The Posttraumatic Stress Disorder Checklist (PCL-5; Weathers et al., 2013) was recently revised to reflect the changed diagnostic criteria for posttraumatic stress disorder (PTSD) in the fifth ...edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013). We investigated the psychometric properties of PCL-5 scores in a large cohort (N = 912) of military service members seeking PTSD treatment while stationed in garrison. We examined the internal consistency, convergent and discriminant validity, and DSM-5 factor structure of PCL-5 scores, their sensitivity to clinical change relative to PTSD Symptom Scale-Interview (PSS-I; Foa, Riggs, Dancu, & Rothbaum, 1993) scores, and their diagnostic utility for predicting a PTSD diagnosis based on various measures and scoring rules. PCL-5 scores exhibited high internal consistency. There was strong agreement between the order of hypothesized and observed correlations among PCL-5 and criterion measure scores. The best-fitting structural model was a 7-factor hybrid model (Armour et al., 2015), which demonstrated closer fit than all other models evaluated, including the DSM-5 model. The PCL-5's sensitivity to clinical change, pre- to posttreatment, was comparable with that of the PSS-I. Optimally efficient cut scores for predicting PTSD diagnosis were consistent with prior research with service members (Hoge, Riviere, Wilk, Herrell, & Weathers, 2014). The results indicate that the PCL-5 is a psychometrically sound measure of DSM-5 PTSD symptoms that is useful for identifying provisional PTSD diagnostic status, quantifying PTSD symptom severity, and detecting clinical change over time in PTSD symptoms among service members seeking treatment.
Dropout from first-line posttraumatic stress disorder (PTSD) treatments is a significant problem. We reported rates and predictors of attendance and dropout in three clinical trials of evidence-based ...PTSD treatments in military service members (N = 557). Service members attended 81.0% of treatment sessions and 30.7% dropped out. Individually delivered treatment was associated with greater attendance rates (β = 0.23, p < .001) than group therapy; trauma-focused treatments were associated with higher dropout (β = 0.19, p < .001) than Present-Centered Therapy. Age was a significant predictor of session attendance (β = 0.17, p < .001) and drop out (β = −0.23, p < .001). History of traumatic brain injury (TBI) predicted lower attendance rates (β = −0.26, p < .001) and greater dropout (β = 0.19, p < .001). Regardless of treatment type or format, patients who did not drop out were more likely to experience clinically significant gains (d = 0.49, p < .001). Results demonstrate that dropout from PTSD treatments in these trials was significantly associated with treatment outcome and suggest that strategies are needed to mitigate dropout, particularly in group and trauma-focused therapies, and among younger service members and those with TBI.
•Predictors of service members' PTSD treatment attendance and dropout were examined.•Dropout from therapy for military-related PTSD is a problem in clinical trials.•Strategies to mitigate dropout should target group and trauma-focused therapies.
Objective:
The authors evaluated the effects of prenatal antidepressant exposure and maternal depression on infant gestational age at birth and risk of preterm birth.
Method:
Ninety women were ...followed in a prospective, naturalistic design through pregnancy with monthly assessments of symptoms of depression and anxiety using the Structured Clinical Interview for DSM-IV mood module for depression, the Hamilton Depression Rating Scale, the Beck Depression Inventory, and the Perceived Stress Scale. Participants included 49 women with major depressive disorder who were treated with antidepressants during pregnancy (group 1), 22 women with major depressive disorder who were either not treated with antidepressants or had limited exposure to them during pregnancy (group 2), and 19 healthy comparison subjects (group 3). The primary outcome variables were the infants' gestational age at birth, birth weight, 1- and 5-minute Apgar scores, and admission to the special care nursery.
Results:
Groups 1, 2, and 3 differed significantly in gestational age at birth (38.5 weeks, 39.4 weeks, 39.7 weeks, respectively), rates of preterm birth (14.3%, 0%, 5.3%, respectively), and rates of admission to the special care nursery (21%, 9%, 0%, respectively). Birth weight and Apgar scores did not differ significantly between groups. Mild to moderate depression during pregnancy did not affect outcome measures.
Conclusions:
Prenatal antidepressant use was associated with lower gestational age at birth and an increased risk of preterm birth. Presence of depressive symptoms was not associated with this risk. These results suggest that medication status, rather than depression, is a predictor of gestational age at birth.
Abstract Objective Myelination of the human brain results in roughly quadratic trajectories of myelin content and integrity, reaching a maximum in mid-life and then declining in older age. This ...trajectory is most evident in vulnerable later myelinating association regions such as frontal lobes and may be the biological substrate for similar trajectories of cognitive processing speed. Speed of movement, such as maximal finger tapping speed (FTS), requires high-frequency action potential (AP) bursts and is associated with myelin integrity. We tested the hypothesis that the age-related trajectory of FTS is related to brain myelin integrity. Methods A sensitive in vivo MRI biomarker of myelin integrity (calculated transverse relaxation rates ( R2 )) of frontal lobe white matter (FLwm) was measured in a sample of very healthy males ( N = 72) between 23 and 80 years of age. To assess specificity, R2 of a contrasting early-myelinating region (splenium of the corpus callosum) was also measured. Results FLwm R2 and FTS measures were significantly correlated ( r = .45, p < .0001) with no association noted in the early-myelinating region (splenium). Both FLwm R2 and FTS had significantly quadratic lifespan trajectories that were virtually indistinguishable and both reached a peak at 39 years of age and declined with an accelerating trajectory thereafter. Conclusions The results suggest that in this very healthy male sample, maximum motor speed requiring high-frequency AP burst may depend on brain myelin integrity. To the extent that the FLwm changes assessed by R2 contribute to an age-related reduction in AP burst frequency, it is possible that other brain functions dependent on AP bursts may also be affected. Non-invasive measures of myelin integrity together with testing of basic measures of processing speed may aid in developing and targeting anti-aging treatments to mitigate age-related functional declines.
Abstract
Study Objectives
To examine sleep disorder symptom reports at baseline and posttreatment in a sample of active duty U.S. Army Soldiers receiving treatment for posttraumatic stress disorder ...(PTSD). Explore sleep-related predictors of outcomes.
Methods
Sleep was evaluated in 128 participants in a parent randomized clinical trial comparing Spaced formats of Prolonged Exposure (PE) or Present Centered Therapy and a Massed format of PE. In the current study, Spaced formats were combined and evaluated separately from Massed.
Results
At baseline, the average sleep duration was < 5 h per night on weekdays/workdays and < 6 h per night on weekends/off days. The majority of participants reported clinically significant insomnia, clinically significant nightmares, and probable sleep apnea and approximately half reported excessive daytime sleepiness at baseline. Insomnia and nightmares improved significantly from baseline to posttreatment in all groups, but many patients reported clinically significant insomnia (>70%) and nightmares (>38%) posttreatment. Excessive daytime sleepiness significantly improved only in the Massed group, but 40% continued to report clinically significant levels at posttreatment. Short sleep (Spaced only), clinically significant insomnia and nightmares, excessive daytime sleepiness, and probable sleep apnea (Massed only) at baseline predicted higher PTSD symptoms across treatment course. Short weekends/off days sleep predicted lower PTSD symptom improvement in the Spaced treatments.
Conclusions
Various sleep disorder symptoms were high at baseline, were largely unchanged with PTSD treatment, and were related to worse PTSD treatment outcomes. Studies are needed with objective sleep assessments and targeted sleep disorders treatments in PTSD patients.
Clinical Trial Registration
NCT01049516.
Objective:DSM-5 introduced the “with mixed features” specifier for major depressive episodes. The authors assessed the prevalence and phenomenology of mixed depression among bipolar disorder patients ...and qualitatively compared a range of diagnostic thresholds for mixed depression.Method:In a naturalistic study, 907 adult outpatients with bipolar disorder participating in the Stanley Foundation Bipolar Network were followed longitudinally across 14,310 visits from 1995 to 2002. The Inventory of Depressive Symptomatology–Clinician-Rated Version (IDS-C) and the Young Mania Rating Scale (YMRS) were administered at each visit.Results:Mixed depression, defined as an IDS-C score ≥15 and a YMRS score >2 and <12 at the same visit, was observed in 2,139 visits (14.9% of total visits, and 43.5% of visits with depression) by 584 patients (64.4% of all patients). Women were significantly more likely than men to experience subthreshold hypomania during visits with depression (40.7% compared with 34.4%). Patients with one or more mixed depression visits had more symptomatic visits and fewer euthymic visits compared with those with no mixed depression visits. DSM-5-based definitions of mixed depression (ranging from narrower definitions requiring ≥3 nonoverlapping YMRS items concurrent with an IDS-C score ≥15, to broader definitions requiring ≥2 nonoverlapping YMRS items) yielded lower mixed depression prevalence rates (6.3% and 10.8% of visits, respectively) but were found to have similar relationships to gender and longitudinal symptom severity.Conclusions:Among outpatients with bipolar disorder, concurrent hypomanic symptoms observed during visits with depression were common, particularly in women. The DSM-5 diagnostic criteria for depression with mixed features may yield inadequate sensitivity to detect patients with mixed depression.
Abstract Background Brain iron promotes oxidative damage and protein oligomerization that result in highly prevalent age-related proteinopathies such as Alzheimer's disease (AD), Parkinson's disease ...(PD), and Dementia with Lewy Bodies (DLB). Men are more likely to develop such diseases at earlier ages than women but brain iron levels increase with age in both genders. We hypothesized that brain iron may influence both the age- and gender-related risks of developing these diseases. Methods The amount of iron in ferritin molecules (ferritin iron) was measured in vivo with MRI by utilizing the field dependent relaxation rate increase (FDRI) method. Ferritin iron was measured in four subcortical nuclei caudate (C), putamen (P), globus pallidus (G), thalamus (T), three white matter regions frontal lobe (Fwm), genu and splenium of the corpus callosum (Gwm, Swm) and hippocampus (Hipp) in 165 healthy adults aged 19–82. Results There was a high correlation ( r > 0.99) between published post-mortem brain iron levels and FDRI. There were significant age-related changes in ferritin iron (increases in Hipp, C, P, G, and decreases in Fwm). Women had significantly lower ferritin iron than men in five regions (C, T, Fwm, Gwm, Swm). Conclusions This is the first demonstration of gender differences in brain ferritin iron levels. It is possible that brain iron accumulation is a risk factor that can be modified. MRI provides the opportunity to assess brain iron levels in vivo and may be useful in targeting individuals or groups for preventive therapeutic interventions.
Insomnia and nightmares are common in patients with posttraumatic stress disorder (PTSD). They are associated with worse psychological and physical health and worse PTSD treatment outcomes. In ...addition, they are resistant to PTSD treatments, which do not typically address sleep disorders. Cognitive behavioral therapy for insomnia and nightmares (CBT‐I&N) and cognitive processing therapy (CPT) for PTSD are first‐line treatments, but limited evidence exists guiding the treatment of individuals with all three disorders. The current study randomized U.S. military personnel (N = 93) to one of three conditions: CBT‐I&N delivered before CPT, CBT‐I&N delivered after CPT, or CPT alone; all groups received 18 sessions. Across groups, participants demonstrated significantly improved PTSD symptoms. Because the study was terminated prematurely due to challenges with recruitment and retention, it was underpowered to answer the initially intended research questions. Nonetheless, statistical findings and relevant clinically meaningful changes were observed. Compared to participants who received CPT alone, those who received CBT‐I&N and CPT, regardless of sequencing, demonstrated larger improvements in PTSD symptoms, d = −0.36; insomnia, d = −0.77; sleep efficiency, d = 0.62; and nightmares, d = −.53. Compared to participants who received CBT‐I&N delivered before CPT, those who received CBT‐I&N delivered after CPT demonstrated larger improvements in PTSD symptoms, d = 0.48, and sleep efficiency, d = −0.44. This pilot study suggests that treating comorbid insomnia, nightmares, and PTSD symptoms results in clinically meaningful advantages in improvement for all three concerns compared to treating PTSD alone.
Until relatively recently, long-acting injectable (LAI) formulations were only available for first-generation antipsychotics and their utilization decreased as use of oral second-generation ...antipsychotics (SGA) increased. Although registry-based naturalistic studies show LAIs reduce rehospitalization more than oral medications in clinical practice, this is not seen in recent randomized clinical trials. PROACTIVE (Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy) relapse prevention study incorporated efficacy and effectiveness features. At 8 US academic centers, 305 patients with schizophrenia or schizoaffective disorder were randomly assigned to LAI risperidone (LAI-R) or physician's choice oral SGAs. Patients were evaluated during the 30-month study by masked, centralized assessors using 2-way video, and monitored biweekly by on-site clinicians and assessors who knew treatment assignment. Relapse was evaluated by a masked Relapse Monitoring Board. Differences between LAI-R and oral SGA treatment in time to first relapse and hospitalization were not significant. Psychotic symptoms and Brief Psychiatric Rating Scale total score improved more in the LAI-R group. In contrast, the LAI group had higher Scale for Assessment of Negative Symptoms Alogia scale scores. There were no other between-group differences in symptoms or functional improvement. Despite the advantage for psychotic symptoms, LAI-R did not confer an advantage over oral SGAs for relapse or rehospitalization. Biweekly monitoring, not focusing specifically on patients with demonstrated nonadherence to treatment and greater flexibility in changing medication in the oral treatment arm, may contribute to the inability to detect differences between LAI and oral SGA treatment in clinical trials.
Human and non-human primate data suggest that the structural integrity of myelin sheaths deteriorates during normal aging, especially in the late-myelinating association regions and may result in ...“disconnection” of widely distributed neural networks. Magnetic resonance imaging (MRI) was used to assess the heterogeneity of this process and its impact on brain aging and Alzheimer’s disease (AD) by evaluating early- and later-myelinating regions of the corpus callosum, the splenium (Scc) and genu (Gcc), respectively. Calculated transverse relaxation rates (
R
2), an indirect measure of white matter structural integrity for the Gcc and Scc, were examined. The relationship between age and
R
2 differed in the two regions. A quadratic (inverted U) function with an accelerating rate of decline beginning at age 31 best represented the Gcc pattern while the Scc decline was three-fold smaller, gradual, and linear. These data suggest that the severity of age-related myelin breakdown is regionally heterogeneous, consistent with the hypothesis that differences in myelin properties make later-myelinating regions more susceptible to this process. In AD this process is globally exacerbated, consistent with an extracellular deleterious process such as amyloid β-peptide toxicity. Non-invasive measures such as
R
2 may be useful in primary prevention studies of AD.
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