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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.
Risk of bacterial bloodstream infection does not vary by central-line type during neutropenic periods in pediatric acute myeloid leukemia
- Caitlin W. Elgarten, William R. Otto, Luke Shenton, Madison T. Stein, Joseph Horowitz, Catherine Aftandilian, Staci D. Arnold, Kira O. Bona, Emi Caywood, Anderson B. Collier, M. Monica Gramatges, Meret Henry, Craig Lotterman, Kelly Maloney, Arunkumar J. Modi, Amir Mian, Rajen Mody, Elaine Morgan, Elizabeth A. Raetz, Anupam Verma, Naomi Winick, Jennifer J. Wilkes, Jennifer C. Yu, Richard Aplenc, Brian T. Fisher, Kelly D. Getz
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 44 / Issue 2 / February 2023
- Published online by Cambridge University Press:
- 25 April 2022, pp. 222-229
- Print publication:
- February 2023
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Background:
Bloodstream infections (BSIs) are a frequent cause of morbidity in patients with acute myeloid leukemia (AML), due in part to the presence of central venous access devices (CVADs) required to deliver therapy.
Objective:To determine the differential risk of bacterial BSI during neutropenia by CVAD type in pediatric patients with AML.
Methods:We performed a secondary analysis in a cohort of 560 pediatric patients (1,828 chemotherapy courses) receiving frontline AML chemotherapy at 17 US centers. The exposure was CVAD type at course start: tunneled externalized catheter (TEC), peripherally inserted central catheter (PICC), or totally implanted catheter (TIC). The primary outcome was course-specific incident bacterial BSI; secondary outcomes included mucosal barrier injury (MBI)-BSI and non-MBI BSI. Poisson regression was used to compute adjusted rate ratios comparing BSI occurrence during neutropenia by line type, controlling for demographic, clinical, and hospital-level characteristics.
Results:The rate of BSI did not differ by CVAD type: 11 BSIs per 1,000 neutropenic days for TECs, 13.7 for PICCs, and 10.7 for TICs. After adjustment, there was no statistically significant association between CVAD type and BSI: PICC incident rate ratio [IRR] = 1.00 (95% confidence interval [CI], 0.75–1.32) and TIC IRR = 0.83 (95% CI, 0.49–1.41) compared to TEC. When MBI and non-MBI were examined separately, results were similar.
Conclusions:In this large, multicenter cohort of pediatric AML patients, we found no difference in the rate of BSI during neutropenia by CVAD type. This may be due to a risk-profile for BSI that is unique to AML patients.
Pain perception and physiological correlates in body-focused repetitive behavior disorders
- Christine Lochner, Janine Roos, Martin Kidd, Gaironeesa Hendricks, Tara S. Peris, Emily J. Ricketts, Darin D. Dougherty, Douglas W. Woods, Nancy J. Keuthen, Dan J. Stein, Jon E. Grant, John Piacentini
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- Journal:
- CNS Spectrums / Volume 28 / Issue 2 / April 2023
- Published online by Cambridge University Press:
- 22 March 2022, pp. 197-204
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Background
Behaviors typical of body-focused repetitive behavior disorders such as trichotillomania (TTM) and skin-picking disorder (SPD) are often associated with pleasure or relief, and with little or no physical pain, suggesting aberrant pain perception. Conclusive evidence about pain perception and correlates in these conditions is, however, lacking.
MethodsA multisite international study examined pain perception and its physiological correlates in adults with TTM (n = 31), SPD (n = 24), and healthy controls (HCs; n = 26). The cold pressor test was administered, and measurements of pain perception and cardiovascular parameters were taken every 15 seconds. Pain perception, latency to pain tolerance, cardiovascular parameters and associations with illness severity, and comorbid depression, as well as interaction effects (group × time interval), were investigated across groups.
ResultsThere were no group differences in pain ratings over time (P = .8) or latency to pain tolerance (P = .8). Illness severity was not associated with pain ratings (all P > .05). In terms of diastolic blood pressure (DBP), the main effect of group was statistically significant (P = .01), with post hoc analyses indicating higher mean DBP in TTM (95% confidence intervals [CI], 84.0-93.5) compared to SPD (95% CI, 73.5-84.2; P = .01), and HCs (95% CI, 75.6-86.0; P = .03). Pain perception did not differ between those with and those without depression (TTM: P = .2, SPD: P = .4).
ConclusionThe study findings were mostly negative suggesting that general pain perception aberration is not involved in TTM and SPD. Other underlying drivers of hair-pulling and skin-picking behavior (eg, abnormal reward processing) should be investigated.
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.
Neurobiology of subtypes of trichotillomania and skin picking disorder
- Jon E. Grant, Richard A. I. Bethlehem, Samuel R. Chamberlain, Tara S. Peris, Emily J. Ricketts, Joseph O’Neill, Darin D. Dougherty, Dan Stein, Christine Lochner, Douglas W. Woods, John Piacentini, Nancy J. Keuthen
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- CNS Spectrums / Volume 28 / Issue 1 / February 2023
- Published online by Cambridge University Press:
- 03 November 2021, pp. 98-103
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Background
Trichotillomania (TTM) and skin picking disorder (SPD) are common and often debilitating mental health conditions, grouped under the umbrella term of body-focused repetitive behaviors (BFRBs). Recent clinical subtyping found that there were three distinct subtypes of TTM and two of SPD. Whether these clinical subtypes map on to any unique neurobiological underpinnings, however, remains unknown.
MethodsTwo hundred and fifty one adults [193 with a BFRB (85.5% [n = 165] female) and 58 healthy controls (77.6% [n = 45] female)] were recruited from the community for a multicenter between-group comparison using structural neuroimaging. Differences in whole brain structure were compared across the subtypes of BFRBs, controlling for age, sex, scanning site, and intracranial volume.
ResultsWhen the subtypes of TTM were compared, low awareness hair pullers demonstrated increased cortical volume in the lateral occipital lobe relative to controls and sensory sensitive pullers. In addition, impulsive/perfectionist hair pullers showed relative decreased volume near the lingual gyrus of the inferior occipital–parietal lobe compared with controls.
ConclusionsThese data indicate that the anatomical substrates of particular forms of BFRBs are dissociable, which may have implications for understanding clinical presentations and treatment response.
The prevalence of mental health problems in sub-Saharan adolescents living with HIV: a systematic review
- A.S. Dessauvagie, A. Jörns-Presentati, A.-K. Napp, D.J. Stein, D. Jonker, E. Breet, W. Charles, R. L. Swart, M. Lahti, S. Suliman, R. Jansen, L.L. van den Heuvel, S. Seedat, G. Groen
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- Journal:
- Global Mental Health / Volume 7 / 2020
- Published online by Cambridge University Press:
- 26 October 2020, e29
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Despite the progress made in HIV treatment and prevention, HIV remains a major cause of adolescent morbidity and mortality in sub-Saharan Africa. As perinatally infected children increasingly survive into adulthood, the quality of life and mental health of this population has increased in importance. This review provides a synthesis of the prevalence of mental health problems in this population and explores associated factors. A systematic database search (Medline, PsycINFO, Scopus) with an additional hand search was conducted. Peer-reviewed studies on adolescents (aged 10–19), published between 2008 and 2019, assessing mental health symptoms or psychiatric disorders, either by standardized questionnaires or by diagnostic interviews, were included. The search identified 1461 articles, of which 301 were eligible for full-text analysis. Fourteen of these, concerning HIV-positive adolescents, met the inclusion criteria and were critically appraised. Mental health problems were highly prevalent among this group, with around 25% scoring positive for any psychiatric disorder and 30–50% showing emotional or behavioral difficulties or significant psychological distress. Associated factors found by regression analysis were older age, not being in school, impaired family functioning, HIV-related stigma and bullying, and poverty. Social support and parental competence were protective factors. Mental health problems among HIV-positive adolescents are highly prevalent and should be addressed as part of regular HIV care.
Comorbidity within mental disorders: a comprehensive analysis based on 145 990 survey respondents from 27 countries
- J. J. McGrath, C. C. W. Lim, O. Plana-Ripoll, Y. Holtz, E. Agerbo, N. C. Momen, P. B. Mortensen, C. B. Pedersen, J. Abdulmalik, S. Aguilar-Gaxiola, A. Al-Hamzawi, J. Alonso, E. J. Bromet, R. Bruffaerts, B. Bunting, J. M. C. de Almeida, G. de Girolamo, Y. A. De Vries, S. Florescu, O. Gureje, J. M. Haro, M. G. Harris, C. Hu, E. G. Karam, N. Kawakami, A. Kiejna, V. Kovess-Masfety, S. Lee, Z. Mneimneh, F. Navarro-Mateu, R. Orozco, J. Posada-Villa, A. M. Roest, S. Saha, K. M. Scott, J. C. Stagnaro, D. J. Stein, Y. Torres, M. C. Viana, Y. Ziv, R. C. Kessler, P. de Jonge
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- Journal:
- Epidemiology and Psychiatric Sciences / Volume 29 / 2020
- Published online by Cambridge University Press:
- 12 August 2020, e153
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Aims
Epidemiological studies indicate that individuals with one type of mental disorder have an increased risk of subsequently developing other types of mental disorders. This study aimed to undertake a comprehensive analysis of pair-wise lifetime comorbidity across a range of common mental disorders based on a diverse range of population-based surveys.
MethodsThe WHO World Mental Health (WMH) surveys assessed 145 990 adult respondents from 27 countries. Based on retrospectively-reported age-of-onset for 24 DSM-IV mental disorders, associations were examined between all 548 logically possible temporally-ordered disorder pairs. Overall and time-dependent hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Absolute risks were estimated using the product-limit method. Estimates were generated separately for men and women.
ResultsEach prior lifetime mental disorder was associated with an increased risk of subsequent first onset of each other disorder. The median HR was 12.1 (mean = 14.4; range 5.2–110.8, interquartile range = 6.0–19.4). The HRs were most prominent between closely-related mental disorder types and in the first 1–2 years after the onset of the prior disorder. Although HRs declined with time since prior disorder, significantly elevated risk of subsequent comorbidity persisted for at least 15 years. Appreciable absolute risks of secondary disorders were found over time for many pairs.
ConclusionsSurvey data from a range of sites confirms that comorbidity between mental disorders is common. Understanding the risks of temporally secondary disorders may help design practical programs for primary prevention of secondary disorders.
Unit cohesion during deployment and post-deployment mental health: is cohesion an individual- or unit-level buffer for combat-exposed soldiers?
- Laura Campbell-Sills, Patrick J. Flynn, Karmel W. Choi, Tsz Hin H. Ng, Pablo A. Aliaga, Catherine Broshek, Sonia Jain, Ronald C. Kessler, Murray B. Stein, Robert J. Ursano, Paul D. Bliese
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- Journal:
- Psychological Medicine / Volume 52 / Issue 1 / January 2022
- Published online by Cambridge University Press:
- 10 June 2020, pp. 121-131
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Background
Unit cohesion may protect service member mental health by mitigating effects of combat exposure; however, questions remain about the origins of potential stress-buffering effects. We examined buffering effects associated with two forms of unit cohesion (peer-oriented horizontal cohesion and subordinate-leader vertical cohesion) defined as either individual-level or aggregated unit-level variables.
MethodsLongitudinal survey data from US Army soldiers who deployed to Afghanistan in 2012 were analyzed using mixed-effects regression. Models evaluated individual- and unit-level interaction effects of combat exposure and cohesion during deployment on symptoms of post-traumatic stress disorder (PTSD), depression, and suicidal ideation reported at 3 months post-deployment (model n's = 6684 to 6826). Given the small effective sample size (k = 89), the significance of unit-level interactions was evaluated at a 90% confidence level.
ResultsAt the individual-level, buffering effects of horizontal cohesion were found for PTSD symptoms [B = −0.11, 95% CI (−0.18 to −0.04), p < 0.01] and depressive symptoms [B = −0.06, 95% CI (−0.10 to −0.01), p < 0.05]; while a buffering effect of vertical cohesion was observed for PTSD symptoms only [B = −0.03, 95% CI (−0.06 to −0.0001), p < 0.05]. At the unit-level, buffering effects of horizontal (but not vertical) cohesion were observed for PTSD symptoms [B = −0.91, 90% CI (−1.70 to −0.11), p = 0.06], depressive symptoms [B = −0.83, 90% CI (−1.24 to −0.41), p < 0.01], and suicidal ideation [B = −0.32, 90% CI (−0.62 to −0.01), p = 0.08].
ConclusionsPolicies and interventions that enhance horizontal cohesion may protect combat-exposed units against post-deployment mental health problems. Efforts to support individual soldiers who report low levels of horizontal or vertical cohesion may also yield mental health benefits.
Influence of birth cohort on age of onset cluster analysis in bipolar I disorder
- M. Bauer, T. Glenn, M. Alda, O.A. Andreassen, E. Angelopoulos, R. Ardau, C. Baethge, R. Bauer, F. Bellivier, R.H. Belmaker, M. Berk, T.D. Bjella, L. Bossini, Y. Bersudsky, E.Y.W. Cheung, J. Conell, M. Del Zompo, S. Dodd, B. Etain, A. Fagiolini, M.A. Frye, K.N. Fountoulakis, J. Garneau-Fournier, A. Gonzalez-Pinto, H. Harima, S. Hassel, C. Henry, A. Iacovides, E.T. Isometsä, F. Kapczinski, S. Kliwicki, B. König, R. Krogh, M. Kunz, B. Lafer, E.R. Larsen, U. Lewitzka, C. Lopez-Jaramillo, G. MacQueen, M. Manchia, W. Marsh, M. Martinez-Cengotitabengoa, I. Melle, S. Monteith, G. Morken, R. Munoz, F.G. Nery, C. O’Donovan, Y. Osher, A. Pfennig, D. Quiroz, R. Ramesar, N. Rasgon, A. Reif, P. Ritter, J.K. Rybakowski, K. Sagduyu, A.M. Scippa, E. Severus, C. Simhandl, D.J. Stein, S. Strejilevich, A. Hatim Sulaiman, K. Suominen, H. Tagata, Y. Tatebayashi, C. Torrent, E. Vieta, B. Viswanath, M.J. Wanchoo, M. Zetin, P.C. Whybrow
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- Journal:
- European Psychiatry / Volume 30 / Issue 1 / January 2015
- Published online by Cambridge University Press:
- 15 April 2020, pp. 99-105
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Purpose:
Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.
Methods:The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.
Results:There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups.
Conclusion:These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.
Using self-report surveys at the beginning of service to develop multi-outcome risk models for new soldiers in the U.S. Army
- A. J. Rosellini, M. B. Stein, D. M. Benedek, P. D. Bliese, W. T. Chiu, I. Hwang, J. Monahan, M. K. Nock, M. V. Petukhova, N. A. Sampson, A. E. Street, A. M. Zaslavsky, R. J. Ursano, R.C. Kessler,
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- Journal:
- Psychological Medicine / Volume 47 / Issue 13 / October 2017
- Published online by Cambridge University Press:
- 04 April 2017, pp. 2275-2287
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Background
The U.S. Army uses universal preventives interventions for several negative outcomes (e.g. suicide, violence, sexual assault) with especially high risks in the early years of service. More intensive interventions exist, but would be cost-effective only if targeted at high-risk soldiers. We report results of efforts to develop models for such targeting from self-report surveys administered at the beginning of Army service.
Methods21 832 new soldiers completed a self-administered questionnaire (SAQ) in 2011–2012 and consented to link administrative data to SAQ responses. Penalized regression models were developed for 12 administratively-recorded outcomes occurring by December 2013: suicide attempt, mental hospitalization, positive drug test, traumatic brain injury (TBI), other severe injury, several types of violence perpetration and victimization, demotion, and attrition.
ResultsThe best-performing models were for TBI (AUC = 0.80), major physical violence perpetration (AUC = 0.78), sexual assault perpetration (AUC = 0.78), and suicide attempt (AUC = 0.74). Although predicted risk scores were significantly correlated across outcomes, prediction was not improved by including risk scores for other outcomes in models. Of particular note: 40.5% of suicide attempts occurred among the 10% of new soldiers with highest predicted risk, 57.2% of male sexual assault perpetrations among the 15% with highest predicted risk, and 35.5% of female sexual assault victimizations among the 10% with highest predicted risk.
ConclusionsData collected at the beginning of service in self-report surveys could be used to develop risk models that define small proportions of new soldiers accounting for high proportions of negative outcomes over the first few years of service.
The cross-national epidemiology of DSM-IV intermittent explosive disorder
- K. M. Scott, C. C. W. Lim, I. Hwang, T. Adamowski, A. Al-Hamzawi, E. Bromet, B. Bunting, M. P. Ferrand, S. Florescu, O. Gureje, H. Hinkov, C. Hu, E. Karam, S. Lee, J. Posada-Villa, D. Stein, H. Tachimori, M. C. Viana, M. Xavier, R. C. Kessler
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- Journal:
- Psychological Medicine / Volume 46 / Issue 15 / November 2016
- Published online by Cambridge University Press:
- 30 August 2016, pp. 3161-3172
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Background
This is the first cross-national study of intermittent explosive disorder (IED).
MethodA total of 17 face-to-face cross-sectional household surveys of adults were conducted in 16 countries (n = 88 063) as part of the World Mental Health Surveys initiative. The World Health Organization Composite International Diagnostic Interview (CIDI 3.0) assessed DSM-IV IED, using a conservative definition.
ResultsLifetime prevalence of IED ranged across countries from 0.1 to 2.7% with a weighted average of 0.8%; 0.4 and 0.3% met criteria for 12-month and 30-day prevalence, respectively. Sociodemographic correlates of lifetime risk of IED were being male, young, unemployed, divorced or separated, and having less education. The median age of onset of IED was 17 years with an interquartile range across countries of 13–23 years. The vast majority (81.7%) of those with lifetime IED met criteria for at least one other lifetime disorder; co-morbidity was highest with alcohol abuse and depression. Of those with 12-month IED, 39% reported severe impairment in at least one domain, most commonly social or relationship functioning. Prior traumatic experiences involving physical (non-combat) or sexual violence were associated with increased risk of IED onset.
ConclusionsConservatively defined, IED is a low prevalence disorder but this belies the true societal costs of IED in terms of the effects of explosive anger attacks on families and relationships. IED is more common among males, the young, the socially disadvantaged and among those with prior exposure to violence, especially in childhood.
A randomised double-blind placebo-controlled trial investigating the behavioural effects of vitamin, mineral and n-3 fatty acid supplementation in typically developing adolescent schoolchildren
- Jonathan D. Tammam, David Steinsaltz, D. W. Bester, Turid Semb-Andenaes, John F. Stein
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- Journal:
- British Journal of Nutrition / Volume 115 / Issue 2 / 28 January 2016
- Published online by Cambridge University Press:
- 17 November 2015, pp. 361-373
- Print publication:
- 28 January 2016
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Nutrient deficiencies have been implicated in anti-social behaviour in schoolchildren; hence, correcting them may improve sociability. We therefore tested the effects of vitamin, mineral and n-3 supplementation on behaviour in a 12-week double-blind randomised placebo-controlled trial in typically developing UK adolescents aged 13–16 years (n 196). Changes in erythrocyte n-3 and 6 fatty acids and some mineral and vitamin levels were measured and compared with behavioural changes, using Conners’ teacher ratings and school disciplinary records. At baseline, the children’s PUFA (n-3 and n-6), vitamin and mineral levels were low, but they improved significantly in the group treated with n-3, vitamins and minerals (P=0·0005). On the Conners disruptive behaviour scale, the group given the active supplements improved, whereas the placebo group worsened (F=5·555, d=0·35; P=0·02). The general level of disciplinary infringements was low, thus making it difficult to obtain improvements. However, throughout the school term school disciplinary infringements increased significantly (by 25 %; Bayes factor=115) in both the treated and untreated groups. However, when the subjects were split into high and low baseline infringements, the low subset increased their offences, whereas the high-misbehaviour subset appeared to improve after treatment. But it was not possible to determine whether this was merely a statistical artifact. Thus, when assessed using the validated and standardised Conners teacher tests (but less clearly when using school discipline records in a school where misbehaviour was infrequent), supplementary nutrition might have a protective effect against worsening behaviour.
Occupational differences in US Army suicide rates
- R. C. Kessler, M. B. Stein, P. D. Bliese, E. J. Bromet, W. T. Chiu, K. L. Cox, L. J. Colpe, C. S. Fullerton, S. E. Gilman, M. J. Gruber, S. G. Heeringa, L. Lewandowski-Romps, A. Millikan-Bell, J. A. Naifeh, M. K. Nock, M. V. Petukhova, A. J. Rosellini, N. A. Sampson, M. Schoenbaum, A. M. Zaslavsky, R. J. Ursano
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- Journal:
- Psychological Medicine / Volume 45 / Issue 15 / November 2015
- Published online by Cambridge University Press:
- 20 July 2015, pp. 3293-3304
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Background
Civilian suicide rates vary by occupation in ways related to occupational stress exposure. Comparable military research finds suicide rates elevated in combat arms occupations. However, no research has evaluated variation in this pattern by deployment history, the indicator of occupation stress widely considered responsible for the recent rise in the military suicide rate.
MethodThe joint associations of Army occupation and deployment history in predicting suicides were analysed in an administrative dataset for the 729 337 male enlisted Regular Army soldiers in the US Army between 2004 and 2009.
ResultsThere were 496 suicides over the study period (22.4/100 000 person-years). Only two occupational categories, both in combat arms, had significantly elevated suicide rates: infantrymen (37.2/100 000 person-years) and combat engineers (38.2/100 000 person-years). However, the suicide rates in these two categories were significantly lower when currently deployed (30.6/100 000 person-years) than never deployed or previously deployed (41.2–39.1/100 000 person-years), whereas the suicide rate of other soldiers was significantly higher when currently deployed and previously deployed (20.2–22.4/100 000 person-years) than never deployed (14.5/100 000 person-years), resulting in the adjusted suicide rate of infantrymen and combat engineers being most elevated when never deployed [odds ratio (OR) 2.9, 95% confidence interval (CI) 2.1–4.1], less so when previously deployed (OR 1.6, 95% CI 1.1–2.1), and not at all when currently deployed (OR 1.2, 95% CI 0.8–1.8). Adjustment for a differential ‘healthy warrior effect’ cannot explain this variation in the relative suicide rates of never-deployed infantrymen and combat engineers by deployment status.
ConclusionsEfforts are needed to elucidate the causal mechanisms underlying this interaction to guide preventive interventions for soldiers at high suicide risk.
Contributors
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- By Andrew Adesman, Lenard A. Adler, Samuel Alperin, Kira E. Armstrong, L. Eugene Arnold, Amy F. T. Arnsten, Russell A. Barkley, Craig W. Berridge, Joseph Biederman, F. Xavier Castellanos, Barbara J. Coffey, Alison M. Cohn, C. Keith Conners, Joan M. Daughton, Stephen V. Faraone, John Fayyad, Lisa G. Hahn, Laura Hans, Elizabeth Hurt, Gagan Joshi, Rahil Jummani, Jesse M. Jun, Ronald C. Kessler, Scott Haden Kollins, Kimberly Kovacs, Christopher J. Kratochvil, Beth Krone, Nicholas Lofthouse, Michael J. Manos, Francis Joseph McClernon, Joel E. Morgan, Nicholas R. Morrison, Sonali Nanayakkara, Jeffrey H. Newcorn, Phillip L. Pearl, Juan D. Pedraza, Guy M. L. Perry, Steven R. Pliszka, Jefferson B. Prince, J. Russell Ramsay, Anthony L. Rostain, David M. Shaw, Mary V. Solanto, Mark A. Stein, Jonathan R. Stevens, Brigette S. Vaughan, Margaret Weiss, Roy E. Weiss, Timothy E. Wilens, Janet Wozniak
- Edited by Lenard A. Adler, New York University School of Medicine, Thomas J. Spencer, Timothy E. Wilens
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- Book:
- Attention-Deficit Hyperactivity Disorder in Adults and Children
- Published online:
- 05 February 2015
- Print publication:
- 08 January 2015, pp vii-x
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- By Lenard A. Adler, Pinky Agarwal, Rehan Ahmed, Jagga Rao Alluri, Fawaz Al-Mufti, Samuel Alperin, Michael Amoashiy, Michael Andary, David J. Anschel, Padmaja Aradhya, Vandana Aspen, Esther Baldinger, Jee Bang, George D. Baquis, John J. Barry, Jason J. S. Barton, Julius Bazan, Amanda R. Bedford, Marlene Behrmann, Lourdes Bello-Espinosa, Ajay Berdia, Alan R. Berger, Mark Beyer, Don C. Bienfang, Kevin M. Biglan, Thomas M. Boes, Paul W. Brazis, Jonathan L. Brisman, Jeffrey A. Brown, Scott E. Brown, Ryan R. Byrne, Rina Caprarella, Casey A. Chamberlain, Wan-Tsu W. Chang, Grace M. Charles, Jasvinder Chawla, David Clark, Todd J. Cohen, Joe Colombo, Howard Crystal, Vladimir Dadashev, Sarita B. Dave, Jean Robert Desrouleaux, Richard L. Doty, Robert Duarte, Jeffrey S. Durmer, Christyn M. Edmundson, Eric R. Eggenberger, Steven Ender, Noam Epstein, Alberto J. Espay, Alan B. Ettinger, Niloofar (Nelly) Faghani, Amtul Farheen, Edward Firouztale, Rod Foroozan, Anne L. Foundas, David Elliot Friedman, Deborah I. Friedman, Steven J. Frucht, Oded Gerber, Tal Gilboa, Martin Gizzi, Teneille G. Gofton, Louis J. Goodrich, Malcolm H. Gottesman, Varda Gross-Tsur, Deepak Grover, David A. Gudis, John J. Halperin, Maxim D. Hammer, Andrew R. Harrison, L. Anne Hayman, Galen V. Henderson, Steven Herskovitz, Caitlin Hoffman, Laryssa A. Huryn, Andres M. Kanner, Gary P. Kaplan, Bashar Katirji, Kenneth R. Kaufman, Annie Killoran, Nina Kirz, Gad E. Klein, Danielle G. Koby, Christopher P. Kogut, W. Curt LaFrance, Patrick J.M. Lavin, Susan W. Law, James L. Levenson, Richard B. Lipton, Glenn Lopate, Daniel J. Luciano, Reema Maindiratta, Robert M. Mallery, Georgios Manousakis, Alan Mazurek, Luis J. Mejico, Dragana Micic, Ali Mokhtarzadeh, Walter J. Molofsky, Heather E. Moss, Mark L. Moster, Manpreet Multani, Siddhartha Nadkarni, George C. Newman, Rolla Nuoman, Paul A. Nyquist, Gaia Donata Oggioni, Odi Oguh, Denis Ostrovskiy, Kristina Y. Pao, Juwen Park, Anastas F. Pass, Victoria S. Pelak, Jeffrey Peterson, John Pile-Spellman, Misha L. Pless, Gregory M. Pontone, Aparna M. Prabhu, Michael T. Pulley, Philip Ragone, Prajwal Rajappa, Venkat Ramani, Sindhu Ramchandren, Ritesh A. Ramdhani, Ramses Ribot, Heidi D. Riney, Diana Rojas-Soto, Michael Ronthal, Daniel M. Rosenbaum, David B. Rosenfield, Durga Roy, Michael J. Ruckenstein, Max C. Rudansky, Eva Sahay, Friedhelm Sandbrink, Jade S. Schiffman, Angela Scicutella, Maroun T. Semaan, Robert C. Sergott, Aashit K. Shah, David M. Shaw, Amit M. Shelat, Claire A. Sheldon, Anant M. Shenoy, Yelizaveta Sher, Jessica A. Shields, Tanya Simuni, Rajpaul Singh, Eric E. Smouha, David Solomon, Mehri Songhorian, Steven A. Sparr, Egilius L. H. Spierings, Eve G. Spratt, Beth Stein, S.H. Subramony, Rosa Ana Tang, Cara Tannenbaum, Hakan Tekeli, Amanda J. Thompson, Michael J. Thorpy, Matthew J. Thurtell, Pedro J. Torrico, Ira M. Turner, Scott Uretsky, Ruth H. Walker, Deborah M. Weisbrot, Michael A. Williams, Jacques Winter, Randall J. Wright, Jay Elliot Yasen, Shicong Ye, G. Bryan Young, Huiying Yu, Ryan J. Zehnder
- Edited by Alan B. Ettinger, Albert Einstein College of Medicine, New York, Deborah M. Weisbrot, State University of New York, Stony Brook
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- Book:
- Neurologic Differential Diagnosis
- Published online:
- 05 June 2014
- Print publication:
- 17 April 2014, pp xi-xx
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- By Zachary W. Adams, Margarita Alegría, Atalay Alem, Jordi Alonso, Victor Aparicio, Rifat Atun, Florence Baingana, Emily Baron, Marco Bertelli, Dinesh Bhugra, Sanchita Biswas, José Miguel Caldas de Almeida, Edwin Cameron, Somnath Chatterji, Erminia Colucci, Janice L. Cooper, Carla Kmett Danielson, Diego De Leo, Mary-Jo DelVecchio Good, Marten W. de Vries, Maureen S. Durkin, Xiangming Fang, Julia W. Felton, Sally Field, Andrea Fiorillo, Lance Gable, Teddy Gafna, Sandro Galea, Patrick Gatonga, Sofia Halperin-Goldstein, Yanling He, Grace A. Herbert, Sabrina Hermosilla, Simone Honikman, Takashi Izutsu, Ruwan M. Jayatunge, Janis H. Jenkins, Rachel Jenkins, Lynne Jones, Jayanthi Karunaratne, Ronald C. Kessler, Rob Keukens, Lincoln I. Khasakhala, Hanna Kienzler, Sarah Kippen Wood, M. Thomas Kishore, Robert Kohn, Natasja Koitzsch Jensen, Sheri Lapatin, Anna Lessios, Isabel Louro Bernal, Feijun Luo, Laura MacPherson, Matthew J. Maenner, Anne W. Mbwayo, David McDaid, Ingrid Meintjes, Victoria N. Mutiso, David M. Ndetei, Samuel O. Okpaku, Lijing Ouyang, Ramachandran Padmavati, Clare Pain, Duncan Pedersen, Jordan Pfau, Felipe Picon, Rodney D. Presley, Reima Pryor, Shoba Raja, Thara Rangaswamy, Jorge Rodriguez, Diana Rose, Moosa Salie, Norman Sartorius, Ester Shapiro, Manuela Silva, Daya Somasundaram, Katherine Sorsdahl, Dan J. Stein, Deborah M. Stone, Heather Stuart, Athula Sumathipala, Hema Tharoor, Rita Thom, Lay San Too, Atsuro Tsutsumi, Chris Underhill, Anne Valentine, Claire van der Westhuizen, Thandi van Heyningen, Robert van Voren, Inka Weissbecker, Gail Wyatt
- Edited by Samuel O. Okpaku
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- Book:
- Essentials of Global Mental Health
- Published online:
- 05 March 2014
- Print publication:
- 27 February 2014, pp x-xiv
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- By Ashok Agarwal, Linda D. Applegarth, Nelson E. Bennett, Nancy L. Brackett, Melissa B. Brisman, Mark F. H. Brougham, Cara B. Cimmino, Owen K. Davis, Rian J. Dickstein, Michael L. Eisenberg, Mikkel Fode, Gretchen A. Gignac, Bruce R. Gilbert, Ellen R. Goldmark, Marc Goldstein, Wayne J. G. Hellstrom, Wayland Hsiao, Jack Huang, Kathleen Hwang, Ann A. Jakubowski, Keith Jarvi, Loren Jones, Hey-Joo Kang, Joanne Frankel Kelvin, Mohit Khera, Thomas F. Kolon, Kate H. Kraft, Andrew C. Kramer, Dolores J. Lamb, Andrew B. Lassman, Helen R. Levey, Larry I. Lipshultz, Charles M. Lynne, Akanksha Mehta, Marvin L. Meistrich, Gregory C. Mitchell, Mark A. Moyad, John P. Mulhall, Lauren Murray, Craig Niederberger, Ariella Noy, Robert D. Oates, Dana A. Ohl, Kutluk Oktay, Ndidiamaka Onwubalili, Fabio Firmbach Pasqualatto, Elena Pentsova, Susanne A. Quallich, Gwendolyn P. Quinn, Alex Ridgeway, Matthew T. Roberts, Kenny A. Rodriguez-Wallberg, Allison B. Rosen, Lisa Rosenzweig, Edmund S. Sabanegh, Hossein Sadeghi-Nejad, Mary K. Samplaski, Jay I. Sandlow, Peter N. Schlegel, Gunapala Shetty, Mark Sigman, Jens Sønksen, Peter J. Stahl, Eytan Stein, Doron S. Stember, Raanan Tal, Susan T. Vadaparampil, W. Hamish, B. Wallace, Leonard H. Wexler, Daniel H. Williams
- Edited by John P. Mulhall, Memorial Sloan-Kettering Cancer Center, New York
- Edited in association with Linda D. Applegarth, Robert D. Oates, Peter N. Schlegel
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- Book:
- Fertility Preservation in Male Cancer Patients
- Published online:
- 05 March 2013
- Print publication:
- 21 February 2013, pp vii-x
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Treatment of suicidal people around the world
- R. Bruffaerts, K. Demyttenaere, I. Hwang, W.-T. Chiu, N. Sampson, R. C. Kessler, J. Alonso, G. Borges, G. de Girolamo, R. de Graaf, S. Florescu, O. Gureje, C. Hu, E. G. Karam, N. Kawakami, S. Kostyuchenko, V. Kovess-Masfety, S. Lee, D. Levinson, H. Matschinger, J. Posada-Villa, R. Sagar, K. M. Scott, D. J. Stein, T. Tomov, M. C. Viana, M. K. Nock
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- Journal:
- The British Journal of Psychiatry / Volume 199 / Issue 1 / July 2011
- Published online by Cambridge University Press:
- 02 January 2018, pp. 64-70
- Print publication:
- July 2011
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Background
Suicide is a leading cause of death worldwide; however, little information is available about the treatment of suicidal people, or about barriers to treatment.
AimsTo examine the receipt of mental health treatment and barriers to care among suicidal people around the world.
MethodTwenty-one nationally representative samples worldwide (n=55 302; age 18 years and over) from the World Health Organization's World Mental Health Surveys were interviewed regarding past-year suicidal behaviour and past-year healthcare use. Suicidal respondents who had not used services in the past year were asked why they had not sought care.
ResultsTwo-fifths of the suicidal respondents had received treatment (from 17% in low-income countries to 56% in high-income countries), mostly from a general medical practitioner (22%), psychiatrist (15%) or non-psychiatrist (15%). Those who had actually attempted suicide were more likely to receive care. Low perceived need was the most important reason for not seeking help (58%), followed by attitudinal barriers such as the wish to handle the problem alone (40%) and structural barriers such as financial concerns (15%). Only 7% of respondents endorsed stigma as a reason for not seeking treatment.
ConclusionsMost people with suicide ideation, plans and attempts receive no treatment. This is a consistent and pervasive finding, especially in low-income countries. Improving the receipt of treatment worldwide will have to take into account culture-specific factors that may influence the process of help-seeking.
Contributors
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- By Charles E. Argoff, Gerard A. Banez, Samantha Boris-Karpel, Barbara K. Bruce, Alexandra S. Bullough, Annmarie Cano, Victor T. Chang, Elizabeth A. Clark, Daniel J. Clauw, June L. Dahl, Tam K. Dao, Amber M. Davis, Courtney L. Dixon, Michael H. Ebert, Robin M. Gallagher, Gerald W. Grass, Carmen R. Green, Jay Gunkelman, Bradford D. Hare, Jennifer A. Haythornthwaite, Jaclyn Heller Issner, W. Michael Hooten, Mark P. Jensen, Mark E. Jones, Robert D. Kerns, Raphael J. Leo, Morris Maizels, Mary E. Murawski, Brooke Myers-Sorger, Akiko Okifuji, Renata Okonkwo, John D. Otis, Stacy C. Parenteau, Laura E. Pence, Donald B. Penzien, Donna B. Pincus, Ellyn Poltrock Stein, Wendy J. Quinton, Jeanetta C. Rains, M. Carrington Reid, Thomas J. Romano, Jeffrey D. Rome, Robert L. Ruff, Suzanne S. Ruff, Steven H. Sanders, Ingra Schellenberg, John J. Sellinger, Howard S. Smith, Brenda Stoelb, Jon Streltzer, Mark D. Sullivan, Kimberly S. Swanson, Gabriel Tan, Stephen Thielke, Beverly E. Thorn, Cynthia O. Townsend, Dennis C. Turk, Stephanie C. Wallio, Lawrence J. Weinberger, David A. Williams, Hilary Wilson
- Edited by Michael H. Ebert, Yale University, Connecticut, Robert D. Kerns, Yale University, Connecticut
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- Book:
- Behavioral and Psychopharmacologic Pain Management
- Published online:
- 10 January 2011
- Print publication:
- 25 November 2010, pp ix-xii
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