Diagnostic and Statistical Manual of Mental Disorders, fifth edition, personality disorders and the alternative model: Prediction of naturalistically observed behavior, interpersonal functioning, and psychiatric symptoms, 1 year later.

Traditional personality disorders (PDs; e.g., Diagnostic and Statistical Manual of Mental Disorders, fifth edition [DSM-5] Section II PDs), as well as dimensional traits (e.g., alternative model for PD [AMPD]), offer unique advantages in personality pathology assessment. However, very little is known about how these systems compare in predicting observable behavior. This study compares self-report ratings of PD symptoms (i.e., Structured Clinical Interview for DSM-IV PD) with self-reports of AMPD traits (i.e., Personality Inventory for DSM-5) in predicting clinical outcomes, 1 year later, via three different methods: (a) naturalistically observed psychosocial functioning (i.e., electronically activated recorder [EAR]), (b) informant-reported interpersonal functioning (i.e., Inventory of Interpersonal Problems-32), and (c) self-reported suicidality (SI), depression, anxiety, and substance use symptoms (i.e., Psychiatric Diagnostic Screening Questionnaire). Data were analyzed from 72 individuals in current or recent psychiatric treatment meeting diagnosis for at least one PD. Results showed that DSM Section II PD and AMPD ratings yielded meaningful and comparable predictions of naturalistically observed EAR variables and informant-rated interpersonal functioning. The AMPD appeared to offer slight advantages in the prediction of EAR-observed negative affect, hostile words, and informant-rated interpersonal functioning, with clearer advantages at the facet level. Overall, these results provide tentative evidence that both DSM Section II PD and AMPD systems show meaningful links with clinical outcomes measured via multiple methods 1 year later, but with clearer advantages for the AMPD at the facet level. Moreover, results show that the EAR is a viable method for capturing naturalistically observed clinically meaningful, in vivo behavior of individuals exhibiting maladaptive personality patterns. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Understanding the association between normal and maladaptive personality traits: Replication and extension of Morey et al. (2020).

BACKGROUND/OBJECTIVE: The Alternative Model for Personality Disorders (AMPD) within the DSM-5 includes separable components representing general personality dysfunction (Criterion A) and maladaptive personality traits (Criterion B). Some critique Criterion A for accounting for little incremental variance in PD beyond Criterion B. However, Morey et al. (2020) hypothesized that personality dysfunction is a key mechanism through which normal-range traits account for the maladaptive component of personality traits, justifying its inclusion. We sought to replicate and extend this work in a psychiatric sample with mixed methods. METHOD: In total, 152 participants recruited from mental health clinics completed multiple measures of personality dysfunction and normal-range and maladaptive traits. RESULTS: Replication was only partially achieved. The degree of incremental prediction of maladaptive traits and the extent to which personality dysfunction explained the relations between normal-range and maladaptive traits varied significantly across traits, and those effects that reached significance were small in magnitude. Removing variance due to personality dysfunction reduced intercorrelations among maladaptive traits by only a small amount. CONCLUSION: Counter to Morey et al. (2020), our results failed to support maladaptive traits as composites of normal-range traits and personality dysfunction, suggesting that other methods of distinguishing personality pathology severity and style are needed.

Do self and interpersonal dysfunction cross-sectionally mediate the association between adverse childhood experiences and personality pathology?

Two primary limitations of research on the association between adverse childhood experiences (ACEs) and personality disorder (PD) are (1) failure to consider mechanisms of association and (2) inconsistent results due, in part, to inconsistent approaches to quantifying ACE exposure. The current study will address these limitations by examining the cross-sectional mediating role of self- and interpersonal dysfunction on the association between ACE and three PDs (antisocial, schizotypal, and borderline) using three quantifications of ACE exposure (cumulative, individual, and unique risk). Participants were 149 current or recent psychiatric patients, and data analyses were performed through estimation of a series of cross-sectional mediation models. Taken together, results suggest that (1) the association between ACE and PD is moderate, (2) self- and interpersonal dysfunction cross-sectionally mediate this association, (3) after accounting for variance shared among ACEs, associations between specific ACE subtypes and PD were negligible, (4) much of the association between ACE and PD is accounted for by general processes impacted by all forms of ACE and implicated in all forms of PD, and (5) emotional neglect may uniquely contribute to self- and interpersonal dysfunction and thereby, PD risk.

Single gene non-invasive prenatal screening for autosomal dominant conditions in a high-risk cohort.

PURPOSE: To determine the utility of single gene non-invasive prenatal screening (NIPS-SGD) in a high-risk reproductive genetics clinic. METHODS: A clinical pilot for NIPS-SGD was conducted from March 2020 to November 2021. A NIPS-SGD panel assessing pathogenic variants in 30 genes was offered to pregnant individuals for the following indications: (1) advanced sperm age ≥40 years, (2) nuchal translucency (NT) ≥ 3.5 mm, (3) fetal anomaly, or (4) family history of a condition covered by the panel. Diagnostic testing was offered concurrently. RESULTS: NIPS-SGD was ordered for 253 individuals: 88 (34.8%) for fetal anomalies, 96 (37.9%) for advanced sperm age, 37 (14.6%) for increased NT, and 5 (2.0%) for family history. Among 228 (90.1%) completed tests, 8 (3.5%) were positive. Diagnostic testing for 78 individuals revealed no false positive or negative results. Of 41 (25.9%) individuals who received a molecular diagnosis, 34 (82.9%) were outside the scope of NIPS-SGD. Positive NIPS-SGD altered medical management in five cases. CONCLUSIONS: NIPS-SGD in a high-risk population can lead to earlier prenatal diagnosis, enhanced surveillance, and targeted genetic analysis, but should not replace clinically indicated diagnostic testing. Potential incidental findings include parental diagnoses and misattributed parentage.

Profiling the Murine Acute Phase and Inflammatory Responses to African Snake Venom: An Approach to Inform Acute Snakebite Pathology.

Snake envenoming causes rapid systemic and local effects that often result in fatal or long-term disability outcomes. It seems likely that acute phase and inflammatory responses contribute to these haemorrhagic, coagulopathic, neurotoxic, nephrotoxic and local tissue destructive pathologies. However, the contributory role of acute phase/inflammatory responses to envenoming is under-researched and poorly understood-particularly for envenoming by sub-Saharan African venomous snakes. To provide data to help guide future studies of human patients, and to explore the rationale for adjunct anti-inflammatory medication, here we used an in vivo murine model to systematically assess acute phase and inflammatory responses of mice to ten African snake venoms. In addition to investigating snake species-specific effects of venom on the cardiovascular system and other key organs and tissues, we examined the response to intravascular envenoming by acute phase reactants, including serum amyloid A, P-selectin and haptoglobin, and several cytokines. Venoms of the spitting (Naja nigricollis) and forest (N. melanoleuca) cobras resulted in higher acute phase and inflammatory responses than venoms from the other cobras, mambas and vipers tested. Naja nigricollis venom also stimulated a 100-fold increase in systemic interleukin 6. Thin blood films from venom-treated mice revealed species-specific changes in red blood cell morphology, indicative of membrane abnormalities and functional damage, lymphopenia and neutrophil leukocytosis. Our ex vivo assays with healthy human blood treated with these venoms identified that N. nigricollis venom induced marked levels of haemolysis and platelet aggregation. We conclude that African snake venoms stimulate very diverse responses in this mouse model of acute systemic envenoming, and that venoms of the African cobras N. nigricollis and N. melanoleuca, in particular, cause marked inflammatory and non-specific acute phase responses. We also report that several African snake venoms cause haemolytic changes. These findings emphasise the importance of understanding acute responses to envenoming, and that further research in this area may facilitate new diagnostic and treatment approaches, which in turn may lead to better clinical outcomes for snakebite patients.

Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for hemotoxic snakebite.

Snakebite envenoming causes 138,000 deaths annually, and ~400,000 victims are left with permanent disabilities. Envenoming by saw-scaled vipers (Viperidae: Echis) leads to systemic hemorrhage and coagulopathy and represents a major cause of snakebite mortality and morbidity in Africa and Asia. The only specific treatment for snakebite, antivenom, has poor specificity and low affordability and must be administered in clinical settings because of its intravenous delivery and high rates of adverse reactions. This requirement results in major treatment delays in resource-poor regions and substantially affects patient outcomes after envenoming. Here, we investigated the value of metal ion chelators as prehospital therapeutics for snakebite. Among the tested chelators, dimercaprol (British anti-Lewisite) and its derivative 2,3-dimercapto-1-propanesulfonic acid (DMPS) were found to potently antagonize the activity of Zn2+-dependent snake venom metalloproteinases in vitro. Moreover, DMPS prolonged or conferred complete survival in murine preclinical models of envenoming against a variety of saw-scaled viper venoms. DMPS also considerably extended survival in a "challenge and treat" model, where drug administration was delayed after venom injection and the oral administration of this chelator provided partial protection against envenoming. Last, the potential clinical scenario of early oral DMPS therapy combined with a delayed, intravenous dose of conventional antivenom provided prolonged protection against the lethal effects of envenoming in vivo. Our findings demonstrate that the safe and affordable repurposed metal chelator DMPS can effectively neutralize saw-scaled viper venoms in vitro and in vivo and highlight the promise of this drug as an early, prehospital, therapeutic intervention for hemotoxic snakebite envenoming.

The latent structure of self-harm.

The underlying structure of self-harm behaviors is not well-understood; for example, whether suicidality and nonsuicidal self-injury (NSSI) lie on a single dimension or two separate dimensions is unknown. We used confirmatory factor analyses to examine the factor structure of self-harm items in a clinical/community sample (N = 641). Of three alternative factor structures (one-factor, correlated-factors, bifactor), the bifactor model fit best. The general factor, representing overlap between suicidality and NSSI, captured the majority of model variance and was the strongest predictor of psychosocial correlates. The NSSI-specific factor captured a moderate amount of variance and correlated uniquely with both antagonistic traits and obsessive-compulsive tendencies; this factor was named NSSI. The suicidality-specific factor explained little model variance and was weakly associated with external criteria; this factor was named low attraction to life. Results are interpreted as preliminary evidence for the utility of bifactor modeling in understanding the latent structure of self-harm. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Assessing inter-model continuity between the Section II and Section III conceptualizations of borderline personality disorder in DSM-5.

DSM-5 includes 2 competing models of borderline personality disorder (BPD) in Sections II and III. Empirical comparisons between these models are required to understand and improve intermodel continuity. We compared Section III BPD traits to Section II BPD criteria assessed via semistructured interviews in 455 current/recent psychiatric patients using correlation and regression analyses, and also evaluated the incremental predictive power of other Section III traits. In addition, we tested the hypothesis that self-harm would incrementally predict BPD Criterion 5 over the Section III traits. Results supported Section III BPD traits as an adequate representation of traditional BPD symptomatology, although modifications that would increase intermodel continuity were identified. Finally, we found support for the incremental validity of suspiciousness, anhedonia, perceptual dysregulation, and self-harm, suggesting possible gaps in the Section III PD trait definitions. (PsycINFO Database Record