Shame in Response to Affective Expression and Its Relation to Social Anhedonia and Schizotypy Traits.

ABSTRACT: Schizotypy is marked by negative symptoms including blunted affect, social isolation, and social anhedonia. Contemporary personality theory suggests that maladaptive shame regulation may disrupt interpersonal function across personality disorders. We hypothesized that "affect shame"-a conditioned response of shame evoked by openly expressing emotions would co-occur with interpersonal deficits in schizotypy. As hypothesized, affect shame was associated with interpersonal deficits (r = 0.17, p < 0.001), physical anhedonia (r = 0.13, p = 0.001), and social anhedonia (r = 0.17, p = 0.001). The observed findings were upheld in analyses controlling for demographic characteristics, depression symptom severity, and neuroticism and were maintained consistently across sensitivity analyses. Findings suggest that shame related to emotional expression is related to interpersonal deficits in schizotypy and have implications for our understanding of the etiology and treatment of this disorder.

A randomized, phase 1, placebo-controlled trial of APG-157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor-associated microbes.

BACKGROUND: Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target. METHODS: A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity. RESULTS: Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1ß, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment. CONCLUSIONS: The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy. LAY SUMMARY: Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs.

Inflamed by the flames? The impact of terrorism and war on immunity.

The physiological impact on citizens of prolonged exposure to violence and conflict is a crucial, yet underexplored, issue within the political science and biology literature. We examined the effect of high levels of exposure to rocket and terrorist attacks on biological markers of immunity and inflammation in a sample of 92 Israelis. A stratified random sample of individuals was drawn from a pool of subjects in Israel who had previously been interviewed regarding their stress exposure and psychological distress during a period of active rocket and terrorist attacks. These individuals were reinterviewed and blood samples were collected to assess antibodies to cytomegalovirus (CMV antibodies) and C-reactive protein (CRP). Posttraumatic stress disorder (PTSD) was significantly related to CRP, ß = .33, p = .034, with body mass index, depression, and exposure to terrorism included in the model. Depression scores were not significantly associated with CRP or CMV antibody levels. In contrast to the established convention that psychological distress is the sole outcome of terrorism exposure, these findings reveal that individuals exposed to terrorism experience higher levels of both PTSD/depression, and inflammation. This study has important ramifications for how policy makers and medical health professionals should formulate public health policies and medically treat individuals living in conflict zones.

Serum microRNA profile of rhesus macaques following ionizing radiation exposure and treatment with a medical countermeasure, Ex-Rad.

Exposure to ionizing radiation (IR) presents a formidable clinical challenge. Total-body or significant partial-body exposure at a high dose and dose rate leads to acute radiation syndrome (ARS), the complex pathologic effects that arise following IR exposure over a short period of time. Early and accurate diagnosis of ARS is critical for assessing the exposure dose and determining the proper treatment. Serum microRNAs (miRNAs) may effectively predict the impact of irradiation and assess cell viability/senescence changes and inflammation. We used a nonhuman primate (NHP) model-rhesus macaques (Macaca mulatta)-to identify the serum miRNA landscape 96 h prior to and following 7.2 Gy total-body irradiation (TBI) at four timepoints: 24, 36, 48, and 96 h. To assess whether the miRNA profile reflects the therapeutic effect of a small molecule ON01210, commonly known as Ex-Rad, that has demonstrated radioprotective efficacy in a rodent model, we administered Ex-Rad at two different schedules of NHPs; either 36 and 48 h post-irradiation or 48 and 60 h post-irradiation. Results of this study corroborated our previous findings obtained using a qPCR array for several miRNAs and their modulation in response to irradiation: some miRNAs demonstrated a temporary increased serum concentration within the first 24-36 h (miR-375, miR-185-5p), whereas others displayed either a prolonged decline (miR-423-5p) or a long-term increase (miR-30a-5p, miR-27b-3p). In agreement with these time-dependent changes, hierarchical clustering of differentially expressed miRNAs showed that the profiles of the top six miRNA that most strongly correlated with radiation exposure were inconsistent between the 24 and 96 h timepoints following exposure, suggesting that different biodosimetry miRNA markers might be required depending on the time that has elapsed. Finally, Ex-Rad treatment restored the level of several miRNAs whose expression was significantly changed after radiation exposure, including miR-16-2, an miRNA previously associated with radiation survival. Taken together, our findings support the use of miRNA expression as an indicator of radiation exposure and the use of Ex-Rad as a potential radioprotectant.

Endogenous Retroviruses as Modulators of Innate Immunity.

Endogenous retroviruses (ERVs), or LTR retrotransposons, are a class of transposable elements that are highly represented in mammalian genomes. Human ERVs (HERVs) make up roughly 8.3% of the genome and over the course of evolution, HERV elements underwent positive selection and accrued mutations that rendered them non-infectious; thereby, the genome could co-opt them into constructive roles with important biological functions. In the past two decades, with the help of advances in sequencing technology, ERVs are increasingly considered to be important components of the innate immune response. While typically silenced, expression of HERVs can be induced in response to traumatic, toxic, or infection-related stress, leading to a buildup of viral transcripts and under certain circumstances, proteins, including functionally active reverse transcriptase and viral envelopes. The biological activity of HERVs in the context of the innate immune response can be based on the functional effect of four major viral components: (1) HERV LTRs, (2) HERV-derived RNAs, (3) HERV-derived RNA:DNA duplexes and cDNA, and (4) HERV-derived proteins and ribonucleoprotein complexes. In this review, we will discuss the implications of HERVs in all four contexts in relation to innate immunity and their association with various pathological disease states.

Expression of Human Endogenous Retrovirus Group K (HERV-K) HML-2 Correlates with Immune Activation of Macrophages and Type I Interferon Response.

Human endogenous retroviruses (HERVs) comprise about 8.3% of the human genome and are capable of producing RNA molecules that can be sensed by pattern recognition receptors, leading to the activation of innate immune response pathways. The HERV-K (HML-2) subgroup is the youngest HERV clade with the highest degree of coding competence. Its expression is associated with inflammation-related diseases. However, the precise HML-2 loci, stimuli, and signaling pathways involved in these associations are not well understood or defined. To elucidate HML-2 expression on a locus-specific level, we used the retroelement sequencing tools TEcount and Telescope to analyze publicly available transcriptome sequencing (RNA-seq) and chromatin immunoprecipitation (ChIP) sequencing data sets of macrophages treated with a wide range of agonists. We found that macrophage polarization significantly correlates with modulation of the expression of specific HML-2 proviral loci. Further analysis demonstrated that the provirus HERV-K102, located in an intergenic region of locus 1q22, constituted the majority of the HML-2 derived transcripts following pro-inflammatory (M1) polarization and was upregulated explicitly in response to interferon gamma (IFN-γ) signaling. We found that signal transducer and activator of transcription 1 and interferon regulatory factor 1 interact with a solo long terminal repeat (LTR) located upstream of HERV-K102, termed LTR12F, following IFN-γ signaling. Using reporter constructs, we demonstrated that LTR12F is critical for HERV-K102 upregulation by IFN-γ. In THP1-derived macrophages, knockdown of HML-2 or knockout of MAVS, an adaptor of RNA-sensing pathways, significantly downregulated genes containing interferon-stimulated response elements (ISREs) in their promoters, suggesting an intermediate role of HERV-K102 in the switch from IFN-γ signaling to the activation of type I interferon expression and, therefore, in a positive feedback loop to enhance pro-inflammatory signaling. IMPORTANCE The human endogenous retrovirus group K subgroup, HML-2, is known to be elevated in a long list of inflammation-associated diseases. However, a clear mechanism for HML-2 upregulation in response to inflammation has not been defined. In this study, we identify a provirus of the HML-2 subgroup, HERV-K102, which is significantly upregulated and constitutes the majority of the HML-2 derived transcripts in response to pro-inflammatory activation of macrophages. Moreover, we identify the mechanism of HERV-K102 upregulation and demonstrate that HML-2 expression enhances interferon-stimulated response element activation. We also demonstrate that this provirus is elevated in vivo and correlates with interferon gamma signaling activity in cutaneous leishmaniasis patients. This study provides key insights into the HML-2 subgroup and suggests that it may participate in enhancing pro-inflammatory signaling in macrophages and probably other immune cells.

Cellular RNA and DNA sensing pathways are essential for the dose-dependent response of human monocytes to ionizing radiation.

Circulating monocytes are important players of the inflammatory response to ionizing radiation (IR). These IR-resistant immune cells migrate to radiation-damaged tissues and differentiate into macrophages that phagocytize dying cells, but also facilitate inflammation. Besides the effect of damage-associated molecular patterns, released from irradiated tissues, the inflammatory activation of monocytes and macrophages is largely dependent on IR-induced DNA damage and aberrant transcriptional activity, which may facilitate expression of type I interferons (IFN-I) and numerous inflammation-related genes. We analyzed the accumulation of dsRNA, dsDNA fragments, and RNA:DNA hybrids in the context of induction of RNA-triggered MAVS-mediated and DNA-triggered STING-mediated signaling pathways, in primary human monocytes and a monocytic cell line, THP1, in response to various doses of gamma IR. We found that exposure to lower doses (<7.5 Gy) led to the accumulation of dsRNA, along with dsDNA and RNA:DNA hybrids and activated both MAVS and STING pathway-induced gene expression and signaling activity of IFN-I. Higher doses of IR resulted in the reduced dsRNA level, degradation of RNA-sensing mediators involved in MAVS signaling and coincided with an increased accumulation of dsDNA and RNA:DNA hybrids that correlated with elevated STING signaling and NF-κB-dependent gene expression. While both pathways activate IFN-I expression, using MAVS- and STING-knockout THP1 cells, we identified differences in the spectra of interferon-stimulated genes (ISGs) that are associated with each specific signaling pathway and outlined a large group of STING signaling-associated genes. Using the RNAi technique, we found that increasing the dose of IR activates STING signaling through the DNA sensor cGAS, along with suppression of the DDX41 helicase, which is known to reduce the accumulation of RNA:DNA hybrids and thereby limit cGAS/STING signaling activity. Together, these results indicate that depending on the applied dose, IR leads to the activation of either dsRNA-induced MAVS signaling, which predominantly leads to the expression of both pro- and anti-inflammatory markers, or dsDNA-induced STING signaling that contributes to pro-inflammatory activation of the cells. While RNA:DNA hybrids boost both MAVS- and STING-mediated signaling pathways, these structures being accumulated upon high IR doses promote type I interferon expression and appear to be potent enhancers of radiation dose-dependent pro-inflammatory activation of monocytes.

Comparison of the Medical Uses and Cellular Effects of High and Low Linear Energy Transfer Radiation.

Exposure to ionizing radiation can occur during medical treatments, from naturally occurring sources in the environment, or as the result of a nuclear accident or thermonuclear war. The severity of cellular damage from ionizing radiation exposure is dependent upon a number of factors including the absorbed radiation dose of the exposure (energy absorbed per unit mass of the exposure), dose rate, area and volume of tissue exposed, type of radiation (e.g., X-rays, high-energy gamma rays, protons, or neutrons) and linear energy transfer. While the dose, the dose rate, and dose distribution in tissue are aspects of a radiation exposure that can be varied experimentally or in medical treatments, the LET and eV are inherent characteristics of the type of radiation. High-LET radiation deposits a higher concentration of energy in a shorter distance when traversing tissue compared with low-LET radiation. The different biological effects of high and low LET with similar energies have been documented in vivo in animal models and in cultured cells. High-LET results in intense macromolecular damage and more cell death. Findings indicate that while both low- and high-LET radiation activate non-homologous end-joining DNA repair activity, efficient repair of high-LET radiation requires the homologous recombination repair pathway. Low- and high-LET radiation activate p53 transcription factor activity in most cells, but high LET activates NF-kB transcription factor at lower radiation doses than low-LET radiation. Here we review the development, uses, and current understanding of the cellular effects of low- and high-LET radiation exposure.

Circulating Cell-free DNA in Serum as a Marker for the Early Detection of Tumor Recurrence in Breast Cancer Patients.

BACKGROUND/AIM: Circulating cell-free DNA (cfDNA) isolated from serum by noninvasive procedures can serve as a potential biomarker for the early detection of many cancers. The aim of this study was to implement a simple, yet effective quantitative method for measuring the cfDNA in serum and to investigate the relationship between cfDNA and the occurrence of recurrence in breast cancer (BrCa) patients. PATIENTS AND METHODS: A total of 240 cases were selected, which comprised different subtypes of BrCa patients and control individuals. We selected 20 serum samples from patients which showed recurrence after 4-7 years of disease-free survival. SYBR green was used as a reporter molecule to estimate the amount of cfDNA in these serum samples. RESULTS: A global Wilcoxon analysis was performed to compare the cfDNA abundance between non-recurrent and recurrent patients. The amount of cfDNA was higher in recurrent patients (recurrent vs. non-recurrent ratio=1.3; p=0.03; AUC=0.76) compared to non-recurrent patients. The data between normal/healthy controls and non-recurrent patients indicated no significant differences (n=20 in each group, healthy to non-recurrent ratio=1.03; p=0.20; AUC=0.61). CONCLUSION: We implemented a straightforward one-step technique to measure the amount of cfDNA in serum, which can translate into a clinical diagnostic tool in the near future. The high levels of cfDNA in the serum of recurrent BrCa patients compared to non-recurrent BrCa patients indicates a possible uncovered role for circulating genetic information, which either contributes to the cancer recurrence phenomenon or at the very least, serves as an identifier for the potential of recurrence.

High mRNA expression of LY6 gene family is associated with overall survival outcome in pancreatic ductal adenocarcinoma.

Pancreatic cancer ranks one of the worst in overall survival outcome with a 5 year survival rate being less than 10%. Pancreatic cancer faces unique challenges in its diagnosis and treatment, such as the lack of clinically validated biomarkers and the immensely immunosuppressive tumor microenvironment. Recently, the LY6 gene family has received increasing attention for its multi-faceted roles in cancer development, stem cell maintenance, immunomodulation, and association with more aggressive and hard-to-treat cancers. A detailed study of mRNA expression of LY6 gene family and its association with overall survival (OS) outcome in pancreatic cancers is lacking. We used publicly available clinical datasets to analyze the mRNA expression of a set of LY6 genes and its effect on OS outcome in the context of the tumor microenvironment and immunomodulation. We used web-based tools Kaplan-Meier Plotter, cBioPortal, Oncomine and R-programming to analyze copy number alterations, mRNA expression and its association with OS outcome in pancreatic cancer. These analyses demonstrated that high expression of LY6 genes is associated with OS and disease free survival (DFS) outcome. High expression of LY6 genes and their association with OS outcome is dependent on the composition of tumor microenvironment. Considering that LY6 proteins are anchored to the outer cell membrane or secreted, making them readily accessible, these findings highlight the potential of LY6 family members in the future of pancreatic cancer diagnosis and treatment.

Liver Function Enzymes are Potential Predictive Markers for Kidney Allograft Dysfunction.

INTRODUCTION: Biopsy of the allograft is the gold standard for assessing kidney allograft dysfunction. The aim of our pilot study was to identify serum biomarkers that could obviate the need for biopsy. MATERIALS AND METHODS: We conducted a study to identify the biomarkers in the serum from different groups of chronic kidney disease (CKD) patients and kidney transplanted patients vs. healthy individuals. The four groups (n=25 in each group) were as follows: 1) Patients with unstable kidney allograft transplants requiring biopsy for cause, 2) Patients with stable kidney allograft transplants, 3) Patients with CKD not on immunosuppressive therapy and, 4) healthy subjects. We measured the activity and level of serum alkaline phosphatase (ALP) and other liver enzymes (alanine transaminase (ALT) and aspartate transaminase (AST)) as potential serum biomarkers in acute allograft dysfunction. RESULTS: We found that ALP correlated with allograft biopsy findings, liver function, and clinical outcomes and possibly graft survival. Additionally, AST and ALT were higher in patients with graft rejection compared to non-rejected and stable kidney transplants. Moreover, the low Pearson correlations (r- values) between ALP level with age (r=0.179), gender, body mass index (r=0.236), creatinine (r=0.044) or estimated glomerular filtration rate (r=0.048) suggest that ALP may be an independent biomarker which is relatively unaffected by other individual-level variables. CONCLUSION: ALP may be a putative biomarker to predict kidney allograft function and rejection. Data also indicated that liver function plays an important role for the overall success of kidney transplantation.

Proteomic Analysis of Inflammatory Biomarkers Associated With Breast Cancer Recurrence.

INTRODUCTION: Breast cancer is the most frequent cancer detected for women, and while our ability to treat breast cancer has improved substantially over the years, recurrence remains a major obstacle. Standard screening for new and recurrent breast cancer involves clinical breast imaging. However, there is no clinically approved noninvasive body fluid test for the early detection of recurrent breast cancer. Materials and Method: In this study, we analyzed serum samples from both recurrent and nonrecurrent breast cancer patients by different proteomics methods to identify biomarkers in patients with recurrence of disease. RESULTS: Comparative data analysis identified several histone deacetylase (HDAC) proteins, which were found at significantly higher levels in the serum of recurrent breast cancer patients: HDAC9 (C-term) (P = 0.0035), HDAC5 (C-term) (P = 0.013), small ubiquitin-like modifier 1 (N-term) (P = 0.017), embryonic stem cell-expressed Ras (inter) (P = 0.018), and HDAC7 (C-term) (P = 0.020). Chronic inflammation plays a critical role in the development of the breast cancer recurrence, and we identified several proinflammatory cytokines that were present at elevated levels only in recurrent breast cancer patient serum. CONCLUSIONS: Our data indicated that the epigenetic regulation of inflammatory processes plays a critical role in breast cancer recurrence. The identified proteins could lay the groundwork for the development of a serum-based breast cancer recurrence assay.

A multidimensional meta-analysis of psychotherapy for PTSD.

OBJECTIVE: The authors present a multidimensional meta-analysis of studies published between 1980 and 2003 on psychotherapy for PTSD. METHOD: Data on variables not previously meta-analyzed such as inclusion and exclusion criteria and rates, recovery and improvement rates, and follow-up data were examined. RESULTS: Results suggest that psychotherapy for PTSD leads to a large initial improvement from baseline. More than half of patients who complete treatment with various forms of cognitive behavior therapy or eye movement desensitization and reprocessing improve. Reporting of metrics other than effect size provides a somewhat more nuanced account of outcome and generalizability. CONCLUSIONS: The majority of patients treated with psychotherapy for PTSD in randomized trials recover or improve, rendering these approaches some of the most effective psychosocial treatments devised to date. Several caveats, however, are important in applying these findings to patients treated in the community. Exclusion criteria and failure to address polysymptomatic presentations render generalizability to the population of PTSD patients indeterminate. The majority of patients posttreatment continue to have substantial residual symptoms, and follow-up data beyond very brief intervals have been largely absent. Future research intended to generalize to patients in practice should avoid exclusion criteria other than those a sensible clinician would impose in practice (e.g., schizophrenia), should avoid wait-list and other relatively inert control conditions, and should follow patients through at least 2 years.

Parental bonding and personality pathology assessed by clinician report.

The present study focused on the link between parental bonding and personality pathology. We developed a clinician-report version of the Parental Bonding Instrument (PBI; Parker, Tupling, and Brown, 1979), which 203 clinicians applied to a randomly selected patient in their care. The goal of the study was to examine the reliability and validity of a clinician-report PBI, and to provide a preliminary examination of the relation between personality disorder (PD) symptoms and parental bonding in a national sample of patients in treatment in the community. Factor analysis yielded two factors (parental rejection/care and parental overprotection) for each parent, which had high internal consistency (coefficient alphas all >.80). The factor structure of the clinician-report measure strongly resembled the factor structure of the widely used self-report instrument. Parental bonding as assessed by clinician report showed coherent patterns of association with PD diagnoses, which resembled those found in other samples. Maternal rejection/care showed a particular link to borderline PD (BPD), and remained a significant predictor of BPD along with sexual abuse and physical abuse in multiple regression analysis. These data, along with others from recent studies using clinicians as informants, suggest that clinicians can provide reliable and valid data when their observations are quantified using psychometrically sound instruments. Clinician-report methods may provide a useful complement to studies of personality disorders that rely primarily on self-reports or structured interviews.

Sleep disturbances predict later trauma-related distress: cross-panel investigation amidst violent turmoil.

OBJECTIVE: Sleep disturbances, including trouble falling and remaining asleep and recurrent nightmares, are symptoms of posttraumatic stress. A growing body of literature indicates that sleep disturbance may also convey vulnerability for the continuation of other symptoms of posttraumatic stress, including fear, anxiety, and heightened arousal. However, longitudinal research, which could help understand how these relationships unfold over time, has been limited. METHOD: The longitudinal relationships between sleep disturbance and posttraumatic stress were investigated in 779 Palestinian adults randomly selected and interviewed twice during the period from April 2008 to November 2008, amid ongoing violent political turmoil. The recruitment method produced a representative sample and excellent retention. Cross-panel structural equation modeling was used to examine relationships between sleep and distress across two study periods. RESULTS: Results indicated that initial sleep problems were associated with increased posttraumatic stress disorder (PTSD), depression, and intrapersonal resource loss at follow-up 6 months later, but initial PTSD, depression, and intrapersonal resource loss were not associated with increased sleep problems at follow-up. CONCLUSIONS: Sleep problems may confer vulnerability to longer-term distress in the presence of ongoing political violence. Future research should examine whether interventions targeting trauma-related sleep problems may improve prevention and treatment for PTSD and related disorders.

The moderating effects of cluster B personality traits on violence reduction training: a mixed-model analysis.

Cognitive behavioral therapies have positive effects on anger and aggression; however, individuals differ in their response to treatment. The authors previously found that dynamic factors, such as increases in readiness to change, are associated with enhanced outcomes for violence reduction training. This study investigated how less dynamic factors, specifically Cluster B personality traits, moderate the effects of violence reduction training. The authors used mixed modeling to fit growth curves to 14 weeks of anger strategies data and evaluated whether the presence of Cluster B traits affected pretreatment anger levels and rates of change. As expected, overall levels of negative anger strategies decreased across the 14-week treatment. Participants with antisocial, borderline, and histrionic personality features reported higher rates of negative anger strategies, whereas those with narcissistic personality features reported fewer negative anger strategies. Those with antisocial personality features improved at a rate similar to the overall trend of those without Cluster B traits. Those with borderline and histrionic features improved at an accelerated rate.

Reciprocal relationships between resource loss and psychological distress following exposure to political violence: an empirical investigation of COR theory's loss spirals.

We conducted a four-wave prospective study of Palestinian adults living in the West Bank, Gaza Strip, and East Jerusalem, interviewed between 2007 and 2009 at 6-month interval to explore transactional relationships between resource loss (i.e., intra and interpersonal resource loss) and psychological distress (i.e., posttraumatic stress disorder and depression symptoms). Initially, 1196 Palestinians completed the first wave interview and 752 of these participants completed all four interviews. A cross-lagged panel design was constructed to model the effects of trauma exposure on both resource loss and psychological distress and the subsequent reciprocal effects of resource loss and psychological distress across four time waves. Specifically, resource loss was modeled to predict distress, which in turn was expected to predict further resource loss. Structural equation modeling was used to test this design. We found that psychological distress significantly predicts resource loss across shorter, 6-month time waves, but that resource loss predicts distress across longer, 12-month intervals. These findings support the Conservation of Resources theory's corollary of loss spirals.

Refining the construct of narcissistic personality disorder: diagnostic criteria and subtypes.

OBJECTIVE: Narcissistic personality disorder has received relatively little empirical attention. This study was designed to provide an empirically valid and clinically rich portrait of narcissistic personality disorder and to identify subtypes of the disorder. METHOD: A random national sample of psychiatrists and clinical psychologists (N=1,201) described a randomly selected current patient with personality pathology. Clinicians provided detailed psychological descriptions of the patients using the Shedler-Westen Assessment Procedure-II (SWAP-II), completed a checklist of axis II diagnostic criteria, and provided construct ratings for each axis II personality disorder. Descriptions of narcissistic patients based on both raw and standardized SWAP-II item scores were aggregated to identify, respectively, the most characteristic and the most distinctive features of narcissistic personality disorder. RESULTS: A total of 255 patients met DSM-IV criteria for narcissistic personality disorder based on the checklist and 122 based on the construct ratings; 101 patients met criteria by both methods. Q-factor analysis identified three subtypes of narcissistic personality disorder, which the authors labeled grandiose/malignant, fragile, and high-functioning/exhibitionistic. Core features of the disorder included interpersonal vulnerability and underlying emotional distress, along with anger, difficulty in regulating affect, and interpersonal competitiveness, features that are absent from the DSM-IV description of narcissistic personality disorder. CONCLUSIONS: These findings suggest that DSM-IV criteria for narcissistic personality disorder are too narrow, underemphasizing aspects of personality and inner experience that are empirically central to the disorder. The richer and more differentiated view of narcissistic personality disorder suggested by this study may have treatment implications and may help bridge the gap between empirically and clinically derived concepts of the disorder.