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Description of the Public Safety Medical Response and Patient Encounters Within and During the Indianapolis (USA) Spring 2020 Civil Unrest
- Thomas P. Arkins, Mark Liao, Daniel O’Donnell, Nancy Glober, Gregory Faris, Elizabeth Weinstein, Michael W. Supples, Julia Vaizer, Benton R. Hunter, Thomas Lardaro
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- Journal:
- Prehospital and Disaster Medicine / Volume 39 / Issue 1 / February 2024
- Published online by Cambridge University Press:
- 25 January 2024, pp. 73-77
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- February 2024
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Objective:
This study describes the local Emergency Medical Services (EMS) response and patient encounters corresponding to the civil unrest occurring over a four-day period in Spring 2020 in Indianapolis, Indiana (USA).
Methods:This study describes the non-conventional EMS response to civil unrest. The study included patients encountered by EMS in the area of the civil unrest occurring in Indianapolis, Indiana from May 29 through June 1, 2020. The area of civil unrest defined by Indianapolis Metropolitan Police Department covered 15 blocks by 12 blocks (roughly 4.0 square miles) and included central Indianapolis. The study analyzed records and collected demographics, scene times, interventions, dispositions, EMS clinician narratives, transport destinations, and hospital course with outcomes from receiving hospitals for patients extracted from the area of civil unrest by EMS.
Results:Twenty-nine patients were included with ages ranging from two to sixty-eight years. In total, EMS transported 72.4% (21 of 29) of the patients, with the remainder declining transport. Ballistic injuries from gun violence accounted for 10.3% (3 of 29) of injuries. Two additional fatalities from penetrating trauma occurred among patients without EMS contact within and during the civil unrest. Conditions not involving trauma occurred in 37.9% (11 of 29). Among transported patients, 33.3% (7 of 21) were admitted to the hospital and there was one fatality.
Conclusions:While most EMS transports did not result in hospitalization, it is important to note that the majority of EMS calls did result in a transport. There was a substantial amount of non-traumatic patient encounters. Trauma in many of the encounters was relatively severe, and the findings imply the need for rapid extraction methods from dangerous areas to facilitate timely in-hospital stabilization.
Guidottiite, the Mn-Analogue of Cronstedtite: A New Serpentine-Group Mineral from South Africa
- Michael W. Wahle, Thomas J. Bujnowski, Stephen Guggenheim, Toshihiro Kogure
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- Journal:
- Clays and Clay Minerals / Volume 58 / Issue 3 / June 2010
- Published online by Cambridge University Press:
- 01 January 2024, pp. 364-376
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The objective of this paper is to describe the new serpentine group mineral, guidottiite, which is analogous to cronstedtite. Guidottiite has an ideal chemical composition of (Mn2Fe3+)(SiFe3+)O5(OH)4. The sample is from the N’chwaning 2 mine, Kalahari manganese field, Republic of South Africa, and apparently forms from hydrothermal solutions. Grains are optically near opaque [average index of refraction 1.765, with variable extinction on the (001)], vitreous, and black, with perfect {001} platy cleavage. A non-separable fibrous substructure exists perpendicular to cleavage that results in a silky luster under optical examination. The average chemical analysis determined from electron microprobe based on four grains with ten analyses each resulted in a structural formula of (Mn1.86Fe0.613+Mg0.54)Σ=3.01(Si1.36Fe0.643+)Σ=2.00O5(OH)4, with calculated density of 3.236 g/cm3. Analysis from another area of the sample showed a slightly different chemical composition and resulted in a formula of (Mn1.70Fe0.963+Mg0.24Σ=2.89(Si1.26Fe0.743+)Σ=2.00O5(OH)4, with calculated density of 3.291 g/cm3. The measured density on a bulk sample (with impurities) was 3.33 g/cm3. Thermal analysis suggested a dehydroxylation temperature of 535°C, a decomposition/recrystallization temperature of 722°C, and weight loss (= H2O loss) of 9.4%. The derived Mohs hardness from nano-indentation is H = 4.25.
The sample is mostly the 2H1 polytype with minor amounts of the 2H2 polytype. Using a predominantly 2H2 crystal, which has better crystallinity, the strongest observed X-ray peaks are: 7.21 Å (Io/Io = 100%), 3.543 (50), 2.568 (39), 1.982 (26), and 2.381 (25). All Gandolfi simulations, even with three crystal remountings, showed preferred orientation effects. Transmission electron microscope (TEM) analysis showed stacking disorder within Group D serpentine polytypes. Thus, a regular alternation of the occupancy of octahedral sets within each layer along the stacking exists, but disorder of the layer displacements of 0 and ±b/3 (b defined here as the orthohexagonal cell) exists. Ordered 2H1 (no layer displacement) and 2H2 (alternating + and —b/3 displacement) domains were also frequently observed. X-ray diffraction analysis showed that even apparent single crystals contain impurity phases, presumably Mn-rich and Ca phases that were detected in the microprobe study. The single-crystal structure refinement used a well (stacking) ordered apparent 2H2 crystal with little to no streaking in the diffraction pattern. Results showed that the crystal has a random interstratification of 2H2 and 2H1. The 2H2 polytype is hexagonal, space group P63, with a = 5.5472(3), c = 14.293(2) Å, and Z = 2, and was refined to R1 = 0.072 and wR = 0.108 from 656 unique reflections. Because the two polytypes in the composite have only small differences in the lower 1:1 layer, a large displacement parameter for the basal oxygen atom results, which was constrained to B = 1.5 Å2 (Ueq = 0.0190) in the refinement. Half of the tetrahedral sites in the 2H1 upper layer superpose over half of the tetrahedral sites in the 2H2 upper layer (T1 sites only) per unit cell. This superposition produces an apparent excess of electron densities of the T1 site relative to the T2 site (T1 = 21.9 electrons, T2 = 15.8). Comparison with the microprobe data indicates that observed tetrahedral bond lengths are generally not affected by this intergrowth. Tetrahedral bond lengths indicated that the tetrahedral sites contain T1 = Si0.678 Fe0.3223+ and T2 = Si0.631Fe0.3693+. This excess of electron densities and other refinement problems associated with the guidottiite single-crystal refinement closely parallel all single-crystal cronstedtite-2H2 refinements to date, suggesting that these refinements also involve random interstratifications of 2H2 and 2H1 polytypes.
4 Evaluating Plasma GFAP for the Detection of Alzheimer’s Disease Dementia
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Ann C. McKee, Thor D. Stein, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Michael L. Alosco
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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. 408-409
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Objective:
Blood-based biomarkers represent a scalable and accessible approach for the detection and monitoring of Alzheimer’s disease (AD). Plasma phosphorylated tau (p-tau) and neurofilament light (NfL) are validated biomarkers for the detection of tau and neurodegenerative brain changes in AD, respectively. There is now emphasis to expand beyond these markers to detect and provide insight into the pathophysiological processes of AD. To this end, a reactive astrocytic marker, namely plasma glial fibrillary acidic protein (GFAP), has been of interest. Yet, little is known about the relationship between plasma GFAP and AD. Here, we examined the association between plasma GFAP, diagnostic status, and neuropsychological test performance. Diagnostic accuracy of plasma GFAP was compared with plasma measures of p-tau181 and NfL.
Participants and Methods:This sample included 567 participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry, including individuals with normal cognition (n=234), mild cognitive impairment (MCI) (n=180), and AD dementia (n=153). The sample included all participants who had a blood draw. Participants completed a comprehensive neuropsychological battery (sample sizes across tests varied due to missingness). Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa platform. Binary logistic regression analyses tested the association between GFAP levels and diagnostic status (i.e., cognitively impaired due to AD versus unimpaired), controlling for age, sex, race, education, and APOE e4 status. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate diagnostic groups compared with plasma p-tau181 and NfL. Linear regression models tested the association between plasma GFAP and neuropsychological test performance, accounting for the above covariates.
Results:The mean (SD) age of the sample was 74.34 (7.54), 319 (56.3%) were female, 75 (13.2%) were Black, and 223 (39.3%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having cognitive impairment (GFAP z-score transformed: OR=2.233, 95% CI [1.609, 3.099], p<0.001; non-z-transformed: OR=1.004, 95% CI [1.002, 1.006], p<0.001). ROC analyses, comprising of GFAP and the above covariates, showed plasma GFAP discriminated the cognitively impaired from unimpaired (AUC=0.75) and was similar, but slightly superior, to plasma p-tau181 (AUC=0.74) and plasma NfL (AUC=0.74). A joint panel of the plasma markers had greatest discrimination accuracy (AUC=0.76). Linear regression analyses showed that higher GFAP levels were associated with worse performance on neuropsychological tests assessing global cognition, attention, executive functioning, episodic memory, and language abilities (ps<0.001) as well as higher CDR Sum of Boxes (p<0.001).
Conclusions:Higher plasma GFAP levels differentiated participants with cognitive impairment from those with normal cognition and were associated with worse performance on all neuropsychological tests assessed. GFAP had similar accuracy in detecting those with cognitive impairment compared with p-tau181 and NfL, however, a panel of all three biomarkers was optimal. These results support the utility of plasma GFAP in AD detection and suggest the pathological processes it represents might play an integral role in the pathogenesis of AD.
15 Exploratory Factor Analysis of Cognitive and Positive Valence Measures for the RDoC
- Emily T Sturm, John R Duffy, Anastasia G Sares, Andrea Mendez-Colmenares, Lauren Sarabia, Eve Delao, Max Henneke, Raana Manavi, Donald C Rojas, Jason R Tregellas, Jared W Young, Michael L Thomas
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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. 698-699
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Objective:
As part of the Research Domain Criteria (RDoC) initiative, the NIMH seeks to improve experimental measures of cognitive and positive valence systems for use in intervention research. However, many RDoC tasks have not been psychometrically evaluated as a battery of measures. Our aim was to examine the factor structure of 7 such tasks chosen for their relevance to schizophrenia and other forms of serious mental illness. These include the n-back, Sternberg, and self-ordered pointing tasks (measures of the RDoC cognitive systems working memory construct); flanker and continuous performance tasks (measures of the RDoC cognitive systems cognitive control construct); and probabilistic learning and effort expenditure for reward tasks (measures of reward learning and reward valuation constructs).
Participants and Methods:The sample comprised 286 cognitively healthy participants who completed novel versions of all 7 tasks via an online recruitment platform, Prolific, in the summer of 2022. The mean age of participants was 38.6 years (SD = 14.5, range 18-74), 52% identified as female, and stratified recruitment ensured an ethnoracially diverse sample. Excluding time for instructions and practice, each task lasted approximately 6 minutes. Task order was randomized. We estimated optimal scores from each task including signal detection d-prime measures for the n-back, Sternberg, and continuous performance task, mean accuracy for the flanker task, win-stay to win-shift ratio for the probabilistic learning task, and trials completed for the effort expenditure for reward task. We used parallel analysis and a scree plot to determine the number of latent factors measured by the 7 task scores. Exploratory factor analysis with oblimin (oblique) rotation was used to examine the factor loading matrix.
Results:The scree plot and parallel analyses of the 7 task scores suggested three primary factors. The flanker and continuous performance task both strongly loaded onto the first factor, suggesting that these measures are strong indicators of cognitive control. The n-back, Sternberg, and self-ordered pointing tasks strongly loaded onto the second factor, suggesting that these measures are strong indicators of working memory. The probabilistic learning task solely loaded onto the third factor, suggesting that it is an independent indicator of reinforcement learning. Finally, the effort expenditure for reward task modestly loaded onto the second but not the first and third factors, suggesting that effort is most strongly related to working memory.
Conclusions:Our aim was to examine the factor structure of 7 RDoC tasks. Results support the RDoC suggestion of independent cognitive control, working memory, and reinforcement learning. However, effort is a factorially complex construct that is not uniquely or even most strongly related to positive valance. Thus, there is reason to believe that the use of at least 6 of these tasks are appropriate measures of constructs such as working memory, reinforcement learning and cognitive control.
19 Consistency of self-reported sport-related concussion history
- Spencer W Liebel, Katherine M Breedlove, Steven P Broglio, James T Eckner, Michael A McCrea, Benjamin L Brett, Thomas W McAllister
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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. 895-896
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Objective:
An accurate accounting of prior sport-related concussion (SRC) is critical to optimizing the clinical care of athletes with SRC. Yet, obtaining such a history via medical records or lifetime monitoring is often not feasible necessitating the use of self-report histories. The primary objective of the current project is to determine the degree to which athletes consistently report their SRC history on serial assessments throughout their collegiate athletic career.
Participants and Methods:Data were obtained from the NCAA-DoD CARE Consortium and included 1621 athletes (914 male) from a single Division 1 university who participated in athletics during the 2014-2017 academic years. From this initial cohort, 752 athletes completed a second-year assessment and 332 completed a third-year assessment. Yearly assessments included a brief self-report survey that queried SRC history of the previous year. Consistency of self-reported SRC history was defined as reporting the same number of SRC on subsequent yearly evaluation as had been reported the previous year.
For every year of participation, the number of SRC reported on the baseline exam (Reported) and the number of SRC recorded by athletes and medical staff during the ensuing season (Recorded) were tabulated. In a subsequent year, the expected number of SRC (Expected) was computed as the sum of Reported and Recorded. For participation years in which Expected could be computed, the reporting deviation (RepDev) gives the difference between the number of SRCs which were expected to be reported at a baseline exam based on previous participation year data and the number of SRCs which was actually reported by the athlete or medical record during the baseline exam. The reporting deviation was computed only for those SRC that occurred while the participant was enrolled in the current study (RepDevSO). Oneway intraclass correlations (ICC) were computed between the expected and reported numbers of SRC.
Results:341 athletes had a history of at least one SRC and 206 of those (60.4%) had a RepDev of 0. The overall ICC for RepDev was 0.761 (95% CI 0.73-0.79). The presence of depression (ICC 0.87, 95% CI 0.79-0.92) and loss of consciousness (ICC 0.80, 95% CI 0.720.86) were associated with higher ICCs compared to athletes without these variables. Female athletes demonstrated higher self-report consistency (ICC 0.82, 95% CI 0.79-0.85) compared to male athletes (ICC 0.72, 95% CI 0.68-0.76). Differences in the classification of RepDev according to sex and sport were found to be significant (x2=77.6, df=56, p=0.03). The sports with the highest consistency were Women’s Tennis, Men’s Diving, and Men’s Tennis with 100% consistency between academic years. Sports with the lowest consistency were Women’s Gymnastics (69%), Men’s Lacrosse (70%), and Football (72%). 96 athletes had at least one study-only SRC in the previous year and 69 of those (71.9%) had a RepDevSO of 0 (ICC 0.673, 95% CI 0.64-0.71).
Conclusions:Approximately 40% of athletes do not consistently report their SRC history, potentially further complicating the clinical management of SRC. These findings encourage clinicians to be aware of factors which could influence the reliability of self-reported SRC history.
5 Antemortem Plasma GFAP Predicts Alzheimer’s Disease Neuropathological Changes
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Bertran R. Huber, Ann C. McKee, Thor D. Stein, Michael L. Alosco
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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. 409-410
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Objective:
Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).
Participants and Methods:This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.
Results:Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.
Conclusions:The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.
5 Meta-Analysis of Cognitive Functioning Following Non-Severe COVID-19 Infection
- Tara A Austin, Cooper Hodges, Emily Darowski, Michael L Thomas, Rachel Bergsmans, Sarah Parr, Crystal Lantrip, Elizabeth W. Twamley
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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. 879-880
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Objective:
To effectively diagnose and treat cognitive post-COVID-19 symptoms, it is important to understand objective cognitive difficulties across the range of acute COVID-19 severity. The aim of this meta-analysis is to describe objective neuropsychological test performance in individuals with non-severe (mild/moderate) COVID-19 cases in the post-acute stage of infection (>28 days after initial infection).
Participants and Methods:This meta-analysis was pre-registered with Prospero (CRD42021293124) and utilized the PRISMA reporting guidelines, with screening conducted by at least two independent reviewers for all aspects of the screening and data extraction process. Inclusion criteria were established before the article search and were as follows: (1) Studies using adult participants with a probable or formal and documented diagnosis of COVID-19 in the post-acute stage of infection; (2) Studies comparing cognitive functioning using objective neuropsychological tests in one or more COVID-19 groups and a comparison group, or one group designs using tests with normative data; (3) Asymptomatic, mild, or moderate cases of COVID-19. Twenty-seven articles (n=18,202) with three types of study designs and three articles with additional longitudinal data met our full criteria.
Results:Individuals with non-severe initial COVID-19 infection demonstrated worse cognitive performance compared to healthy comparison participants (d=-0.412 [95% CI, -0.718, -0.176)], p=0.001). We used metaregression to examine the relationship between both average age of the sample and time since initial COVID-19 infection (as covariates in two independent models) and effect size in studies with comparison groups. There was no significant effect for age (b=-0.027 [95% CI (0.091, 0.038)], p=0.42). There was a significant effect for time since diagnosis, with a small improvement in cognitive performance for every day following initial acute COVID-19 infection (b=0.011 [95% CI (0.0039, 0.0174)], p=0.002). However, those with mild (non-hospitalized) initial COVID-19 infections performed better than did those who were hospitalized for initial COVID-19 infections (d=0.253 [95% CI (0.372, 0.134)], p<0.001). For studies that used normative data comparisons, there was a small, non-significant effect compared to normative data (d=-0.165 [95% CI (-0.333, 0.003)], p=0.055).
Conclusions:Individuals who have recovered from non-severe cases of COVID-19 may be at risk for cognitive decline or impairment and may benefit from cognitive health interventions.
South American Maize and Political Economy of the Middle and Late Formative Soconusco Region of Guatemala
- Thomas C. Hart, Neil A. Duncan, Deborah M. Pearsall, Michael W. Love
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- Latin American Antiquity , First View
- Published online by Cambridge University Press:
- 15 June 2023, pp. 1-14
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We present macrobotanical, starch, and phytolith data from artifacts and sediments from Middle Formative La Blanca (1000–600 cal BC) and Late Formative El Ujuxte (600 cal BC–cal AD 115 ) in the Soconusco region in Guatemala. Potential economic plants identified included palm (cf. Arecaceae), two varieties of maize (Zea mays), guava (Psidium guajava), bean (Phaseolus), chili peppers (Capsicum), squash (Cucurbitaceae), custard apple (Annonaceae), coco plum (Chrysobalanaceae), lerén (Calathea), arrowroot (Maranta), and bird-of-paradise (Heliconia). The results suggest that control of food production and consumption was critical for the transition from complex chiefdoms during the Middle Formative to the archaic state in the Late Formative. The arrival of a more productive South American variety of maize at El Ujuxte (about 2549 BP) allowed elites to exploit an already existing broad-based economic system and to use the maize-based religious system to increase control over maize agricultural practices and maintain power through ideology and disciplinary power. These data suggest that the arrival of fully domesticated South American maize likely influenced the overall development of Mesoamerican state-level societies.
Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals
- Cecilia A. Hinojosa, Amanda Liew, Xinming An, Jennifer S. Stevens, Archana Basu, Sanne J. H. van Rooij, Stacey L. House, Francesca L. Beaudoin, Donglin Zeng, Thomas C. Neylan, Gari D. Clifford, Tanja Jovanovic, Sarah D. Linnstaedt, Laura T. Germine, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Michael C. Kurz, Robert A. Swor, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Elizabeth M. Datner, Anna M. Chang, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Paulina Sergot, Leon D. Sanchez, Steven E. Bruce, Mark W. Miller, Robert H. Pietrzak, Jutta Joormann, Diego A. Pizzagalli, John F. Sheridan, Steven E. Harte, James M. Elliott, Ronald C. Kessler, Karestan C. Koenen, Samuel A. McLean, Kerry J. Ressler, Negar Fani
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- Journal:
- Psychological Medicine / Volume 54 / Issue 2 / January 2024
- Published online by Cambridge University Press:
- 13 June 2023, pp. 338-349
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Background
Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.
MethodsIn total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.
ResultsThree trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.
ConclusionsOur findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
Effect of 25-hydroxyvitamin D levels on the internalising dimension as a transdiagnostic risk factor: Mendelian randomisation study
- Julian Konzok, Sebastian-Edgar Baumeister, Thomas W. Winkler, Michael F. Leitzmann, Hansjörg Baurecht
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- Journal:
- The British Journal of Psychiatry / Volume 222 / Issue 6 / June 2023
- Published online by Cambridge University Press:
- 19 May 2023, pp. 257-263
- Print publication:
- June 2023
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Background
Observational studies indicate a relationship between vitamin D (25-hydroxyvitamin D; 25OHD) deficiency and the development of internalising disorders, especially depression. However, causal inference approaches (e.g. Mendelian randomisation) did not confirm this relationship. Findings from biobehavioural research suggests that new insights are revealed when focusing on psychopathological dimensions rather than on clinical diagnoses. This study provides further evidence on the relationship between 25OHD and the internalising dimension.
AimsThis investigation aimed at examining the causality between 25OHD and internalising disorders including a common internalising factor.
MethodWe performed a two-sample Mendelian randomisation using genome-wide association study (GWAS) summary data for 25OHD (417 580 participants), major depressive disorder (45 591 cases; 97 674 controls), anxiety (5580 cases; 11 730 controls), post-traumatic stress disorder (12 080 cases; 33 446 controls), panic disorder (2248 cases; 7992 controls), obsessive–compulsive disorder (2688 cases; 7037 controls) and anorexia nervosa (16 992 cases; 55 525 controls). GWAS results of the internalising phenotypes were combined to a common factor representing the internalising dimension. We performed several complementary analyses to reduce the risk of pleiotropy and used a second 25OHD GWAS for replication.
ResultsWe found no causal relationship between 25OHD and any of the internalising phenotypes studied, nor with the common internalising factor. Several pleiotropy-robust methods corroborated the null association.
ConclusionsFollowing current transdiagnostic approaches to investigate mental disorders, our results focused on the shared genetic basis between different internalising phenotypes and provide no evidence for an effect of 25OHD on the internalising dimension.
Cognitive determinants of affective forecasting errors
- Michael Hoerger, Stuart W. Quirk, Richard E. Lucas, Thomas H. Carr
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- Judgment and Decision Making / Volume 5 / Issue 5 / August 2010
- Published online by Cambridge University Press:
- 01 January 2023, pp. 365-373
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Often to the detriment of human decision making, people are prone to an impact bias when making affective forecasts, overestimating the emotional consequences of future events. The cognitive processes underlying the impact bias, and methods for correcting it, have been debated and warrant further exploration. In the present investigation, we examined both individual differences and contextual variables associated with cognitive processing in affective forecasting for an election. Results showed that the perceived importance of the event and working memory capacity were both associated with an increased impact bias for some participants, whereas retrieval interference had no relationship with bias. Additionally, an experimental manipulation effectively reduced biased forecasts, particularly among participants who were most distracted thinking about peripheral life events. These findings have theoretical implications for understanding the impact bias, highlight the importance of individual differences in affective forecasting, and have ramifications for future decision making research. The possible functional role of the impact bias is discussed within the context of evolutionary psychology.
Rebuilding the foundation of late Paleozoic pinnid bivalve study (family Pinnidae)
- Thomas E. Yancey, Michael R. W. Amler, Paweł Raczyński, Silvio Brandt
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- Journal of Paleontology / Volume 97 / Issue 1 / January 2023
- Published online by Cambridge University Press:
- 11 August 2022, pp. 140-151
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The early geologic history of family Pinnidae, a diverse and abundant component of mud-dominated shallow marine environments of the late Paleozoic, is obscured by ill-defined genus and species concepts. Mistakes in descriptions and reconstructions have provided a basis for suggestions that older taxa in the family differ from younger taxa and may not belong in family Pinnidae. This report provides improved documentation that removes the basis for the concept of divergence. Late Paleozoic genera and species have definite pinnid bivalve characters, including a dorsomarginal fold that holds the ligament, a thick outer columnar prismatic shell layer, and an equivalved, triangular shell, all of which provide evidence for confident assignment of the genus to family Pinnidae. The suggested synonymy of Aviculopinna with Pteronites is invalid, and genus Aviculopinna is limited to occurrence in Permian strata. The two genera belong in different families. A neotype is designated for genus Aviculopinna type species Aviculopinna pinnaeformis Geinitz from Gera, Germany, and a lectotype for Aviculopinna neukirchensis Langenhan from Nowy Kościół, Poland. Inferences on the life habits of Aviculopinna based on its occurrence in Poland are presented. An evaluation of the subterminal beak versus terminal beak concept in pinnids is presented and conclusion presented that there are few data available to support the concept or to test it. In its present form, the concept has no utility in the study of pinnid bivalves.
The prescriber’s guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression
- Vincent Van den Eynde, Wegdan R. Abdelmoemin, Magid M. Abraham, Jay D. Amsterdam, Ian M. Anderson, Chittaranjan Andrade, Glen B. Baker, Aartjan T.F. Beekman, Michael Berk, Tom K. Birkenhäger, Barry B. Blackwell, Pierre Blier, Marc B.J. Blom, Alexander J. Bodkin, Carlo I. Cattaneo, Bezalel Dantz, Jonathan Davidson, Boadie W. Dunlop, Ryan F. Estévez, Shalom S. Feinberg, John P.M. Finberg, Laura J. Fochtmann, David Gotlib, Andrew Holt, Thomas R. Insel, Jens K. Larsen, Rajnish Mago, David B. Menkes, Jonathan M. Meyer, David J. Nutt, Gordon Parker, Mark D. Rego, Elliott Richelson, Henricus G. Ruhé, Jerónimo Sáiz-Ruiz, Stephen M. Stahl, Thomas Steele, Michael E. Thase, Sven Ulrich, Anton J.L.M. van Balkom, Eduard Vieta, Ian Whyte, Allan H. Young, Peter K. Gillman
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- Journal:
- CNS Spectrums / Volume 28 / Issue 4 / August 2023
- Published online by Cambridge University Press:
- 15 July 2022, pp. 427-440
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This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach – CORRIGENDUM
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, JeanMichel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, HsiChung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil TekolaAyele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 221 / Issue 2 / August 2022
- Published online by Cambridge University Press:
- 04 May 2022, p. 494
- Print publication:
- August 2022
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Abbreviated San Diego Wisdom Scale (SD-WISE-7) and Jeste-Thomas Wisdom Index (JTWI) – CORRIGENDUM
- Michael L. Thomas, Barton W. Palmer, Ellen E. Lee, Jinyuan Liu, Rebecca Daly, Xin M. Tu, Dilip V. Jeste
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- Journal:
- International Psychogeriatrics / Volume 35 / Issue 10 / October 2023
- Published online by Cambridge University Press:
- 23 March 2022, p. 587
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Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil Tekola-Ayele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 220 / Issue 4 / April 2022
- Published online by Cambridge University Press:
- 28 February 2022, pp. 219-228
- Print publication:
- April 2022
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Background
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
AimsTo use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
MethodThis study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
ResultsThe best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
ConclusionsUsing PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Elevated cardiac biomarkers and outcomes in children and adolescents with acute COVID-19
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- Michael A. Fremed, Emma W. Healy, Nak Hyun Choi, Eva W. Cheung, Tarif A. Choudhury, Pengfei Jiang, Leonardo Liberman, Jason Zucker, Irene D. Lytrivi, Thomas J. Starc
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- Journal:
- Cardiology in the Young / Volume 33 / Issue 2 / February 2023
- Published online by Cambridge University Press:
- 28 January 2022, pp. 183-189
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Cardiac involvement associated with multi-system inflammatory syndrome in children has been extensively reported, but the prevalence of cardiac involvement in children with SARS-CoV-2 infection in the absence of inflammatory syndrome has not been well described. In this retrospective, single centre, cohort study, we describe the cardiac involvement found in this population and report on outcomes of patients with and without elevated cardiac biomarkers. Those with multi-system inflammatory syndrome in children, cardiomyopathy, or complex CHD were excluded. Inclusion criteriaz were met by 80 patients during the initial peak of the pandemic at our institution. High-sensitivity troponin T and/or N-terminal pro-brain type natriuretic peptide were measured in 27/80 (34%) patients and abnormalities were present in 5/27 (19%), all of whom had underlying comorbidities. Advanced respiratory support was required in all patients with elevated cardiac biomarkers. Electrocardiographic abnormalities were identified in 14/38 (37%) studies. Echocardiograms were performed on 7/80 patients, and none demonstrated left ventricular dysfunction. Larger studies to determine the true extent of cardiac involvement in children with COVID-19 would be useful to guide recommendations for standard workup and management.
Abbreviated San Diego Wisdom Scale (SD-WISE-7) and Jeste-Thomas Wisdom Index (JTWI)
- Michael L. Thomas, Barton W. Palmer, Ellen E. Lee, Jinyuan Liu, Rebecca Daly, Xin M. Tu, Dilip V. Jeste
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- Journal:
- International Psychogeriatrics / Volume 34 / Issue 7 / July 2022
- Published online by Cambridge University Press:
- 03 December 2021, pp. 617-626
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Objectives:
Wisdom is a personality trait comprising seven components: self-reflection, pro-social behaviors, emotional regulation, acceptance of diverse perspectives, decisiveness, social advising, and spirituality. Wisdom, a potentially modifiable trait, is strongly associated with well-being. We have published a validated 28-item San Diego Wisdom Scale, the SD-WISE-28. Brief scales are necessary for use in large population-based studies and in clinical practice. The present study aimed to create an abbreviated 7-item version of the SD-WISE.
Method:Participants included 2093 people, aged 20-82 years, recruited and surveyed through the online crowdsourcing platform Amazon Mechanical Turk. The participants’ mean age was 46 years, with 55% women. Participants completed the SD-WISE-28 as well as validation scales for various positive and negative constructs. Psychometric analyses (factor analysis and item response theory) were used to select one item from each of the seven SD-WISE-28 subscales.
Results:We selected a combination of items that produced acceptable unidimensional model fit and good reliability (ω = 0.74). Item statistics suggested that all seven items were strong indicators of wisdom, although the association was weakest for spirituality. Analyses indicated that the 28-item and 7-item SD-WISE are both very highly correlated (r = 0.92) and produce a nearly identical pattern of correlations with demographic and validity variables.
Conclusion:The SD-WISE-7, and its derived Jeste-Thomas Wisdom Index (JTWI) score, balances reliability and brevity for research applications.
Compounding and complementary carnivores: Australian bird species eaten by the introduced European red fox Vulpes vulpes and domestic cat Felis catus
- JOHN C.Z. WOINARSKI, ALYSON M. STOBO-WILSON, HEATHER M. CRAWFORD, STUART J. DAWSON, CHRIS R. DICKMAN, TIM S. DOHERTY, PATRICIA A. FLEMING, STEPHEN T. GARNETT, MATTHEW N. GENTLE, SARAH M. LEGGE, THOMAS M. NEWSOME, RUSSELL PALMER, MATTHEW W. REES, EUAN G. RITCHIE, JAMES SPEED, JOHN-MICHAEL STUART, EILYSH THOMPSON, JEFF TURPIN, BRETT P. MURPHY
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- Journal:
- Bird Conservation International / Volume 32 / Issue 3 / September 2022
- Published online by Cambridge University Press:
- 02 December 2021, pp. 506-522
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Two introduced carnivores, the European red fox Vulpes vulpes and domestic cat Felis catus, have had extensive impacts on Australian biodiversity. In this study, we collate information on consumption of Australian birds by the fox, paralleling a recent study reporting on birds consumed by cats. We found records of consumption by foxes on 128 native bird species (18% of the non-vagrant bird fauna and 25% of those species within the fox’s range), a smaller tally than for cats (343 species, including 297 within the fox’s Australian range, a subset of that of the cat). Most (81%) bird species eaten by foxes are also eaten by cats, suggesting that predation impacts are compounded. As with consumption by cats, birds that nest or forage on the ground are most likely to be consumed by foxes. However, there is also some partitioning, with records of consumption by foxes but not cats for 25 bird species, indicating that impacts of the two predators may also be complementary. Bird species ≥3.4 kg were more likely to be eaten by foxes, and those <3.4 kg by cats. Our compilation provides an inventory and describes characteristics of Australian bird species known to be consumed by foxes, but we acknowledge that records of predation do not imply population-level impacts. Nonetheless, there is sufficient information from other studies to demonstrate that fox predation has significant impacts on the population viability of some Australian birds, especially larger birds, and those that nest or forage on the ground.
Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
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