Reward-based option competition in human dorsal stream and transition from stochastic exploration to exploitation in continuous space.

Primates exploring and exploiting a continuous sensorimotor space rely on dynamic maps in the dorsal stream. Two complementary perspectives exist on how these maps encode rewards. Reinforcement learning models integrate rewards incrementally over time, efficiently resolving the exploration/exploitation dilemma. Working memory buffer models explain rapid plasticity of parietal maps but lack a plausible exploration/exploitation policy. The reinforcement learning model presented here unifies both accounts, enabling rapid, information-compressing map updates and efficient transition from exploration to exploitation. As predicted by our model, activity in human frontoparietal dorsal stream regions, but not in MT+, tracks the number of competing options, as preferred options are selectively maintained on the map, while spatiotemporally distant alternatives are compressed out. When valuable new options are uncovered, posterior ß1/α oscillations desynchronize within 0.4 to 0.7 s, consistent with option encoding by competing ß1-stabilized subpopulations. Together, outcomes matching locally cached reward representations rapidly update parietal maps, biasing choices toward often-sampled, rewarded options.

Bright light therapy for CPAP-resistant OSA symptoms.

STUDY OBJECTIVES: Sleep fragmentation and daytime sleepiness often persist in patients with sleep apnea despite correctly administered continuous positive airway pressure (CPAP). Our proof-of-concept study tested the acceptability and efficacy of morning bright light therapy (BLT) to improve sleep, circadian rhythms, and CPAP-resistant daytime symptoms in patients with sleep apnea. METHODS: In this within-subject crossover study, 14 individuals completed 4 weeks of BLT and sham BLT in randomized order. Outcomes included actigraphy-based objective sleep measures, sleepiness, depressive symptoms, and sleep-related functional impairment, analyzed with multilevel models. RESULTS: Patients experienced greater reductions in wake after sleep onset and increased amplitude of rest-activity rhythms in a shorter photoperiod with BLT compared with sham. Patients also reported reductions in self-reported sleepiness and depressive symptoms with BLT compared with sham only during the early stages of treatment and shorter photoperiod. CONCLUSIONS: These results suggest the potential for novel applications for existing chronotherapeutic interventions for improving symptoms and quality of life for those patients who experience residual symptoms with current available treatments. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Bright Light Therapy for Residual Daytime Symptoms Associated With Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT04299009; Identifier: NCT04299009. CITATION: Soreca I, Arnold N, Dombrovski AY. Bright light therapy for CPAP-resistant OSA symptoms. J Clin Sleep Med. 2024;20(2):211-219.

The Dark Side of Mentalizing: Learning Signals in the Default Network During Social Exchanges Support Cooperation and Exploitation.

The evolution of human social cognitive capacities such as mentalizing was associated with the expansion of frontoparietal cortical networks, particularly the default network. Mentalizing supports prosocial behaviors, but recent evidence indicates it may also serve a darker side of human social behavior. Using a computational reinforcement learning model of decision-making on a social exchange task, we examined how individuals optimized their approach to social interactions based on a counterpart's behavior and prior reputation. We found that learning signals encoded in the default network scaled with reciprocal cooperation and were stronger in individuals who were more exploitative and manipulative, but weaker in those who were more callous and less empathic. These learning signals, which help to update predictions about others' behavior, accounted for associations between exploitativeness, callousness, and social reciprocity. Separately, we found that callousness, but not exploitativeness, was associated with a behavioral insensitivity to prior reputation effects. While the entire default network was involved in reciprocal cooperation, sensitivity to reputation was selectively related to the activity of the medial temporal subsystem. Overall, our findings suggest that the emergence of social cognitive capacities associated with the expansion of the default network likely enabled humans to not only cooperate effectively with others, but to exploit and manipulate others as well.

Dynamic Feedback Between Antidepressant Placebo Expectancies and Mood.

Importance: Despite high antidepressant placebo response rates, the mechanisms underlying the persistence of antidepressant placebo effects are still poorly understood. Objective: To investigate the neurobehavioral mechanisms underlying the evolution of antidepressant placebo effects using a reinforcement learning (RL) framework. Design, Setting, and Participants: In this acute within-patient cross-sectional study of antidepressant placebos, patients aged 18 to 55 years not receiving medication for major depressive disorder (MDD) were recruited at the University of Pittsburgh between February 21, 2017, to March 1, 2021. Interventions: The antidepressant placebo functional magnetic resonance imaging task manipulates placebo-associated expectancies using visually cued fast-acting antidepressant infusions and controls their reinforcement with sham visual neurofeedback while assessing expected and experienced mood improvement. Main Outcomes and Measures: The trial-by-trial evolution of expectancies and mood was examined using multilevel modeling and RL, relating model-predicted signals to spatiotemporal dynamics of blood oxygenation level-dependent (BOLD) response. Results: A bayesian RL model comparison in 60 individuals (mean [SE] age, 24.5 [0.8] years; 51 females [85%]) with MDD revealed that antidepressant placebo trial-wise expectancies were updated by composite learning signals multiplexing sensory evidence (neurofeedback) and trial-wise mood (bayesian omnibus risk <0.001; exceedance probability = 97%). Placebo expectancy, neurofeedback manipulations, and composite learning signals modulated the visual cortex and dorsal attention network (threshold-free cluster enhancement [TFCE] = 1 - P >.95). As participants anticipated antidepressant infusions, learned placebo expectancies modulated the salience network (SN, TFCE = 1 - P >.95), positively scaling with depression severity. Conclusions and Relevance: Results of this cross-sectional study suggest that on a timescale of minutes, antidepressant placebo effects were maintained by positive feedback loops between expectancies and mood improvement. During learning, representations of placebos and their perceived effects were enhanced in primary and secondary sensory cortices. Latent learned placebo expectancies were encoded in the SN.

Anxiety as a disorder of uncertainty: implications for understanding maladaptive anxiety, anxious avoidance, and exposure therapy.

In cognitive-behavioral conceptualizations of anxiety, exaggerated threat expectancies underlie maladaptive anxiety. This view has led to successful treatments, notably exposure therapy, but is not consistent with the empirical literature on learning and choice alterations in anxiety. Empirically, anxiety is better described as a disorder of uncertainty learning. How disruptions in uncertainty lead to impairing avoidance and are treated with exposure-based methods, however, is unclear. Here, we integrate concepts from neurocomputational learning models with clinical literature on exposure therapy to propose a new framework for understanding maladaptive uncertainty functioning in anxiety. Specifically, we propose that anxiety disorders are fundamentally disorders of uncertainty learning and that successful treatments, particularly exposure therapy, work by remediating maladaptive avoidance from dysfunctional explore/exploit decisions in uncertain, potentially aversive situations. This framework reconciles several inconsistencies in the literature and provides a path forward to better understand and treat anxiety.

Personality (Dys)Function and General Instability.

Humans adapt to a dynamic environment while maintaining psychological equilibrium. Systems theories of personality hold that generalized processes control stability by regulating how strongly a person reacts to various situations. Research shows there are higher-order traits of general personality function (Stability) and dysfunction (general personality pathology; GPP), but whether or not they capture individual differences in reactivity is largely theoretical. We tested this hypothesis by examining how general personality functioning manifests in everyday life in two samples (Ns=205; 342 participants and 24,920; 17,761 observations) that completed an ambulatory assessment protocol. Consistent with systems theories, we found (1) there is a general factor reflecting reactivity across major domains of functioning, and (2) reactivity is strongly associated with Stability and GPP. Results provide insight into how people fundamentally adapt (or not) to their environments, and lays the foundation for more practical, empirical models of human functioning.

Suicidal urges and attempted suicide at multiple time scales in borderline personality disorder.

BACKGROUND: There is strong evidence for an enduring suicidal diathesis among individuals with a history of suicide attempts, particularly among people diagnosed with borderline personality disorder (BPD). However, the progression of suicidal crises among people predisposed to suicidal behavior remains poorly understood. METHODS: Via multilevel structural equation modeling we tested the hypothesis that a history of attempted suicide predicts a stronger dynamic link between affect and impulsivity with suicidal ideation (i.e., suicidal urges) - both moment-to-moment and day-to-day. 153 patients diagnosed with BPD, 105 of whom had a history of medically serious suicide attempts completed a 21-day ecological momentary assessment protocol (17,926 total assessments). RESULTS: Individuals with higher average levels of negative affect reported more suicidal thoughts. Moments characterized by more negative affect, hostility, impulsivity, and less positive affect were also characterized by elevated suicidal ideation. For hostility and positive affect, these significant links generalized to the daily level. At the same time, for negative affect and hostility the within-person coupling was stronger among attempters in comparison to non-attempters, and these effects did not significantly differ across timescales. LIMITATIONS: Follow-up studies replicating our findings of the dysregulation-suicidality nexus in clinically more diverse samples are needed. CONCLUSIONS: The diathesis for suicidal behavior manifests in tighter dynamic links between negative affect or hostility and suicidal ideation. Because these within-person links were amplified in attempters compared to non-attempters, differential coupling patterns may index potentially lethal processes that generalize beyond BPD reflecting distinct diathesis components.

Rivalry and admiration-seeking in a social competition: From traits to behaviors through contextual cues.

To gain social status, humans employ two strategies, rivalry and admiration-seeking, and these strategies are over-expressed in trait narcissism, according to the Narcissistic Admiration and Rivalry Concept (NARC) and the Status Pursuit in Narcissism (SPIN) model. Whether one engages in rivalry or admiration-seeking behaviors is thought to depend on the interaction between underlying traits and status-relevant social cues, with status threats encouraging rivalry and status-boosting experiences encouraging admiration-seeking. However, experimental studies of how traits and environment influence rivalry and admiration-seeking are lacking, and we do not know whether status-relevant cues selectively activate congruent traits (i.e., whether defeat primarily activates trait rivalry and victory, trait admiration-seeking). We used a rigged video game tournament with three randomized blocks with defeat manipulations of varying intensity, measuring behavioral rivalry (stealing points from opponents) and admiration-seeking (paying to boost rank in the tournament) in a sample of 434 undergraduates assessed for trait rivalry and trait admiration-seeking with the Narcissistic Admiration and Rivalry Questionnaire. We found trait-congruent main effects: behavioral rivalry scaled with trait rivalry and behavioral admiration-seeking with trait admiration-seeking. Exploratory analyses found modest support for trait × environment interactions wherein trait rivalry primarily increased status-pursuit behaviors following defeats and trait admiration-seeking following victories. However, these effects were not robust. These results support the NARC's two-dimensional conceptualization of narcissistic grandiosity. Future studies with greater within-subject power are needed to test the interactionist model of status pursuit. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Negative affectivity and disinhibition as moderators of an interpersonal pathway to suicidal behavior in borderline personality disorder.

This longitudinal study examined whether personality traits moderate the link between interpersonal dysfunction and suicidal behavior in a high-risk sample of 458 individuals diagnosed with borderline personality disorder (BPD). Participants were assessed annually for up to 30 years (mean number of follow-ups = 7.82). Using multilevel structural equation modeling, we examined i) longitudinal, within-person relationships among interpersonal dysfunction, suicidal ideation, and suicide attempts; and ii) moderation of these relationships by negative affectivity and disinhibition. Negative affectivity predicted a stronger within-person coupling between interpersonal dysfunction and suicidal ideation. Disinhibition predicted a stronger coupling between ideation and suicide attempts. Assessing negative affectivity and disinhibition in a treatment setting may guide clinician vigilance toward those at highest risk for interpersonally triggered suicidal behaviors.

Humans adaptively resolve the explore-exploit dilemma under cognitive constraints: Evidence from a multi-armed bandit task.

When navigating uncertain worlds, humans must balance exploring new options versus exploiting known rewards. Longer horizons and spatially structured option values encourage humans to explore, but the impact of real-world cognitive constraints such as environment size and memory demands on explore-exploit decisions is unclear. In the present study, humans chose between options varying in uncertainty during a multi-armed bandit task with varying environment size and memory demands. Regression and cognitive computational models of choice behavior showed that with a lower cognitive load, humans are more exploratory than a simulated value-maximizing learner, but under cognitive constraints, they adaptively scale down exploration to maintain exploitation. Thus, while humans are curious, cognitive constraints force people to decrease their strategic exploration in a resource-rational-like manner to focus on harvesting known rewards.

Protective effects of reasons for living against suicidal ideation in daily life.

How do individuals resist suicidal urges in a crisis? Deterrents for suicide can be conceptualized as reasons for living (RFL), but our understanding of their protective effects is predominantly informed by cross-sectional research. We examined the protective effects of RFL on suicidal ideation (SI) in daily life in a high-risk sample. We also tested whether personality traits moderated the strength of the dynamic RFL-SI link. Adults with a borderline personality disorder diagnosis (N = 153, nsuicide attempters = 105) completed a 21-day ambulatory assessment protocol. Daily endorsements of RFL were negatively linked to SI at the within-person but not the between-person level. Whereas suicide attempters endorsed RFL less frequently than non-attempters, the protective effect of RFL was undiminished in this group. Furthermore, RFL's protective effect was particularly pronounced in those with higher average levels of suicidal ideation. While people high on extraversion endorsed RFL more often, this increase was not protective against SI, indicating that RFL reflect heterogeneous underlying psychological processes, only some of which protect against SI.

Integrating a functional view on suicide risk into idiographic statistical models.

Acute risk of death by suicide manifests in heightened suicidal ideation in certain contexts and time periods. These increases are thought to emerge from complex and mutually reinforcing relationships between dispositional vulnerability factors and individually suicidogenic short-term stressors. Together, these processes inform clinical safety planning and our therapeutic tools accommodate a reasonable degree of idiosyncrasy when we individualize interventions. Unraveling these multifaceted factors and processes on a quantitative level, however, requires estimation frameworks capable of representing idiosyncrasies relevant to intervention and psychotherapy. Using, data from a 21-day ambulatory assessment protocol that included six random prompts per day, we developed personalized (i.e., idiographic) models of interacting risk factors and suicidal ideation via Group Iterative Multiple Model Estimation (GIMME) in a sample of people diagnosed with borderline personality disorder (N = 95) stratified for a history of high lethality suicide attempts. Our models revealed high levels of heterogeneity in state risk factors related to suicidal ideation, with no features shared among the majority of participants or even among relatively homogenous clusters of participants (i.e., empirically derived subgroups). We discuss steps toward clinical implementation of personalized models, which can eventually capture suicidogenic changes in proximal risk factors and inform safety planning and interventions.

Borderline personality disorder: stress reactivity or stress generation? A prospective dimensional study.

BACKGROUND: Individuals diagnosed with borderline personality disorder (BPD) often describe their lives as stressful and unpredictable. However, it is unclear whether the adversity faced by those with BPD is a product of stress reactivity or stress generation. Here, we examined the dynamic, prospective associations between BPD and stressful life events over 3 years. Given the heterogeneity present in BPD, we sought to understand which empirically derived dimensions of this heterogeneous disorder explain stress reactivity v. stress generation. METHODS: Participants included 355 individuals diagnosed with BPD and followed longitudinally at three annual assessments. Auto-regressive cross-lagged panel models were used to examine prospective associations between stressful life events and three latent dimensions implicated in BPD: negative affect, disinhibition, and antagonism. RESULTS: Antagonism and disinhibition, but not negative affect, prospectively predicted dependent stressful life events (events the individual may have some role in). Evidence for decompensation under stress was more tenuous, with independent stressful life events (those presumably outside the individual's control) predicting increases in negative affect. CONCLUSIONS: Our longitudinal study of a well-characterized clinical sample found more evidence for stress generation than for stress-induced decompensation in BPD. Stress generation in BPD is driven by externalizing dimensions: antagonism and disinhibition. These results highlight the utility of empirically derived dimensions for parsing heterogeneity present in BPD, leading to improvements in diagnostic evaluation, clinical prediction, and individualized approaches to treatment planning.

Sleep and next-day negative affect and suicidal ideation in borderline personality disorder.

Sleep disturbance is associated with elevated suicidal ideation and negative affect. To date, however, no study has investigated the temporal relationship between sleep and suicidality among those diagnosed with borderline personality disorder (BPD). This preregistered (https://osf.io/4vugk) study tested whether nightly sleep (self-reported sleep duration, sleep onset latency, and subjective sleep quality) represents a (within-person) short-term risk factor for affective dysregulation and increases in suicide risk from day-to-day, as well as whether between-person differences in sleep, negative affect, and suicidality were associated. We used a 21-day ecological momentary assessment protocol in a sample of 153 people diagnosed with BPD, 105 of which had a history of serious suicide attempts, and 52 healthy controls (N = 4076 days). We found a within-person association between worse subjective sleep quality and greater next-day negative affect. At the between-person level, we found positive relationships between sleep latency and suicidal ideation, and a negative association between subjective sleep quality and negative affect. BPD severity did not significantly moderate the strength of any within-person associations, although BPD was positively associated with average levels of suicidal ideation, sleep latency, and negative affect, and negatively related to subjective sleep quality. These findings suggest that the association of sleep with suicidal ideation and BPD exists largely at the between-persons rather than the within-person level. Disturbed sleep, therefore, seems to largely coincide, rather than specifically contribute to, the exacerbation of suicidal crises in BPD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Search for solutions, learning, simulation, and choice processes in suicidal behavior.

Suicide may be viewed as an unfortunate outcome of failures in decision processes. Such failures occur when the demands of a crisis exceed a person's capacity to (i) search for options, (ii) learn and simulate possible futures, and (iii) make advantageous value-based choices. Can individual-level decision deficits and biases drive the progression of the suicidal crisis? Our overview of the evidence on this question is informed by clinical theory and grounded in reinforcement learning and behavioral economics. Cohort and case-control studies provide strong evidence that limited cognitive capacity and particularly impaired cognitive control are associated with suicidal behavior, imposing cognitive constraints on decision-making. We conceptualize suicidal ideation as an element of impoverished consideration sets resulting from a search for solutions under cognitive constraints and mood-congruent Pavlovian influences, a view supported by mostly indirect evidence. More compelling is the evidence of impaired learning in people with a history of suicidal behavior. We speculate that an inability to simulate alternative futures using one's model of the world may undermine alternative solutions in a suicidal crisis. The hypothesis supported by the strongest evidence is that the selection of suicide over alternatives is facilitated by a choice process undermined by randomness. Case-control studies using gambling tasks, armed bandits, and delay discounting support this claim. Future experimental studies will need to uncover real-time dynamics of choice processes in suicidal people. In summary, the decision process framework sheds light on neurocognitive mechanisms that facilitate the progression of the suicidal crisis. This article is categorized under: Economics > Individual Decision-Making Psychology > Emotion and Motivation Psychology > Learning Neuroscience > Behavior.

Momentary interpersonal processes of suicidal surges in borderline personality disorder.

BACKGROUND: Suicide rates are high in borderline personality disorder (BPD) where interpersonal problems trigger intense affective dysregulation and impulses to act on suicidal thoughts. To date, however, no study has examined how interpersonal stressors contribute to momentary within-person links among affect and impulsivity with suicidal ideation (SI), and how those links vary over time in people's daily lives. METHODS: A total of 153 individuals diagnosed with BPD and 52 healthy controls completed a 21-day ecological momentary assessment protocol. Of these 153 individuals with BPD, 105 had a history of suicide attempts. Multilevel structural equation modeling was used to examine dynamic links among interpersonal perceptions, affect, state impulsivity, and suicidal intent. RESULTS: Aggregated across interactions, lower perceived warmth in others was associated with SI. This direct relationship, however, did not extend to momentary within-person associations. Instead, interpersonal conflicts were linked to SI indirectly via greater negative affect and lower positive affect. While a robust within-person link between interpersonal perceptions and impulsivity emerged, impulsivity did not account for the relationship between interpersonal perceptions and SI. CONCLUSION: This intensive longitudinal study illustrates momentary interpersonal signatures of an emerging suicidal crisis. Among people with BPD at high risk for suicide, interpersonal triggers initiate a cascade of affective dysregulation, which in turn gives rise to SI.

Delay discounting in suicidal behavior: Myopic preference or inconsistent valuation?

Prior studies sought to explain the predisposition to suicidal behavior in terms of myopic preference for immediate versus delayed reward, generating mixed evidence. Data from gambling and bandit tasks, however, suggest that suboptimal decisions in suicidal individuals are explained by inconsistent valuation rather than myopic preferences. We tested these two alternative hypotheses using a delay discounting task in 622 adults (suicide attempters with depression, suicide ideators with depression, nonsuicidal participants with depression, and healthy controls) recruited across three sites through inpatient psychiatric units, mood disorders clinics, primary care, and advertisements. Multilevel models revealed group differences in valuation consistencies in all three samples, with high-lethality suicide attempters exhibiting less consistent valuation than all other groups in Samples 1 and 3 and less consistent valuation than the healthy controls or participants with depression in Sample 2. In contrast, group differences in preference for immediate versus delayed reward were observed only in Sample 1 and were due to the high-lethality suicide attempters displaying a weaker preference for immediate reward than low-lethality suicide attempters. The findings were robust to confounds such as cognitive functioning and comorbidities. Seemingly impulsive choices in suicidal behavior are explained by inconsistent reward valuation rather than a true preference for immediate reward. In a suicidal crisis, this inconsistency may result in a misestimation of the value of suicide relative to constructive alternatives and deterrents. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Understanding the Neurocomputational Mechanisms of Antidepressant Placebo Effects.

Over the last two decades, neuroscientists have used antidepressant placebo probes to examine the biological mechanisms implicated in antidepressant placebo effects. However, findings from these studies have not yet elucidated a model-based theory that would explain the mechanism through which antidepressant expectancies evolve to induce persistent mood changes. Emerging evidence suggests that antidepressant placebo effects may be informed by models of reinforcement learning (RL). Such that an individual's expectation of improvement is updated with the arrival of new sensory evidence, by incorporating a reward prediction error (RPE), which signals the mismatch between the expected (expected value) and perceived improvement. Consistent with this framework, neuroimaging studies of antidepressant placebo effects have demonstrated placebo-induced µ-opioid activation and increased blood-oxygen-level dependent (BOLD) responses in regions tracking expected values (e.g., ventromedial prefrontal cortex (vmPFC)) and RPEs (e.g., ventral striatum (VS)). In this study, we will demonstrate the causal contribution of reward learning signals (expected values and RPEs) to antidepressant placebo effects by experimentally manipulating expected values using transcranial magnetic stimulation (TMS) targeting the vmPFC and µ-opioid striatal RPE signal using pharmacological approaches. We hypothesized that antidepressant placebo expectancies are represented in the vmPFC (expected value) and updated by means of µ-opioid-modulated striatal learning signal. In a 3 × 3 factorial double-blind design, we will randomize 120 antidepressant-free individuals with depressive symptoms to one of three between-subject opioid conditions: the µ-opioid agonist buprenorphine, the µ-opioid antagonist naltrexone, or an inert pill. Within each arm, individuals will be assigned to receive three within-subject counterbalanced forms of TMS targeting the vmPFC-intermittent Theta Burst Stimulation (TBS) expected to potentiate the vmPFC, continuous TBS expected to de-potentiate the vmPFC, or sham TBS. These experimental manipulations will be used to modulate trial-by-trial reward learning signals and related brain activity during the Antidepressant Placebo functional MRI (fMRI) Task to address the following aims: (1) investigate the relationship between reward learning signals within the vmPFC-VS circuit and antidepressant placebo effects; (2) examine the causal contribution of vmPFC expected value computations to antidepressant placebo effects; and (3) investigate the causal contribution of µ-opioid-modulated striatal RPEs to antidepressant placebo effects. The proposed study will be the first to investigate the causal contribution of µ-opioid-modulated vmPFC-VS learning signals to antidepressant placebo responses, paving the way for developing novel treatments modulating learning processes and objective means of quantifying and potentially reducing placebo effects during drug development. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04276259.

µ Opioid Antagonist Naltrexone Partially Abolishes the Antidepressant Placebo Effect and Reduces Orbitofrontal Cortex Encoding of Reinforcement.

BACKGROUND: Like placebo analgesia, the antidepressant placebo effect appears to involve cortical and subcortical endogenous opioid signaling, yet the mechanism through which opioid release affects mood remains unclear. The orbitofrontal cortex (OFC)-which integrates various attributes of a stimulus to predict associated outcomes-has been implicated in placebo effects and is rich in µ opioid receptors. We hypothesized that naltrexone blockade of µ opioid receptors would blunt OFC-dependent antidepressant placebo effects. METHODS: Twenty psychotropic-free patients with major depressive disorder completed a randomized, double-blind, placebo-controlled crossover study of 1 oral dose of 50 mg of naltrexone or matching placebo immediately before completing 2 sessions of the antidepressant placebo functional magnetic resonance imaging task. This task manipulates placebo-associated expectancies and their reinforcement while assessing expected and actual mood improvement. RESULTS: Behaviorally, manipulations of antidepressant placebo expectancies and their reinforcement had positive, interactive effects on participants' expectancy and mood ratings. The high-expectancy condition recruited the dorsolateral and ventrolateral prefrontal cortex, as well as dorsal attention stream regions. Interestingly, increased dorsolateral and ventrolateral prefrontal cortex brain responses appeared to attenuate the antidepressant placebo effect. The administration of 1 oral dose of naltrexone, compared with placebo, partially abolished the interaction of the expectancy and reinforcement manipulation on mood and blocked reinforcement-induced responses in the right central OFC. CONCLUSIONS: Our results show preliminary evidence for the role of µ opioid central OFC modulation in antidepressant placebo effects by positively biasing the value of placebo based on reinforcement and enhancing subsequent hedonic experiences.

Late-Onset Suicide: A Dementia Prodrome?

OBJECTIVES: This study examined whether late-onset (versus early-onset) suicidal behavior is associated with worse cognition. METHODS: Participants included 278 adults aged 50+ years (56 nonpsychiatric comparison group; 67 nonsuicidal depressed older adults; 63 depressed suicide ideators; and 44 late-onset (55+ years) and 48 early-onset suicide attempters (<55 years). Using a case-control design, this study examined group differences in global cognition, episodic memory, information processing speed, and executive functioning, assessed using the Repeatable Battery of Neuropsychological Status and the Trail Making Test from the Delis-Kaplan Executive Function System. Linear regression was used for data analyses. RESULTS: Both attempter groups displayed worse executive functioning than nonsuicidal depressed older adults. Late-onset attempters additionally displayed poorer global cognition and processing speed than nonsuicidal depressed older adults and poorer memory than early-onset attempters. CONCLUSIONS: Late-onset suicidal behavior is associated with worse performance in a broad range of cognitive domains, possibly reflective of a dementia prodrome.