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Developmental perspectives on the origins of psychotic disorders: The need for a transdiagnostic approach
- Elaine F. Walker, Katrina Aberizk, Emerald Yuan, Zarina Bilgrami, Benson S. Ku, Ryan M. Guest
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- Journal:
- Development and Psychopathology , First View
- Published online by Cambridge University Press:
- 26 February 2024, pp. 1-11
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Research on serious mental disorders, particularly psychosis, has revealed highly variable symptom profiles and developmental trajectories prior to illness-onset. As Dante Cicchetti pointed out decades before the term “transdiagnostic” was widely used, the pathways to psychopathology emerge in a system involving equifinality and multifinality. Like most other psychological disorders, psychosis is associated with multiple domains of risk factors, both genetic and environmental, and there are many transdiagnostic developmental pathways that can lead to psychotic syndromes. In this article, we discuss our current understanding of heterogeneity in the etiology of psychosis and its implications for approaches to conceptualizing etiology and research. We highlight the need for examining risk factors at multiple levels and to increase the emphasis on transdiagnostic developmental trajectories as a key variable associated with etiologic subtypes. This will be increasingly feasible now that large, longitudinal datasets are becoming available and researchers have access to more sophisticated analytic tools, such as machine learning, which can identify more homogenous subtypes with the ultimate goal of enhancing options for treatment and preventive intervention.
The association between neighborhood-level social fragmentation and distressing psychotic-like experiences in early adolescence: the moderating role of close friends
- Benson S. Ku, Jiyuan Ren, Michael T. Compton, Benjamin G. Druss, Shuyi Guo, Elaine F. Walker
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- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 16 February 2024, pp. 1-9
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Background
Early exposure to neighborhood social fragmentation has been shown to be associated with schizophrenia. The impact of social fragmentation and friendships on distressing psychotic-like experiences (PLE) remains unknown. We investigate the relationships between neighborhood social fragmentation, number of friends, and distressing PLE among early adolescents.
MethodsData were collected from the Adolescent Brain Cognitive Development Study. Generalized linear mixed models tested associations between social fragmentation and distressing PLE, as well as the moderating role of the number of total and close friends.
ResultsParticipants included 11 133 adolescents aged 9 to 10, with 52.3% being males. Greater neighborhood social fragmentation was associated with higher levels of distressing PLE (adjusted β = 0.05; 95% CI: 0.01–0.09). The number of close but not total friends significantly interacted with social fragmentation to predict distressing PLE (adjusted β = −0.02; 95% CI: −0.04 to <−0.01). Among those with fewer close friends, the association between neighborhood social fragmentation and distressing PLE was significant (adjusted β = 0.07; 95% CI: 0.03–0.11). However, among those with more close friends, the association was non-significant (adjusted β = 0.03; 95% CI: −0.01 to 0.07).
ConclusionsGreater neighborhood social fragmentation is associated with higher levels of distressing PLE, particularly among those with fewer close friends. Further research is needed to disentangle aspects of the interaction between neighborhood characteristics and the quality of social interactions that may contribute to psychosis, which would have implications for developing effective interventions at the individual and community levels.
73 Identification of 24-Month Cognitive Trajectories Among Clinical High Risk for Psychosis (CHR-P) Using Latent Class Mixture Modeling
- Ryan M. Guest, Jean Addington, Carrie E. Bearden, Kristin S. Cadenhead, Barbara A. Cornblatt, Daniel H. Mathalon, Diana O. Perkins, Ming T. Tsuang, Scott W. Woods, Tyrone D. Cannon, Matcheri S. Keshavan, William S. Stone, Elaine F. Walker
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 857-858
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Objective:
Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period (known as CHR-P) are at heightened risk for developing psychosis (~35%) and begin to exhibit cognitive deficits. Cognitive impairments in CHR-P (as a singular group) appear to be relatively stable or ameliorate over time. A sizeable proportion has been described to decline on measures related to processing speed or verbal learning. The purpose of this analysis is to use data-driven approaches to identify latent subgroups among CHR-P based on cognitive trajectories. This will yield a clearer understanding of the timing and presentation of both general and domain-specific deficits.
Participants and Methods:Participants included 684 young people at CHR-P (ages 12–35) from the second cohort of the North American Prodromal Longitudinal Study. Performance on the MATRICS Consensus Cognitive Battery (MCCB) and the Wechsler Abbreviated Scale of Intelligence (WASI-I) was assessed at baseline, 12-, and 24-months. Tested MCCB domains include verbal learning, speed of processing, working memory, and reasoning & problem-solving. Sex- and age-based norms were utilized. The Oral Reading subtest on the Wide Range Achievement Test (WRAT4) indexed pre-morbid IQ at baseline. Latent class mixture models were used to identify distinct trajectories of cognitive performance across two years. One- to 5-class solutions were compared to decide the best solution. This determination depended on goodness-of-fit metrics, interpretability of latent trajectories, and proportion of subgroup membership (>5%).
Results:A one-class solution was found for WASI-I Full-Scale IQ, as people at CHR-P predominantly demonstrated an average IQ that increased gradually over time. For individual domains, one-class solutions also best fit the trajectories for speed of processing, verbal learning, and working memory domains. Two distinct subgroups were identified on one of the executive functioning domains, reasoning and problem-solving (NAB Mazes). The sample divided into unimpaired performance with mild improvement over time (Class I, 74%) and persistent performance two standard deviations below average (Class II, 26%). Between these classes, no significant differences were found for biological sex, age, years of education, or likelihood of conversion to psychosis (OR = 1.68, 95% CI 0.86 to 3.14). Individuals assigned to Class II did demonstrate a lower WASI-I IQ at baseline (96.3 vs. 106.3) and a lower premorbid IQ (100.8 vs. 106.2).
Conclusions:Youth at CHR-P demonstrate relatively homogeneous trajectories across time in terms of general cognition and most individual domains. In contrast, two distinct subgroups were observed with higher cognitive skills involving planning and foresight, and they notably exist independent of conversion outcome. Overall, these findings replicate and extend results from a recently published latent class analysis that examined 12-month trajectories among CHR-P using a different cognitive battery (Allott et al., 2022). Findings inform which individuals at CHR-P may be most likely to benefit from cognitive remediation and can inform about the substrates of deficits by establishing meaningful subtypes.
Improving prediction of psychosis in youth at clinical high-risk: pre-baseline symptom duration and cortical thinning as moderators of the NAPLS2 risk calculator
- Michelle A. Worthington, Meghan A. Collins, Jean Addington, Carrie E. Bearden, Kristin S. Cadenhead, Barbara A. Cornblatt, Matcheri Keshavan, Daniel H. Mathalon, Diana O. Perkins, William S. Stone, Elaine F. Walker, Scott W. Woods, Tyrone D. Cannon
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- Journal:
- Psychological Medicine / Volume 54 / Issue 3 / February 2024
- Published online by Cambridge University Press:
- 29 August 2023, pp. 611-619
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Background
Clinical implementation of risk calculator models in the clinical high-risk for psychosis (CHR-P) population has been hindered by heterogeneous risk distributions across study cohorts which could be attributed to pre-ascertainment illness progression. To examine this, we tested whether the duration of attenuated psychotic symptom (APS) worsening prior to baseline moderated performance of the North American prodrome longitudinal study 2 (NAPLS2) risk calculator. We also examined whether rates of cortical thinning, another marker of illness progression, bolstered clinical prediction models.
MethodsParticipants from both the NAPLS2 and NAPLS3 samples were classified as either ‘long’ or ‘short’ symptom duration based on time since APS increase prior to baseline. The NAPLS2 risk calculator model was applied to each of these groups. In a subset of NAPLS3 participants who completed follow-up magnetic resonance imaging scans, change in cortical thickness was combined with the individual risk score to predict conversion to psychosis.
ResultsThe risk calculator models achieved similar performance across the combined NAPLS2/NAPLS3 sample [area under the curve (AUC) = 0.69], the long duration group (AUC = 0.71), and the short duration group (AUC = 0.71). The shorter duration group was younger and had higher baseline APS than the longer duration group. The addition of cortical thinning improved the prediction of conversion significantly for the short duration group (AUC = 0.84), with a moderate improvement in prediction for the longer duration group (AUC = 0.78).
ConclusionsThese results suggest that early illness progression differs among CHR-P patients, is detectable with both clinical and neuroimaging measures, and could play an essential role in the prediction of clinical outcomes.
Characterizing sustained social anxiety in individuals at clinical high risk for psychosis: trajectory, risk factors, and functional outcomes
- Wisteria Deng, Jean Addington, Carrie E. Bearden, Kristin S. Cadenhead, Barbara A. Cornblatt, Daniel H. Mathalon, Diana O. Perkins, Larry J. Seidman, Ming T. Tsuang, Scott W. Woods, Elaine F. Walker, Tyrone D. Cannon
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- Journal:
- Psychological Medicine / Volume 53 / Issue 8 / June 2023
- Published online by Cambridge University Press:
- 11 February 2022, pp. 3644-3651
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Background
While comorbidity of clinical high-risk for psychosis (CHR-P) status and social anxiety is well-established, it remains unclear how social anxiety and positive symptoms covary over time in this population. The present study aimed to determine whether there are more than one covariant trajectory of social anxiety and positive symptoms in the North American Prodrome Longitudinal Study cohort (NAPLS 2) and, if so, to test whether the different trajectory subgroups differ in terms of genetic and environmental risk factors for psychotic disorders and general functional outcome.
MethodsIn total, 764 CHR individuals were evaluated at baseline for social anxiety and psychosis risk symptom severity and followed up every 6 months for 2 years. Application of group-based multi-trajectory modeling discerned three subgroups based on the covariant trajectories of social anxiety and positive symptoms over 2 years.
ResultsOne of the subgroups showed sustained social anxiety over time despite moderate recovery in positive symptoms, while the other two showed recovery of social anxiety below clinically significant thresholds, along with modest to moderate recovery in positive symptom severity. The trajectory group with sustained social anxiety had poorer long-term global functional outcomes than the other trajectory groups. In addition, compared with the other two trajectory groups, membership in the group with sustained social anxiety was predicted by higher levels of polygenic risk for schizophrenia and environmental stress exposures.
ConclusionsTogether, these analyses indicate differential relevance of sustained v. remitting social anxiety symptoms in the CHR-P population, which in turn may carry implications for differential intervention strategies.
Stress perception following childhood adversity: Unique associations with adversity type and sex
- Allison M. LoPilato, Jean Addington, Carrie E. Bearden, Kristin S. Cadenhead, Tyrone D. Cannon, Barbara A. Cornblatt, Daniel H. Mathalon, Thomas H. McGlashan, Diana O. Perkins, Ming T. Tsuang, Scott W. Woods, Elaine F. Walker
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- Development and Psychopathology / Volume 32 / Issue 1 / February 2020
- Published online by Cambridge University Press:
- 08 March 2019, pp. 343-356
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Childhood adversity is associated with poor mental and physical health outcomes across the life span. Alterations in the hypothalamic–pituitary–adrenal axis are considered a key mechanism underlying these associations, although findings have been mixed. These inconsistencies suggest that other aspects of stress processing may underlie variations in this these associations, and that differences in adversity type, sex, and age may be relevant. The current study investigated the relationship between childhood adversity, stress perception, and morning cortisol, and examined whether differences in adversity type (generalized vs. threat and deprivation), sex, and age had distinct effects on these associations. Salivary cortisol samples, daily hassle stress ratings, and retrospective measures of childhood adversity were collected from a large sample of youth at risk for serious mental illness including psychoses (n = 605, mean age = 19.3). Results indicated that childhood adversity was associated with increased stress perception, which subsequently predicted higher morning cortisol levels; however, these associations were specific to threat exposures in females. These findings highlight the role of stress perception in stress vulnerability following childhood adversity and highlight potential sex differences in the impact of threat exposures.
Clinical and functional characteristics of youth at clinical high-risk for psychosis who do not transition to psychosis
- Jean Addington, Jacqueline Stowkowy, Lu Liu, Kristin S. Cadenhead, Tyrone D. Cannon, Barbara A. Cornblatt, Thomas H. McGlashan, Diana O. Perkins, Larry J. Seidman, Ming T. Tsuang, Elaine F. Walker, Carrie E. Bearden, Daniel H. Mathalon, Olga Santesteban-Echarri, Scott W. Woods
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- Psychological Medicine / Volume 49 / Issue 10 / July 2019
- Published online by Cambridge University Press:
- 04 September 2018, pp. 1670-1677
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Background
Much of the interest in youth at clinical high risk (CHR) of psychosis has been in understanding conversion. Recent literature has suggested that less than 25% of those who meet established criteria for being at CHR of psychosis go on to develop a psychotic illness. However, little is known about the outcome of those who do not make the transition to psychosis. The aim of this paper was to examine clinical symptoms and functioning in the second North American Prodrome Longitudinal Study (NAPLS 2) of those individuals whose by the end of 2 years in the study had not developed psychosis.
MethodsIn NAPLS-2 278 CHR participants completed 2-year follow-ups and had not made the transition to psychosis. At 2-years the sample was divided into three groups – those whose symptoms were in remission, those who were still symptomatic and those whose symptoms had become more severe.
ResultsThere was no difference between those who remitted early in the study compared with those who remitted at one or 2 years. At 2-years, those in remission had fewer symptoms and improved functioning compared with the two symptomatic groups. However, all three groups had poorer social functioning and cognition than healthy controls.
ConclusionsA detailed examination of the clinical and functional outcomes of those who did not make the transition to psychosis did not contribute to predicting who may make the transition or who may have an earlier remission of attenuated psychotic symptoms.
Potentially important periods of change in the development of social and role functioning in youth at clinical high risk for psychosis
- Eva Velthorst, Jamie Zinberg, Jean Addington, Kristin S. Cadenhead, Tyrone D. Cannon, Ricardo E. Carrión, Andrea Auther, Barbara A. Cornblatt, Thomas H. McGlashan, Daniel H. Mathalon, Diana O. Perkins, Larry J. Seidman, Ming T. Tsuang, Elaine F. Walker, Scott W. Woods, Abraham Reichenberg, Carrie E. Bearden
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- Development and Psychopathology / Volume 30 / Issue 1 / February 2018
- Published online by Cambridge University Press:
- 19 April 2017, pp. 39-47
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The developmental course of daily functioning prior to first psychosis-onset remains poorly understood. This study explored age-related periods of change in social and role functioning. The longitudinal study included youth (aged 12–23, mean follow-up years = 1.19) at clinical high risk (CHR) for psychosis (converters [CHR-C], n = 83; nonconverters [CHR-NC], n = 275) and a healthy control group (n = 164). Mixed-model analyses were performed to determine age-related differences in social and role functioning. We limited our analyses to functioning before psychosis conversion; thus, data of CHR-C participants gathered after psychosis onset were excluded. In controls, social and role functioning improved over time. From at least age 12, functioning in CHR was poorer than in controls, and this lag persisted over time. Between ages 15 and 18, social functioning in CHR-C stagnated and diverged from that of CHR-NC, who continued to improve (p = .001). Subsequently, CHR-C lagged behind in improvement between ages 21 and 23, further distinguishing them from CHR-NC (p < .001). A similar period of stagnation was apparent for role functioning, but to a lesser extent (p = .007). The results remained consistent when we accounted for the time to conversion. Our findings suggest that CHR-C start lagging behind CHR-NC in social and role functioning in adolescence, followed by a period of further stagnation in adulthood.
Core Schemas in Youth at Clinical High Risk for Psychosis
- Jacqueline Stowkowy, Lu Liu, Kristin S. Cadenhead, Tyrone D. Cannon, Barbara A. Cornblatt, Thomas H. McGlashan, Diana O. Perkins, Larry J. Seidman, Ming T. Tsuang, Elaine F. Walker, Scott W. Woods, Carrie E. Bearden, Daniel H. Mathalon, Robert Heinssen, Jean Addington
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- Journal:
- Behavioural and Cognitive Psychotherapy / Volume 44 / Issue 2 / March 2016
- Published online by Cambridge University Press:
- 21 April 2015, pp. 203-213
- Print publication:
- March 2016
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Background: Schema Theory proposes that the development of maladaptive schemas are based on a combination of memories, emotions and cognitions regarding oneself and one's relationship to others. A cognitive model of psychosis suggests that schemas are crucial to the development and persistence of psychosis. Little is known about the impact that schemas may have on those considered to be at clinical high risk (CHR) of developing psychosis. Aims: To investigate schemas over time in a large sample of CHR individuals and healthy controls. Method: Sample included 765 CHR participants and 280 healthy controls. Schemas were assessed at baseline, 6 and 12 months using the Brief Core Schema Scale (BCSS). Baseline schemas were compared to 2-year clinical outcome. Results: CHR participants evidenced stable and more maladaptive schemas over time compared to controls. Schemas at initial contact did not vary amongst the different clinical outcome groups at 2 years although all CHR outcome groups evidenced significantly worse schemas than healthy controls. Although there were no differences on baseline schemas between those who later transitioned to psychosis compared to those who did not, those who transitioned to psychosis had more maladaptive negative self-schemas at the time of transition. Associations between negative schemas were positively correlated with earlier abuse and bullying. Conclusions: These findings demonstrate a need for interventions that aim to improve maladaptive schemas among the CHR population. Therapies targeting self-esteem, as well as schema therapy may be important work for future studies.
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- By John M. Alexander, Jeremy Bendik-Keymer, Hilde Bojer, Harry Brighouse, Flavio Comim, Marc Fleurbaey, Des Gasper, Muriel Gilardone, Ian Gough, Isabelle Guérin, Breena Holland, Ulrike Knobloch, Santosh Mehrotra, Martha C. Nussbaum, Jane Palier, Henry S. Richardson, Patricia Welch Saleeby, Elaine Unterhalter, Melanie Walker, Jonathan Warner
- Edited by Flavio Comim, Universidade Federal do Rio Grande do Sul, Brazil, Martha C. Nussbaum, University of Chicago
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- Capabilities, Gender, Equality
- Published online:
- 05 May 2014
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- 17 April 2014, pp ix-x
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Premorbid functional development and conversion to psychosis in clinical high-risk youths
- Sarah I. Tarbox, Jean Addington, Kristin S. Cadenhead, Tyrone D. Cannon, Barbara A. Cornblatt, Diana O. Perkins, Larry J. Seidman, Ming T. Tsuang, Elaine F. Walker, Robert Heinssen, Thomas H. McGlashan, Scott W. Woods
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- Development and Psychopathology / Volume 25 / Issue 4pt1 / November 2013
- Published online by Cambridge University Press:
- 08 November 2013, pp. 1171-1186
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Deterioration in premorbid functioning is a common feature of schizophrenia, but sensitivity to psychosis conversion among clinical high-risk samples has not been examined. This study evaluates premorbid functioning as a predictor of psychosis conversion among a clinical high-risk sample, controlling for effects of prior developmental periods. Participants were 270 clinical high-risk individuals in the North American Prodrome Longitudinal Study—I, 78 of whom converted to psychosis over the next 2.5 years. Social, academic, and total maladjustment in childhood, early adolescence, and late adolescence were rated using the Cannon–Spoor Premorbid Adjustment Scale. Early adolescent social dysfunction significantly predicted conversion to psychosis (hazard ratio = 1.30, p = .014), independently of childhood social maladjustment and independently of severity of most baseline positive and negative prodromal symptoms. Baseline prodromal symptoms of disorganized communication, social anhedonia, suspiciousness, and diminished ideational richness mediated this association. Early adolescent social maladjustment and baseline suspiciousness together demonstrated moderate positive predictive power (59%) and high specificity (92.1%) in predicting conversion. Deterioration of academic and total functioning, although observed, did not predict conversion to psychosis. Results indicate early adolescent social dysfunction to be an important early predictor of conversion. As such, it may be a good candidate for inclusion in prediction algorithms and could represent an advantageous target for early intervention.
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- By Rose Teteki Abbey, K. C. Abraham, David Tuesday Adamo, LeRoy H. Aden, Efrain Agosto, Victor Aguilan, Gillian T. W. Ahlgren, Charanjit Kaur AjitSingh, Dorothy B E A Akoto, Giuseppe Alberigo, Daniel E. Albrecht, Ruth Albrecht, Daniel O. Aleshire, Urs Altermatt, Anand Amaladass, Michael Amaladoss, James N. Amanze, Lesley G. Anderson, Thomas C. Anderson, Victor Anderson, Hope S. Antone, María Pilar Aquino, Paula Arai, Victorio Araya Guillén, S. Wesley Ariarajah, Ellen T. Armour, Brett Gregory Armstrong, Atsuhiro Asano, Naim Stifan Ateek, Mahmoud Ayoub, John Alembillah Azumah, Mercedes L. García Bachmann, Irena Backus, J. Wayne Baker, Mieke Bal, Lewis V. Baldwin, William Barbieri, António Barbosa da Silva, David Basinger, Bolaji Olukemi Bateye, Oswald Bayer, Daniel H. Bays, Rosalie Beck, Nancy Elizabeth Bedford, Guy-Thomas Bedouelle, Chorbishop Seely Beggiani, Wolfgang Behringer, Christopher M. Bellitto, Byard Bennett, Harold V. Bennett, Teresa Berger, Miguel A. Bernad, Henley Bernard, Alan E. Bernstein, Jon L. Berquist, Johannes Beutler, Ana María Bidegain, Matthew P. Binkewicz, Jennifer Bird, Joseph Blenkinsopp, Dmytro Bondarenko, Paulo Bonfatti, Riet en Pim Bons-Storm, Jessica A. Boon, Marcus J. Borg, Mark Bosco, Peter C. Bouteneff, François Bovon, William D. Bowman, Paul S. Boyer, David Brakke, Richard E. Brantley, Marcus Braybrooke, Ian Breward, Ênio José da Costa Brito, Jewel Spears Brooker, Johannes Brosseder, Nicholas Canfield Read Brown, Robert F. Brown, Pamela K. Brubaker, Walter Brueggemann, Bishop Colin O. Buchanan, Stanley M. Burgess, Amy Nelson Burnett, J. Patout Burns, David B. Burrell, David Buttrick, James P. Byrd, Lavinia Byrne, Gerado Caetano, Marcos Caldas, Alkiviadis Calivas, William J. Callahan, Salvatore Calomino, Euan K. Cameron, William S. Campbell, Marcelo Ayres Camurça, Daniel F. Caner, Paul E. Capetz, Carlos F. Cardoza-Orlandi, Patrick W. Carey, Barbara Carvill, Hal Cauthron, Subhadra Mitra Channa, Mark D. Chapman, James H. Charlesworth, Kenneth R. Chase, Chen Zemin, Luciano Chianeque, Philip Chia Phin Yin, Francisca H. Chimhanda, Daniel Chiquete, John T. Chirban, Soobin Choi, Robert Choquette, Mita Choudhury, Gerald Christianson, John Chryssavgis, Sejong Chun, Esther Chung-Kim, Charles M. A. Clark, Elizabeth A. Clark, Sathianathan Clarke, Fred Cloud, John B. Cobb, W. Owen Cole, John A Coleman, John J. Collins, Sylvia Collins-Mayo, Paul K. Conkin, Beth A. Conklin, Sean Connolly, Demetrios J. Constantelos, Michael A. Conway, Paula M. Cooey, Austin Cooper, Michael L. Cooper-White, Pamela Cooper-White, L. William Countryman, Sérgio Coutinho, Pamela Couture, Shannon Craigo-Snell, James L. Crenshaw, David Crowner, Humberto Horacio Cucchetti, Lawrence S. Cunningham, Elizabeth Mason Currier, Emmanuel Cutrone, Mary L. Daniel, David D. Daniels, Robert Darden, Rolf Darge, Isaiah Dau, Jeffry C. Davis, Jane Dawson, Valentin Dedji, John W. de Gruchy, Paul DeHart, Wendy J. Deichmann Edwards, Miguel A. De La Torre, George E. Demacopoulos, Thomas de Mayo, Leah DeVun, Beatriz de Vasconcellos Dias, Dennis C. Dickerson, John M. Dillon, Luis Miguel Donatello, Igor Dorfmann-Lazarev, Susanna Drake, Jonathan A. Draper, N. Dreher Martin, Otto Dreydoppel, Angelyn Dries, A. J. Droge, Francis X. D'Sa, Marilyn Dunn, Nicole Wilkinson Duran, Rifaat Ebied, Mark J. Edwards, William H. Edwards, Leonard H. Ehrlich, Nancy L. Eiesland, Martin Elbel, J. Harold Ellens, Stephen Ellingson, Marvin M. Ellison, Robert Ellsberg, Jean Bethke Elshtain, Eldon Jay Epp, Peter C. Erb, Tassilo Erhardt, Maria Erling, Noel Leo Erskine, Gillian R. Evans, Virginia Fabella, Michael A. Fahey, Edward Farley, Margaret A. Farley, Wendy Farley, Robert Fastiggi, Seena Fazel, Duncan S. Ferguson, Helwar Figueroa, Paul Corby Finney, Kyriaki Karidoyanes FitzGerald, Thomas E. FitzGerald, John R. Fitzmier, Marie Therese Flanagan, Sabina Flanagan, Claude Flipo, Ronald B. Flowers, Carole Fontaine, David Ford, Mary Ford, Stephanie A. Ford, Jim Forest, William Franke, Robert M. Franklin, Ruth Franzén, Edward H. Friedman, Samuel Frouisou, Lorelei F. Fuchs, Jojo M. Fung, Inger Furseth, Richard R. Gaillardetz, Brandon Gallaher, China Galland, Mark Galli, Ismael García, Tharscisse Gatwa, Jean-Marie Gaudeul, Luis María Gavilanes del Castillo, Pavel L. Gavrilyuk, Volney P. Gay, Metropolitan Athanasios Geevargis, Kondothra M. George, Mary Gerhart, Simon Gikandi, Maurice Gilbert, Michael J. Gillgannon, Verónica Giménez Beliveau, Terryl Givens, Beth Glazier-McDonald, Philip Gleason, Menghun Goh, Brian Golding, Bishop Hilario M. Gomez, Michelle A. Gonzalez, Donald K. Gorrell, Roy Gottfried, Tamara Grdzelidze, Joel B. Green, Niels Henrik Gregersen, Cristina Grenholm, Herbert Griffiths, Eric W. Gritsch, Erich S. Gruen, Christoffer H. Grundmann, Paul H. Gundani, Jon P. Gunnemann, Petre Guran, Vidar L. Haanes, Jeremiah M. Hackett, Getatchew Haile, Douglas John Hall, Nicholas Hammond, Daphne Hampson, Jehu J. Hanciles, Barry Hankins, Jennifer Haraguchi, Stanley S. Harakas, Anthony John Harding, Conrad L. Harkins, J. William Harmless, Marjory Harper, Amir Harrak, Joel F. Harrington, Mark W. Harris, Susan Ashbrook Harvey, Van A. Harvey, R. Chris Hassel, Jione Havea, Daniel Hawk, Diana L. Hayes, Leslie Hayes, Priscilla Hayner, S. Mark Heim, Simo Heininen, Richard P. Heitzenrater, Eila Helander, David Hempton, Scott H. Hendrix, Jan-Olav Henriksen, Gina Hens-Piazza, Carter Heyward, Nicholas J. Higham, David Hilliard, Norman A. Hjelm, Peter C. Hodgson, Arthur Holder, M. Jan Holton, Dwight N. Hopkins, Ronnie Po-chia Hsia, Po-Ho Huang, James Hudnut-Beumler, Jennifer S. Hughes, Leonard M. Hummel, Mary E. Hunt, Laennec Hurbon, Mark Hutchinson, Susan E. Hylen, Mary Beth Ingham, H. Larry Ingle, Dale T. Irvin, Jon Isaak, Paul John Isaak, Ada María Isasi-Díaz, Hans Raun Iversen, Margaret C. Jacob, Arthur James, Maria Jansdotter-Samuelsson, David Jasper, Werner G. Jeanrond, Renée Jeffery, David Lyle Jeffrey, Theodore W. Jennings, David H. Jensen, Robin Margaret Jensen, David Jobling, Dale A. Johnson, Elizabeth A. Johnson, Maxwell E. Johnson, Sarah Johnson, Mark D. Johnston, F. Stanley Jones, James William Jones, John R. Jones, Alissa Jones Nelson, Inge Jonsson, Jan Joosten, Elizabeth Judd, Mulambya Peggy Kabonde, Robert Kaggwa, Sylvester Kahakwa, Isaac Kalimi, Ogbu U. Kalu, Eunice Kamaara, Wayne C. Kannaday, Musimbi Kanyoro, Veli-Matti Kärkkäinen, Frank Kaufmann, Léon Nguapitshi Kayongo, Richard Kearney, Alice A. Keefe, Ralph Keen, Catherine Keller, Anthony J. Kelly, Karen Kennelly, Kathi Lynn Kern, Fergus Kerr, Edward Kessler, George Kilcourse, Heup Young Kim, Kim Sung-Hae, Kim Yong-Bock, Kim Yung Suk, Richard King, Thomas M. King, Robert M. Kingdon, Ross Kinsler, Hans G. Kippenberg, Cheryl A. Kirk-Duggan, Clifton Kirkpatrick, Leonid Kishkovsky, Nadieszda Kizenko, Jeffrey Klaiber, Hans-Josef Klauck, Sidney Knight, Samuel Kobia, Robert Kolb, Karla Ann Koll, Heikki Kotila, Donald Kraybill, Philip D. W. Krey, Yves Krumenacker, Jeffrey Kah-Jin Kuan, Simanga R. Kumalo, Peter Kuzmic, Simon Shui-Man Kwan, Kwok Pui-lan, André LaCocque, Stephen E. Lahey, John Tsz Pang Lai, Emiel Lamberts, Armando Lampe, Craig Lampe, Beverly J. Lanzetta, Eve LaPlante, Lizette Larson-Miller, Ariel Bybee Laughton, Leonard Lawlor, Bentley Layton, Robin A. Leaver, Karen Lebacqz, Archie Chi Chung Lee, Marilyn J. Legge, Hervé LeGrand, D. L. LeMahieu, Raymond Lemieux, Bill J. Leonard, Ellen M. Leonard, Outi Leppä, Jean Lesaulnier, Nantawan Boonprasat Lewis, Henrietta Leyser, Alexei Lidov, Bernard Lightman, Paul Chang-Ha Lim, Carter Lindberg, Mark R. Lindsay, James R. Linville, James C. Livingston, Ann Loades, David Loades, Jean-Claude Loba-Mkole, Lo Lung Kwong, Wati Longchar, Eleazar López, David W. Lotz, Andrew Louth, Robin W. Lovin, William Luis, Frank D. Macchia, Diarmaid N. J. MacCulloch, Kirk R. MacGregor, Marjory A. MacLean, Donald MacLeod, Tomas S. Maddela, Inge Mager, Laurenti Magesa, David G. Maillu, Fortunato Mallimaci, Philip Mamalakis, Kä Mana, Ukachukwu Chris Manus, Herbert Robinson Marbury, Reuel Norman Marigza, Jacqueline Mariña, Antti Marjanen, Luiz C. L. Marques, Madipoane Masenya (ngwan'a Mphahlele), Caleb J. D. Maskell, Steve Mason, Thomas Massaro, Fernando Matamoros Ponce, András Máté-Tóth, Odair Pedroso Mateus, Dinis Matsolo, Fumitaka Matsuoka, John D'Arcy May, Yelena Mazour-Matusevich, Theodore Mbazumutima, John S. McClure, Christian McConnell, Lee Martin McDonald, Gary B. McGee, Thomas McGowan, Alister E. McGrath, Richard J. McGregor, John A. McGuckin, Maud Burnett McInerney, Elsie Anne McKee, Mary B. McKinley, James F. McMillan, Ernan McMullin, Kathleen E. McVey, M. 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Yee, Viktor Yelensky, Yeo Khiok-Khng, Gustav K. K. Yeung, Angela Yiu, Amos Yong, Yong Ting Jin, You Bin, Youhanna Nessim Youssef, Eliana Yunes, Robert Michael Zaller, Valarie H. Ziegler, Barbara Brown Zikmund, Joyce Ann Zimmerman, Aurora Zlotnik, Zhuo Xinping
- Edited by Daniel Patte, Vanderbilt University, Tennessee
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- Book:
- The Cambridge Dictionary of Christianity
- Published online:
- 05 August 2012
- Print publication:
- 20 September 2010, pp xi-xliv
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Mupirocin-Resistant, Methicillin-Resistant Staphylococcus aureus: Does Mupirocin Remain Effective?
- Elaine S. Walker, Jose E. Vasquez, Roy Dula, Hollie Bullock, Felix A. Sarubbi
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 24 / Issue 5 / May 2003
- Published online by Cambridge University Press:
- 02 January 2015, pp. 342-346
- Print publication:
- May 2003
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Objective:
To determine the efficacy of mupirocin ointment in reducing nasal colonization with mupirocin-susceptible, methicillin-resistant Staphylococcus aureus (MS MRSA) as well as mupirocin-resistant MRSA (MR MRSA).
Design:Prospective evaluation in which patients colonized with MRSA were treated twice daily with 2% topical mupirocin ointment for 5 days.
Setting:James H. Quillen Veterans' Affairs Medical Center.
Patients:Forty hospitalized patients with two anterior nares cultures positive for MRSA within a 7-day period.
Methods:Treated patients had post-treatment cultures at day 3 and weeks 1,2, and 4. Isolates underwent mupirocin-susceptibility testing and DNA typing. MRSA clearance and type turnover were assessed for isolates that were mupirocin-susceptible, low-level (LL) MR MRSA and high-level (HL) MR MRSA.
Results:Post-treatment nares cultures on day 3 were negative for 78.5%, 80%, and 27.7% of patients with MS MRSA, LL-MR MRSA, and HL-MR MRSA, respectively. Sustained culture negativity at 1 to 4 weeks was more common in the MS MRSA group (91%) than in the LL-MR MRSA group (25%) or the HL-MR MRSA group (25%). Positive post-treatment cultures usually showed the same DNA pattern relative to baseline. Plasmid curing of 18 HL-MR MRSA resulted in 15 MS MRSA and 3 LL-MR MRSA.
Conclusions:Mupirocin was effective in eradicating MS MRSA, but strains of MR MRSA often persisted after treatment. This appeared to reflect treatment failure rather than exogenous recolonization. MR MRSA is now more prevalent and it is appropriate to sample MRSA populations for mupirocin susceptibility prior to incorporating mupirocin into infection control programs.
The Epidemiology of Mupirocin Resistance Among Methicillin-Resistant Staphylococcus aureus at a Veterans' Affairs Hospital
- Jose E. Vasquez, Elaine S. Walker, Bettylene W. Franzus, Barbara K. Overbay, David R. Reagan, Felix A. Sarubbi
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 21 / Issue 7 / July 2000
- Published online by Cambridge University Press:
- 02 January 2015, pp. 459-464
- Print publication:
- July 2000
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Objective:
To describe the clinical and molecular epidemiology of mupirocin-resistant (MR) and mupirocin-susceptible (MS) methicillin-resistant Staphylococcus aureus (MRSA) at a Veterans' Affairs hospital and to assess risk factors associated with the acquisition of MR MRSA.
Design:All clinical MRSA isolates for the period October 1990 through March 1995 underwent susceptibility testing to mupirocin. Mupirocin resistance trends were measured, and MS MRSA and MR MRSA isolates underwent typing by pulsed-field gel electrophoresis (PFGE). A retrospective case-control study was conducted to evaluate risk factors for having MR versus MS MRSA.
Setting:The James H. Quillen Veterans' Affairs Medical Center in Mountain Home, Tennessee, included a 324-bed acute-care hospital, a 120-bed nursing home, and a 525-bed domiciliary. Colonizations and infections with MRSA were endemic, and mupirocin ointment was commonly used.
Patients:Inpatients and outpatients at the facility.
Results:MS MRSA was recovered from 506 patients and MR MRSA from 126. Among MR MRSA isolates, 58% showed low-level mupirocin resistance (minimum inhibitory concentration [MIC] ≥4 to 256 μg/mL), and 42% showed high-level mupirocin resistance (MIC ≥512 μg/mL). A significant increase (P=.002) in the number of high-level MR isolates occurred during the 1993 to 1995 period. A case-control study showed that presence of a decubitus ulcer correlated with high-level resistant isolates (P<.05). The distribution of PFGE patterns did not differ for MR and MS MRSA.
Conclusions:Use of mupirocin ointment in a program aimed at managing endemic MRSA infection or colonization resulted in a significant increase in the recovery of high-level MR MRSA isolates. These isolates appeared to emerge from our existing MRSA pool. A case-control study provided few clues concerning patients likely to harbor MR MRSA We confirmed the position that the extended use of mupirocin ointment should be avoided in settings where MRSA is endemic.