Faculty Bibliography

Winning increases the readiness to attack and the probability of winning, a widespread phenomenon known as the "winner effect." Here, we reveal a transition from target-specific to generalized aggression enhancement over 10 days of winning in male mice. This behavioral change is supported by three causally linked plasticity events in the ventrolateral part of the ventromedial hypothalamus (VMHvl), a critical node for aggression. Over 10 days of winning, VMHvl cells experience monotonic potentiation of long-range excitatory inputs, transient local connectivity strengthening, and a delayed excitability increase. Optogenetically coactivating the posterior amygdala (PA) terminals and VMHvl cells potentiates the PA-VMHvl pathway and triggers the same cascade of plasticity events observed during repeated winning. Optogenetically blocking PA-VMHvl synaptic potentiation eliminates all winning-induced plasticity. These results reveal the complex Hebbian synaptic and excitability plasticity in the aggression circuit during winning, ultimately leading to increased "aggressiveness" in repeated winners.

OBJECTIVE/UNASSIGNED:Young Latinas and Black women drink less than women of other racial/ethnic groups but experience more alcohol-related problems in midlife. This study aims to identify modifiable factors to prevent adult onset of alcohol use disorder (AUD) in this population. METHODS/UNASSIGNED:Data were collected at six time points as part of the Harlem Longitudinal Development Study from 365 Latinas (47%) and Black (53%) women (mean age at time 1 = 14, standard deviation 1.3). Structural equation modeling was used to test hypothesized pathways from childhood physical and sexual abuse to AUD via depressive mood, anxiety disorders, and somatic complaints in the 20s. We also tested the moderation effect of the high school academic environment by including in the structural equation model two latent variable interaction terms between the school environment and each of the abuse variables. RESULTS/UNASSIGNED: = -9.56, 95% CI [-13.95, -5.17]) in the early 20s. CONCLUSIONS/UNASSIGNED:Our findings underscore the need to invest in early violence prevention interventions and in education to ensure equitable access to quality, academically oriented, and safe schools.

Ionic imbalances and sodium channel dysfunction, well-known sequelae of traumatic brain injury (TBI), promote functional impairment in affected subjects. Therefore, non-invasive measurement of sodium concentrations using ²³Na MRI has the potential to detect clinically relevant injury and predict persistent symptoms. Recently, we reported diffusely lower apparent total sodium concentrations (aTSC) in mild TBI patients compared to controls, as well as correlations between lower aTSC and worse clinical outcomes. The main goal of this study was to determine whether these aTSC findings, and their changes over time, predict outcomes at 3- and 12-month from injury. Twenty-seven patients previously studied with ²³Na MRI and outcome measures at 22 ± 10 days (average ± standard deviation) after injury (visit-1, v1) were contacted at 3- (visit-2, v2) and 12-month after injury (visit-3, v3) to complete the Rivermead post-concussion symptoms questionnaire (RPQ), the extended Glasgow outcome scale (GOSE), and the brief test of adult cognition by telephone (BTACT). Follow-up ¹H and ²³Na MRI were additionally scheduled at v2. Linear regression was used to calculate aTSC in global grey and white matters. Six hypotheses were tested in relation to the serial changes in outcome measures and in aTSC, and in relation to the cross-sectional and serial relationships between aTSC and outcome. Twenty patients contributed data at v2 and fifteen at v3. Total RPQ and composite BTACT z-scores differed significantly for v2 and v3 in comparison to v1 (each P < 0.01), reflecting longitudinally reduced symptomatology and improved performance on cognitive testing. No associations between aTSC and outcome were observed at v2. Previously lower grey and white matter aTSC normalized at v2 in comparison to controls, in line with a statistically detectable longitudinal increase in grey matter aTSC between v1 and v2 (P = 0.0004). aTSC values at v1 predicted a subset of future BTACT subtest scores, but not future RPQ scores nor GOSE-defined recovery status. Similarly, aTSC rates of change correlated with BTACT rates of change, but not with those of RPQ. Tissue aTSC, previously shown to be diffusely decreased compared to controls at v1, was no longer reduced by v2, suggesting normalization of the sodium ionic equilibrium. These changes were accompanied by marked improvement in outcome. The results support the notion that early aTSC from ²³Na MRI predicts future BTACT, but not RPQ scores, nor future GOSE status.

Objective: Disclosure of deployment-related experiences among military couples is generally beneficial to mental health and relationship adjustment. Yet, disclosure by the spouse is rarely studied, as are the dyadic associations between disclosure and outcomes in both partners. The present study used a dyadic approach to study the relationship between disclosure or concealment on one hand and mental health and relationship adjustment on the other hand among Israeli military couples. Method: Sixty-three Israel Defense Force (IDF) combat veterans (all male) and their spouses (all female; N = 126) completed self-report questionnaires about disclosure and concealment of deployment-related experiences to their partner; relationship adjustment; depression; and posttraumatic stress symptoms (PTSS). Six Actor"“Partner Interdependence Models (APIM) were used for dyadic analysis. Results: We found lower disclosure and higher concealment of deployment-related experiences by veterans compared to spouses. The veteran"™s concealment of deployment-related experiences was associated with lower relationship adjustment for both partners and with the veteran"™s own higher PTSS. The spouse"™s concealment was associated with greater depression for both partners and with the spouse"™s own higher PTSS. Neither actor nor partner effects were found for disclosure regarding all three outcomes. Conclusions: Concealment of deployment-related experiences among military couples may have detrimental implications on the mental health and relationship adjustment of both the concealer and their partner. The spouse"™s concealment of their experience was as related to mental health and relationship adjustment as the veteran"™s concealment. The findings highlight the need to address communication about deployment-related experiences by both partners among military couples.

BACKGROUND:Hypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer's disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain. In this study, we investigated the effects of mitovesicles on synaptic function, and the molecular players involved. METHODS:Hippocampal slices from wild-type mice were perfused with the three known types of EVs, mitovesicles, microvesicles, or exosomes, isolated from the brain of a mouse model of Down syndrome or of a diploid control and long-term potentiation (LTP) recorded. The role of the monoamine oxidases type B (MAO-B) and type A (MAO-A) in mitovesicle-driven LTP impairments was addressed by treatment of mitovesicles with the irreversible MAO inhibitors pargyline and clorgiline prior to perfusion of the hippocampal slices. RESULTS:Mitovesicles from the brain of the Down syndrome model reduced LTP within minutes of mitovesicle addition. Mitovesicles isolated from control brains did not trigger electrophysiological effects, nor did other types of brain EVs (microvesicles and exosomes) from any genotype tested. Depleting mitovesicles of their MAO-B, but not MAO-A, activity eliminated their ability to alter LTP. CONCLUSIONS:Mitovesicle impairment of LTP is a previously undescribed paracrine-like mechanism by which EVs modulate synaptic activity, demonstrating that mitovesicles are active participants in the propagation of cellular and functional homeostatic changes in the context of neurodegenerative disorders.

Objective: The growth of psychedelic medicine creates new challenges in psychiatric education as physicians may soon be responsible for prescribing a number of psychedelic interventions. Despite this growing need for educated providers, very little is known about the training psychiatry residents receive in psychedelic medicine. We conducted a survey to determine the current educational opportunities as well as the priorities and concerns held by training directors about this emerging field. Methods: We emailed an online survey to US psychiatry residency training directors. Respondents answered questions about current offerings in psychedelic medicine, as well as their interest, priorities, and concerns about curricular materials and their delivery. Results: Sixty-one programs responded to our survey. The majority of respondents (64%) favored devoting additional time to psychedelic education, but many endorsed concerns about the dearth of educational materials (54%) and limited availability of faculty to deliver content (46%). The majority of programs (94%) expressed some interest in implementing a standardized curriculum in psychedelic medicine. Conclusion: Training directors recognized that their current curricular materials are limited, and they appeared interested in additional support to meet the upcoming demand in psychedelic education. Further research can inform curriculum development and implementation of psychedelic education in residency training.

Considering the escalating gap between the population-level need for substance use services and the availability of board-certified addiction specialty physicians, all psychiatrists must be equipped to treat substance use disorders. Residency training programs must therefore ensure that graduates are equipped with a sufficient knowledge base and skill set to treat substance use disorders, including an understanding of medications for addiction treatment and appropriate selection and utilization of psychotherapy for substance use disorders. Resources for teaching psychiatric residents about psychotherapeutic approaches to substance use disorders are often limited, and many programs may struggle to include this content in their curricula. The authors highlight the core evidence-based psychotherapeutic approaches relevant to the care of patients with substance use disorders and identify supervised experiential learning opportunities for psychiatric residents to practice psychotherapy for substance use disorders during existing clinical rotations within their general psychiatry residency programs.

BACKGROUND AND OBJECTIVES/UNASSIGNED:Obstructive sleep apnea (SA) is common in older men and a contributor to negative cognitive, psychiatric, and brain health outcomes. Little is known about SA in those who played contact sports and are at increased risk of neurodegenerative disease(s) and other neuropathologies associated with repetitive head impacts (RHI). In this study, we investigated the frequency of diagnosed and witnessed SA and its contribution to clinical symptoms and tau pathology using PET imaging among male former college and former professional American football players. METHODS/UNASSIGNED:The sample included 120 former National Football League (NFL) players, 60 former college players, and 60 asymptomatic men without exposure to RHI (i.e., controls). Diagnosed SA was self-reported, and all participants completed the Mayo Sleep Questionnaire (MSQ, informant version), the Epworth Sleepiness Scale (ESS), neuropsychological testing, and tau (flortaucipir) PET imaging. Associations between sleep indices (diagnosed SA, MSQ items, and the ESS) and derived neuropsychological factor scores, self-reported depression (Beck Depression Inventory-II [BDI-II]), informant-reported neurobehavioral dysregulation (Behavior Rating Inventory of Executive Function-Adult Version [BRIEF-A] Behavioral Regulation Index [BRI]), and tau PET uptake, were tested. RESULTS/UNASSIGNED:gene carrier status. Higher ESS scores correlated with higher BDI-II and BRIEF-A BRI scores. Continuous positive airway pressure use mitigated all of the abovementioned associations. Among the former college football players, witnessed apnea and higher ESS scores were associated with higher BRIEF-A BRI and BDI-II scores, respectively. No other associations were observed in this subgroup. DISCUSSION/UNASSIGNED:Former elite American football players are at risk of SA. Our findings suggest that SA might contribute to cognitive, neuropsychiatric, and tau outcomes in this population. Like all neurodegenerative diseases, this study emphasizes the multifactorial contributions to negative brain health outcomes and the importance of sleep for optimal brain health.

OBJECTIVE/UNASSIGNED:Few studies have focused on medical students and residents' mental health impact on medical residency selection (MRS) performance. The authors evaluated the association of performance in MRS with depressive and anxiety symptoms and with a reported psychiatric diagnosis (rPD). METHODS/UNASSIGNED:The authors enrolled candidates after the second round of MRS examinations at a Brazilian Medical School. Performance was assessed by final grade. Depressive and anxiety symptoms were assessed by the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) and the State-Trait Anxiety Inventory (STAI). The authors performed mediation analysis and multiple linear regression analysis to investigate the impact of rPD, state and trait anxiety, and depressive symptom severity on performance. RESULTS/UNASSIGNED:515 of the 643 MRS candidates (80.1%) participated in the study. Higher age, attending a preparatory course for MRS, rPD, and the number of MRS applications that year were associated with poorer performance. In mediation analysis, trait anxiety was associated with a direct effect on performance and an indirect effect mediated by rPD. CONCLUSION/UNASSIGNED:The data suggest that psychiatric diagnosis is associated with poorer performance on MRS, regardless of current symptoms of anxiety and depression. Additionally, increased levels of trait anxiety may negatively impact performance, directly and indirectly.

PURPOSE/UNASSIGNED:Endometrial cancer (EMCA) is the most common gynecologic malignancy, and new diagnoses are increasing in the United States. Black patients are more likely to present with advanced stage, be diagnosed with high-risk uterine serous carcinoma (USC) and die of their cancer. METHODS/UNASSIGNED:Patients with endometrial adenocarcinoma who received tumor FoundationOne CDx testing at our institution between January 2017 and August 2022 were identified. Genomic alterations, demographic and clinical characteristics were collected. Descriptive statistics and Fisher's exact test were used to analyze data. RESULTS/UNASSIGNED:amplification had significantly shorter median overall survival (97.3 months vs 44.3; HR (95%CI): 7.1 (10.03, 59.4) p< 0.05). CONCLUSIONS/UNASSIGNED:amplification had shorter overall survival. Identifying actionable mutations in this high unmet need population is crucial to improving outcomes among Black patients with uterine malignancy. Development of new targeted-therapies will need to keep these alterations at the forefront as trials are being designed.