Ketamine induces multiple individually distinct whole-brain functional connectivity signatures.

Background: Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine's molecular mechanisms connect to its neural and behavioral effects. Methods: We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets. Results: We found that: (i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; (ii) ketamine's data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, while the mean effect did not; and (iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level. Conclusions: These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry. Funding: This study was supported by NIH grants DP5OD012109-01 (A.A.), 1U01MH121766 (A.A.), R01MH112746 (J.D.M.), 5R01MH112189 (A.A.), 5R01MH108590 (A.A.), NIAAA grant 2P50AA012870-11 (A.A.); NSF NeuroNex grant 2015276 (J.D.M.); Brain and Behavior Research Foundation Young Investigator Award (A.A.); SFARI Pilot Award (J.D.M., A.A.); Heffter Research Institute (Grant No. 1-190420) (FXV, KHP); Swiss Neuromatrix Foundation (Grant No. 2016-0111) (FXV, KHP); Swiss National Science Foundation under the framework of Neuron Cofund (Grant No. 01EW1908) (KHP); Usona Institute (2015 - 2056) (FXV). Clinical trial number: NCT03842800.

Ketamine is a widely used anesthetic as well as a popular illegal recreational drug. Recently, it has also gained attention as a potential treatment for depression, particularly in cases that don't respond to conventional therapies. However, individuals can vary in their response to ketamine. For example, the drug can alter some people's perception, such as seeing objects as larger or small than they are, while other individuals are unaffected. Although a single dose of ketamine was shown to improve depression symptoms in approximately 65% of patients, the treatment does not work for a significant portion of patients. Understanding why ketamine does not work for everyone could help to identify which patients would benefit most from the treatment. Previous studies investigating ketamine as a treatment for depression have typically included a group of individuals given ketamine and a group given a placebo drug. Assuming people respond similarly to ketamine, the responses in each group were averaged and compared to one another. However, this averaging of results may have masked any individual differences in response to ketamine. As a result, Moujaes et al. set out to investigate whether individuals show differences in brain activity and behavior in response to ketamine. Moujaes et al. monitored the brain activity and behavior of 40 healthy individuals that were first given a placebo drug and then ketamine. The results showed that brain activity and behavior varied significantly between individuals after ketamine administration. Genetic analysis revealed that different gene expression patterns paired with differences in ketamine response in individuals ­ an effect that was hidden when the results were averaged. Ketamine also caused greater differences in brain activity and behavior between individuals than other drugs, such as psychedelics, suggesting ketamine generates a particularly complex response in people. In the future, extending these findings in healthy individuals to those with depression will be crucial for determining whether differences in response to ketamine align with how effective ketamine treatment is for an individual.

Borderline personality disorder features are associated with inflexible social interpretations.

BACKGROUND: Borderline personality disorder (BPD) is thought to involve aberrant social learning, including impaired revision of social interpretations with new evidence (social interpretation inflexibility). However, this topic has received little empirical attention outside of specific literatures, such as moral inference or behavioral economics. Further, the contribution of comorbid depression to BPD-related interpretation inflexibility has not yet been assessed. METHODS: In two independent samples (Study 1: N = 213; Study 2: N = 210, oversampled for BPD features), we assessed the associations between BPD symptoms, depressive symptoms, and task-based measures of social interpretation flexibility. RESULTS: We found that BPD symptoms, particularly volatility of identity and relationships, were associated with less revision of social interpretations with both positive and negative evidence. Meanwhile, depressive symptoms were associated with a pattern of less revision of social interpretations with positive versus negative information. LIMITATIONS: The use of cross-sectional, crowdsourced samples limits causal interpretations. Translation to clinical populations should be assessed in future studies. CONCLUSIONS: Results suggest that inflexible social interpretations across valences may be a feature of BPD-related pathology, and could be connected to symptoms involving volatility in social contexts. Future studies should investigate whether treatments geared toward increasing the flexibility of social interpretations are effective in treating BPD symptoms, especially those involving interpersonal difficulties.

Modulation of Trust in Borderline Personality Disorder by Script-Based Imaginal Exposure to Betrayal.

Interpersonal and trust-related difficulties are central features of borderline personality disorder (BPD). In this study, we applied script-driven betrayal imagery to evoke mistrustful behavior in a social reinforcement learning task. In 21 BPD and 20 healthy control (HC) participants, we compared this approach to the standard confederate paradigm used in research studies. The script-driven imagery evoked a transient increase in negative affect and also decreased trusting behavior to a similar degree in both groups. Across conditions, we also replicated previously reported between-group differences in negative affect (increased in BPD) and task behavior (more sensitive to social cues in BPD). These results support the validity of script-driven imagery as an alternative social task stimulus. This script-driven imagery approach is appealing for clinical research studies on reinforcement learning because it eliminates deception, scales easily, and evokes disorder-specific states of social difficulty.

The association between evening social media use and delayed sleep may be causal: Suggestive evidence from 120 million Reddit timestamps.

Public health officials and clinicians routinely advise social media users to avoid nighttime social media use due to the perception that this delays the onset of sleep and predisposes to the health risks of insufficient sleep. With some exceptions, the evidence behind this advice mostly derives from surveys identifying an association between self-reported social media usage and self-reported sleep patterns. In principle, these associations could alternatively be explained by users turning to social media to pass the time when they are otherwise having difficulty sleeping, or by individual differences that draw some people to frequent social media use, or by offline activities that overlap with both social media use and delayed sleep. To attempt to distinguish among these explanations, we leveraged estimated bedtimes from 44,000 Reddit users reported in a recent study and their 120 million posts to test whether the relationship between sleep and social media has properties suggestive of a causal relationship. We find that users are especially likely to be active on Reddit after their bedtime (and therefore awake) on nights that they posted to Reddit shortly before bedtime, especially if they posted multiple times or in high-engagement forums that night. Overall, this study lends additional support to the notion that there likely is some causal effect of evening social media use on delayed sleep onset.

A pilot randomized controlled trial of ketamine in Borderline Personality Disorder.

This study is the first randomized controlled trial to test the effects of ketamine in Borderline Personality Disorder (BPD). BPD remains undertreated in the community and no medication has FDA approval for this indication. People with BPD experience chronic mood disturbances with depressed mood, suicidal ideation, and severe social difficulties. In this double-blind, randomized controlled pilot study, we tested the effects of one infusion of ketamine (0.5 mg/kg, n = 10) or the psychoactive comparator drug midazolam (0.04 mg/kg, n = 12) in adults with BPD. Infusions were well tolerated in both groups. Dissociative symptoms during infusion were more intense with ketamine than midazolam (t(12.3) = 3.61, p = 0.01), but they resolved by 40 min after infusion in both groups. Post-infusion adverse events were at the expected low levels in both groups. For our primary outcome measure of suicidal ideation and our secondary outcome measure of depression, we found numerical reduction but not significant group or group x timepoint difference (p > 0.05). For our secondary outcome measures of anxiety and BPD symptoms, we did not observe group or group x timepoint differences. There was a group x timepoint effect for socio-occupational functioning (F(1,20.12) = 5.16, p = 0.03, at Day 14, ketamine group showed more improvement than midazolam group). An exploratory analysis revealed that improvement in socio-occupational functioning was correlated with improvement in depression in the ketamine group (r(8) = 0.65, p = 0.04) but not midazolam group (r(9) = 0.41, p = 0.216). This pilot study provides the first randomized controlled evidence of the effects of antidepressant-dosed ketamine in people with BPD. Our results provide reason for optimism that antidepressant-dosed ketamine will be well-tolerated in larger studies and may provide clinical benefit for mood symptoms and related impairments in people with BPD.

Estimation of Bedtimes of Reddit Users: Integrated Analysis of Time Stamps and Surveys.

BACKGROUND: Individuals with later bedtimes have an increased risk of difficulties with mood and substances. To investigate the causes and consequences of late bedtimes and other sleep patterns, researchers are exploring social media as a data source. Pioneering studies inferred sleep patterns directly from social media data. While innovative, these efforts are variously unscalable, context dependent, confined to specific sleep parameters, or rest on untested assumptions, and none of the reviewed studies apply to the popular Reddit platform or release software to the research community. OBJECTIVE: This study builds on this prior work. We estimate the bedtimes of Reddit users from the times tamps of their posts, test inference validity against survey data, and release our model as an R package (The R Foundation). METHODS: We included 159 sufficiently active Reddit users with known time zones and known, nonanomalous bedtimes, together with the time stamps of their 2.1 million posts. The model's form was chosen by visualizing the aggregate distribution of the timing of users' posts relative to their reported bedtimes. The chosen model represents a user's frequency of Reddit posting by time of day, with a flat portion before bedtime and a quadratic depletion that begins near the user's bedtime, with parameters fitted to the data. This model estimates the bedtimes of individual Reddit users from the time stamps of their posts. Model performance is assessed through k-fold cross-validation. We then apply the model to estimate the bedtimes of 51,372 sufficiently active, nonbot Reddit users with known time zones from the time stamps of their 140 million posts. RESULTS: The Pearson correlation between expected and observed Reddit posting frequencies in our model was 0.997 on aggregate data. On average, posting starts declining 45 minutes before bedtime, reaches a nadir 4.75 hours after bedtime that is 87% lower than the daytime rate, and returns to baseline 10.25 hours after bedtime. The Pearson correlation between inferred and reported bedtimes for individual users was 0.61 (P<.001). In 90 of 159 cases (56.6%), our estimate was within 1 hour of the reported bedtime; 128 cases (80.5%) were within 2 hours. There was equivalent accuracy in hold-out sets versus training sets of k-fold cross-validation, arguing against overfitting. The model was more accurate than a random forest approach. CONCLUSIONS: We uncovered a simple, reproducible relationship between Reddit users' reported bedtimes and the time of day when high daytime posting rates transition to low nighttime posting rates. We captured this relationship in a model that estimates users' bedtimes from the time stamps of their posts. Limitations include applicability only to users who post frequently, the requirement for time zone data, and limits on generalizability. Nonetheless, it is a step forward for inferring the sleep parameters of social media users passively at scale. Our model and precomputed estimated bedtimes of 50,000 Reddit users are freely available.

The State of Overmedication in Borderline Personality Disorder: Interpersonal and Structural Factors.

Purpose of review: a)This review paper describes the state of prescribing practice in Borderline Personality Disorder (BPD), wherein medications are prescribed far more than either evidence or practice guideline would recommend. First, we describe the frequencies of medication use and polypharmacy in people with BPD. Recent findings: b)In subsequent sections, we elaborate two main categories of factors that lead to overmedication of people with BPD: the interpersonally mediated and the structural. We consider interpersonally mediated factors to arise from communications of patients in distress and the well-meaning efforts of their prescribers to provide relief for certain overwhelming affective states. We are particularly focused on patterns of countertransference in prescribing that are directly linked to specific aspects of BPD pathology. We consider structural factors to arise from the complexities of medical and medicolegal systems and the contemporary patterns of financing medical care; we postulate that these complexities often compel prescribers to start medications, with associated disincentives for decreasing or discontinuing those medications over time. Summary: c)More research is needed to understand how to best use medications in BPD, for example in targeted combination with psychotherapeutic and psychosocial interventions. However, current practice often departs markedly from the evidence. We recommend the dissemination of accessible, generalist BPD-treatment models in outpatient and inpatient practice; increased early detection of BPD; and increased diagnostic disclosure. We also recommend for individual providers and systems to implement prospective treatment plans that draw from BPD-specific psychosocial models. This approach can employ tiers of interventions to minimize reactive prescribing by anticipating high affect and offering BPD patients steadily empathic evidence-supported care.

Naltrexone-Bupropion and Behavior Therapy, Alone and Combined, for Binge-Eating Disorder: Randomized Double-Blind Placebo-Controlled Trial.

OBJECTIVE: Binge-eating disorder, the most prevalent eating disorder, is a serious public health problem associated with obesity, psychiatric and medical comorbidities, and functional impairments. Binge-eating disorder remains underrecognized and infrequently treated, and few evidence-based treatments exist. The authors tested the effectiveness of naltrexone-bupropion and behavioral weight loss therapy (BWL), alone and combined, for binge-eating disorder comorbid with obesity. METHODS: In a randomized double-blind placebo-controlled trial conducted from February 2017 to February 2021, using a 2×2 balanced factorial design, 136 patients with binge-eating disorder (81.6% women; mean age, 46.5 years; mean BMI, 37.1) were randomized to one of four 16-week treatments: placebo (N=34), naltrexone-bupropion (N=32), BWL+placebo (N=35), or BWL+naltrexone-bupropion (N=35). Overall, 81.7% of participants completed independent posttreatment assessments. RESULTS: Intention-to-treat binge-eating remission rates were 17.7% in the placebo group, 31.3% in the naltrexone-bupropion group, 37.1% in the BWL+placebo group, and 57.1% in the BWL+naltrexone-bupropion group. Logistic regression of binge-eating remission revealed that BWL was significantly superior to no BWL, and that naltrexone-bupropion was significantly superior to placebo, but there was no significant interaction between BWL and medication. Mixed models of complementary measures of binge-eating frequency also indicated that BWL was significantly superior to no BWL. The rates of participants attaining 5% weight loss were 11.8% in the placebo group, 18.8% in the naltrexone-bupropion group, 31.4% in the BWL+placebo group, and 38.2% in the BWL+naltrexone-bupropion group. Logistic regression of 5% weight loss and mixed models of percent weight loss both revealed that BWL was significantly superior to no BWL. Mixed models revealed significantly greater improvements for BWL than no BWL on secondary measures (eating disorder psychopathology, depression, eating behaviors, and cholesterol and HbA1c levels). CONCLUSIONS: BWL and naltrexone-bupropion were associated with significant improvements in binge-eating disorder, with a consistent pattern of BWL being superior to no BWL.

The Stress and Resilience Town Hall: A systems response to support the health workforce during COVID-19 and beyond.

OBJECTIVE: The COVID-19 pandemic is a traumatic stressor resulting in anxiety, depression, post-traumatic stress, and burnout among healthcare workers. We describe an intervention to support the health workforce and summarize results from its 40-week implementation in a large, tri-state health system during the COVID-19 pandemic. METHOD: We conducted 121 virtual and interactive Stress and Resilience Town Halls attended by 3555 healthcare workers. Town hall participants generated 1627 stressors and resilience strategies that we coded and analyzed using rigorous qualitative methods (Kappa = 0.85). RESULTS: We identify six types of stressors and eight types of resilience strategies reported by healthcare workers, how these changed over time, and how town halls were responsive to emerging health workforce needs. We show that town halls dedicated to groups working together yielded 84% higher mean attendance and more sharing of stressors and resilience strategies than those offered generally across the health system, and that specific stressors and strategies are reported consistently while others vary markedly over time. CONCLUSIONS: The virtual and interactive Stress and Resilience Town Hall is an accessible, scalable, and sustainable intervention to build mutual support, wellness, and resilience among healthcare workers and within hospitals and health systems responding to emerging crises, pandemics, and disasters.

Mentalization and embodied selfhood in Borderline Personality Disorder.

Aberrations of self-experience are considered a core feature of Borderline Personality Disorder (BPD). While prominent etiologic accounts of BPD, such as the mentalization based approach, appeal to the developmental constitution of self in early infant-caregiver environments, they often rely on a conception of self that is not explicitly articulated. Moreover, self-experience in BPD is often theorized at the level of narrative identity, thus minimizing the role of embodied experience. In this article, we present the hypothesis that disordered self and interpersonal functioning in BPD result, in part, from impairments in "embodied mentalization," that manifest foundationally as alterations in minimal embodied selfhood, i.e. the first-person experience of being an individuated embodied subject. This account of BPD, which engages early intersubjective experiences has the potential to integrate phenomenological, developmental, and symptomatic findings in BPD, and is consistent with contemporary theories of brain function.

Improving Research Practice for Studying Borderline Personality Disorder: Lessons From the Clinic.

Borderline personality disorder is an often misunderstood and underdiagnosed mental illness characterized in part by affective lability. Clinicians' unique understanding of the disorder has allowed them to develop disorder-specific approaches to treatment. In this review, we highlight how borderline personality disorder research can benefit from greater engagement with key disorder-specific features, including symptom variability and interpersonal sensitivity. In addition, we propose that research which employs interactive tasks will be more reflective of the kinds of volatility found in the real-life situations. Finally, we discuss how mixed-methodology can serve as a way for recovery-oriented research to practice the very ideals and recommendations it suggests. We use a patient case to contextualize each section. As interest in borderline personality disorder continues to grow, an intentional emphasis on a person-centered, recovery-focused, and disorder-specific approach to research is needed.

Collaborative Deprescribing in Borderline Personality Disorder: A Narrative Review.

LEARNING OBJECTIVES: After participating in this activity, learners should be better able to:• Assess medication management in patients with borderline personality disorder (BPD)• Evaluate the role of deprescribing as an active intervention in patients with BPD treated with polypharmacy ABSTRACT: Psychopharmacology in borderline personality disorder (BPD) is complicated by comorbid disorders, substance use, sensitivity to side effects, risk of self-harm through medication misuse, and intense but transient symptoms. Patients' relationships with medications may range from tenuous to highly enmeshed, and may profoundly influence the response to treatment. For these reasons, awareness of current evidence and flexible approaches are particularly relevant to prescribing in BPD. In this narrative review, we illustrate the current status of medication management in BPD by focusing on polypharmacy. We use a single vignette to explore the limitations of prescribing multiple medications and the factors contributing to polypharmacy. With the same vignette, and using the framework of deprescribing, we describe how medication regimens can be reduced to a necessary minimum. Deprescribing, originally developed in geriatric medicine, is an active intervention that involves a risk-benefit analysis for each medication, keeping in mind the patient's medical and psychiatric status and his or her preferences and values. Deprescribing lends itself well to use in psychiatry and especially in BPD because of its emphasis on the patient's preferences and on repeated conversations to revisit and update decisions. In addition to elaborating on the deprescribing framework, we provide recommendations for conducting these critical discussions about medications in BPD, with particular attention to the patient's relationship to the medication. Finally, we summarize our recommendations and strategies for implementing flexible and responsive medication management for patients with BPD. We suggest areas of future research, including testing the efficacy of targeted intermittent medication treatments.

Induced illusory body ownership in borderline personality disorder.

One aspect of selfhood that may have relevance for borderline personality disorder (BPD) is variation in sense of body ownership. We employed the rubber hand illusion to manipulate sense of body ownership in BPD. We extended previous research on illusory body ownership in BPD by testing: (i) two illusion conditions: asynchronous and synchronous stimulation, (ii) relationship between illusion experience and BPD symptoms, and (iii) relationship between illusion experience and maladaptive personality traits. We measured illusion strength (questionnaire responses), proprioceptive drift (perceived shift in physical hand position), BPD symptoms (Revised Diagnostic Interview for Borderlines score), and maladaptive personality traits (Personality Inventory for DSM-5) in 24 BPD and 21 control participants. For subjective illusion strength, we found main effects of group (BPD > healthy control, F(1, 43) = 11.94, P = 0.001) and condition (synchronous > asynchronous, F(1, 43) = 22.80, P < 0.001). There was a group × condition interaction for proprioceptive drift (F(1, 43) = 6.48, P = 0.015) such that people with BPD maintained illusion susceptibility in the asynchronous condition. Borderline symptom severity correlated with illusion strength within the BPD group, and this effect was specific to affective (r = 0.45, P < 0.01) and cognitive symptoms (r = 0.46, P < 0.01). Across all participants, trait psychoticism correlated with illusion strength (r = 0.44, P < 0.01). People with BPD are more susceptible to illusory body ownership than controls. This is consistent with the clinical literature describing aberrant physical and emotional experiences of self in BPD. A predictive coding framework holds promise to develop testable mechanistic hypotheses for disrupted bodily self in BPD.

Differential Valuation and Learning From Social and Nonsocial Cues in Borderline Personality Disorder.

BACKGROUND: Volatile interpersonal relationships are a core feature of borderline personality disorder (BPD) and lead to devastating disruption of patients' personal and professional lives. Quantitative models of social decision making and learning hold promise for defining the underlying mechanisms of this problem. In this study, we tested BPD and control subject weighting of social versus nonsocial information and their learning about choices under stable and volatile conditions. We compared behavior using quantitative models. METHODS: Subjects (n = 20 BPD, n = 23 control subjects) played an extended reward learning task with a partner (confederate) that requires learning about nonsocial and social cue reward probability (the social valuation task). Task experience was measured using language metrics: explicit emotions/beliefs, talk about the confederate, and implicit distress (using the previously established marker self-referentiality). Subjects' weighting of social and nonsocial cues was tested in mixed-effect regression models. Subjects' learning rates under stable and volatile conditions were modeled (Rescorla-Wagner approach) and group × condition interactions tested. RESULTS: Compared to control subjects, BPD subject debriefings included more mentions of the confederate and less distress language. BPD subjects also weighted social cues more heavily but had blunted learning responses to (nonsocial and social) volatility. CONCLUSIONS: This is the first report of patient behavior in the social valuation task. The results suggest that BPD subjects expect higher volatility than control subjects. These findings lay the groundwork for a neurocomputational dissection of social and nonsocial belief updating in BPD, which holds promise for the development of novel clinical interventions that more directly target pathophysiology.

Individuals with Borderline Personality Disorder show larger preferred social distance in live dyadic interactions.

Personal space regulation is a key component of effective social engagement. Personal space varies among individuals and with some mental health conditions. Simulated personal space intrusions in Borderline Personality Disorder (BPD) reveal larger preferred interpersonal distance in that setting. These findings led us to conduct the first test of live interpersonal distance preferences in symptoms in BPD. With direct observation of subjects' personal space behavior in the stop-distance paradigm, we found a 2-fold larger preferred interpersonal distance in BPD than control (n = 30, n = 23). We discuss this result in context of known biology and etiology of BPD. Future work is needed to identify neural circuits underlying personal space regulation in BPD, individual differences in preferred interpersonal distance in relation to specific symptoms and relationship to recovery status.

Computational Psychiatry in Borderline Personality Disorder.

PURPOSE OF REVIEW: We review the literature on the use and potential use of computational psychiatry methods in Borderline Personality Disorder. RECENT FINDINGS: Computational approaches have been used in psychiatry to increase our understanding of the molecular, circuit, and behavioral basis of mental illness. This is of particular interest in BPD, where the collection of ecologically valid data, especially in interpersonal settings, is becoming more common and more often subject to quantification. Methods that test learning and memory in social contexts, collect data from real-world settings, and relate behavior to molecular and circuit networks are yielding data of particular interest. SUMMARY: Research in BPD should focus on collaborative efforts to design and interpret experiments with direct relevance to core BPD symptoms and potential for translation to the clinic.

Utility of pretransplant psychological measures to predict posttransplant outcomes in liver transplant patients: a systematic review.

OBJECTIVE: Evaluation of liver transplant (LT) candidacy involves psychosocial evaluation to ensure appropriate organ allocation. However, the utility of pre-LT psychiatric and neuropsychological factors in predicting posttransplant outcomes remains uncertain. We reviewed current evidence on the prognostic value of pre-LT psychological factors for outcomes after LT. METHOD: We conducted a systematic review of studies with adult LT recipients that investigate the relationship between pre-LT psychiatric and neuropsychological variables and posttransplant outcomes. We searched Ovid, MEDLINE, PsycINFO, EMBASE/Scopus, Cochrane Controlled trials register and Web of Science (January 1975 to May 2015) for longitudinal, peer-reviewed studies of at least 20 subjects and written in English. RESULTS: The 19 studies included in this review are heterogeneous in population, prognosis and duration of follow-up (from 20days to more than 3 years). Findings on the prognostic value of pre-LT depression or anxiety on post-LT outcomes are mixed, though depression appears to predict lower quality of life (QOL). Pre-LT suicidal thoughts in particular are associated with post-LT depression. High submissiveness may predict rejection within 20days of LT, and low conscientiousness is associated with greater nonadherence. Whereas pre-LT cognitive performance has not been shown to predict survival, poorer performance may predict poorer QOL after LT. CONCLUSION: Further studies are needed to examine this important element of LT candidacy evaluation. Studies should evaluate psychiatric factors in large samples, include systematic evaluations by mental health clinicians and explore broader neuropsychological domains in predicting posttransplant outcomes.