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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.
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.
4 Methamphetamine, cannabis, HIV, and their combined effects on neurocognition
- Jeffrey M Rogers, Igor Grant, Maria Cecilia Marcondes, Erin E Morgan, Mariana Cherner, Ronald J Ellis, Scott L Letendre, Robert K Heaton, Jennifer E Iudicello
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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. 797-798
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Objective:
Methamphetamine and cannabis are two widely used substances with possibly opposing effects on aspects of central nervous system functioning. Use of these substances is prevalent among people with HIV (PWH), though their combined effects on HIV-associated neurocognitive impairment (NCI) are unknown. Adverse effects of methamphetamine use on cognition are well documented. Cannabis may disturb cognition acutely, though its longer-term effects in PWH are not well understood. Our prior analysis of people without HIV (PWoH) found that cotemporaneous cannabis use was associated with better neurocognitive outcomes among methamphetamine users. The aim of this study was to assess how lifetime cannabis and methamphetamine use disorder relate to neurocognitive outcomes in PWH.
Participants and Methods:HIV-positive participants (n=472) were on average 45.6±11.5 years of age, male (86.4%), White (60.6%), and educated 13.9±2.5 years. Most participants were on ART (81.9%) and virally suppressed (70%). Participants were stratified by lifetime methamphetamine (M-/M+) and cannabis (C-/C+) DSM-IV abuse/dependence disorder into four groups: M-C- (n=187), M-C+ (n=68), M+C-, (n=82) and M+C+ (n=135) and completed a comprehensive neurobehavioral assessment. Demographically corrected T-scores and deficit scores were used for analyses. Group differences in global and domain NC performances (i.e., T-scores) were examined using multiple linear regression, holding constant covariates that were associated with study groups and/or cognition. Specifically, M+ participants displayed higher rates of Hepatitis C infection (p=.004), higher current depressive symptom scores (p<.001), and higher rates of detectable plasma HIV RNA (p=.014). Multiple logistic regression was used to test for group differences in probability of neurocognitive impairment (i.e., deficit scores>0.5), including the same covariates. Pooling data with a sample of HIV-negative participants (n=423), we used generalized linear mixed effect models to examine how neurocognitive performance and impairment profiles varied by methamphetamine and/or cannabis use group, HIV disease characteristics, and their interactions.
Results:Compared to M+C+, M+C- performed worse on measures of executive functions (ß=-3.17), learning (ß=-3.95), memory (ß=-5.58), and working memory (ß=-4.05) and were more likely to be classified as impaired in the learning (OR=2.93), memory (OR=5.24), and working memory (OR=2.48) domains. M-C- performed better than M+C+ on measures of learning (ß=3.46) and memory (ß=5.19), but worse than M-C+ on measures of executive functions (ß=-3.90), learning (ß=-3.32), memory (ß=-3.38), and working memory (ß=-3.38). Generalized linear mixed effect models indicate that detectable plasma HIV RNA (ß=-1.85) and low nadir CD4 T-cell counts (nadir CD4<200; ß=-1.07) were associated with worse neurocognitive performance, and these effects did not differ in size or direction by substance use group.
Conclusions:In PWH, lifetime methamphetamine use disorder and both current and legacy markers of HIV disease severity are associated with worse neurocognitive outcomes. Cannabis use disorder does not appear to exacerbate methamphetamine-related deficits in PWH. Instead, results are consistent with findings from preclinical studies that cannabis use may protect against methamphetamine’s deleterious effects. Profile analysis models showed that participants with a history of cannabis use disorder display better overall neurocognitive performance than comparison (M-C-) participants. Mechanisms underlying a potential protective effect of cannabis may be elucidated by examining the temporal relationship between cannabis and methamphetamine consumption and neurocognitive performance.
3 The Relationship Between Apolipoprotein-E4 Genotype, Memory, and the Medial Temporal Lobe and How These Relationships Vary by Race in Middle-Aged Persons with HIV
- Laura M Campbell, Maulika Kohli, Erin E Sundermann, Christine Fennema-Notestine, Averi Barrett, Cinnamon Bloss, Mark W Bondi, David B Clifford, Ronald J Ellis, Donald Franklin, Benjamin Gelman, Igor Grant, Robert K Heaton, Scott Letendre, Payal B Patel, David J Moore, Susan Morgello, Raeanne C Moore
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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. 683-684
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Objective:
Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.
Participants and Methods:The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and
relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).
Results:APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).
Conclusions:Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.
Prospective association of attachment style with suicide attempts among US Army soldiers
- James A. Naifeh, Robert J. Ursano, Murray B. Stein, Jing Wang, Holly B. Herberman Mash, Pablo A. Aliaga, Carol S. Fullerton, Hieu M. Dinh, Tzu-Cheg Kao, Nancy A. Sampson, Ronald C. Kessler
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- Psychological Medicine / Volume 54 / Issue 4 / March 2024
- Published online by Cambridge University Press:
- 31 August 2023, pp. 785-793
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Background
Insecure attachment styles are associated with retrospectively reported suicide attempts (SAs). It is not known if attachment styles are prospectively associated with medically documented SAs.
MethodsA representative sample of US Army soldiers entering service (n = 21 772) was surveyed and followed via administrative records for their first 48 months of service. Attachment style (secure, preoccupied, fearful, dismissing) was assessed at baseline. Administrative medical records identified SAs. Discrete-time survival analysis examined associations of attachment style with future SA during service, adjusting for time in service, socio-demographics, service-related variables, and mental health diagnosis (MH-Dx). We examined whether associations of attachment style with SA differed based on sex and MH-Dx.
ResultsIn total, 253 respondents attempted suicide. Endorsed attachment styles included secure (46.8%), preoccupied (9.1%), fearful (15.7%), and dismissing (19.2%). Examined separately, insecure attachment styles were associated with increased odds of SA: preoccupied [OR 2.5 (95% CI 1.7–3.4)], fearful [OR 1.6 (95% CI 1.1–2.3)], dismissing [OR 1.8 (95% CI 1.3–2.6)]. Examining attachment styles simultaneously along with other covariates, preoccupied [OR 1.9 (95% CI 1.4–2.7)] and dismissing [OR 1.7 (95% CI 1.2–2.4)] remained significant. The dismissing attachment and MH-Dx interaction was significant. In stratified analyses, dismissing attachment was associated with SA only among soldiers without MH-Dx. Other interactions were non-significant. Soldiers endorsing any insecure attachment style had elevated SA risk across the first 48 months in service, particularly during the first 12 months.
ConclusionsInsecure attachment styles, particularly preoccupied and dismissing, are associated with increased future SA risk among soldiers. Elevated risk is most substantial during first year of service but persists through the first 48 months. Dismissing attachment may indicate risk specifically among soldiers not identified by the mental healthcare system.
Cannabis use may attenuate neurocognitive performance deficits resulting from methamphetamine use disorder
- Jeffrey M. Rogers, Igor Grant, Maria Cecilia G. Marcondes, Erin E. Morgan, Mariana Cherner, Ronald J. Ellis, Scott L. Letendre, Robert K. Heaton, Jennifer E. Iudicello
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- Journal:
- Journal of the International Neuropsychological Society / Volume 30 / Issue 1 / January 2024
- Published online by Cambridge University Press:
- 09 August 2023, pp. 84-93
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Objective:
Methamphetamine and cannabis are two widely used, and frequently co-used, substances with possibly opposing effects on the central nervous system. Evidence of neurocognitive deficits related to use is robust for methamphetamine and mixed for cannabis. Findings regarding their combined use are inconclusive. We aimed to compare neurocognitive performance in people with lifetime cannabis or methamphetamine use disorder diagnoses, or both, relative to people without substance use disorders.
Method:423 (71.9% male, aged 44.6 ± 14.2 years) participants, stratified by presence or absence of lifetime methamphetamine (M−/M+) and/or cannabis (C−/C+) DSM-IV abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. Neurocognitive domain T-scores and impairment rates were examined using multiple linear and binomial regression, respectively, controlling for covariates that may impact cognition.
Results:Globally, M+C+ performed worse than M−C− but better than M+C−. M+C+ outperformed M+C− on measures of verbal fluency, information processing speed, learning, memory, and working memory. M−C+ did not display lower performance than M−C− globally or on any domain measures, and M−C+ even performed better than M−C− on measures of learning, memory, and working memory.
Conclusions:Our findings are consistent with prior work showing that methamphetamine use confers risk for worse neurocognitive outcomes, and that cannabis use does not appear to exacerbate and may even reduce this risk. People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains. These findings warrant further investigation as to whether cannabis use may ameliorate methamphetamine neurotoxicity.
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.
Emotional health and its association with neurocognition in Hispanic and non-Hispanic White people with HIV
- Lesley A. Guareña, Lily Kamalyan, Caitlin Wei-Ming Watson, Kayle Karcher, Anya Umlauf, Erin Morgan, David Moore, Ronald Ellis, Igor Grant, Mariana Cherner, Raeanne C. Moore, Zvinka Z. Zlatar, Robert K. Heaton, María J. Marquine
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- Journal:
- Journal of the International Neuropsychological Society / Volume 30 / Issue 1 / January 2024
- Published online by Cambridge University Press:
- 20 April 2023, pp. 56-66
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Objective:
Emotional functioning is linked to HIV-associated neurocognitive impairment, yet research on this association among diverse people with HIV (PWH) is scant. We examined emotional health and its association with neurocognition in Hispanic and White PWH.
Methods:Participants included 107 Hispanic (41% primarily Spanish-speakers; 80% Mexican heritage/origin) and 216 White PWH (Overall age: M = 53.62, SD = 12.19; 86% male; 63% AIDS; 92% on antiretroviral therapy). Emotional health was assessed via the National Institute of Health Toolbox (NIHTB)-Emotion Battery, which yields T-scores for three factor-based summary scores (negative affect, social satisfaction, and psychological well-being) and 13 individual component scales. Neurocognition was measured via demographically adjusted fluid cognition T-scores from the NIHTB-cognition battery.
Results:27%–39% of the sample had problematic socioemotional summary scores. Hispanic PWH showed less loneliness, better social satisfaction, higher meaning and purpose, and better psychological well-being than Whites (ps <.05). Within Hispanics, Spanish-speakers showed better meaning and purpose, higher psychological well-being summary score, less anger hostility, but greater fear affect than English speakers. Only in Whites, worse negative affect (fear affect, perceived stress, and sadness) was associated with worse neurocognition (p <.05); and in both groups, worse social satisfaction (emotional support, friendship, and perceived rejection) was linked with worse neurocognition (p <.05).
Conclusion:Adverse emotional health is common among PWH, with subgroups of Hispanics showing relative strengths in some domains. Aspects of emotional health differentially relate to neurocogntition among PWH and cross-culturally. Understanding these varying associations is an important step towards the development of culturally relevant interventions that promote neurocognitive health among Hispanic PWH.
A practical risk calculator for suicidal behavior among transitioning U.S. Army soldiers: results from the Study to Assess Risk and Resilience in Servicemembers-Longitudinal Study (STARRS-LS)
- Jaclyn C. Kearns, Emily R. Edwards, Erin P. Finley, Joseph C. Geraci, Sarah M. Gildea, Marianne Goodman, Irving Hwang, Chris J. Kennedy, Andrew J. King, Alex Luedtke, Brian P. Marx, Maria V. Petukhova, Nancy A. Sampson, Richard W. Seim, Ian H. Stanley, Murray B. Stein, Robert J. Ursano, Ronald C. Kessler
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- Psychological Medicine / Volume 53 / Issue 15 / November 2023
- Published online by Cambridge University Press:
- 09 March 2023, pp. 7096-7105
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Background
Risk of suicide-related behaviors is elevated among military personnel transitioning to civilian life. An earlier report showed that high-risk U.S. Army soldiers could be identified shortly before this transition with a machine learning model that included predictors from administrative systems, self-report surveys, and geospatial data. Based on this result, a Veterans Affairs and Army initiative was launched to evaluate a suicide-prevention intervention for high-risk transitioning soldiers. To make targeting practical, though, a streamlined model and risk calculator were needed that used only a short series of self-report survey questions.
MethodsWe revised the original model in a sample of n = 8335 observations from the Study to Assess Risk and Resilience in Servicemembers-Longitudinal Study (STARRS-LS) who participated in one of three Army STARRS 2011–2014 baseline surveys while in service and in one or more subsequent panel surveys (LS1: 2016–2018, LS2: 2018–2019) after leaving service. We trained ensemble machine learning models with constrained numbers of item-level survey predictors in a 70% training sample. The outcome was self-reported post-transition suicide attempts (SA). The models were validated in the 30% test sample.
ResultsTwelve-month post-transition SA prevalence was 1.0% (s.e. = 0.1). The best constrained model, with only 17 predictors, had a test sample ROC-AUC of 0.85 (s.e. = 0.03). The 10–30% of respondents with the highest predicted risk included 44.9–92.5% of 12-month SAs.
ConclusionsAn accurate SA risk calculator based on a short self-report survey can target transitioning soldiers shortly before leaving service for intervention to prevent post-transition SA.
Associations of polygenic risk scores with posttraumatic stress symptom trajectories following combat deployment
- Laura Campbell-Sills, Santiago Papini, Sonya B. Norman, Karmel W. Choi, Feng He, Xiaoying Sun, Ronald C. Kessler, Robert J. Ursano, Sonia Jain, Murray B. Stein
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- Journal:
- Psychological Medicine / Volume 53 / Issue 14 / October 2023
- Published online by Cambridge University Press:
- 06 March 2023, pp. 6733-6742
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Background
Identification of genetic risk factors may inform the prevention and treatment of posttraumatic stress disorder (PTSD). This study evaluates the associations of polygenic risk scores (PRS) with patterns of posttraumatic stress symptoms following combat deployment.
MethodUS Army soldiers of European ancestry (n = 4900) provided genomic data and ratings of posttraumatic stress symptoms before and after deployment to Afghanistan in 2012. Latent growth mixture modeling was used to model posttraumatic stress symptom trajectories among participants who provided post-deployment data (n = 4353). Multinomial logistic regression models tested independent associations between trajectory membership and PRS for PTSD, major depressive disorder (MDD), schizophrenia, neuroticism, alcohol use disorder, and suicide attempt, controlling for age, sex, ancestry, and exposure to potentially traumatic events, and weighted to account for uncertainty in trajectory classification and missing data.
ResultsParticipants were classified into low-severity (77.2%), increasing-severity (10.5%), decreasing-severity (8.0%), and high-severity (4.3%) posttraumatic stress symptom trajectories. Standardized PTSD-PRS and MDD-PRS were associated with greater odds of membership in the high-severity v. low-severity trajectory [adjusted odds ratios and 95% confidence intervals, 1.23 (1.06–1.43) and 1.18 (1.02–1.37), respectively] and the increasing-severity v. low-severity trajectory [1.12 (1.01–1.25) and 1.16 (1.04–1.28), respectively]. Additionally, MDD-PRS was associated with greater odds of membership in the decreasing-severity v. low-severity trajectory [1.16 (1.03–1.31)]. No other associations were statistically significant.
ConclusionsHigher polygenic risk for PTSD or MDD is associated with more severe posttraumatic stress symptom trajectories following combat deployment. PRS may help stratify at-risk individuals, enabling more precise targeting of treatment and prevention programs.
Respiratory culture nudge improves antibiotic prescribing for Moraxella catarrhalis and Haemophilus influenzae lower respiratory tract infections
- Christen J. Arena, Rachel M. Kenney, Ronald E. Kendall, Robert J. Tibbetts, Michael P. Veve
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- Journal:
- Antimicrobial Stewardship & Healthcare Epidemiology / Volume 3 / Issue 1 / 2023
- Published online by Cambridge University Press:
- 02 February 2023, e23
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We compared optimal antibiotic prescribing before and after implementing an interpretive β-lactamase microbiology comment for Haemophilus influenzae and Moraxella catarrhalis in lower respiratory-tract infections. The postintervention group was associated with 5-fold increased odds of optimal de-escalation (adjusted odds ratio, 5.03; 95% confidence interval, 2.57–9.87).
Prospective associations of emotion reactivity and risk behaviors with suicide attempts in US Army soldiers
- James A. Naifeh, Robert J. Ursano, Murray B. Stein, Holly B. Herberman Mash, Pablo A. Aliaga, Carol S. Fullerton, Hieu M. Dinh, Tzu-Cheg Kao, Nancy A. Sampson, Ronald C. Kessler
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- Psychological Medicine / Volume 53 / Issue 13 / October 2023
- Published online by Cambridge University Press:
- 04 November 2022, pp. 6124-6131
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Background
Emotion reactivity and risk behaviors (ERRB) are transdiagnostic dimensions associated with suicide attempt (SA). ERRB patterns may identify individuals at increased risk of future SAs.
MethodsA representative sample of US Army soldiers entering basic combat training (n = 21 772) was surveyed and followed via administrative records for their first 48 months of service. Latent profile analysis of baseline survey items assessing ERRB dimensions, including emotion reactivity, impulsivity, and risk-taking behaviors, identified distinct response patterns (classes). SAs were identified using administrative medical records. A discrete-time survival framework was used to examine associations of ERRB classes with subsequent SA during the first 48 months of service, adjusting for time in service, socio-demographic and service-related variables, and mental health diagnosis (MH-Dx). We examined whether associations of ERRB classes with SA differed by year of service and for soldiers with and without a MH-Dx.
ResultsOf 21 772 respondents (86.2% male, 61.8% White non-Hispanic), 253 made a SA. Four ERRB classes were identified: ‘Indirect Harming’ (8.9% of soldiers), ‘Impulsive’ (19.3%), ‘Risk-Taking’ (16.3%), and ‘Low ERRB’ (55.6%). Compared to Low ERRB, Impulsive [OR 1.8 (95% CI 1.3–2.4)] and Risk-Taking [OR 1.6 (95% CI 1.1–2.2)] had higher odds of SA after adjusting for covariates. The ERRB class and MH-Dx interaction was non-significant. Within each class, SA risk varied across service time.
ConclusionsSA risk within the four identified ERRB classes varied across service time. Impulsive and Risk-Taking soldiers had increased risk of future SA. MH-Dx did not modify these associations, which may therefore help identify risk in those not yet receiving mental healthcare.
Social network size and personality traits independently and prospectively predict distress disorders and suicidal behavior in U.S. Army soldiers
- Charles T. Taylor, Laura Campbell-Sills, Ronald C. Kessler, Xiaoying Sun, Matthew K. Nock, Robert J. Ursano, Sonia Jain, Murray B. Stein
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- Journal:
- Psychological Medicine / Volume 53 / Issue 11 / August 2023
- Published online by Cambridge University Press:
- 18 August 2022, pp. 5081-5090
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Background
Personality traits (e.g. neuroticism) and the social environment predict risk for internalizing disorders and suicidal behavior. Studying these characteristics together and prospectively within a population confronted with high stressor exposure (e.g. U.S. Army soldiers) has not been done, yet could uncover unique and interactive predictive effects that may inform prevention and early intervention efforts.
MethodsFive broad personality traits and social network size were assessed via self-administered questionnaires among experienced soldiers preparing for deployment (N = 4645) and new soldiers reporting for basic training (N = 6216). Predictive models examined associations of baseline personality and social network variables with recent distress disorders or suicidal behaviors assessed 3- and 9-months post-deployment and approximately 5 years following enlistment.
ResultsAmong the personality traits, elevated neuroticism was consistently associated with increased mental health risk following deployment. Small social networks were also associated with increased mental health risk following deployment, beyond the variance accounted for by personality. Limited support was found for social network size moderating the association between personality and mental health outcomes. Small social networks also predicted distress disorders and suicidal behavior 5 years following enlistment, whereas unique effects of personality traits on these more distal outcomes were rare.
ConclusionsHeightened neuroticism and small social networks predict a greater risk for negative mental health sequelae, especially following deployment. Social ties may mitigate adverse impacts of personality traits on psychopathology in some contexts. Early identification and targeted intervention for these distinct, modifiable factors may decrease the risk of distress disorders and suicidal behavior.
Development of a model to predict antidepressant treatment response for depression among Veterans
- Victor Puac-Polanco, Hannah N. Ziobrowski, Eric L. Ross, Howard Liu, Brett Turner, Ruifeng Cui, Lucinda B. Leung, Robert M. Bossarte, Corey Bryant, Jutta Joormann, Andrew A. Nierenberg, David W. Oslin, Wilfred R. Pigeon, Edward P. Post, Nur Hani Zainal, Alan M. Zaslavsky, Jose R. Zubizarreta, Alex Luedtke, Chris J. Kennedy, Andrea Cipriani, Toshiaki A. Furukawa, Ronald C. Kessler
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- Journal:
- Psychological Medicine / Volume 53 / Issue 11 / August 2023
- Published online by Cambridge University Press:
- 15 July 2022, pp. 5001-5011
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Background
Only a limited number of patients with major depressive disorder (MDD) respond to a first course of antidepressant medication (ADM). We investigated the feasibility of creating a baseline model to determine which of these would be among patients beginning ADM treatment in the US Veterans Health Administration (VHA).
MethodsA 2018–2020 national sample of n = 660 VHA patients receiving ADM treatment for MDD completed an extensive baseline self-report assessment near the beginning of treatment and a 3-month self-report follow-up assessment. Using baseline self-report data along with administrative and geospatial data, an ensemble machine learning method was used to develop a model for 3-month treatment response defined by the Quick Inventory of Depression Symptomatology Self-Report and a modified Sheehan Disability Scale. The model was developed in a 70% training sample and tested in the remaining 30% test sample.
ResultsIn total, 35.7% of patients responded to treatment. The prediction model had an area under the ROC curve (s.e.) of 0.66 (0.04) in the test sample. A strong gradient in probability (s.e.) of treatment response was found across three subsamples of the test sample using training sample thresholds for high [45.6% (5.5)], intermediate [34.5% (7.6)], and low [11.1% (4.9)] probabilities of response. Baseline symptom severity, comorbidity, treatment characteristics (expectations, history, and aspects of current treatment), and protective/resilience factors were the most important predictors.
ConclusionsAlthough these results are promising, parallel models to predict response to alternative treatments based on data collected before initiating treatment would be needed for such models to help guide treatment selection.
Cereal and oil seed crops response to organic nitrogen when grown in rotation with annual aerial-seeded pasture legumes
- Angelo Loi, Dean T. Thomas, Ronald J. Yates, Robert J. Harrison, Mario D'Antuono, Giovanni A. Re, Hayley C. Norman, John G. Howieson
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- Journal:
- The Journal of Agricultural Science / Volume 160 / Issue 3-4 / June 2022
- Published online by Cambridge University Press:
- 29 June 2022, pp. 207-219
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Nitrogen fixation from pasture legumes is a fundamental process that contributes to the profitability and sustainability of dryland agricultural systems. The aim of this research was to determine whether well-managed pastures, based on aerial-seeding pasture legumes, could partially or wholly meet the nitrogen (N) requirements of subsequent grain crops in an annual rotation. Fifteen experiments were conducted in Western Australia with wheat, barley or canola crops grown in a rotation that included the pasture legume species French serradella (Ornithopus sativus), biserrula (Biserrula pelecinus), bladder clover (Trifolium spumosum), annual medics (Medicago spp.) and the non-aerial seeded subterranean clover (Trifolium subterraneum). After the pasture phase, five rates of inorganic N fertilizer (Urea, applied at 0, 23, 46, 69 and 92 kg/ha) were applied to subsequent cereal and oil seed crops. The yields of wheat grown after serradella, biserrula and bladder clover, without the use of applied N fertilizer, were consistent with the target yields for growing conditions of the trials (2.3 to 5.4 t/ha). Crop yields after phases of these pasture legume species were similar or higher than those following subterranean clover or annual medics. The results of this study suggest a single season of a legume-dominant pasture may provide sufficient organic N in the soil to grow at least one crop, without the need for inorganic N fertilizer application. This has implications for reducing inorganic N requirements and the carbon footprint of cropping in dryland agricultural systems.
Associations of vulnerability to stressful life events with suicide attempts after active duty among high-risk soldiers: results from the Study to Assess Risk and Resilience in Servicemembers-longitudinal study (STARRS-LS)
- Carol Chu, Ian H. Stanley, Brian P. Marx, Andrew J. King, Dawne Vogt, Sarah M. Gildea, Irving H. Hwang, Nancy A. Sampson, Robert O'Brien, Murray B. Stein, Robert J. Ursano, Ronald C. Kessler
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- Journal:
- Psychological Medicine / Volume 53 / Issue 9 / July 2023
- Published online by Cambridge University Press:
- 27 May 2022, pp. 4181-4191
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Background
The transition from military service to civilian life is a high-risk period for suicide attempts (SAs). Although stressful life events (SLEs) faced by transitioning soldiers are thought to be implicated, systematic prospective evidence is lacking.
MethodsParticipants in the Army Study to Assess Risk and Resilience in Servicemembers (STARRS) completed baseline self-report surveys while on active duty in 2011–2014. Two self-report follow-up Longitudinal Surveys (LS1: 2016–2018; LS2: 2018–2019) were subsequently administered to probability subsamples of these baseline respondents. As detailed in a previous report, a SA risk index based on survey, administrative, and geospatial data collected before separation/deactivation identified 15% of the LS respondents who had separated/deactivated as being high-risk for self-reported post-separation/deactivation SAs. The current report presents an investigation of the extent to which self-reported SLEs occurring in the 12 months before each LS survey might have mediated/modified the association between this SA risk index and post-separation/deactivation SAs.
ResultsThe 15% of respondents identified as high-risk had a significantly elevated prevalence of some post-separation/deactivation SLEs. In addition, the associations of some SLEs with SAs were significantly stronger among predicted high-risk than lower-risk respondents. Demographic rate decomposition showed that 59.5% (s.e. = 10.2) of the overall association between the predicted high-risk index and subsequent SAs was linked to these SLEs.
ConclusionsIt might be possible to prevent a substantial proportion of post-separation/deactivation SAs by providing high-risk soldiers with targeted preventive interventions for exposure/vulnerability to commonly occurring SLEs.
Development of a model to predict psychotherapy response for depression among Veterans
- Hannah N. Ziobrowski, Ruifeng Cui, Eric L. Ross, Howard Liu, Victor Puac-Polanco, Brett Turner, Lucinda B. Leung, Robert M. Bossarte, Corey Bryant, Wilfred R. Pigeon, David W. Oslin, Edward P. Post, Alan M. Zaslavsky, Jose R. Zubizarreta, Andrew A. Nierenberg, Alex Luedtke, Chris J. Kennedy, Ronald C. Kessler
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- Journal:
- Psychological Medicine / Volume 53 / Issue 8 / June 2023
- Published online by Cambridge University Press:
- 11 February 2022, pp. 3591-3600
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Background
Fewer than half of patients with major depressive disorder (MDD) respond to psychotherapy. Pre-emptively informing patients of their likelihood of responding could be useful as part of a patient-centered treatment decision-support plan.
MethodsThis prospective observational study examined a national sample of 807 patients beginning psychotherapy for MDD at the Veterans Health Administration. Patients completed a self-report survey at baseline and 3-months follow-up (data collected 2018–2020). We developed a machine learning (ML) model to predict psychotherapy response at 3 months using baseline survey, administrative, and geospatial variables in a 70% training sample. Model performance was then evaluated in the 30% test sample.
Results32.0% of patients responded to treatment after 3 months. The best ML model had an AUC (SE) of 0.652 (0.038) in the test sample. Among the one-third of patients ranked by the model as most likely to respond, 50.0% in the test sample responded to psychotherapy. In comparison, among the remaining two-thirds of patients, <25% responded to psychotherapy. The model selected 43 predictors, of which nearly all were self-report variables.
ConclusionsPatients with MDD could pre-emptively be informed of their likelihood of responding to psychotherapy using a prediction tool based on self-report data. This tool could meaningfully help patients and providers in shared decision-making, although parallel information about the likelihood of responding to alternative treatments would be needed to inform decision-making across multiple treatments.
Effects of prior deployments and perceived resilience on anger trajectories of combat-deployed soldiers
- Laura Campbell-Sills, Jason D. Kautz, Karmel W. Choi, James A. Naifeh, Pablo A. Aliaga, Sonia Jain, Xiaoying Sun, Ronald C. Kessler, Murray B. Stein, Robert J. Ursano, Paul D. Bliese
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- Journal:
- Psychological Medicine / Volume 53 / Issue 5 / April 2023
- Published online by Cambridge University Press:
- 22 November 2021, pp. 2031-2040
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Background
Problematic anger is frequently reported by soldiers who have deployed to combat zones. However, evidence is lacking with respect to how anger changes over a deployment cycle, and which factors prospectively influence change in anger among combat-deployed soldiers.
MethodsReports of problematic anger were obtained from 7298 US Army soldiers who deployed to Afghanistan in 2012. A series of mixed-effects growth models estimated linear trajectories of anger over a period of 1–2 months before deployment to 9 months post-deployment, and evaluated the effects of pre-deployment factors (prior deployments and perceived resilience) on average levels and growth of problematic anger.
ResultsA model with random intercepts and slopes provided the best fit, indicating heterogeneity in soldiers' levels and trajectories of anger. First-time deployers reported the lowest anger overall, but the most growth in anger over time. Soldiers with multiple prior deployments displayed the highest anger overall, which remained relatively stable over time. Higher pre-deployment resilience was associated with lower reports of anger, but its protective effect diminished over time. First- and second-time deployers reporting low resilience displayed different anger trajectories (stable v. decreasing, respectively).
ConclusionsChange in anger from pre- to post-deployment varies based on pre-deployment factors. The observed differences in anger trajectories suggest that efforts to detect and reduce problematic anger should be tailored for first-time v. repeat deployers. Ongoing screening is needed even for soldiers reporting high resilience before deployment, as the protective effect of pre-deployment resilience on anger erodes over time.
Daily Cannabis Use is Associated With Lower CNS Inflammation in People With HIV
- C. Wei-Ming Watson, Laura M. Campbell, Ni Sun-Suslow, Suzi Hong, Anya Umlauf, Ronald J. Ellis, Jennifer E. Iudicello, Scott Letendre, Thomas D. Marcotte, Robert K. Heaton, Erin E. Morgan, Igor Grant
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- Journal:
- Journal of the International Neuropsychological Society / Volume 27 / Issue 6 / July 2021
- Published online by Cambridge University Press:
- 15 July 2021, pp. 661-672
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Objective:
Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis’s anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH.
Methods:263 individuals were categorized into four groups: HIV− non-cannabis users (n = 65), HIV+ non-cannabis users (n = 105), HIV+ moderate cannabis users (n = 62), and HIV+ daily cannabis users (n = 31). Differences in pro-inflammatory biomarkers (IL-6, MCP-1/CCL2, IP-10/CXCL10, sCD14, sTNFR-II, TNF-α) by study group were determined by Kruskal–Wallis tests. Multivariable linear regressions examined relationships between biomarkers and seven cognitive domains, adjusting for age, sex/gender, race, education, and current CD4 count.
Results:HIV+ daily cannabis users showed lower MCP-1 and IP-10 levels in CSF compared to HIV+ non-cannabis users (p = .015; p = .039) and were similar to HIV− non-cannabis users. Plasma biomarkers showed no differences by cannabis use. Among PWH, lower CSF MCP-1 and lower CSF IP-10 were associated with better learning performance (all ps < .05).
Conclusions:Current daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning which is commonly impaired in PWH. Cannabinoid-related reductions of MCP-1 and IP-10, if confirmed, suggest a role for medicinal cannabis in the mitigation of persistent inflammation and cognitive impacts of HIV.
Dissecting the heterogeneity of posttraumatic stress disorder: differences in polygenic risk, stress exposures, and course of PTSD subtypes
- Laura Campbell-Sills, Xiaoying Sun, Karmel W. Choi, Feng He, Robert J. Ursano, Ronald C. Kessler, Daniel F. Levey, Jordan W. Smoller, Joel Gelernter, Sonia Jain, Murray B. Stein
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- Journal:
- Psychological Medicine / Volume 52 / Issue 15 / November 2022
- Published online by Cambridge University Press:
- 05 May 2021, pp. 3646-3654
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Background
Definition of disorder subtypes may facilitate precision treatment for posttraumatic stress disorder (PTSD). We aimed to identify PTSD subtypes and evaluate their associations with genetic risk factors, types of stress exposures, comorbidity, and course of PTSD.
MethodsData came from a prospective study of three U.S. Army Brigade Combat Teams that deployed to Afghanistan in 2012. Soldiers with probable PTSD (PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition ≥31) at three months postdeployment comprised the sample (N = 423) for latent profile analysis using Gaussian mixture modeling and PTSD symptom ratings as indicators. PTSD profiles were compared on polygenic risk scores (derived from external genomewide association study summary statistics), experiences during deployment, comorbidity at three months postdeployment, and persistence of PTSD at nine months postdeployment.
ResultsLatent profile analysis revealed profiles characterized by prominent intrusions, avoidance, and hyperarousal (threat-reactivity profile; n = 129), anhedonia and negative affect (dysphoric profile; n = 195), and high levels of all PTSD symptoms (high-symptom profile; n = 99). The threat-reactivity profile had the most combat exposure and the least comorbidity. The dysphoric profile had the highest polygenic risk for major depression, and more personal life stress and co-occurring major depression than the threat-reactivity profile. The high-symptom profile had the highest rates of concurrent mental disorders and persistence of PTSD.
ConclusionsGenetic and trauma-related factors likely contribute to PTSD heterogeneity, which can be parsed into subtypes that differ in symptom expression, comorbidity, and course. Future studies should evaluate whether PTSD typology modifies treatment response and should clarify distinctions between the dysphoric profile and depressive disorders.