DSM-5 specifies bulimia nervosa (BN) severity based on specific thresholds of compensatory behavior frequency. There is limited empirical support for such severity groupings. Limited support could be because the DSM-5’s compensatory behavior frequency cutpoints are inaccurate or because compensatory behavior frequency does not capture true underlying differences in severity. In support of the latter possibility, some work has suggested shape/weight overvaluation or use of single versus multiple purging methods may be better severity indicators. We used structural equation modeling (SEM) Trees to empirically determine the ideal variables and cutpoints for differentiating BN severity, and compared the SEM Tree groupings to alternate severity classifiers: the DSM-5 indicators, single versus multiple purging methods, and a binary indicator of shape/weight overvaluation.

Treatment-seeking adolescents and adults with BN (N = 1017) completed self-report measures assessing BN and comorbid symptoms. SEM Trees specified an outcome model of BN severity and recursively partitioned this model into subgroups based on shape/weight overvaluation and compensatory behaviors. We then compared groups on clinical characteristics (eating disorder symptoms, depression, anxiety, and binge eating frequency).

SEM Tree analyses resulted in five severity subgroups, all based on shape/weight overvaluation: overvaluation <1.25; overvaluation 1.25–3.74; overvaluation 3.75–4.74; overvaluation 4.75–5.74; and overvaluation ≥5.75. SEM Tree groups explained 1.63–6.41 times the variance explained by other severity schemes.

Shape/weight overvaluation outperformed the DSM-5 severity scheme and single versus multiple purging methods, suggesting the DSM-5 severity scheme should be reevaluated. Future research should examine the predictive utility of this severity scheme.

The Institute for Implementation Science Scholars (IS-2) is a dissemination and implementation (D&I) science training and mentoring program. A key component of IS-2 is collaborating and networking. To build knowledge on effective networking and mentoring, this study sought to 1) conduct a social network analysis to determine whether underrepresented scholars have equivalent levels of connection and 2) gain insights into the differences in networking among racial/ethnic subgroups of scholars.

Social network survey data were used to select participants based on number of collaborative connections (highest, lowest) and racial/ ethnic category (underrepresented, not underrepresented). Interviews were recorded, transcribed, and coded using an iterative process.

The sample consisted of eight highly networked scholars, eight less networked scholars, seven from underrepresented racial and ethnic groups, and nine from not underrepresented groups. Qualitative data showed a lack of connection, reluctance to network, and systematic issues including institutional biases as possible drivers of group differences. In addition, scholars provided suggestions on how to overcome barriers to networking and provided insights into how IS-2 has impacted their D&I research and knowledge.

Underrepresented scholars have fewer network contacts than not underrepresented scholars in the IS-2 training program. It is imperative for leadership to be intentional with mentorship pairing, especially for underrepresented scholars. Future research might include interviews with program leaders to understand how network pairings are built to improve the mentorship experience.

Fasedienol (PH94B; 3β-androsta-4,16-dien-3-ol) is a synthetic neuroactive nasal spray from the androstane family of pherines. Intranasal fasedienol activates receptors in peripheral nasal chemosensory neurons connected to subsets of neurons in the olfactory bulbs that in turn are neurally connected to neurons in the limbic amygdala involved in the pathophysiology of SAD and potentially other anxiety and mood disorders. Fasedienol is locally metabolized in the olfactory mucosa without systemic uptake or binding to CNS receptors. The objective of the present study was to compare fasedienol vs. placebo during a public speaking challenge in subjects with SAD.

This was a multi-center, double-blind, randomized, placebo-controlled study (NCT05011396). After screening (Visit 1), all subjects completed Visit 2 (V2, Baseline, placebo nasal spray administered to all subjects) and participated in a 5-minute public speaking challenge (PSC) during which Subjective Units of Distress Scores (SUDS) were recorded. Subjects with SUDS >= to 70 were invited back a week later for the Visit 3 (V3) treatment visit and randomly allocated to receive either fasedienol (3.2 μg intranasally) or placebo, then undergo a second 5-minute PSC, with SUDS scores recorded. After the V3 PSC, subjects completed a Patient Global Impression of Change (PGI-C) and trained raters completed a Clinical Global Impression of Improvement (CGI-I). CGI-I responders were defined as those assigned scores of 1 (very much improved) or 2 (much improved); PGI-C responders reported scores of 1 (very much less anxious) or 2 (much less anxious). ANCOVA with baseline SUDS as a covariate was used to compare change in mean SUDS from V2 to V3 for the subjects administered fasedienol at V3 vs those who received placebo at V3.

Fasedienol-treated patients (n=70) demonstrated a statistically significant greater change in mean SUDS score (least-squares (LS) mean = -13.8) compared with placebo (n=71, LS mean = -8.0), for a difference between groups of -5.8 (p=0.015). The proportion of CGI-I responders was higher in the fasedienol group 37.7% vs. placebo 21.4% (p=0.033), as was the proportion of PGI-C responders: fasedienol 40.6% vs. placebo 18.6% (p=0.003). Fasedienol was well-tolerated with no treatment-emergent adverse events above 1.5% occurrence.

The Phase 3 PALISADE-2 trial results demonstrated that a single dose of fasedienol prior to a stressful PSC produced efficacy on patient-rated SUDS and PGI-C, as well as the clinician-rated CGI-I. The results also confirmed the nasal-amygdala neural circuits as a new portal for administration of pharmaceuticals. The data support continued development of fasedienol as a first-in-class, rapid-onset, well-tolerated treatment option for SAD without addictive properties.

Vistagen Therapeutics

To determine whether poorer performance on the Boston Naming Test (BNT) in individuals with transactive response DNA-binding protein 43 pathology (TDP-43+) is due to greater loss of word knowledge compared to retrieval-based deficits.

Retrospective clinical-pathologic study of 282 participants with Alzheimer’s disease neuropathologic changes (ADNC) and known TDP-43 status. We evaluated item-level performance on the 60-item BNT for first and last available assessment. We fit cross-sectional negative binomial count models that assessed total number of incorrect items, number correct of responses with phonemic cue (reflecting retrieval difficulties), and number of “I don’t know” (IDK) responses (suggestive of loss of word knowledge) at both assessments. Models included TDP-43 status and adjusted for sex, age, education, years from test to death, and ADNC severity. Models that evaluated the last assessment adjusted for number of prior BNT exposures.

43% were TDP-43+. The TDP-43+ group had worse performance on BNT total score at first (p = .01) and last assessments (p = .01). At first assessment, TDP-43+ individuals had an estimated 29% (CI: 7%–56%) higher mean number of incorrect items after adjusting for covariates, and a 51% (CI: 15%–98%) higher number of IDK responses compared to TDP-43−. At last assessment, compared to TDP-43−, the TDP-43+ group on average missed 31% (CI: 6%–62%; p = .01) more items and had 33% more IDK responses (CI: 1% fewer to 78% more; p = .06).

An important component of poorer performance on the BNT in participants who are TDP-43+ is having loss of word knowledge versus retrieval difficulties.

Loss of control eating is more likely to occur in the evening and is uniquely associated with distress. No studies have examined the effect of treatment on within-day timing of loss of control eating severity. We examined whether time of day differentially predicted loss of control eating severity at baseline (i.e. pretreatment), end-of-treatment, and 6-month follow-up for individuals with binge-eating disorder (BED), hypothesizing that loss of control eating severity would increase throughout the day pretreatment and that this pattern would be less pronounced following treatment. We explored differential treatment effects of cognitive-behavioral guided self-help (CBTgsh) and Integrative Cognitive-Affective Therapy (ICAT).

Individuals with BED (N = 112) were randomized to receive CBTgsh or ICAT and completed a 1-week ecological momentary assessment protocol at baseline, end-of-treatment, and 6-month follow-up to assess loss of control eating severity. We used multilevel models to assess within-day slope trajectories of loss of control eating severity across assessment periods and treatment type.

Within-day increases in loss of control eating severity were reduced at end-of-treatment and 6-month follow-up relative to baseline. Evening acceleration of loss of control eating severity was greater at 6-month follow-up relative to end-of-treatment. Within-day increases in loss of control severity did not differ between treatments at end-of-treatment; however, evening loss of control severity intensified for individuals who received CBTgsh relative to those who received ICAT at 6-month follow-up.

Findings suggest that treatment reduces evening-shifted loss of control eating severity, and that this effect may be more durable following ICAT relative to CBTgsh.

A minority of naturally cycling individuals experience clinically significant affective changes across the menstrual cycle. However, few studies have examined cognitive and behavioral constructs that may maintain or worsen these changes. Several small studies link rumination with premenstrual negative affect, with authors concluding that a tendency to ruminate amplifies and perpetuates hormone-sensitive affective symptoms. Replication in larger samples is needed to confirm the validity of rumination as a treatment target.

190 cycling individuals (M = 30.82 years; 61.1% Caucasian) were recruited for moderate perceived stress, a risk factor for cyclical symptoms. They completed the Rumination Response Scale at baseline, then reported daily affective and physical symptoms across 1–6 cycles. Multilevel growth models tested trait rumination as a predictor of baseline levels, luteal increases, and follicular decreases in symptoms.

The degree of affective cyclicity was normally distributed across a substantial range, supporting feasibility of hypothesis tests and validating the concept of dimensional hormone sensitivity. Contrary to prediction, higher brooding did not predict levels or cyclical changes of any symptom. In a subsample selected for luteal increases in negative affect, brooding predicted higher baseline negative affect but still did not predict affective cyclicity.

An individual's trait-like propensity to engage in rumination may not be a valid treatment target in premenstrual mood disorders. State-like changes in rumination should still be further explored, and well-powered prospective studies should explore other cognitive and behavioral factors to inform development of targeted psychological treatments for patients with cyclical affective symptoms.