Testing for t(3;8) in MYC/BCL6-rearranged large B-cell lymphoma identifies a high-risk subgroup with inferior survival.

ABSTRACT: A reciprocal t(3;8) BCL6::MYC fusion is common in large B-cell lymphoma (LBCL) with MYC and BCL6 disruption. These pseudo-double-hit cases are not adverse, whereas t(3;8)-MYC/BCL6 lymphoma has an inferior prognosis relative to other MYC-rearranged LBCL.

Negative association between neurovascular coupling and cortical gray matter volume during the lifespan.

Recent studies have established the moment-to-moment turnover of the blood-oxygen-level-dependent signal (TBOLD) at resting state as a key measure of local cortical brain function. Here, we sought to extend that line of research by evaluating TBOLD in 70 cortical areas with respect to corresponding brain volume, age, and sex across the lifespan in 1,344 healthy participants including 633 from the Human Connectome Project (HCP)-Development cohort (294 males and 339 females, age range 8-21 yr) and 711 healthy participants from HCP-Aging cohort (316 males and 395 females, 36-90 yr old). In both groups, we found that 1) TBOLD increased with age, 2) volume decreased with age, and 3) TBOLD and volume were highly significantly negatively correlated, independent of age. The inverse association between TBOLD and volume was documented in nearly all 70 brain areas and for both sexes, with slightly stronger associations documented for males. The strong correspondence between TBOLD and volume across age and sex suggests a common influence such as chronic neuroinflammation contributing to reduced cortical volume and increased TBOLD across the lifespan.NEW & NOTEWORTHY We report a significant negative association between resting functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) signal turnover (TBOLD) and cortical gray matter volume across the lifespan, such that TBOLD increased whereas volume decreased. We attribute this association to a hypothesized chronic, low-grade neuroinflammation, probably induced by various neurotropic pathogens, including human herpes viruses known to be dormant in the brain in a latent state and reactivated by stress, fever, and various environmental exposures, such as ultraviolet light.

Dependence of cognitive ability on synchronous neural interactions determined by magnetoencephalography.

Previous studies have shown that synchronous neural interactions (SNIs) underlying healthy brain function can be readily distinguished from neural anomalies associated with diseases including dementia; however, it is imperative to identify biomarkers that facilitate early identification of individuals at risk for cognitive decline before the onset of clinical symptoms. Here, we evaluated whether variation in brain function, controlling for age, corresponds with subtle decrements in cognitive performance in cognitively healthy women. A total of 251 women (age range 24-102 yr) who performed above established cutoffs on the Montreal cognitive assessment (MoCA) also underwent a task-free magnetoencephalography scan from which SNIs were computed. The results demonstrated that increased SNI was significantly associated with decreased cognitive performance (r2 = 0.923, P = 0.009), controlling for age. Compared with the lowest performers with normal cognition (MoCA = 26), SNI of the highest performers (MoCA = 30) was associated with decorrelation primarily in the right anterior temporal cortex region, with additional (weaker) foci in left anterior temporal cortex, right posterior temporal cortex, and cerebellum. The findings highlight the relevance of neural network decorrelation on cognitive functioning and suggest that subtle increases in SNI may presage future cognitive impairment.NEW & NOTEWORTHY This study in cognitively healthy women showed that decreased cognitive performance is associated with increased neural network correlations, particularly involving the temporal cortices. As healthy brain function relies on dynamic neural network communication, these findings suggest that subtle increases in correlated neural network activity may be a useful early indicator of decrements in cognitive function.

The dynamic shaping of local cortical circuitry by sex and age, and its relation to pattern comparison processing speed.

Previous resting-state functional magnetic resonance imaging (fMRI) studies have shown that the strength of local neural interactions decreases with distance. Here, we extend that line of research to evaluate effects of sex and age on local cortical circuitry in six cortical areas (superior frontal, precentral, postcentral, superior parietal, inferior parietal, and lateral occipital) using data acquired from 1,054 healthy young adults who participated in the Human Connectome Project. We confirmed previous findings that the strength of zero-lag correlations between prewhitened, resting-state, blood level oxygenation-dependent (BOLD) fMRI time series decreased with distance locally and documented that the rate of decrease with distance (spatial steepness) 1) was progressively lower from anterior to posterior areas, 2) was greater in women, especially in anterior areas, 3) increased with age, particularly for women, 4) was significantly correlated with percent inhibition, and 5) was positively and highly significantly correlated with pattern comparison processing speed (PCPS). A hierarchical tree clustering analysis of this dependence of PCPS on spatial steepness revealed a differential organization in processing that information between the two hemispheres, namely, a more independent vs. a more integrative processing in the left and right hemispheres, respectively. These findings document sex and age differences in dynamic local cortical interactions and provide evidence that spatial sharpening of these interactions may underlie cognitive processing speed differently organized in the two hemispheres.NEW & NOTEWORTHY Sex and age significantly affect shaping of local cortical interactions that are more limited in women and older brains. The net result is an increase in local spatial steepness of interactions, leading to a reduction of overlap among local ensembles and, hence, a more efficient information processing and an increase in the number of independent local cortical "processors." Remarkably, cognitive processing speed was positively associated with local spatial steepness, in keeping with the reasoning earlier.

The brain landscape of the two-hit model of posttraumatic stress disorder.

The neurophysiological mechanisms underlying the development of posttraumatic stress disorder (PTSD) are poorly understood. Here we test a proposal that PTSD symptoms reflect fixed, highly correlated neural networks resulting from massive engagement of sensory inputs and the sequential involvement of those projections to limbic areas. Three-tesla functional magnetic resonance imaging (fMRI) data were acquired at rest in 15 veterans diagnosed with PTSD and 21 healthy control veterans from which zero-lag cross correlations between 50 brain areas (N = 1,225 pairs) were computed and analyzed. The brain areas were assigned to tiers based on the neurocircuitry of successively converging sensory pathways proposed by Jones and Powell (Jones EG, Powell TP. Brain 93: 793-820, 1970). The primary analyses assessed normalized proportional differences in cross correlation strength within and across tiers in veterans with PTSD and control veterans. Compared with control veterans, cross correlation strength was higher in veterans with PTSD, within and across tiers of areas involved in processing sensory inputs, and systematically increased from sensory processing areas to limbic areas. The functional relevance of this hypercorrelation was further documented by the finding that the severity of self-reported PTSD symptomatology was positively associated with higher neural correlations.NEW & NOTEWORTHY The neurophysiological mechanisms underlying the development of PTSD are poorly understood. Here we document that massive engagement of sensory modalities during trauma exposure leads to fixed, hypercorrelated frontal, parietal, temporal, and limbic networks, reflecting the successive integration of salient sensory inputs along the framework of Jones and Powell.

BOLD turnover in task-free state: variation among brain areas and effects of age and human leukocyte antigen (HLA) DRB1*13.

Blood oxygen level dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) is frequently used as a proxy for underlying neural activity. Although this is a plausible assumption for experiments where a task is performed, it may not hold to the same degree for conditions of fMRI recording in a task-free, "resting" state where neural synaptic events are weak and, hence, neurovascular coupling and endothelial vascular factors become more prominent (Hillman Annu Rev Neurosci 37:161-181, 2014, 10.1146/annurev-neuro-071013-014111). Here we investigated the magnitude of change of BOLD in consecutive samples over the acquisition time period (turnover of BOLD, "TBOLD") by first-order differencing of single-voxel BOLD time series acquired in 70 areas of the cerebral cortex of 57 cognitively healthy women in a task-free resting state. More specifically, we evaluated (a) the variation of TBOLD among different cortical areas, (b) its dependence on age, and (c) its dependence on the presence (or absence) of the neuroprotective Human Leukocyte Antigen (HLA) gene DRB1*13 (DRB1*13:02 and DRB1*13:01). We found that TBOLD (a) varied substantially by 2.2 × among cortical areas, being highest in parahippocampal and entorhinal areas and lowest in parietal-occipital areas, (b) was significantly reduced in DRB1*13 carriers across cortical areas (from ~ 15% reduction in orbitofrontal cortex to 2% reduction in cuneus), and (c) increased with age in noncarriers of DRB1*13 but decreased with age in DRB1*13 carriers. These findings document significant dependencies of TBOLD on cortical area location, HLA DRB1*13 and age.

Effects of sex and age on presumed inhibitory interactions in 6 areas of the human cerebral cortex as revealed by the fMRI Human Connectome Project.

Cortical inhibition is theorized to reflect an underlying property of human brain function, sharpening tuning and shaping connectivity. Although age and sex effects on large-scale resting-state brain connectivity have been well documented, effects on local cortical inhibition have received relatively limited attention. Here, we evaluated age and sex effects on presumed local inhibitory interactions in 6 lateral cortical areas using resting-state functional magnetic resonance imaging (fMRI) data acquired from 1054 young adults who participated in the Human Connectome Project. For each area, all possible pairwise crosscorrelations between prewhitened blood oxygenation level-dependent (BOLD) time series were calculated, and the highest value (CCmax) was retained to determine the mean and percentage of negative and positive CCmax. Here, we focused on the percentage of negative CCmax which we referred to as presumed "percent inhibition". The results documented regional differences in percent inhibition as well as age and sex effects, such that women's brains were characterized by significantly higher percent inhibition than men overall and in 4 of the 6 cortical areas, and the percent inhibition increased significantly with age in all 6 areas for women but in only one area for men. The findings from this young adult sample are presumed to reflect ongoing maturational processes involving local network connectivity that may be shaped by sex differences in brain structure, function, and neurochemistry.

MEG neural signature of sexual trauma in women veterans with PTSD.

Previous research has documented the utility of synchronous neural interactions (SNI) in classifying women veterans with and without posttraumatic stress disorder (PTSD) and other trauma-related outcomes based on functional connectivity using magnetoencephalography (MEG). Here, we extend that line of research to evaluate trauma-specific PTSD neural signatures with MEG in women veterans. Participants completed diagnostic interviews and underwent a task-free MEG scan from which SNI was computed. Thirty-five women veterans were diagnosed with PTSD due to sexual trauma and sixteen with PTSD due to non-sexual trauma. Strength of SNI was compared in women with and without sexual trauma, and linear discriminant analysis was used to classify the brain patterns of women with PTSD due to sexual trauma and non-sexual trauma. Comparison of SNI strength between the two groups revealed widespread hypercorrelation in women with sexual trauma relative to those without sexual trauma. Furthermore, using SNI, the brains of participants were classified as sexual trauma or non-sexual trauma with 100% accuracy. These findings bolster evidence supporting the utility of task-free SNI and suggest that neural signatures of PTSD are trauma-specific.

Classification of posttraumatic stress disorder and related outcomes in women veterans using magnetoencephalography.

Women veterans represent a unique population whose experiences and neurobiology differ from that of their male counterparts. Thus, while previous research has demonstrated the utility of synchronous neural interactions (SNI) as a biomarker of posttraumatic stress disorder (PTSD) in male veterans, the utility of SNI as a biomarker of PTSD in women veterans is unclear. Here we extend that line of research to evaluate classification of women veterans with and without PTSD and other trauma-related outcomes based on functional connectivity using magnetoencephalography (MEG). A total of 121 U.S. women veterans completed diagnostic interviews and underwent a task-free MEG scan from which SNI was computed. Linear discriminant analysis was used to classify PTSD and control groups according to SNI. That discriminant function was then used to classify each individual in the partial recovery and full recovery diagnostic groups as PTSD or control. All individuals were classified correctly (100% accuracy) according to their SNI in their PTSD and control groups. Seventy-seven percent of the full recovery group and 69% of the partial recovery group were classified as control. Individual staging in PTSD recovery was captured by the Mahalanobis D2 distances from the center of the control and PTSD centroid clusters. These findings provide compelling evidence supporting the utility of task-free SNI as a biomarker of PTSD and related outcomes in women veterans.

Effectiveness of a Third Dose of MMR Vaccine for Mumps Outbreak Control.

BACKGROUND: The effect of a third dose of the measles-mumps-rubella (MMR) vaccine in stemming a mumps outbreak is unknown. During an outbreak among vaccinated students at the University of Iowa, health officials implemented a widespread MMR vaccine campaign. We evaluated the effectiveness of a third dose for outbreak control and assessed for waning immunity. METHODS: Of 20,496 university students who were enrolled during the 2015-2016 academic year, mumps was diagnosed in 259 students. We used Fisher's exact test to compare unadjusted attack rates according to dose status and years since receipt of the second MMR vaccine dose. We used multivariable time-dependent Cox regression models to evaluate vaccine effectiveness, according to dose status (three vs. two doses and two vs. no doses) after adjustment for the number of years since the second dose. RESULTS: Before the outbreak, 98.1% of the students had received at least two doses of MMR vaccine. During the outbreak, 4783 received a third dose. The attack rate was lower among the students who had received three doses than among those who had received two doses (6.7 vs. 14.5 cases per 1000 population, P<0.001). Students had more than nine times the risk of mumps if they had received the second MMR dose 13 years or more before the outbreak. At 28 days after vaccination, receipt of the third vaccine dose was associated with a 78.1% lower risk of mumps than receipt of a second dose (adjusted hazard ratio, 0.22; 95% confidence interval, 0.12 to 0.39). The vaccine effectiveness of two doses versus no doses was lower among students with more distant receipt of the second vaccine dose. CONCLUSIONS: Students who had received a third dose of MMR vaccine had a lower risk of mumps than did those who had received two doses, after adjustment for the number of years since the second dose. Students who had received a second dose of MMR vaccine 13 years or more before the outbreak had an increased risk of mumps. These findings suggest that the campaign to administer a third dose of MMR vaccine improved mumps outbreak control and that waning immunity probably contributed to propagation of the outbreak. (Funded by the Centers for Disease Control and Prevention.).

Mumps Outbreak in a Highly Vaccinated University-Affiliated Setting Before and After a Measles-Mumps-Rubella Vaccination Campaign-Iowa, July 2015-May 2016.

Background: In response to a mumps outbreak at the University of Iowa and surrounding community, university, state, and local health officials implemented a vaccination campaign targeting students <25 years of age with an additional dose of measles-mumps-rubella (MMR) vaccine. More than 4700 vaccine campaign doses were administered; 97% were documented third doses. We describe the epidemiology of the outbreak before and after the campaign, focusing on cases in university students. Methods: Mumps cases were identified from reportable disease databases and university health system records. Detailed information on student cases was obtained from interviews, medical chart abstractions, university and state vaccination records, and state public health laboratory results. Pre- and postcampaign incidence among students, university faculty/staff, and community members <25 vs ≥25 years old were compared using Fisher exact test. Multivariable regression modeling was performed to identify variables associated with a positive mumps polymerase chain reaction test. Results: Of 453 cases in the county, 301 (66%) occurred in university students. Student cases were primarily undergraduates (90%) and highly vaccinated (86% had 2 MMR doses, and 12% had 3 MMR doses). Fewer cases occurred in students after the campaign (75 [25%]) than before (226 [75%]). Cases in the target group (students <25 years of age) declined 9% postcampaign (P=.01). A positive mumps polymerase chain reaction test was associated with the presence of parotitis and early sample collection, and inversely associated with recent receipt of MMR vaccine. Conclusions: Following a large additional dose MMR vaccination campaign, fewer mumps cases occurred overall and in the target population.

Apolipoprotein E: the resilience gene.

The apolipoprotein E (apoE) gene has been implicated in various conditions, most notably Alzheimer's disease and coronary artery disease. A predisposing role of the apoE4 isoform and a protective role of apoE2 isoform in those diseases have been documented. Here we investigated the role of apoE in resilience to trauma. Three hundred and forty-three US veterans were genotyped for apoE and were assessed for their lifetime trauma exposure (trauma score, T) and severity of posttraumatic stress disorder symptoms (PCL). The ratio PCL/T indicates sensitivity to trauma; hence, its inverse indicates resilience, R, to trauma. We found a significantly higher resilience in participants with apoE genotype containing the E2 allele (E2/2, E2/3) as compared to participants with the E4 allele (E4/4, E4/3). In addition, when the categorical apoE genotype was reexpressed as the number of cysteine residues per apoE mole (CysR/mole), a highly significant positive association was found between resilience and CysR/mole, such that resilience was systematically higher as the number of CysR/mole increased, from zero CysR/mole in E4/4 to four CysR/mole in E2/2. These findings demonstrate the protective role of the CysR/mole apoE in resilience to trauma: the more CysR/mole, the higher the resilience. Thus, they are in accord with other findings pointing to a generally protective role of increasing number of CysR/mole (from E4/4 to E2/2) in other diseases. However, unlike other conditions (e.g., Alzheimer's disease and coronary artery disease), resilience to trauma is not a disease but an adaptive response to trauma. Therefore, the effects of apoE seem to be more pervasive along the CysR/mole continuum, most probably reflecting underlying effects on brain synchronicity and its variability that we have documented previously (Leuthold et al., Exp Brain Res 226:525-536, 2013).

Subcortical brain atrophy in Gulf War Illness.

Gulf War Illness (GWI) is a multisystem disorder that has affected a substantial number of veterans who served in the 1990-1991 Gulf War. The brain is prominently affected, as manifested by the presence of neurological, cognitive and mood symptoms. Although brain dysfunction in GWI has been well documented (EBioMedicine 12:127-32, 2016), abnormalities in brain structure have been debated. Here we report a substantial (~10%) subcortical brain atrophy in GWI comprising mainly the brainstem, cerebellum and thalamus, and, to a lesser extent, basal ganglia, amygdala and diencephalon. The highest atrophy was observed in the brainstem, followed by left cerebellum and right thalamus, then by right cerebellum and left thalamus. These findings indicate graded atrophy of regions anatomically connected through the brainstem via the crossed superior cerebellar peduncle (left cerebellum â†’ right thalamus, right cerebellum â†’ left thalamus). This distribution of atrophy, together with the observed systematic reduction in volume of other subcortical areas (basal ganglia, amygdala and diencephalon), resemble the distribution of atrophy seen in toxic encephalopathy (Am J Neuroradiol 13:747-760, 1992) caused by a variety of substances, including organic solvents. Given the potential exposure of Gulf War veterans to "a wide range of biological and chemical agents including sand, smoke from oil-well fires, paints, solvents, insecticides, petroleum fuels and their combustion products, organophosphate nerve agents, pyridostigmine bromide, …" (Institute of Medicine National Research Council. Gulf War and Health: Volume 1. Depleted uranium, pyridostigmine bromide, sarin, and vaccines. National Academies Press, Washington DC, 2000), it is reasonable to suppose that such exposures, alone or in combination, could underlie the subcortical atrophy observed.

Gulf War illness (GWI) as a neuroimmune disease.

Gulf War illness (GWI) is a chronic disease characterized by the involvement of several organs, including the brain (Christova et al., Exp Brain Res doi: 10.1007/s00221-017-5010-8 , 2017). In a previous study (Georgopoulos et al., J Neural Eng 4:349-355, 2015), we identified six protective alleles from Class II human leukocyte antigen (HLA) genes, and more recently, we investigated the brain correlates of this protection (James et al., EBioMedicine 13:72-79, 2016). Those and other studies (Israeli, Lupus, 21:190-194, 2012) suggested an involvement of the immune system in GWI. In a recent study (Engdahl et al., EBioMedicine doi: 10.1016/j.ebiom.2016.08.030 , 2016), we showed that the brain pattern of synchronous neural interactions (SNI; Georgopoulos et al., J Neural Eng 4:349-355, 2007) in GWI is distinctly different from that in healthy controls. Here we focused on the SNI itself, as a basic measure of neural communication (irrespective of specific connections) and compared it between GWI and seven other diseases that cover a broad spectrum of etiology and pathophysiology. Specifically, we sought to determine which, if any, of those diseases might resemble GWI SNI, overall and within the HLA protective domain, and thus gain further knowledge regarding the nature of GWI brain abnormality. We studied a total of 962 participants from a healthy control population (N = 583) and eight different diseases, including GWI (N = 40), schizophrenia (SZ; N = 21), Alzheimer's disease (AD; N = 66), posttraumatic stress disorder (PTSD; N = 159), major depressive disorder (MDD; N = 10), relapsing-remitting multiple sclerosis (RRMS; N = 43), Sjögren's syndrome (SS; N = 32), and rheumatoid arthritis (RA; N = 8). They all underwent a resting-state magnetoencephalographic (MEG) scan to calculate SNIs. Data were analyzed using analysis of covariance (ANCOVA) with disease as fixed factor, and sex and age as covariates. We found that GWI SNIs differed significantly from control SZ, AD, PTSD and MDD but not from RRMS, SS and RA. In addition, we compared GWI to RRMS, SS and RA with respect to SNIs of MEG sensor pairs that were related to the HLA alleles protective for GWI (James et al., EBioMedicine 13:72-79, 2016). We found that GWI SNIs did not differ significantly from any of these three diseases but they did so from control SZ, AD, PTSD and MDD. These findings indicate that (a) GWI brain synchronicity does not differ significantly from that of known immune-related diseases (RRMS, SS, RA), and (b) that this SNI similarity is present within the HLA-related SNIs. In contrast, GWI SNIs differed significantly from those of the other diseases. We conclude that altered brain communication in GWI likely reflects immune-related processes, as postulated previously (James et al., EBioMedicine 13:72-79, 2016). By extension, these findings also indicate that functional brain abnormalities in RRMS, SS and RA might be, in part, due to lack of protective HLA alleles as documented for GWI (Georgopoulos et al., EBioMedicine 3:79-85, 2015).

Pathological personality traits modulate neural interactions.

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), includes an empirically supported dimensional model of personality pathology that is assessed via the Personality Inventory for the DSM-5 (PID-5). Here we used magnetoencephalography (MEG; 248 sensors) to evaluate resting-state neural network properties associated with the five primary DSM-5 maladaptive personality domains (negative affect, detachment, antagonism, disinhibition, and psychoticism) in 150 healthy veterans ("control" group) and 179 veterans with various psychiatric disorders ("psychopathology" group). Since a fundamental network property is the strength of functional connectivity among network elements, we used the absolute value of the pairwise correlation coefficient (aCC) between prewhitened MEG sensor time series as a measure of neural functional connectivity and assessed its relations to the quantitative PID-5 scores in a linear regression model, where the log-transformed aCC was the dependent variable and individual PID scores, age, and gender were the independent variables. The partial regression coefficient (pRC) for a specific PID-5 score in that model provided information concerning the direction (positive, negative) and size (absolute value) of the PID effect on the strength of neural correlations. We found that, overall, PID domains had a negative effect (i.e., negative pRC; decorrelation) on aCC in the control group, but a positive one (i.e., positive pRC; hyper-correlation) in the psychopathology group. This dissociation of PID effects on aCC was especially pronounced for disinhibition, psychoticism, and negative affect. These results document for the first time a fundamental difference in neural-PID relations between control and psychopathology groups.

Neural communication in posttraumatic growth.

Posttraumatic growth (PTG), or positive psychological changes following exposure to traumatic events, is commonly reported among trauma survivors. In the present study, we examined neural correlates of PTG in 106 veterans with PTSD and 193 veteran controls using task-free magnetoencephalography (MEG), diagnostic interviews and measures of PTG, and traumatic event exposure. Global synchronous neural interactions (SNIs) were significantly modulated downward with increasing PTG scores in controls (p = .005), but not in veterans with PTSD (p = .601). This effect was primarily characterized by negative slopes in local neural networks, was strongest in the medial prefrontal cortex, and was much stronger and more extensive in the control than the PTSD group. The present study complements previous research highlighting the role of neural adaptation in healthy functioning.

Diagnosis of posttraumatic stress disorder (PTSD) based on correlations of prewhitened fMRI data: outcomes and areas involved.

Successful diagnosis of PTSD has been achieved using neural correlations from prewhitened magnetoencephalographic (MEG) time series (Georgopoulos et al. in J Neural Eng 7:16011, 2010. doi:10.1088/1741-2560/7/1/016011; James et al. 2015). Here, we show that highly successful classification of PTSD and control subjects can be obtained using neural correlations from prewhitened resting-state fMRI data. All but one PTSD (14/15; sensitivity = 93.3 %) and all but one control (20/21; specificity = 95.2 %) subjects were correctly classified using 15 out of 2701 possible correlations between 74 brain areas. In contrast, correlations of the same but non-prewhitened data yielded chance-level classifications. We conclude that, if properly processed, fMRI has the prospect of aiding significantly in PTSD diagnosis. Twenty-five brain areas were most prominently involved in correct subject classification, including areas from all cortical lobes and the left pallidum.

DSM-5 personality traits discriminate between posttraumatic stress disorder and control groups.

The relevance of personality traits to the study of psychopathology has long been recognized, particularly in terms of understanding patterns of comorbidity. In fact, a multidimensional personality trait model reflecting five higher-order personality dimensions-negative affect, detachment, antagonism, disinhibition, and psychoticism-is included in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and represented in the Personality Inventory for DSM-5 (PID-5). However, evaluation of these dimensions and underlying personality facets within clinical samples has been limited. In the present study, we utilized the PID-5 to evaluate the personality profile elevation and composition of 150 control veterans and 35 veterans diagnosed with posttraumatic stress disorder (PTSD). Results indicated that veterans with PTSD endorsed significantly more personality pathology than control veterans, with scores on detachment and psychoticism domains most clearly discriminating between the two groups. When personality domain scores were considered as parts of each subject's personality profile, a slightly different picture emerged. Specifically, the PTSD composition was primarily characterized by detachment and negative affect, followed by disinhibition, psychoticism, and antagonism in that order of relative importance. The profile of the control group was significantly different, mostly accounted for differences in antagonism and psychoticism. Using these complementary analytic strategies, the findings demonstrate the relevance of personality pathology to PTSD, highlight internalizing features of PTSD, and pave the way for future research aimed at evaluating the role of shared maladaptive personality traits in underlying the comorbidity of PTSD and related disorders.

The Number of Cysteine Residues per Mole in Apolipoprotein E Is Associated With the Severity of PTSD Re-Experiencing Symptoms.

Apolipoprotien E (ApoE) is involved in critical neural functions and is associated with various neuropsychiatric disorders. ApoE exists in three isoforms that differ in the number of cysteine residues per mole (CysR/mole). This study evaluated associations between this informative ordinal biochemical scale (CysR/mole) and symptom severity in veterans with posttraumatic stress disorder (PTSD) or subthreshold PTSD. Results demonstrated a significant negative relationship between the CysR/mole and severity of PTSD re-experiencing symptoms, adjusted for trauma. The findings suggest a genetic influence on PTSD symptomatology and dovetail with recent advances regarding the molecular mechanisms underlying the differential effects of ApoE in the brain.

Predictive Validity of the Expanded Susceptibility to Smoke Index.

OBJECTIVES: The susceptibility to smoking index can be improved as it only identifies one third of future adult smokers. Adding curiosity to this index may increase the identification of future smokers and improve the identification of effective prevention messages. METHODS: Analyses used data from the California Longitudinal Study of Smoking Transitions in Youth, for whom tobacco use behaviors, attitudes, and beliefs were assessed at 3 time points from age 12 through early adulthood. Logistic regressions were used to evaluate whether baseline curiosity about smoking was predictive of smoking during the 6-year follow-up period and whether curiosity about smoking provided evidence of incremental validity over existing measures of susceptibility to smoking. RESULTS: Compared to those who were classified as definitely not curious about smoking, teens who were classified as probably not curious (OR adj = 1.90, 95% CI = 1.28-2.81) and those classified as definitely curious (OR adj = 2.38, 95% CI= 1.49-3.79) had an increase in the odds of becoming a young adult smoker. Adding curiosity to the original susceptibility to smoking index increased the sensitivity of the enhanced susceptibility index to 78.9% compared to 62.2% identified by the original susceptibility index. However, a loss of specificity meant there was no improvement in the positive predictive value. CONCLUSIONS: The enhanced susceptibility index significantly improves identification of teens at risk for becoming young adult smokers. Thus, this enhanced index is preferred for identifying and testing potentially effective prevention messages.