age-Specific Deviations in Cerebellar Structure and Their Link With Symptom Dimensions and Clinical Outcome in Individuals at Clinical High Risk for Psychosis.</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3AWoods%2C%20Scott">Woods, Scott</a>; </li><li><a href="/search/?q=author%3ACannon%2C%20Tyrone">Cannon, Tyrone</a>; </li><li><a href="/search/?q=author%3AWalker%2C%20Elaine">Walker, Elaine</a>; </li><li><a href="/search/?q=author%3ASefik%2C%20Esra">Sefik, Esra</a>; </li><li><a href="/search/?q=author%3ABoamah%2C%20Michelle">Boamah, Michelle</a>; </li><li><a href="/search/?q=author%3AAddington%2C%20Jean">Addington, Jean</a>; </li><li><a href="/search/?q=author%3ACornblatt%2C%20Barbara">Cornblatt, Barbara</a>; </li><li><a href="/search/?q=author%3AKeshavan%2C%20Matcheri">Keshavan, Matcheri</a>; </li><li><a href="/search/?q=author%3APerkins%2C%20Diana">Perkins, Diana</a>; </li><li><a href="/search/?q=author%3AStone%2C%20William">Stone, William</a>; </li><li><a href="/search/?q=author%3AMathalon%2C%20Daniel">Mathalon, Daniel</a>; </li><li><a href="/search/?q=author%3ABearden%2C%20Carrie">Bearden, Carrie</a>; </li><li><a href="/search/?q=author%3ACadenhead%2C%20Kristin">Cadenhead, Kristin</a>; </li><li class="c-authorlist__end"><a href="/search/?q=author%3ATsuang%2C%20Ming">Tsuang, Ming</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/ucsf_postprints">UC San Francisco Previously Published Works</a> (<!-- -->2023<!-- -->)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup">BACKGROUND: The clinical high-risk (CHR) period offers a temporal window into neurobiological deviations preceding psychosis onset, but little attention has been given to regions outside the cerebrum in large-scale studies of CHR. Recently, the North American Prodrome Longitudinal Study (NAPLS)-2 revealed altered functional connectivity of the cerebello-thalamo-cortical circuitry among individuals at CHR; however, cerebellar morphology remains underinvestigated in this at-risk population, despite growing evidence of its involvement in psychosis. STUDY DESIGN: In this multisite study, we analyzed T1-weighted magnetic resonance imaging scans obtained from N = 469 CHR individuals (61% male, ages = 12-36 years) and N = 212 healthy controls (52% male, ages = 12-34 years) from NAPLS-2, with a focus on cerebellar cortex and white matter volumes separately. Symptoms were rated by the Structured Interview for Psychosis-Risk Syndromes (SIPS). The outcome by two-year follow-up was categorized as in-remission, symptomatic, prodromal-progression, or psychotic. General linear models were used for case-control comparisons and tests for volumetric associations with baseline SIPS ratings and clinical outcomes. STUDY RESULTS: Cerebellar cortex and white matter volumes differed between the CHR and healthy control groups at baseline, with sex moderating the difference in cortical volumes, and both sex and age moderating the difference in white matter volumes. Baseline ratings for major psychosis-risk dimensions as well as a clinical outcome at follow-up had tissue-specific associations with cerebellar volumes. CONCLUSIONS: These findings point to clinically relevant deviations in cerebellar cortex and white matter structures among CHR individuals and highlight the importance of considering the complex interplay between sex and age when studying the neuromaturational substrates of psychosis risk.</div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/8j42s24m"><img src="/cms-assets/f05a725d546a91e264392937a9ba4ff55f91b236eaa802323956c51ac63ed7d0" alt="Cover page: Sex- and Age-Specific Deviations in Cerebellar Structure and Their Link With Symptom Dimensions and Clinical Outcome in Individuals at Clinical High Risk for Psychosis."/></a></div></section><section class="c-scholworks"><div class="c-scholworks__main-column"><ul class="c-scholworks__tag-list"><li class="c-scholworks__tag-article">Article</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/93m2x62j"><div class="c-clientmarkup">T116. PREDICTION OF REMISSION IN NON-CONVERTING INDIVIDUALS AT CLINICAL HIGH RISK FOR PSYCHOSIS</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3AWorthington%2C%20Michelle">Worthington, Michelle</a>; </li><li><a href="/search/?q=author%3AAddington%2C%20Jean">Addington, Jean</a>; </li><li><a href="/search/?q=author%3ABearden%2C%20Carrie">Bearden, Carrie</a>; </li><li><a href="/search/?q=author%3ACadenhead%2C%20Kristin">Cadenhead, Kristin</a>; </li><li><a href="/search/?q=author%3ACornblatt%2C%20Barbara">Cornblatt, Barbara</a>; </li><li><a href="/search/?q=author%3AMathalon%2C%20Daniel">Mathalon, Daniel</a>; </li><li><a href="/search/?q=author%3AMcGlashan%2C%20Thomas">McGlashan, Thomas</a>; </li><li><a href="/search/?q=author%3APerkins%2C%20Diana">Perkins, Diana</a>; </li><li><a href="/search/?q=author%3ASeidman%2C%20Larry">Seidman, Larry</a>; </li><li><a href="/search/?q=author%3ATsuang%2C%20Ming">Tsuang, Ming</a>; </li><li><a href="/search/?q=author%3AWalker%2C%20Elaine">Walker, Elaine</a>; </li><li><a href="/search/?q=author%3AWoods%2C%20Scott">Woods, Scott</a>; </li><li class="c-authorlist__end"><a href="/search/?q=author%3ACannon%2C%20Tyrone">Cannon, Tyrone</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/ucsd_postprints">UC San Diego Previously Published Works</a> (<!-- -->2020<!-- -->)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup">Abstract <h3>Background</h3> The clinical high-risk period before a first episode of psychosis (CHR-P) has been widely studied in the past 30 years with the goal of understanding the development of psychosis. Despite the progress in understanding what factors are associated with conversion to psychosis from the CHR-P state, less attention has been paid to the individuals who do not transition to psychosis. It is estimated that approximately 75–80% of individuals do not go on to convert to psychosis from the CHR-P state and this group should not simply be characterized as the inverse of conversion. To date, only a handful of studies have examined the characteristics and predictors of those who do not convert to psychosis and ultimately either remit or continue to meet symptom-based CHR-P criteria. The present study took an exploratory empirical approach to determining potential factors that predict remission in non-converters. <h3>Methods</h3> Participants were drawn from the North American Prodrome Longitudinal Study (NAPLS2). Univariate Kaplan Meier survival analyses were performed on a pool of available demographic and clinical variables. Variables that were significant (p < 0.05) in the univariate analyses were then included in a multivariate Cox proportional hazard regression to predict remission. Remission was defined as all SOPS positive symptom subscale items rated as a 2 or lower at any given follow-up visit. <h3>Results</h3> A total of 359 participants from the NAPLS2 study who did not convert to psychosis and had data for at least the baseline and first follow-up visit and were included in this study. Of these participants, 174 met criteria for symptomatic remission. A total of 57 clinical variables were tested in univariate analyses and 14 of these variables met criteria for inclusion in the multivariate model. The variables included in the multivariate model were demographic variables (ethnicity, stressful life events), items from the Scale of Prodromal Symptoms (SOPS) (avolition, dysphoric mood), subtest scores from the MATRICS Cognitive Battery (speed of processing, verbal learning, verbal and non-verbal working memory, reasoning and problem solving, visual learning), one item from the Calgary Depression Scale for Schizophrenia (CDSS) (pathological guilt) and measures of functioning (GAF decline in past year, lowest GAF score in the past year). Overall, the multivariate model achieved a C-index of 0.64 (SE = 0.02) and p-value of 0.001 in predicting remission. In the multivariate model, significant covariates included stressful life events (HR = .95, p = .006), Hispanic ethnicity (HR = 1.45, p = .045), and avolition (HR = .89, p = .04). Covariates approaching significance included visual learning (HR = 1.02, p = .07), and GAF decline in the past year (HR = 1.01, p = .09). <h3>Discussion</h3> This study is the first to use a data-driven approach to systematically assess clinical and demographic predictors of symptomatic remission in individuals who do not convert to psychosis. The identified set of significant clinical variables is novel, suggesting that remission represents a unique clinical phenomenon and suggesting that further study is warranted to best understand factors contributing to resilience and recovery from the CHR-P period.</div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/93m2x62j"><img src="/cms-assets/dc5330705c0284aba97b14187054fe8793f35faf9fe378706165514a92dfa495" alt="Cover page: T116. PREDICTION OF REMISSION IN NON-CONVERTING INDIVIDUALS AT CLINICAL HIGH RISK FOR PSYCHOSIS"/></a></div></section><section class="c-scholworks"><div class="c-scholworks__main-column"><ul class="c-scholworks__tag-list"><li class="c-scholworks__tag-article">Article</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/9wp452k7"><div class="c-clientmarkup">M118. Functional Capacity: A New Predictor of Role Functioning in Individuals at Clinical High Risk for Psychosis</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3ACarrion%2C%20Ricardo">Carrion, Ricardo</a>; </li><li><a href="/search/?q=author%3AMcLaughlin%2C%20Danielle">McLaughlin, Danielle</a>; </li><li><a href="/search/?q=author%3AAuther%2C%20Andrea">Auther, Andrea</a>; </li><li><a href="/search/?q=author%3AAddington%2C%20Jean">Addington, Jean</a>; </li><li><a href="/search/?q=author%3ABearden%2C%20Carrie">Bearden, Carrie</a>; </li><li><a href="/search/?q=author%3ACadenhead%2C%20Kristin">Cadenhead, Kristin</a>; </li><li><a href="/search/?q=author%3ACannon%2C%20Tyrone">Cannon, Tyrone</a>; </li><li><a href="/search/?q=author%3ATsuang%2C%20Ming">Tsuang, Ming</a>; </li><li><a href="/search/?q=author%3AWalker%2C%20Elaine">Walker, Elaine</a>; </li><li><a href="/search/?q=author%3AWoods%2C%20Scott%20W">Woods, Scott W</a>; </li><li class="c-authorlist__end"><a href="/search/?q=author%3ACornblatt%2C%20Barbara">Cornblatt, Barbara</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/ucsd_postprints">UC San Diego Previously Published Works</a> (<!-- -->2017<!-- -->)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup">Abstract Background: Recent studies have recognized that signs of functional disability in schizophrenia are evident in early phases of the disorder, and, as a result, can potentially serve as vulnerability markers of future illness. However, functional measures in the psychosis prodrome have focused exclusively on real-world accomplishment (ie, achievement), rather than on the skills required to carry-out a particular real-world function (ie, capacity). From this perspective capacity provides the foundation for what can actually be achieved. This is comparable to the comparison between IQ (capacity) vs grades at school (achievement). In one of the first reports of its kind, we introduced the Map task, a laboratory-based measure specifically designed to assess a young person’s basic capacity to carry-out age-appropriate skills that lead to independent community living (McLaughlin et al., 2016). Poor performance on the Map task was found to be predictive of conversion to psychosis, suggesting that functional capacity in the prodrome may represent a basic biologically-based vulnerability factor. Given that diminished functional capacity is often a key barrier to good functional outcomes in patients with schizophrenia, the current study sought to next evaluate whether deficits in capacity can also predict social and role (ie, academic) functioning in the prodrome. Methods: The Map task was administered to 609 subjects at Clinical High-Risk (CHR) for psychosis and 242 Healthy Controls (HCs) participating in the North American Prodrome Longitudinal Study (NAPLS2). Subjects were required to efficiently complete a set of specified errands in a fictional town. Results: Individuals with poor role functioning at study outcome had a lower Map efficiency score than those with good role outcome. In addition, the Map efficiency score predicted role functioning at outcome (OR = −0.971, 95% CI = 0.946 to 0.997; P = .027), even after accounting for conversion status, baseline IQ, and baseline role functioning). In contrast, the Map Efficiency score did not predict social outcome (OR = 0.989, 95% CI = 0.964–1.015; P = .416), supporting previous findings that social and role functioning are 2 distinct functional domains, with different developmental courses, with each having potential to provide predictors of long-term prognosis. Conclusion: Our findings support the notion that functional capacity may well represent a distinct vulnerability factor related to the multi-faceted long-term disability typically associated with schizophrenia. Poor performance on the Map task was significantly associated with impaired role functioning at study outcome, even after controlling for the contribution of conversion and intellectual performance. Thus, deficits in both role “capacity” and role “achievement” are present before the onset of the illness, and are not an artifact of psychosis onset or intellectual impairments.</div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/9wp452k7"><img src="/cms-assets/78d2992b482f6baf78f7e34e7ec16ff92a85fe7e4be1c441c9bebafd4c7f0301" alt="Cover page: M118. Functional Capacity: A&nbsp;New Predictor of Role Functioning in Individuals at Clinical High Risk for Psychosis"/></a></div></section><nav class="c-pagination--next"><ul><li><a href="" aria-label="you are on result set 1" class="c-pagination__item--current">1</a></li><li><a href="" aria-label="go to result set 2" class="c-pagination__item">2</a></li><li><a href="" aria-label="go to result set 3" class="c-pagination__item">3</a></li><li><a href="" aria-label="go to result set 4" class="c-pagination__item">4</a></li><li><a href="" aria-label="go to result set 14" class="c-pagination__item">14</a></li><li class="c-pagination__next"><a href="" aria-label="go to Next result set">Next</a></li></ul></nav></section></main></form></div><div><div class="c-toplink"><a href="javascript:window.scrollTo(0, 0)">Top</a></div><footer class="c-footer"><nav class="c-footer__nav"><ul><li><a href="/">Home</a></li><li><a href="/aboutEschol">About eScholarship</a></li><li><a href="/campuses">Campus 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Merced"},{"id":"ucr","name":"UC Riverside"},{"id":"ucsd","name":"UC San Diego"},{"id":"ucsf","name":"UCSF"},{"id":"ucsb","name":"UC Santa Barbara"},{"id":"ucsc","name":"UC Santa Cruz"},{"id":"ucop","name":"UC Office of the President"},{"id":"lbnl","name":"Lawrence Berkeley National Laboratory"},{"id":"anrcs","name":"UC Agriculture & Natural Resources"}],"query":{"q":"author:Cornblatt, Barbara","sort":"rel","rows":"10","info_start":"0","start":"0","filters":{}},"count":135,"info_count":0,"infoResults":[],"searchResults":[{"id":"qt7kp468h0","title":"Cognitive-Behavioral Social Skills Training: Outcome of a Randomized Controlled Trial for Youth at Risk of Psychosis.","abstract":"AIM: Difficulties in social functioning have been observed in youth at clinical high-risk (CHR) of psychosis even in those who do not go on to develop a psychotic illness. Few treatment studies have attempted to improve social functioning in this population. The aim of this study was to conduct a randomized trial comparing the effects of Cognitive-Behavioral Social Skills Training (CBSST) with a supportive therapy (ST). METHODS: Both CBSST and ST were weekly group therapies, delivered over 18 weeks. This was a 2-arm trial with single-blinded ratings and intention-to-treat analyses. Assessments occurred at baseline, end-of-treatment, and 12 months after the baseline assessment. The primary outcome was social and role functioning and defeatist performance attitudes were the secondary outcome. Attenuated positive and negative symptoms, anxiety, depression, self-efficacy, and beliefs about self and others were examined as exploratory outcomes. RESULTS: There were no significant differences between the 2 groups at baseline or either of the 2 follow-ups. However, at follow-ups, in each group there were significant improvements in clinical symptoms. These could not be attributed to group treatment since there was no control or wait-list group. CONCLUSIONS: Since poor social functioning is one of the most observed difficulties in CHR individuals, and a decline in social functioning may be a significant predictor of later transition to psychosis, future work will be needed to find effective treatments for this decline in functioning for CHR youth.","content_type":"application/pdf","author_hide":null,"authors":[{"name":"Cornblatt, Barbara","fname":"Barbara","lname":"Cornblatt"},{"name":"Holden, Jason","fname":"Jason","lname":"Holden"},{"name":"Granholm, Eric","fname":"Eric","lname":"Granholm"},{"name":"Addington, Jean","fname":"Jean","lname":"Addington"},{"name":"Liu, Lu","fname":"Lu","lname":"Liu"},{"name":"Braun, Amy","fname":"Amy","lname":"Braun"},{"name":"Brummitt, Kali","fname":"Kali","lname":"Brummitt"},{"name":"Cadenhead, Kristin","email":"kcadenhead@ucsd.edu","fname":"Kristin","lname":"Cadenhead"}],"supp_files":[{"type":"pdf","count":0},{"type":"image","count":0},{"type":"video","count":0},{"type":"audio","count":0},{"type":"zip","count":0},{"type":"other","count":0}],"thumbnail":{"width":121,"height":165,"asset_id":"2e89a78009d186425611d3cb86a26e58ae7b30acf423bb295f2303a903743f3b","timestamp":1695148136,"image_type":"png"},"pub_year":2023,"genre":"article","rights":null,"peerReviewed":true,"unitInfo":{"displayName":"UC San Diego Previously Published Works","link_path":"ucsd_postprints"}},{"id":"qt23r3p0mp","title":"Cognitive-Behavioural Social Skills Training: Mediation of Treatment Outcomes in a Randomized Controlled Trial for Youth at Risk of Psychosis: Lentra\u00EEnement aux comp\u00E9tences sociales cognitivo-comportementales : variables m\u00E9diatrices des r\u00E9sultats th\u00E9rapeutiques dans le cadre dun essai clinique randomis\u00E9 pour les jeunes pr\u00E9sentant un risque de psychose.","abstract":"OBJECTIVES: Currently, there are no effective treatments for functional outcomes (i.e., role and social) and negative symptoms for youth at clinical high-risk (CHR) for psychosis. Investigations into possible mechanisms that may contribute to the improvement of functioning and negative symptoms are needed in CHR research to help inform psychosocial treatments. The present study examined whether functioning and negative symptoms were mediated by asocial beliefs, defeatist beliefs, self-efficacy, maladaptive schemas, anxiety, depression, social cognition, or attenuated psychotic symptoms (APS) in a large clinical trial. METHODS: CHR participants (n\u2009=\u2009203; 104 females; 99 males) were recruited as part of a three-site randomized control trial comparing group cognitive-behavioural social skills training (CBSST) versus a supportive therapy group. Mediation analyses were conducted to test the relationships between treatment group, mediators (asocial beliefs, defeatist beliefs, self-efficacy, maladaptive schemas, anxiety, depression, social cognition, and APS), and outcome (social and role functioning, and negative symptoms). The mediation analyses employed conditional process path analysis via ordinary least squares regression. RESULTS: At the end of treatment, but not 12-month follow-up, more severe APS were found to mediate the impact of treatment on negative symptoms, and social and role functioning. The greater the severity of APS, the less likely that CBSST would result in improvement in negative symptoms and social and role functioning. Many of the other variables showed significant associations with social (less for role) functioning and negative symptoms but did not mediate the effect of treatment on these outcomes at the end of treatment or 12-month follow-up. CONCLUSIONS: There were no significant mediators except for APS at the end of treatment. Since more severe APS may result in participants being unable to fully participate in therapy and thus limit their gains, clinical implications may include offering some individual therapy to prepare these young people to benefit from the group treatment.","content_type":"application/pdf","author_hide":null,"authors":[{"name":"Devoe, Daniel","fname":"Daniel","lname":"Devoe"},{"name":"Liu, Lu","fname":"Lu","lname":"Liu"},{"name":"Braun, Amy","fname":"Amy","lname":"Braun"},{"name":"Cadenhead, Kristin","fname":"Kristin","lname":"Cadenhead"},{"name":"Cornblatt, Barbara","fname":"Barbara","lname":"Cornblatt"},{"name":"Granholm, Eric","fname":"Eric","lname":"Granholm"},{"name":"Addington, Jean","fname":"Jean","lname":"Addington"}],"supp_files":[{"type":"pdf","count":0},{"type":"image","count":0},{"type":"video","count":0},{"type":"audio","count":0},{"type":"zip","count":0},{"type":"other","count":0}],"thumbnail":{"width":121,"height":168,"asset_id":"52266e39e5452cd26b38f15e1699fc684261f517c5c5ccc1b61249127d187299","timestamp":1732635410,"image_type":"png"},"pub_year":2024,"genre":"article","rights":null,"peerReviewed":true,"unitInfo":{"displayName":"UC San Diego Previously Published Works","link_path":"ucsd_postprints"}},{"id":"qt85g271k0","title":"39.1 DNA METHYLATION OF IMMUNE CELLS IN PERSONS AT CLINICAL HIGH RISK FOR PSYCHOSIS","abstract":"Abstract <h4>Background</h4> A dysregulated immune system is implicated in the development of psychotic disorders. Persons with schizophrenia have altered levels of circulating immune cell signaling molecules (cytokines), and elevation of specific cytokines predict conversion to psychosis in persons at clinical high risk. Whether these peripheral signals are a causal or a secondary phenomenon is unclear. But, subpopulations of circulating immune cells do regulate the brain from meningeal and perivascular locations influencing cognition, mood, and behavior, and thus may be relevant to schizophrenia vulnerability. Hematopoietic stem cells in the bone marrow differentiate into cascading subtypes depending on signals from other organs, especially the brain. For example, a monocyte subpopulation emerges with repeated social defeat that establish the persistence of anxiety-like behaviors; blocking their release or inhibiting their attachment to brain vascular endothelium prevents the emergence of anxiety-like behaviors. In humans, a similar monocyte subpopulation is associated with social isolation and other adversities including low SES, chronic stress, and bereavement. <h4>Methods</h4> The North American Prodrome Longitudinal Study (NAPLS2) is an eight-site observational study of predictors and mechanisms of conversion to psychosis The full cohort includes 763 at clinical high risk (CHR) based on the Criteria of Prodromal State (COPS) and 279 demographically similar unaffected comparison (UC) subjects. Methylation of whole blood DNA collected in PAXgene tubes at baseline was analyzed with the Illumina 450k array in a subgroup of 59 subjects who converted to psychosis (CHR-C), 84 CHR subjects followed for 2 years who did not develop psychosis (CHR-NC) and 67 unaffected subjects (UC). Our analyses focused on methylation of promoter regions of genes, associated with gene expression. Classifier construction used Coarse Approximation Linear Function (CALF) with bootstrapping of 1000 random 80% subsets with replacement to determine statistical likelihood. <h4>Results</h4> We found highly overlapping sets of differentially methylated promoter regions in CHR-C subjects compared to CHR-NC and to UC subjects. A set of 10 markers correctly classified CHR-C and CHR-NC subjects with high accuracy (AUC=0.94, 95% CI 0.89\u20130.98). Included was SIRT1, a gene that is upregulated with HSV reactivation. <h4>Discussion</h4> Circulating immune cells excerpt powerful influences on mood, cognition and behavior. An obvious example is the experience of most human with \u201Csickness syndrome\u201D, characterized by apathy, avolition, and withdrawal, and triggered by immune-cell-released cytokines producing an adaptive, resource conserving, behavioral response. While at an early stage, our findings further implicate immune system dysregulation as a mechanism in the development of psychosis.","content_type":"application/pdf","author_hide":null,"authors":[{"name":"Perkins, Diana","fname":"Diana","lname":"Perkins"},{"name":"Clark, Jeffries","fname":"Jeffries","lname":"Clark"},{"name":"Addington, Jean","fname":"Jean","lname":"Addington"},{"name":"Beardon, Carrie","fname":"Carrie","lname":"Beardon"},{"name":"Cadenhead, Kristin","fname":"Kristin","lname":"Cadenhead"},{"name":"Cannon, Tyrone","fname":"Tyrone","lname":"Cannon"},{"name":"Cornblatt, Barbara","fname":"Barbara","lname":"Cornblatt"},{"name":"Mathalon, Daniel","fname":"Daniel","lname":"Mathalon"},{"name":"McGlashan, Thomas","fname":"Thomas","lname":"McGlashan"},{"name":"Seidman, Larry","fname":"Larry","lname":"Seidman"},{"name":"Tsuang, Ming","email":"mtsuang@ucsd.edu","fname":"Ming","lname":"Tsuang","ORCID_id":"0000-0002-0076-5340"},{"name":"Walker, Elaine","fname":"Elaine","lname":"Walker"},{"name":"Woods, Scott","fname":"Scott","lname":"Woods"}],"supp_files":[{"type":"pdf","count":0},{"type":"image","count":0},{"type":"video","count":0},{"type":"audio","count":0},{"type":"zip","count":0},{"type":"other","count":0}],"thumbnail":{"width":121,"height":167,"asset_id":"c1a89740f2be8244d329319dacf0a575e667c9389e3af373246e3e12cef8f5c8","timestamp":1689402925,"image_type":"png"},"pub_year":2018,"genre":"article","rights":null,"peerReviewed":true,"unitInfo":{"displayName":"UC San Diego Previously Published Works","link_path":"ucsd_postprints"}},{"id":"qt5666t6qw","title":"SU127. Negative Symptoms in Youth at Clinical High Risk of Psychosis","abstract":"Abstract Background: Longitudinal studies examining youth at clinical high risk (CHR) of psychosis have predominantly focused on positive symptoms. However, youth at CHR often demonstrate persistent and significant negative symptoms, which have been reported to be predictive of conversion to psychosis. The goal of this study was to examine negative symptoms over time in youth at CHR of psychosis and compare baseline negative symptoms in those who convert to psychosis with those who did not convert. Methods: Youth at CHR (N = 764) were recruited for the North American Prodrome Longitudinal Study (NAPLS 2) at 8 sites across North America. Negative symptoms were rated on the Scale of Prodromal Symptoms (SOPS) at baseline, 6, 12, 18, and 24 months. Difference in prevalence of negative symptoms was assessed using Z test and change in negative symptom severity over time was assessed using repeated measures analysis of variance ANOVA. Wilcoxon rank sum test and 2-sample t test were utilized to compare baseline negative symptoms in converters vs nonconverters. Results: The mean total negative symptom score at baseline was 11.90 (SD = 9.80). A majority of participants (84.57%) had at least one negative symptom rated \u22653 at baseline. Negative symptom severity significantly decreased over time compared to baseline measures. Eighty-six participants converted in total. In participants with at least one negative symptom of moderate severity or above (N \u2265 3), nonconverters had lower severity ratings on expression of emotion (M = 1.49, SD = 1.47 vs M = 1.94, SD = 1.64, P = .02) and ideational richness (M = 1.23, SD = 1.37 vs M = 1.60, SD = 1.35, P = .04) compared to converters at baseline. In participants who completed 24 months of assessment and had negative symptom severity of moderate severity or above (N \u2265 3), nonconverters had significantly better expression of emotion (M = 1.40, SD = 1.51) compared to converters (M = 1.79, SD = 1.63, P = .03). Conclusion: First, this study demonstrated that the majority of youth at CHR have moderate to severe negative symptoms at baseline. Second, both decreased expression of emotion and decreased ideational richness was significantly more severe in participants who converted and may be indicative of later conversion to psychosis. Thus, early and persistent higher negative symptom scores may represent subsequent risk of conversion to psychosis.","content_type":"application/pdf","author_hide":null,"authors":[{"name":"Devoe, Daniel","fname":"Daniel","lname":"Devoe"},{"name":"Cadenhead, Kristen","fname":"Kristen","lname":"Cadenhead"},{"name":"Cannon, Tyrone","fname":"Tyrone","lname":"Cannon"},{"name":"Cornblatt, Barbara","fname":"Barbara","lname":"Cornblatt"},{"name":"McGlashan, Tom","fname":"Tom","lname":"McGlashan"},{"name":"Perkins, Diana","fname":"Diana","lname":"Perkins"},{"name":"Seidman, Larry J","fname":"Larry J","lname":"Seidman"},{"name":"Tsuang, Ming","email":"mtsuang@ucsd.edu","fname":"Ming","lname":"Tsuang","ORCID_id":"0000-0002-0076-5340"},{"name":"Walker, Elaine","fname":"Elaine","lname":"Walker"},{"name":"Woods, Scott","fname":"Scott","lname":"Woods"},{"name":"Bearden, Carrie","fname":"Carrie","lname":"Bearden"},{"name":"Mathalon, Daniel","fname":"Daniel","lname":"Mathalon"},{"name":"Addington, Jean","fname":"Jean","lname":"Addington"}],"supp_files":[{"type":"pdf","count":0},{"type":"image","count":0},{"type":"video","count":0},{"type":"audio","count":0},{"type":"zip","count":0},{"type":"other","count":0}],"thumbnail":{"width":121,"height":163,"asset_id":"4f75c4f2a44c9ede1a107b6e4d80f3a743cf5fc75d85f50da3598a9ef7e70728","timestamp":1689405155,"image_type":"png"},"pub_year":2017,"genre":"article","rights":null,"peerReviewed":true,"unitInfo":{"displayName":"UC San Diego Previously Published Works","link_path":"ucsd_postprints"}},{"id":"qt5jd2p259","title":"23. Omega-3 Fatty Acid Versus Placebo in a Clinical High-Risk Sample From the North American Prodrome Longitudinal Studies (NAPLS) Consortium","abstract":"Abstract Background: Omega-3 Fatty Acids (FAs), EPA (eicosapentaenoic acid) and DHA (Docosahexaenoic acid), are essential for normal brain development and may also have neuroprotective properties. Dietary supplementation of EPA and DHA has beneficial effects in medical illnesses as well as depression, bipolar disorder, and dementia. Abnormal FA metabolism may play a role in the etiology of psychiatric illness. Studies of erythrocytes and skin fibroblasts have shown reduced levels of FAs and phospholipids in schizophrenia. Studies of Omega-3FA supplementation in schizophrenia have been mixed. Amminger et al performed a randomized, double-blind, placebo-controlled trial in 81 subjects with prodromal symptoms of psychosis. The treatment consisted of 1.2g/day of Omega-3FAs (700\u2009mg EPA, 480\u2009mg DHA). After 12 weeks, 2 (4.9%) of 41 individuals in the Omega-3FA group and 11 of 40 (27.5%) in the placebo group converted to a psychotic disorder. Omega-3FAs also significantly reduced symptoms and improved functioning. The Aims of the current study were to replicate the Amminger study in Clinical High Risk (CHR) subjects from the NAPLS consortium. Methods: This was a 24-week, randomized, double-blind, placebo, fixed dose-controlled study of Omega-3FA versus placebo in 127 CHR subjects. The Omega-3FA compound contained a 2:1 proportion of EPA to DHA. The total dose was 740\u2009mg of EPA and 400\u2009mg of DHA. Baseline diet characterization was assessed using a systematic checklist that includes Omega-3FA foods. In addition, fasting erythrocyte FA composition was assessed. Results: Of the 127 CHR subjects recruited into the trial, 118 completed baseline assessment, and 70 (59%) completed the 6-month trial. Seven (10% Kaplan-Meier) subjects converted to psychosis during the 24 months. The rate of psychotic conversion did not differ in the Omega-3FA (13%) versus Placebo (8%) samples. Conversion to psychosis was predicted by low Omega-3FA rich foods in the diet (Wald Statistic = 4.96, P < .05). Although there were significant improvements in symptom and functioning over time in Mixed Model analyses, there were no significant group or Group \u00D7 Time interaction effects. Conclusion: The rate of conversion to psychosis in the present sample was lower than is typically observed in an at-risk population. Given the study attrition and low rate of conversion to psychosis, the trial was underpowered to replicate the conversion effect in the Amminger et al.\u2019s study. Despite the overall improvement in symptoms and functioning over time in all subjects, there was no clear evidence of a differential effect in the sample on Omega-3FA vs Placebo. Further work is needed to better tease out the role of diet and Omega-3FA in mental illness. The finding of a significant association between baseline diet low in Omega-3FA rich foods and later conversion to psychosis raises the question of whether it is possible to influence both physical and mental health with lifestyle choices including diet.","content_type":"application/pdf","author_hide":null,"authors":[{"name":"Cadenhead, Kristin","fname":"Kristin","lname":"Cadenhead"},{"name":"Addington, Jean","fname":"Jean","lname":"Addington"},{"name":"Cannon, Tyrone","fname":"Tyrone","lname":"Cannon"},{"name":"Cornblatt, Barbara","fname":"Barbara","lname":"Cornblatt"},{"name":"Mathalon, Daniel","fname":"Daniel","lname":"Mathalon"},{"name":"McGlashan, Tom","fname":"Tom","lname":"McGlashan"},{"name":"Perkins, Diana","fname":"Diana","lname":"Perkins"},{"name":"Seidman, Larry J","fname":"Larry J","lname":"Seidman"},{"name":"Tsuang, Ming","email":"mtsuang@ucsd.edu","fname":"Ming","lname":"Tsuang","ORCID_id":"0000-0002-0076-5340"},{"name":"Walker, Elaine","fname":"Elaine","lname":"Walker"},{"name":"Woods, Scott","fname":"Scott","lname":"Woods"}],"supp_files":[{"type":"pdf","count":0},{"type":"image","count":0},{"type":"video","count":0},{"type":"audio","count":0},{"type":"zip","count":0},{"type":"other","count":0}],"thumbnail":{"width":121,"height":167,"asset_id":"0d42bcaf8ad048fd0ee8123a8d5b3da501aedef669a69070369b824d8ac3e8d9","timestamp":1689404206,"image_type":"png"},"pub_year":2017,"genre":"article","rights":null,"peerReviewed":true,"unitInfo":{"displayName":"UC San Diego Previously Published Works","link_path":"ucsd_postprints"}},{"id":"qt53534296","title":"24.2 NEUROCOGNITIVE PROFILES IN THE PRODROME TO PSYCHOSIS IN NAPLS-1","abstract":"Abstract <h4>Background</h4> The vast majority of studies of neuropsychological (NP) functioning in Clinical High Risk (CHR) cohorts have examined group averages, possibly concealing a range of subgroups ranging from very impaired to high functioning. Our objective was to assess NP profiles and to explore associations with conversion to psychosis, functional and diagnostic outcome. <h4>Methods</h4> Data were acquired from 324 participants (mean age 18.4) in the first phase of the North American Prodrome Longitudinal Study (NAPLS-1), a multi-site consortium following individuals for up to 2\u00BD years. We applied Ward\u2019s method for hierarchical clustering data to 8 baseline neurocognitive measures, in 166 CHR individuals, 49 non-CHR youth with a family history of psychosis, and 109 healthy controls. We tested whether cluster membership was associated with conversion to psychosis, social and role functioning, and follow-up diagnosis. Analyses were repeated after data were clustered based on independently developed clinical decision rules. <h4>Results</h4> Four neurocognitive clusters were identified: Significantly Impaired (n=33); Mildly Impaired (n=82); Normal (n=145) and High (n=64). The Significantly Impaired subgroup demonstrated the largest deviations on processing speed and memory tasks and had a conversion rate of 58%, a 40% chance of developing a schizophrenia spectrum diagnosis (compared to 24.4% in the Mildly Impaired, and 10.3% in the other two groups combined), and significantly worse functioning at baseline and 12-months. Data clustered using clinical decision rules yielded similar results, pointing to high convergent validity. <h4>Discussion</h4> Despite extensive neuropsychological investigations within CHR cohorts, this is one of the first studies to investigate NP clustering profiles as a contributor to heterogeneity in outcome. Our results indicate that the four NP profiles vary substantially in their outcome, underscoring the relevance of cognitive functioning in the prediction of illness progression. Our findings tentatively suggest that individualized cognitive profiling should be explored in clinical settings.","content_type":"application/pdf","author_hide":null,"authors":[{"name":"Velthorst, Eva","fname":"Eva","lname":"Velthorst"},{"name":"Bearden, Carrie","fname":"Carrie","lname":"Bearden"},{"name":"Meyer, Eric","fname":"Eric","lname":"Meyer"},{"name":"Giuliano, Anthony","fname":"Anthony","lname":"Giuliano"},{"name":"Addington, Jean","fname":"Jean","lname":"Addington"},{"name":"Cadenhead, Kristin","fname":"Kristin","lname":"Cadenhead"},{"name":"Cannon, Tyrone","fname":"Tyrone","lname":"Cannon"},{"name":"Cornblatt, Barbara","fname":"Barbara","lname":"Cornblatt"},{"name":"Mcglashan, Thomas","fname":"Thomas","lname":"Mcglashan"},{"name":"Perkins, Diana","fname":"Diana","lname":"Perkins"},{"name":"Tsuang, Ming","email":"mtsuang@ucsd.edu","fname":"Ming","lname":"Tsuang","ORCID_id":"0000-0002-0076-5340"},{"name":"Walker, Elaine","fname":"Elaine","lname":"Walker"},{"name":"Woods, Scott","fname":"Scott","lname":"Woods"},{"name":"Seidman, Larry","fname":"Larry","lname":"Seidman"}],"supp_files":[{"type":"pdf","count":0},{"type":"image","count":0},{"type":"video","count":0},{"type":"audio","count":0},{"type":"zip","count":0},{"type":"other","count":0}],"thumbnail":{"width":121,"height":164,"asset_id":"657a3125df11cbcd556b3cf3a95485228ac64c40f2e47acd76e6f7fad3d1c789","timestamp":1689402809,"image_type":"png"},"pub_year":2018,"genre":"article","rights":null,"peerReviewed":true,"unitInfo":{"displayName":"UC San Diego Previously Published Works","link_path":"ucsd_postprints"}},{"id":"qt0t23x1cq","title":"59.4 Networks of Blood Analytes are Collectively Informative of Risk of Conversion to Schizophrenia","abstract":"Abstract Background: The presence and severity of attenuated-psychosis symptoms define a clinical high risk (CHR) population at elevated risk for psychotic disorders. The NAPLS project is a prospective study of mechanisms contributing to psychosis vulnerability in persons at CHR. Here we investigated a hypothesized role for the highly-integrated immune and redox systems in the development of psychosis. Methods: We examined expression of 143 plasma analytes from a subgroup of the NAPLS2 cohort, including 32 CHR with subsequent psychosis conversion, 40 CHR followed for 2 years without psychosis, and 35 unaffected subjects. We used a Luminex platform with analytes chosen to reflect immune, redox, hormonal, and metabolic system status, including many analytes previously associated with schizophrenia and psychosis risk. We applied correlation network analysis to discover potentially co-regulated networks associated with later development of psychosis. Results: Several robust (r > .75) and highly significant (P < .0001 after correction for multiple testing) correlation networks were found in all groups, including a network involving IL3, IL5, IL7, and IL13, and a network involving CCL5, BDNF, TSH, and PDGF. There were significantly fewer nodes in CHR-converters compared with CHR-nonconverters and unaffected subjects. In unaffected subjects, plasminogen activator inhibitor-1 (PAI-1) was highly correlated with matrix metallopeptidases (MMP) 7, 9 and 10 and CD40LG, this network was absent in CHR subjects, and in CHR-converters PAI-1 was robustly and significantly correlated with TIMP1, CCL13, and TIMP1. Conclusion: A pattern of robust and highly significant correlation networks in plasma analytes suggests shared regulatory mechanisms for the inter-correlated analytes. The lower number of correlated analytes in CHR subjects who converted to psychosis suggest a shift in regulation, as does the change in the correlation network involving PAI-1. PAI-1 is of interest given studies linking schizophrenia with reduced tissue plasminogen activator (tPA) and increases in negative regulators of tPA, including activation of both PAI-1and TIMP1 with oxidative stress. In addition, a recent study links toxoplasmosis infection and schizophrenia risk to a pathway involving PAI-1 and TIMP1. Patricio O\u2019Donnell, Pfizer Inc.","content_type":"application/pdf","author_hide":null,"authors":[{"name":"Jeffries, Clark","fname":"Clark","lname":"Jeffries"},{"name":"Perkins, Diana","fname":"Diana","lname":"Perkins"},{"name":"Addington, Jean","fname":"Jean","lname":"Addington"},{"name":"Bearden, Carrie","fname":"Carrie","lname":"Bearden"},{"name":"Cadenhead, Kristen","fname":"Kristen","lname":"Cadenhead"},{"name":"Cannon, Tyrone","fname":"Tyrone","lname":"Cannon"},{"name":"Cornblatt, Barbara","fname":"Barbara","lname":"Cornblatt"},{"name":"Mathalon, Daniel","fname":"Daniel","lname":"Mathalon"},{"name":"McGlashan, Tom","fname":"Tom","lname":"McGlashan"},{"name":"Seidman, Larry J","fname":"Larry J","lname":"Seidman"},{"name":"Tsuang, Ming","email":"mtsuang@ucsd.edu","fname":"Ming","lname":"Tsuang","ORCID_id":"0000-0002-0076-5340"},{"name":"Walker, Elaine","fname":"Elaine","lname":"Walker"},{"name":"Woods, Scott","fname":"Scott","lname":"Woods"}],"supp_files":[{"type":"pdf","count":0},{"type":"image","count":0},{"type":"video","count":0},{"type":"audio","count":0},{"type":"zip","count":0},{"type":"other","count":0}],"thumbnail":{"width":121,"height":167,"asset_id":"d7f57468db9e0db827d0c1e60b1022a1c2a6b060ce52f3cb5f499b566cb43147","timestamp":1689405387,"image_type":"png"},"pub_year":2017,"genre":"article","rights":null,"peerReviewed":true,"unitInfo":{"displayName":"UC San Diego Previously Published Works","link_path":"ucsd_postprints"}},{"id":"qt8j42s24m","title":"Sex- and Age-Specific Deviations in Cerebellar Structure and Their Link With Symptom Dimensions and Clinical Outcome in Individuals at Clinical High Risk for Psychosis.","abstract":"BACKGROUND: The clinical high-risk (CHR) period offers a temporal window into neurobiological deviations preceding psychosis onset, but little attention has been given to regions outside the cerebrum in large-scale studies of CHR. Recently, the North American Prodrome Longitudinal Study (NAPLS)-2 revealed altered functional connectivity of the cerebello-thalamo-cortical circuitry among individuals at CHR; however, cerebellar morphology remains underinvestigated in this at-risk population, despite growing evidence of its involvement in psychosis. STUDY DESIGN: In this multisite study, we analyzed T1-weighted magnetic resonance imaging scans obtained from N = 469 CHR individuals (61% male, ages = 12-36 years) and N = 212 healthy controls (52% male, ages = 12-34 years) from NAPLS-2, with a focus on cerebellar cortex and white matter volumes separately. Symptoms were rated by the Structured Interview for Psychosis-Risk Syndromes (SIPS). The outcome by two-year follow-up was categorized as in-remission, symptomatic, prodromal-progression, or psychotic. General linear models were used for case-control comparisons and tests for volumetric associations with baseline SIPS ratings and clinical outcomes. STUDY RESULTS: Cerebellar cortex and white matter volumes differed between the CHR and healthy control groups at baseline, with sex moderating the difference in cortical volumes, and both sex and age moderating the difference in white matter volumes. Baseline ratings for major psychosis-risk dimensions as well as a clinical outcome at follow-up had tissue-specific associations with cerebellar volumes. CONCLUSIONS: These findings point to clinically relevant deviations in cerebellar cortex and white matter structures among CHR individuals and highlight the importance of considering the complex interplay between sex and age when studying the neuromaturational substrates of psychosis risk.","content_type":"application/pdf","author_hide":null,"authors":[{"name":"Woods, Scott","fname":"Scott","lname":"Woods"},{"name":"Cannon, Tyrone","fname":"Tyrone","lname":"Cannon"},{"name":"Walker, Elaine","fname":"Elaine","lname":"Walker"},{"name":"Sefik, Esra","fname":"Esra","lname":"Sefik"},{"name":"Boamah, Michelle","fname":"Michelle","lname":"Boamah"},{"name":"Addington, Jean","fname":"Jean","lname":"Addington"},{"name":"Cornblatt, Barbara","fname":"Barbara","lname":"Cornblatt"},{"name":"Keshavan, Matcheri","fname":"Matcheri","lname":"Keshavan"},{"name":"Perkins, Diana","fname":"Diana","lname":"Perkins"},{"name":"Stone, William","fname":"William","lname":"Stone"},{"name":"Mathalon, Daniel","email":"daniel.mathalon@ucsf.edu","fname":"Daniel","lname":"Mathalon"},{"name":"Bearden, Carrie","email":"cbearden@mednet.ucla.edu","fname":"Carrie","lname":"Bearden"},{"name":"Cadenhead, Kristin","email":"kcadenhead@ucsd.edu","fname":"Kristin","lname":"Cadenhead"},{"name":"Tsuang, Ming","email":"mtsuang@ucsd.edu","fname":"Ming","lname":"Tsuang"}],"supp_files":[{"type":"pdf","count":0},{"type":"image","count":0},{"type":"video","count":0},{"type":"audio","count":0},{"type":"zip","count":0},{"type":"other","count":0}],"thumbnail":{"width":121,"height":165,"asset_id":"f05a725d546a91e264392937a9ba4ff55f91b236eaa802323956c51ac63ed7d0","timestamp":1701271902,"image_type":"png"},"pub_year":2023,"genre":"article","rights":null,"peerReviewed":true,"unitInfo":{"displayName":"UC San Francisco Previously Published Works","link_path":"ucsf_postprints"}},{"id":"qt93m2x62j","title":"T116. PREDICTION OF REMISSION IN NON-CONVERTING INDIVIDUALS AT CLINICAL HIGH RISK FOR PSYCHOSIS","abstract":"Abstract <h4>Background</h4> The clinical high-risk period before a first episode of psychosis (CHR-P) has been widely studied in the past 30 years with the goal of understanding the development of psychosis. Despite the progress in understanding what factors are associated with conversion to psychosis from the CHR-P state, less attention has been paid to the individuals who do not transition to psychosis. It is estimated that approximately 75\u201380% of individuals do not go on to convert to psychosis from the CHR-P state and this group should not simply be characterized as the inverse of conversion. To date, only a handful of studies have examined the characteristics and predictors of those who do not convert to psychosis and ultimately either remit or continue to meet symptom-based CHR-P criteria. The present study took an exploratory empirical approach to determining potential factors that predict remission in non-converters. <h4>Methods</h4> Participants were drawn from the North American Prodrome Longitudinal Study (NAPLS2). Univariate Kaplan Meier survival analyses were performed on a pool of available demographic and clinical variables. Variables that were significant (p < 0.05) in the univariate analyses were then included in a multivariate Cox proportional hazard regression to predict remission. Remission was defined as all SOPS positive symptom subscale items rated as a 2 or lower at any given follow-up visit. <h4>Results</h4> A total of 359 participants from the NAPLS2 study who did not convert to psychosis and had data for at least the baseline and first follow-up visit and were included in this study. Of these participants, 174 met criteria for symptomatic remission. A total of 57 clinical variables were tested in univariate analyses and 14 of these variables met criteria for inclusion in the multivariate model. The variables included in the multivariate model were demographic variables (ethnicity, stressful life events), items from the Scale of Prodromal Symptoms (SOPS) (avolition, dysphoric mood), subtest scores from the MATRICS Cognitive Battery (speed of processing, verbal learning, verbal and non-verbal working memory, reasoning and problem solving, visual learning), one item from the Calgary Depression Scale for Schizophrenia (CDSS) (pathological guilt) and measures of functioning (GAF decline in past year, lowest GAF score in the past year). Overall, the multivariate model achieved a C-index of 0.64 (SE = 0.02) and p-value of 0.001 in predicting remission. In the multivariate model, significant covariates included stressful life events (HR = .95, p = .006), Hispanic ethnicity (HR = 1.45, p = .045), and avolition (HR = .89, p = .04). Covariates approaching significance included visual learning (HR = 1.02, p = .07), and GAF decline in the past year (HR = 1.01, p = .09). <h4>Discussion</h4> This study is the first to use a data-driven approach to systematically assess clinical and demographic predictors of symptomatic remission in individuals who do not convert to psychosis. The identified set of significant clinical variables is novel, suggesting that remission represents a unique clinical phenomenon and suggesting that further study is warranted to best understand factors contributing to resilience and recovery from the CHR-P period.","content_type":"application/pdf","author_hide":null,"authors":[{"name":"Worthington, Michelle","fname":"Michelle","lname":"Worthington"},{"name":"Addington, Jean","fname":"Jean","lname":"Addington"},{"name":"Bearden, Carrie","fname":"Carrie","lname":"Bearden"},{"name":"Cadenhead, Kristin","fname":"Kristin","lname":"Cadenhead"},{"name":"Cornblatt, Barbara","fname":"Barbara","lname":"Cornblatt"},{"name":"Mathalon, Daniel","fname":"Daniel","lname":"Mathalon"},{"name":"McGlashan, Thomas","fname":"Thomas","lname":"McGlashan"},{"name":"Perkins, Diana","fname":"Diana","lname":"Perkins"},{"name":"Seidman, Larry","fname":"Larry","lname":"Seidman"},{"name":"Tsuang, Ming","email":"mtsuang@ucsd.edu","fname":"Ming","lname":"Tsuang","ORCID_id":"0000-0002-0076-5340"},{"name":"Walker, Elaine","fname":"Elaine","lname":"Walker"},{"name":"Woods, Scott","fname":"Scott","lname":"Woods"},{"name":"Cannon, Tyrone","fname":"Tyrone","lname":"Cannon"}],"supp_files":[{"type":"pdf","count":0},{"type":"image","count":0},{"type":"video","count":0},{"type":"audio","count":0},{"type":"zip","count":0},{"type":"other","count":0}],"thumbnail":{"width":121,"height":163,"asset_id":"dc5330705c0284aba97b14187054fe8793f35faf9fe378706165514a92dfa495","timestamp":1689401763,"image_type":"png"},"pub_year":2020,"genre":"article","rights":null,"peerReviewed":true,"unitInfo":{"displayName":"UC San Diego Previously Published Works","link_path":"ucsd_postprints"}},{"id":"qt9wp452k7","title":"M118. Functional Capacity: A New Predictor of Role Functioning in Individuals at Clinical High Risk for Psychosis","abstract":"Abstract Background: Recent studies have recognized that signs of functional disability in schizophrenia are evident in early phases of the disorder, and, as a result, can potentially serve as vulnerability markers of future illness. However, functional measures in the psychosis prodrome have focused exclusively on real-world accomplishment (ie, achievement), rather than on the skills required to carry-out a particular real-world function (ie, capacity). From this perspective capacity provides the foundation for what can actually be achieved. This is comparable to the comparison between IQ (capacity) vs grades at school (achievement). In one of the first reports of its kind, we introduced the Map task, a laboratory-based measure specifically designed to assess a young person\u2019s basic capacity to carry-out age-appropriate skills that lead to independent community living (McLaughlin et al., 2016). Poor performance on the Map task was found to be predictive of conversion to psychosis, suggesting that functional capacity in the prodrome may represent a basic biologically-based vulnerability factor. Given that diminished functional capacity is often a key barrier to good functional outcomes in patients with schizophrenia, the current study sought to next evaluate whether deficits in capacity can also predict social and role (ie, academic) functioning in the prodrome. Methods: The Map task was administered to 609 subjects at Clinical High-Risk (CHR) for psychosis and 242 Healthy Controls (HCs) participating in the North American Prodrome Longitudinal Study (NAPLS2). Subjects were required to efficiently complete a set of specified errands in a fictional town. Results: Individuals with poor role functioning at study outcome had a lower Map efficiency score than those with good role outcome. In addition, the Map efficiency score predicted role functioning at outcome (OR = \u22120.971, 95% CI = 0.946 to 0.997; P = .027), even after accounting for conversion status, baseline IQ, and baseline role functioning). In contrast, the Map Efficiency score did not predict social outcome (OR = 0.989, 95% CI = 0.964\u20131.015; P = .416), supporting previous findings that social and role functioning are 2 distinct functional domains, with different developmental courses, with each having potential to provide predictors of long-term prognosis. Conclusion: Our findings support the notion that functional capacity may well represent a distinct vulnerability factor related to the multi-faceted long-term disability typically associated with schizophrenia. Poor performance on the Map task was significantly associated with impaired role functioning at study outcome, even after controlling for the contribution of conversion and intellectual performance. Thus, deficits in both role \u201Ccapacity\u201D and role \u201Cachievement\u201D are present before the onset of the illness, and are not an artifact of psychosis onset or intellectual impairments.","content_type":"application/pdf","author_hide":null,"authors":[{"name":"Carrion, Ricardo","fname":"Ricardo","lname":"Carrion"},{"name":"McLaughlin, Danielle","fname":"Danielle","lname":"McLaughlin"},{"name":"Auther, Andrea","fname":"Andrea","lname":"Auther"},{"name":"Addington, Jean","fname":"Jean","lname":"Addington"},{"name":"Bearden, Carrie","fname":"Carrie","lname":"Bearden"},{"name":"Cadenhead, Kristin","fname":"Kristin","lname":"Cadenhead"},{"name":"Cannon, Tyrone","fname":"Tyrone","lname":"Cannon"},{"name":"Tsuang, Ming","email":"mtsuang@ucsd.edu","fname":"Ming","lname":"Tsuang","ORCID_id":"0000-0002-0076-5340"},{"name":"Walker, Elaine","fname":"Elaine","lname":"Walker"},{"name":"Woods, Scott W","fname":"Scott W","lname":"Woods"},{"name":"Cornblatt, Barbara","fname":"Barbara","lname":"Cornblatt"}],"supp_files":[{"type":"pdf","count":0},{"type":"image","count":0},{"type":"video","count":0},{"type":"audio","count":0},{"type":"zip","count":0},{"type":"other","count":0}],"thumbnail":{"width":121,"height":166,"asset_id":"78d2992b482f6baf78f7e34e7ec16ff92a85fe7e4be1c441c9bebafd4c7f0301","timestamp":1689403625,"image_type":"png"},"pub_year":2017,"genre":"article","rights":null,"peerReviewed":true,"unitInfo":{"displayName":"UC San Diego Previously Published Works","link_path":"ucsd_postprints"}}],"facets":[{"display":"Type of Work","fieldName":"type_of_work","facets":[{"value":"article","count":135,"displayName":"Article"},{"value":"monograph","count":0,"displayName":"Book"},{"value":"dissertation","count":0,"displayName":"Theses"},{"value":"multimedia","count":0,"displayName":"Multimedia"}]},{"display":"Peer Review","fieldName":"peer_reviewed","facets":[{"value":"1","count":135,"displayName":"Peer-reviewed only"}]},{"display":"Supplemental Material","fieldName":"supp_file_types","facets":[{"value":"video","count":0,"displayName":"Video"},{"value":"audio","count":0,"displayName":"Audio"},{"value":"images","count":0,"displayName":"Images"},{"value":"zip","count":0,"displayName":"Zip"},{"value":"other files","count":0,"displayName":"Other files"}]},{"display":"Publication Year","fieldName":"pub_year","range":{"pub_year_start":null,"pub_year_end":null}},{"display":"Campus","fieldName":"campuses","facets":[{"value":"ucb","count":0,"displayName":"UC Berkeley"},{"value":"ucd","count":6,"displayName":"UC Davis"},{"value":"uci","count":13,"displayName":"UC Irvine"},{"value":"ucla","count":93,"displayName":"UCLA"},{"value":"ucm","count":0,"displayName":"UC Merced"},{"value":"ucr","count":0,"displayName":"UC Riverside"},{"value":"ucsd","count":129,"displayName":"UC San Diego"},{"value":"ucsf","count":92,"displayName":"UCSF"},{"value":"ucsb","count":0,"displayName":"UC Santa Barbara"},{"value":"ucsc","count":0,"displayName":"UC Santa Cruz"},{"value":"ucop","count":0,"displayName":"UC Office of the President"},{"value":"lbnl","count":0,"displayName":"Lawrence Berkeley National Laboratory"},{"value":"anrcs","count":0,"displayName":"UC Agriculture & Natural Resources"}]},{"display":"Department","fieldName":"departments","facets":[{"value":"ucsdpsych","count":116,"displayName":"Department of Psychiatry, UCSD"},{"value":"ucsdsom","count":127,"displayName":"School of Medicine"},{"value":"uclapsych","count":93,"displayName":"UCLA Department of Psychology"}]},{"display":"Journal","fieldName":"journals","facets":[]},{"display":"Discipline","fieldName":"disciplines","facets":[]},{"display":"Reuse License","fieldName":"rights","facets":[{"value":"CC BY","count":2,"displayName":"BY - Attribution required"}]}]};</script> <script src="/js/vendors~app-bundle-7424603c338d723fd773.js"></script> <script src="/js/app-bundle-8362e6d7829414ab4baa.js"></script> </body> </html>