Endogenous opioids facilitate stress-induced binge eating via an insular cortex-claustrum pathway.

Stress has been shown to promote the development and persistence of binge eating behaviors. However, the neural circuit mechanisms for stress-induced binge-eating behaviors are largely unreported. The endogenous dynorphin (dyn)/kappa opioid receptor (KOR) opioid neuropeptide system has been well established to be a crucial mediator of the anhedonic component of stress. Here, we aimed to dissect the basis of dynorphinergic control of stress-induced binge-like eating behavior. We first established a mouse behavioral model for stress-induced binge-like eating behaviors. We found that mice exposed to stress increased their food intake of familiar palatable food (high fat, high sugar, HPD) compared to non-stressed mice. Following a brain-wide analysis, we isolated robust cFos-positive cells in the Claustrum (CLA), a subcortical structure with highly abundant KOR expression, following stress-induced binge-eating behavior. We report that KOR signaling in CLA is necessary for this elevated stress-induced binge eating behavior using local pharmacology and local deletion of KOR. In vivo calcium recordings using fiber photometry revealed a disinhibition circuit structure in the CLA during the initiation of HPD feeding bouts. We further established the dynamics of endogenous dynorphinergic control of this behavior using a genetically encoded dynorphin biosensor, Klight. Combined with 1-photon single-cell calcium imaging, we report significant heterogeneity with the CLA population during stress-induced binge eating and such behavior attenuates local dynorphin tone. Furthermore, we isolate the anterior Insular cortex (aIC) as the potential source of endogenous dynorphin afferents in the CLA. By characterizing neural circuits and peptidergic mechanisms within the CLA, we uncover a pathway that implicates endogenous opioid regulation stress-induced binge eating.

Does Researcher Allegiance Bias Outcomes in Psychotherapy Research? A Quasi-Experimental Secondary Analysis.

Researchers who conduct studies comparing the efficacy of two treatments often find that their preferred treatment outperforms the comparison treatment. This finding has been labelled the allegiance association. Although this association is robust, it is unclear whether it reflects an allegiance bias on the part of the researchers or whether it is noncausal, with researchers being allied to the more effective treatments. This study applied a quasi-experimental method proposed by a previous study to 19 pairs of treatment comparison studies. Each member of a pair had used the same two psychotherapies to treat clients with the same disorder, but the researchers in each of the two studies had opposing allegiances. If the authors of one study in the pair concluded that their preferred treatment was superior and the authors of the other study concluded that their preferred treatment was superior or that the two treatments were equivalent, these patterns would suggest allegiance bias. In 10 of the 19 pairs, the patterns were consistent with the operation of an allegiance bias, indicating that although allegiance biases are not inevitable, they are ubiquitous. Practitioners and other psychotherapy research consumers should use caution when interpreting the findings from treatment comparison studies.

MELLODDY: Cross-pharma Federated Learning at Unprecedented Scale Unlocks Benefits in QSAR without Compromising Proprietary Information.

Federated multipartner machine learning has been touted as an appealing and efficient method to increase the effective training data volume and thereby the predictivity of models, particularly when the generation of training data is resource-intensive. In the landmark MELLODDY project, indeed, each of ten pharmaceutical companies realized aggregated improvements on its own classification or regression models through federated learning. To this end, they leveraged a novel implementation extending multitask learning across partners, on a platform audited for privacy and security. The experiments involved an unprecedented cross-pharma data set of 2.6+ billion confidential experimental activity data points, documenting 21+ million physical small molecules and 40+ thousand assays in on-target and secondary pharmacodynamics and pharmacokinetics. Appropriate complementary metrics were developed to evaluate the predictive performance in the federated setting. In addition to predictive performance increases in labeled space, the results point toward an extended applicability domain in federated learning. Increases in collective training data volume, including by means of auxiliary data resulting from single concentration high-throughput and imaging assays, continued to boost predictive performance, albeit with a saturating return. Markedly higher improvements were observed for the pharmacokinetics and safety panel assay-based task subsets.

When, If Ever, Is It Appropriate to Regard a Patient as "Too Medically Complex" for One Inpatient Service, But Not Another?

Patients with chronic health conditions often find their admission for orthopedic surgery from the emergency department held up due to disagreement between orthopedists and internal medicine physicians, such as hospitalists. One reason for this delay is that orthopedists must decide which patients they will admit. Although this decision is based on clinical criteria, variation in orthopedists' practices and views of a patient's condition's medical complexity is a common source of physician disagreement. This commentary on a case describes constraints on hospitalists and orthopedists, as well as other factors in patient disposition, and suggests quality improvements to admissions processes that might help mitigate the distress that patients can experience as a result of health professional disagreement.

Optical Approaches for Investigating Neuromodulation and G Protein-Coupled Receptor Signaling.

Despite the fact that roughly 40% of all US Food and Drug Administration (FDA)-approved pharmacological therapeutics target G protein-coupled receptors (GPCRs), there remains a gap in our understanding of the physiologic and functional role of these receptors at the systems level. Although heterologous expression systems and in vitro assays have revealed a tremendous amount about GPCR signaling cascades, how these cascades interact across cell types, tissues, and organ systems remains obscure. Classic behavioral pharmacology experiments lack both the temporal and spatial resolution to resolve these long-standing issues. Over the past half century, there has been a concerted effort toward the development of optical tools for understanding GPCR signaling. From initial ligand uncaging approaches to more recent development of optogenetic techniques, these strategies have allowed researchers to probe longstanding questions in GPCR pharmacology both in vivo and in vitro. These tools have been employed across biologic systems and have allowed for interrogation of everything from specific intramolecular events to pharmacology at the systems level in a spatiotemporally specific manner. In this review, we present a historical perspective on the motivation behind and development of a variety of optical toolkits that have been generated to probe GPCR signaling. Here we highlight how these tools have been used in vivo to uncover the functional role of distinct populations of GPCRs and their signaling cascades at a systems level. SIGNIFICANCE STATEMENT: G protein-coupled receptors (GPCRs) remain one of the most targeted classes of proteins for pharmaceutical intervention, yet we still have a limited understanding of how their unique signaling cascades effect physiology and behavior at the systems level. In this review, we discuss a vast array of optical techniques that have been devised to probe GPCR signaling both in vitro and in vivo.

Construction and preliminary validation of an inconsistent responding scale for the HEXACO-100.

Inconsistent responding poses a particular risk to self-report data and is a common phenomenon in undergraduate and community subject pools. The HEXACO-100 personality inventory (Lee & Ashton, 2018) lacks internal validity scales that could be used to identify inconsistent responding. To address this need, the present study developed a HEXACO Inconsistent Responding Test (HIRT). Highly correlated and conceptually overlapping HEXACO-100 item pairs were identified from a derivation sample and cross-validated by comparing real data to randomly generated protocols. The HIRT was highly accurate at identifying both randomly generated and half-randomly generated protocols. HIRT scores exhibited significant correlations with other inconsistency measures (i.e., the Triarchic Assessment Procedure for Inconsistent Responding and the HEXACO's Inter-item Standard Deviation) and were as effective as these other measures at differentiating between consistent and inconsistent responders. This preliminary validation of the HIRT provides strong evidence of its ability to improve the quality of data gathered with the HEXACO-100, which may be especially useful for researchers hoping to utilize the measure in clinically relevant research and applications. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Construction and Preliminary Validation of Machiavellianism Scales From the HEXACO-100.

Machiavellian individuals are callous, manipulative, and misanthropic, and they are also strategic and capable of delaying gratification. Many commonly used measures of Machiavellianism focus on the antagonistic aspects of Machiavellianism and devote few items to the strategic aspects of this construct. Because the HEXACO framework includes an Honesty-Humility factor, it may be especially capable of characterizing the full range of Machiavellian characteristics. The current study used a consensus-rating approach to create Machiavellianism scales using items from the HEXACO-100. This approach yielded two HEXACO-Machiavellianism scales that were labeled HEXACO-Manipulative and HEXACO-Disciplined. Data from five community and college student samples were used to examine the internal consistency and validity of these HEXACO-Machiavellianism scales. The scales demonstrated acceptable internal consistency and displayed promising convergent and discriminant validity with criterion variables, including other Machiavellianism scales. The HEXACO-Manipulative and HEXACO-Disciplined scales were negatively correlated, suggesting that Machiavellianism may be better understood as an emergent trait.

Bipolar disorders and narcissism: Diagnostic concerns, conceptual commonalities and potential antecedents.

Narcissistic personality disorder (NPD) and the manic and hypomanic episodes found in the bipolar disorders are characterized by grandiosity. It is possible that this shared grandiosity is a 'homologous structure' or reflects a superficial similarity between two disparate conditions. It is, however, possible that NPD and the bipolar disorders are more closely related than implied by their segregation into the separate superordinate categories of personality disorders and mood disorders. Whereas narcissism is considered to be a life-course, stable trait and the bipolar disorders are characterized by episodes of mania and depression, there is considerable research indicating that narcissism may be linked to mood instability (including depression) and bipolar disorder may have a pervasive personality component (i.e., hypomanic personality). Utilizing dimensional models of psychopathology, the current review examined the evidence linking narcissism and the bipolar disorders and suggests that considerable overlap may exist in the domains associated with reward-seeking, harm avoidance and social functioning.

Brazilian Portuguese adaptation of the spitefulness scale and associations with personality traits.

Spitefulness is a personality trait characterized by an inclination to cause harm to others in a manner that also results in self-harm. Studies considering this trait have mostly been performed in individualistic cultures. Our aim was to adapt and accumulate statistical evidence for the Brazilian Portuguese version of the Spitefulness Scale (SS-BP), examining the functioning of the instrument in a collectivist culture. Study 1 adapted the instrument, investigated dimensionality, and examined item functioning and gender invariance in a sample of 766 participants (53.4% male) aged between 18 and 63 years old (M = 23.71; SD = 7.92). Study 2 examined the association of spitefulness with aversive and healthy personality traits (i.e., the dark triad, honesty-humility, emotionality, extroversion, agreeableness, conscientiousness, and openness [HEXACO], antagonism, and disinhibition) in a sample of 288 individuals (mostly women 84.7%) between 18 and 71 years old (M = 41.82; SD = 13.04). Similar to the original instrument, the SS-BP was unidimensional and there was measurement invariance with respect to gender. Men were more spiteful than women. Spitefulness yielded large correlations with psychopathy, deceitfulness, and irresponsibility. The SS-BP appears to present adequate psychometric properties for Brazilian samples. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Body Image, Self-perception, and Satisfaction Among Girls With Turner Syndrome: A Prospective Cross-sectional Study.

CONTEXT: Delayed puberty and short stature in girls with Turner syndrome (TS) can lead to low body image, self-esteem, and satisfaction. OBJECTIVE: We aimed to evaluate body image, self-perception, and satisfaction among girls with TS using the Multi-Dimensional Body Image Self Relations Questionnaire-Appearance Scale (MBSRQ-AS). METHODS: Patients with karyotype-proven diagnosis of TS between 15 and 21 years were included after they achieved final adult height. We used the MBSRQ-AS instrument with 5 subscales: Appearance Evaluation (AE), Appearance Orientation (AO), Body Areas Satisfaction Scale (BASS), Overweight Preoccupation (OWP), and Self Classified Weight (SCW) subscales. Mean scores were compared with the available sex-matched population norms and compared between different subcohorts. RESULTS: Of 59 eligible girls, 37 girls agreed to participate with mean age 17.35 ± 1.6 years. Girls with TS had significantly lower scores than the sex-matched population norms in AO (mean [SD]: 3.32 [0.42] vs 3.91 [0.6]); P < .001) and SCW (mean [SD]: 3.26 [0.71] vs 3.57 [0.73]; P = .01) subscales. In contrast, they had slightly higher scores in BASS (mean [SD]: 3.38 [0.74] vs 3.23 [0.74]; P = .23) and OWP (mean [SD]: 3.12 [0.39] vs 3.03 [0.96]; P = .21) subscales though not statistically significant. Girls with classic 45X karyotype and those who were overweight/obese had lower scores in AE and AO subscales than the normal population (P < .05). CONCLUSION: Compared with sex-matched population norms, girls with TS are not reporting negative effects due to their appearance and report general satisfaction with most areas of their body; however, girls with TS with classic karyotype or who were obese/overweight were generally unhappy with their physical appearance. They also seem to not focus their attention on their appearance.

Ventral tegmental area GABAergic inhibition of cholinergic interneurons in the ventral nucleus accumbens shell promotes reward reinforcement.

The long-range GABAergic input from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) is relatively understudied, and therefore its role in reward processing has remained unknown. In the present study, we show, in both male and female mice, that long-range GABAergic projections from the VTA to the ventral NAc shell, but not to the dorsal NAc shell or NAc core, are engaged in reward and reinforcement behavior. We show that this GABAergic projection exclusively synapses on to cholinergic interneurons (CINs) in the ventral NAc shell, thereby serving a specialized function in modulating reinforced reward behavior through the inhibition of ventral NAc shell CINs. These findings highlight the diversity in the structural and functional topography of VTA GABAergic projections, and their neuromodulatory interactions across the dorsoventral gradient of the NAc shell. They also further our understanding of neuronal circuits that are directly implicated in neuropsychiatric conditions such as depression and addiction.

Where ketamine and dopamine collide.

Ketamine strengthens connections between two brain regions that are involved in the production and regulation of dopamine, which may explain how the drug can alleviate depression.

A locus coeruleus to dentate gyrus noradrenergic circuit modulates aversive contextual processing.

Dysregulation in contextual processing is believed to affect several forms of psychopathology, such as post-traumatic stress disorder (PTSD). The dentate gyrus (DG), a subregion of the hippocampus, is thought to be an important brain region for disambiguating new experiences from prior experiences. Noradrenergic (NE) neurons in the locus coeruleus (LC) are more tonically active during stressful events and send dense projections to the DG, yet an understanding of their function in DG-dependent contextual discrimination has not been established. Here, we isolate a key function of the LC-NE-DG circuit in contextual aversive generalization using selective manipulations and in vivo single-cell calcium imaging. We report that activation of LC-NE neurons and terminal activity results in contextual generalization. We found that these effects required ß-adrenergic-mediated modulation of hilar interneurons to ultimately promote aversive generalization, suggesting that disruption of noradrenergic tone may serve as an important avenue for treating stress-induced disorders.

Item response theory analysis of the Triarchic Psychopathy Measure.

This study investigated item and scale functioning in the triarchic psychopathy measure (TriPM) using an item response theory (IRT) analysis. TriPM data collected from 937 (410 men and 527 women) college students and community members were analyzed. A graded response model was utilized to analyze the items comprising the TriPM's three scales. Exploratory factor analyses (EFAs) supported the unidimensionality of the Disinhibition and Meanness scales, whereas Boldness was best represented by two domains. Each TriPM scale was found to include some items that had limited ability to differentiate between respondents possessing varying levels of the trait being measured. Across all scales, 34 items (61%) yielded evidence of significantly different responding between men and women possessing similar levels of the underlying trait, or differential item functioning (DIF). The scoring format (i.e., directly scored vs. reverse scored) also influenced item functioning, especially when the given scale included a large majority of one scoring type. Overall, the IRT and DIF results suggest that the TriPM effectively identifies disinhibition and meanness in individuals possessing high levels of those traits, and boldness at lower levels, but does not seem to identify these traits equally well in men and women. Possible revisions to the Boldness scale as well as ideas for addressing female and male DIF were provided. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Betahydroxybutyrate Consumption in Autopsy Brain Tissue from Alzheimer's Disease Subjects.

BACKGROUND: Alzheimer's disease (AD) features perturbed brain glucose utilization, which could contribute to brain bioenergetic failure. This led some to consider using ketone bodies to enhance AD brain bioenergetics and treat AD. OBJECTIVE: We evaluated the rate at which brain homogenates from persons with Alzheimer's disease (AD) metabolize D-ß-hydroxybutyrate (BHB). METHODS: We homogenized pieces of temporal cortex from frozen autopsy brains obtained from recently deceased AD subjects (n = 4), and age-matched subjects that did not have clinical AD (n = 3). Measuring the rate of CO2 production that followed the introduction of radiolabeled BHB to the homogenates yielded a BHB utilization rate. RESULTS: Compared to the control homogenates, the BHB-supported CO2 production rate was 66%lower in the AD homogenates (p < 0.05). CONCLUSIONS: AD brains can utilize BHB, albeit less robustly than control brains. In conjunction with a previous study that demonstrated reduced glucose utilization in AD brain homogenates, our BHB data provide further evidence of AD brain mitochondrial dysfunction or altered mitochondrial biology.

Neuropsychological Phenotypes of Pediatric Anti-Myelin Oligodendrocyte Glycoprotein Associated Disorders: A Case Series.

Emerging research has demonstrated that anti-myelin oligodendrocyte associated disorders (MOG-AD) are associated with a less severe clinical course than demyelinating conditions associated with the presence of aquaporin-4 antibodies. While a heterogeneity of neuropsychological outcomes in pediatric demyelinating conditions have been described in the literature, no studies to date have investigated the neuropsychological sequelae of pediatric MOG-AD specifically. The objective of the present case series was to describe the clinical and neuropsychological phenotypes of seven pediatric patients (ages 3-15 years) with MOG-AD of different diagnoses (e.g., acute disseminated encephalomyelitis, optic neuritis, multiple sclerosis, and neuromyelitis spectrum disorders). Neuropsychological outcomes were evaluated by retrospective chart review. Results indicated largely intact neuropsychological profiles in five of the seven patients, with mild weaknesses in attention, executive functioning, processing speed, visual-motor/fine-motor skills, and mood concerns being observed. Two patients with a Kurtzke Extended Disability Status Scale of 0 still demonstrated findings on neuropsychological testing. Of the other two patients, one demonstrated higher levels of impairment in the context of a complex medical history and premorbid learning difficulties, while the other demonstrated declines in functioning likely associated with an earlier age of onset. Findings suggest that neuropsychological outcomes may be correspondingly less severe in this population compared with what has previously been described in the pediatric demyelinating disease literature. This differential impact may contribute to the heterogeneity of neuropsychological outcomes found in previous studies, and future research should separate participants with myelin oligodendrocyte antibodies given the difference in clinical course, treatment outcomes, and neuropsychological sequelae.

Evidence for the taxonic latent structure for DSM-5 intermittent explosive disorder in adults.

BACKGROUND: Identification of individuals with clinically significant aggressive behavior is critical for the prevention and management of human aggressive behavior. A previous population-based taxometric study reported that the Diagnostic and Statistical Manual of Mental Disorders-4th Edition (DSM-IV) intermittent explosive disorder (IED) belongs to its own discrete class (taxon) rather than existing along a continuum. METHODS: This study sought to extend previous population-based findings in a clinical research sample of adults with DSM-5 IED (n = 346), adults with non-aggressive DSM-5 disorders (n = 293), and adults without any DSM-5 disorder (n = 174), using standardized assessments of DSM-5 diagnoses, aggression, and other related measures not available in past studies. RESULTS: Analyses revealed a taxonic latent structure that overlapped with the DSM-5 diagnosis of IED. Within the sample, taxon group members had higher scores on a variety of measures of psychopathology than did the complement members of the sample. Comorbidity of other diagnoses with IED did not affect these results. CONCLUSION: These findings support the proposition that DSM-5 IED represents a distinct behavioral disorder rather than the severe end of an aggressive behavior continuum.

Computed Tomography in Radiation Oncology During the Coronavirus Disease 2019 Pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, cancer centers must implement effective measures to protect patients and staff from infection with the novel coronavirus. A critical component of this effort is the timely identification of patients undergoing treatment who have COVID-19. Limitations on testing make such efforts challenging. However, the specialty of radiation oncology is unique in its use of computed tomography (CT) imaging for image guidance, and these CT studies have the potential to identify patients with COVID-19 even before they develop symptoms. Several organizations have developed published guidelines for radiologists to identify characteristic findings of COVID-19 on thoracic CT scans. The present article describes these recommendations in order to educate radiation oncologists on how to identify potential cases of COVID-19 and empower physicians in our field to optimally protect patients and staff.