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Utilization of machine learning for prediction of post-traumatic stress: a re-examination of cortisol in the prediction and pathways to non-remitting PTSD

Galatzer-Levy, I R; Ma, S; Statnikov, A; Yehuda, R; Shalev, A Y
To date, studies of biological risk factors have revealed inconsistent relationships with subsequent post-traumatic stress disorder (PTSD). The inconsistent signal may reflect the use of data analytic tools that are ill equipped for modeling the complex interactions between biological and environmental factors that underlay post-traumatic psychopathology. Further, using symptom-based diagnostic status as the group outcome overlooks the inherent heterogeneity of PTSD, potentially contributing to failures to replicate. To examine the potential yield of novel analytic tools, we reanalyzed data from a large longitudinal study of individuals identified following trauma in the general emergency room (ER) that failed to find a linear association between cortisol response to traumatic events and subsequent PTSD. First, latent growth mixture modeling empirically identified trajectories of post-traumatic symptoms, which then were used as the study outcome. Next, support vector machines with feature selection identified sets of features with stable predictive accuracy and built robust classifiers of trajectory membership (area under the receiver operator characteristic curve (AUC)=0.82 (95% confidence interval (CI)=0.80-0.85)) that combined clinical, neuroendocrine, psychophysiological and demographic information. Finally, graph induction algorithms revealed a unique path from childhood trauma via lower cortisol during ER admission, to non-remitting PTSD. Traditional general linear modeling methods then confirmed the newly revealed association, thereby delineating a specific target population for early endocrine interventions. Advanced computational approaches offer innovative ways for uncovering clinically significant, non-shared biological signals in heterogeneous samples.
PMCID:5416681
PMID: 28323285
ISSN: 2158-3188
CID: 2494462

Prevalence of mental disorders in elderly people: the European MentDis_ICF65+ study

Andreas, Sylke; Schulz, Holger; Volkert, Jana; Dehoust, Maria; Sehner, Susanne; Suling, Anna; Ausín, Berta; Canuto, Alessandra; Crawford, Mike; Da Ronch, Chiara; Grassi, Luigi; Hershkovitz, Yael; Muñoz, Manuel; Quirk, Alan; Rotenstein, Ora; Santos-Olmo, Ana Belén; Shalev, Arieh; Strehle, Jens; Weber, Kerstin; Wegscheider, Karl; Wittchen, Hans-Ulrich; Härter, Martin
BACKGROUND:Except for dementia and depression, little is known about common mental disorders in elderly people. AIMS:To estimate current, 12-month and lifetime prevalence rates of mental disorders in different European and associated countries using a standardised diagnostic interview adapted to measure the cognitive needs of elderly people. METHOD:The MentDis_ICF65+ study is based on an age-stratified, random sample of 3142 older men and women (65-84 years) living in selected catchment community areas of participating countries. RESULTS:One in two individuals had experienced a mental disorder in their lifetime, one in three within the past year and nearly one in four currently had a mental disorder. The most prevalent disorders were anxiety disorders, followed by affective and substance-related disorders. CONCLUSIONS:Compared with previous studies we found substantially higher prevalence rates for most mental disorders. These findings underscore the need for improving diagnostic assessments adapted to the cognitive capacity of elderly people. There is a need to raise awareness of psychosocial problems in elderly people and to deliver high-quality mental health services to these individuals.
PMID: 27609811
ISSN: 1472-1465
CID: 4765792

Efficacy and Tolerability of High-Dose Escitalopram in Posttraumatic Stress Disorder

Qi, Wei; Gevonden, Martin; Shalev, Arieh
BACKGROUND: Open-label trials suggest that escitalopram (up to 20 mg/d) is an effective treatment for some, but not all posttraumatic stress disorder (PTSD) patients. Higher doses of escitalopram effectively reduced major depression symptoms in patients who had not responded to regular doses. The current study examines the efficacy, tolerability, and adherence to high-dose escitalopram in PTSD. METHODS: Forty-five PTSD patients received 12 weeks of gradually increasing doses of escitalopram reaching 40 mg daily at 4 weeks. Among those, 12 participants received regular doses of antidepressants at study onset including escitalopram (n = 7). The Clinician-Administered PTSD Scale (CAPS) evaluated PTSD symptoms severity before treatment, at 3 months (upon treatment termination), and at 6 months (maintenance effect). A 20% reduction in CAPS scores was deemed clinically significant. RESULTS: Adverse events and medication adherence were monitored at each clinical session. Linear mixed-models analysis showed a significant reduction of mean CAPS scores (11.5 +/- 18.1 points) at 3 months and maintenance of gains by 6 months (F2,34.56 = 8.15, P = 0.001). Eleven participants (34.3%) showed clinically significant improvement at 3 months. Only 9 participants (20%) left the study. There were no serious adverse events and few mild ones with only 2 adverse events (diarrhea, 11.1%; drowsiness, 11.1%) reported by more than 10% of participants. CONCLUSION: High doses of escitalopram are tolerable and well adhered to in PTSD. Their beneficial effect at a group level is due to a particularly good response in a subset of patients.Variability in prior pharmacological treatment precludes a definite attribution of the results to high doses of escitalopram.
PMID: 27977469
ISSN: 1533-712X
CID: 2363582

Prevalence and correlates of somatoform disorders in the elderly: Results of a European study

Dehoust, Maria Christina; Schulz, Holger; Haerter, Martin; Volkert, Jana; Sehner, Susanne; Drabik, Anna; Wegscheider, Karl; Canuto, Alessandra; Weber, Kerstin; Crawford, Mike; Quirk, Alan; Grassi, Luigi; DaRonch, Chiara; Munoz, Manuel; Ausin, Berta; Santos-Olmo, Anna; Shalev, Arieh; Rotenstein, Ora; Hershkowitz, Yael; Strehle, Jens; Wittchen, Hans-Ulrich; Andreas, Sylke
ISI:000397503900005
ISSN: 1049-8931
CID: 4765622

Robust Prediction of PTSD Likelihood From Early Symptoms Results From the International Consortium to Predict PTSD (ICPP) Pooled Data Analysis [Meeting Abstract]

Shalev, Arieh; Ratanatharathorn, Andrew; Qi, Wei; Gevonden, Martin; Kessler, Ron; Koenen, Karestan; Laska, Eugene
ISI:000416846301021
ISSN: 0893-133x
CID: 4765562

Post-traumatic stress disorder associated with life-threatening motor vehicle collisions in the WHO World Mental Health Surveys

Stein, Dan J; Karam, Elie G; Shahly, Victoria; Hill, Eric D; King, Andrew; Petukhova, Maria; Atwoli, Lukoye; Bromet, Evelyn J; Florescu, Silvia; Haro, Josep Maria; Hinkov, Hristo; Karam, Aimee; Medina-Mora, Maria Elena; Navarro-Mateu, Fernando; Piazza, Marina; Shalev, Arieh; Torres, Yolanda; Zaslavsky, Alan M; Kessler, Ronald C
BACKGROUND: Motor vehicle collisions (MVCs) are a substantial contributor to the global burden of disease and lead to subsequent post-traumatic stress disorder (PTSD). However, the relevant literature originates in only a few countries, and much remains unknown about MVC-related PTSD prevalence and predictors. METHODS: Data come from the World Mental Health Survey Initiative, a coordinated series of community epidemiological surveys of mental disorders throughout the world. The subset of 13 surveys (5 in high income countries, 8 in middle or low income countries) with respondents reporting PTSD after life-threatening MVCs are considered here. Six classes of predictors were assessed: socio-demographics, characteristics of the MVC, childhood family adversities, MVCs, other traumatic experiences, and respondent history of prior mental disorders. Logistic regression was used to examine predictors of PTSD. Mental disorders were assessed with the fully-structured Composite International Diagnostic Interview using DSM-IV criteria. RESULTS: Prevalence of PTSD associated with MVCs perceived to be life-threatening was 2.5 % overall and did not vary significantly across countries. PTSD was significantly associated with low respondent education, someone dying in the MVC, the respondent or someone else being seriously injured, childhood family adversities, prior MVCs (but not other traumatic experiences), and number of prior anxiety disorders. The final model was significantly predictive of PTSD, with 32 % of all PTSD occurring among the 5 % of respondents classified by the model as having highest PTSD risk. CONCLUSION: Although PTSD is a relatively rare outcome of life-threatening MVCs, a substantial minority of PTSD cases occur among the relatively small proportion of people with highest predicted risk. This raises the question whether MVC-related PTSD could be reduced with preventive interventions targeted to high-risk survivors using models based on predictors assessed in the immediate aftermath of the MVCs.
PMCID:4957291
PMID: 27449995
ISSN: 1471-244x
CID: 2191102

Unintended Consequences of Changing the Definition of Posttraumatic Stress Disorder in DSM-5: Critique and Call for Action

Hoge, Charles W; Yehuda, Rachel; Castro, Carl A; McFarlane, Alexander C; Vermetten, Eric; Jetly, Rakesh; Koenen, Karestan C; Greenberg, Neil; Shalev, Arieh Y; Rauch, Sheila A M; Marmar, Charles R; Rothbaum, Barbara O
PMID: 27224895
ISSN: 2168-6238
CID: 2115032

Long-term outcome of early interventions to prevent posttraumatic stress disorder

Shalev, Arieh Y; Ankri, Yael; Gilad, Moran; Israeli-Shalev, Yossi; Adessky, Rhonda; Qian, Meng; Freedman, Sara
BACKGROUND: Failing to prevent posttraumatic stress disorder (PTSD) has major clinical and public health consequences. This work evaluates the 3-year outcome of offering early interventions to survivors with acute PTSD. METHODS: Adults admitted consecutively to the hospital with acute DSM-IV PTSD were randomized, between June 2003 and October 2007, to 12 weeks of prolonged exposure (n = 63) or cognitive therapy (n = 40) or concealed SSRI (escitalopram; n = 23) versus placebo (n = 23). Eighty-two participants who declined treatment were followed as well. Treatment started 1 month after the traumatic event, and participants were reassessed 5 and 36 months later. Assessors were blinded to treatment allocation and acceptance. The Clinician-Administered PTSD Scale (CAPS) evaluated PTSD and PTSD symptoms. Self-reported symptoms, general functioning, and employment status were secondary outcomes. Participants lost to follow-up were missing completely at random. RESULTS: Prolonged exposure and cognitive therapy significantly reduced PTSD and PTSD symptoms between 1 and 5 months (mean CAPS total scores [95% CI] at 1 month: prolonged exposure = 73.59 [68.21-78.96] and cognitive therapy = 71.78 [66.92-78.93]; mean CAPS total scores [95% CI] at 5 months: prolonged exposure = 28.59 [21.89-35.29] and cognitive therapy = 29.48 [21.32-37.95], P < .001), and their results remained stable. At 3 years, however, the study groups had similar levels of PTSD symptoms (mean CAPS total scores [95% CI]: prolonged exposure = 31.51 [20.25-42.78]; cognitive therapy = 32.08 [20.74-43.42]; SSRI = 34.31 [16.54-52.07]; placebo = 32.13 [20.15-44.12]; and no intervention = 30.59 [19.40-41.78]), similar prevalence of PTSD (28.6%-46.2%), and similar secondary outcomes. CONCLUSION: Early prolonged exposure and cognitive therapy accelerated the recovery from acute PTSD. Their effect remained stable, however, without reducing the 3-year prevalence of the disorder. The lingering prevalence of PTSD, despite efficient interventions, illustrates a nonremitting, treatment-refractory subset of survivors and outlines a major clinical and public health challenge. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00146900.
PMID: 27135249
ISSN: 1555-2101
CID: 2101102

Prevention of Post-Traumatic Stress Disorder After Trauma: Current Evidence and Future Directions

Qi, Wei; Gevonden, Martin; Shalev, Arieh
Post-traumatic stress disorder (PTSD) is a frequent, tenacious, and disabling consequence of traumatic events. The disorder's identifiable onset and early symptoms provide opportunities for early detection and prevention. Empirical findings and theoretical models have outlined specific risk factors and pathogenic processes leading to PTSD. Controlled studies have shown that theory-driven preventive interventions, such as cognitive behavioral therapy (CBT), or stress hormone-targeted pharmacological interventions, are efficacious in selected samples of survivors. However, the effectiveness of early clinical interventions remains unknown, and results obtained in aggregates (large groups) overlook individual heterogeneity in PTSD pathogenesis. We review current evidence of PTSD prevention and outline the need to improve the disorder's early detection and intervention in individual-specific paths to chronic PTSD.
PMCID:4723637
PMID: 26800995
ISSN: 1535-1645
CID: 1922362

The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium

Benjet, C; Bromet, E; Karam, E G; Kessler, R C; McLaughlin, K A; Ruscio, A M; Shahly, V; Stein, D J; Petukhova, M; Hill, E; Alonso, J; Atwoli, L; Bunting, B; Bruffaerts, R; Caldas-de-Almeida, J M; de Girolamo, G; Florescu, S; Gureje, O; Huang, Y; Lepine, J P; Kawakami, N; Kovess-Masfety, Viviane; Medina-Mora, M E; Navarro-Mateu, F; Piazza, M; Posada-Villa, J; Scott, K M; Shalev, A; Slade, T; Ten Have, M; Torres, Y; Viana, M C; Zarkov, Z; Koenen, K C
BACKGROUND: Considerable research has documented that exposure to traumatic events has negative effects on physical and mental health. Much less research has examined the predictors of traumatic event exposure. Increased understanding of risk factors for exposure to traumatic events could be of considerable value in targeting preventive interventions and anticipating service needs. METHOD: General population surveys in 24 countries with a combined sample of 68 894 adult respondents across six continents assessed exposure to 29 traumatic event types. Differences in prevalence were examined with cross-tabulations. Exploratory factor analysis was conducted to determine whether traumatic event types clustered into interpretable factors. Survival analysis was carried out to examine associations of sociodemographic characteristics and prior traumatic events with subsequent exposure. RESULTS: Over 70% of respondents reported a traumatic event; 30.5% were exposed to four or more. Five types - witnessing death or serious injury, the unexpected death of a loved one, being mugged, being in a life-threatening automobile accident, and experiencing a life-threatening illness or injury - accounted for over half of all exposures. Exposure varied by country, sociodemographics and history of prior traumatic events. Being married was the most consistent protective factor. Exposure to interpersonal violence had the strongest associations with subsequent traumatic events. CONCLUSIONS: Given the near ubiquity of exposure, limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence. Identifying mechanisms that account for the associations of prior interpersonal violence with subsequent trauma is critical to develop interventions to prevent revictimization.
PMCID:4869975
PMID: 26511595
ISSN: 1469-8978
CID: 1817552