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.

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.

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.

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.

Personality of late- and early-onset elderly suicide attempters.

OBJECTIVES: While suicidal behavior often manifests in adolescence and early adulthood, some people first attempt suicide in late life, often with remarkable lethal intent and determination. Given these individuals' more adaptive functioning earlier in life, they may possess traits that hinder adjustment to aging, such as high conscientiousness, rather than impulsive-aggressive traits associated with suicidal behavior in younger adults. METHODS: A cross-sectional case-control study was conducted in older adults aged ≥50 (mean: 65), divided into early- and late-onset attempters (age at first attempt ≤ or >50, mean: 31 vs 61), suicide ideators as well as non-suicidal depressed and healthy controls. Personality was assessed in terms of the five-factor model (FFM, n = 200) and five DSM personality disorders analyzed on the trait level as continuous scores (PDs, n = 160). Given our starting hypothesis about late-onset attempters, the FFM dimension conscientiousness was further tested on the subcomponent level. RESULTS: All clinical groups displayed more maladaptive profiles than healthy subjects. Compared to depressed controls, higher neuroticism, and borderline traits characterized both suicide ideators and early-onset attempters, while only early-onset attempters further displayed lower extraversion and higher antisocial traits. Late-onset attempters were similar to depressed controls on most measures, but scored higher than them on orderliness, a conscientiousness subcomponent. CONCLUSIONS: While neuroticism, introversion, and cluster B traits are prominent in early-onset suicidal behavior, late-onset cases generally lack these features. In contrast, higher levels of orderliness in late-onset suicidal behavior are compatible with the age-selective maladjustment hypothesis. Key points Personality of elderly attempters differed between those with early- and late-onset first attempts. Early-onset attempters possessed personality traits generally found in younger suicidal populations (high neuroticism, low extraversion, antisocial, and borderline PD traits), supporting that constitutional suicide risk factors persist into late life in some individuals. Late-onset suicide attempters had higher levels of orderliness than non-suicidal depressed participants, suggesting that this generally adaptive trait may facilitate suicidal behavior in a subset of depressed elderly.

Neurocomputational mechanisms of adaptive learning in social exchanges.

Prior work on prosocial and self-serving behavior in human economic exchanges has shown that counterparts' high social reputations bias striatal reward signals and elicit cooperation, even when such cooperation is disadvantageous. This phenomenon suggests that the human striatum is modulated by the other's social value, which is insensitive to the individual's own choices to cooperate or defect. We tested an alternative hypothesis that, when people learn from their interactions with others, they encode prediction error updates with respect to their own policy. Under this policy update account striatal signals would reflect positive prediction errors when the individual's choices correctly anticipated not only the counterpart's cooperation but also defection. We examined behavior in three samples using reinforcement learning and model-free analyses and performed an fMRI study of striatal learning signals. In order to uncover the dynamics of goal-directed learning, we introduced reversals in the counterpart's behavior and provided counterfactual (would-be) feedback when the individual chose not to engage with the counterpart. Behavioral data and model-derived prediction error maps (in both whole-brain and a priori striatal region of interest analyses) supported the policy update model. Thus, as people continually adjust their rate of cooperation based on experience, their behavior and striatal learning signals reveal a self-centered instrumental process corresponding to reciprocal altruism.

Losing the battle: Perceived status loss and contemplated or attempted suicide in older adults.

OBJECTIVE: While loss of socioeconomic status (SES) has been linked to suicidal behavior, it is unclear whether this experience is merely a downstream effect of psychopathology ("downward drift"), a sign of hardship, or an independent psychological contributor to suicide risk. We examined the association between the subjective experience of status loss and suicidal behavior and ideation in old age, while accounting for potential confounders. We were also interested in whether status loss was associated with mere thoughts of suicide vs. suicidal behavior. METHODS: Fifty older (55+) depressed suicide attempters, 29 depressed suicide ideators with no history of attempted suicide, 38 nonsuicidal depressed participants, and 45 nonpsychiatric controls underwent detailed clinical characterization and reported their current and highest lifetime SES. RESULTS: Suicide attempters were more likely to report a decline in their SES compared to healthy controls and nonsuicidal depressed older adults, while not differing from suicide ideators. This difference was not explained by objective predictors of SES, including education, financial difficulties, and the presence of addiction. Interestingly, while the current SES of suicide attempters was much lower than that of comparison groups, their reported highest lifetime SES was just as high, despite the differences in education. CONCLUSION: In older adults, the experience of status loss is associated with contemplated and attempted suicide even after accounting for objective indicators of social status and psychopathology. It is possible that suicidal individuals retrospectively inflate their previous status, making their current standing appear even worse by comparison.

Perceived burdensomeness is associated with low-lethality suicide attempts, dysfunctional interpersonal style, and younger rather than older age.

OBJECTIVES: Perceived burdensomeness is thought to contribute to suicide risk. However, suicidal behavior is clinically and psychologically heterogeneous. Does a high level of perceived burdensomeness differentiate medically serious suicidal acts, most closely resembling death by suicide, from less serious ones? How is perceived burdensomeness related to dysfunctional personality dimensions implicated in suicide? We sought to answer these questions in a cross-sectional, case-control study of adults, aged 42 years or older (n = 165). METHODS: Participants were suicidal depressed with history of high-lethality and low-lethality attempts, depressed with serious suicidal ideation, depressed non-suicidal, and psychiatrically healthy controls. Following detailed clinical characterization, we assessed perceived burdensomeness, the Big Five, impulsivity, and anger rumination. RESULTS: Low-lethality attempters reported the highest levels of perceived burdensomeness, followed by ideators, high-lethality attempters, non-suicidal depressed, and healthy controls. Group differences were robust to confounders, including demographics, severity of depression, and physical illness burden. In suicide attempters, perceived burdensomeness scaled positively with neuroticism, impulsivity, and anger and negatively with extraversion, conscientiousness, and age. CONCLUSIONS: Our findings suggest that perceived burdensomeness is most prominent in a subgroup of younger individuals with lower-lethality suicide attempts and a dysfunctional interpersonal style. Older adults with high-lethality attempts are surprisingly more resilient to the feelings of burdensomeness. Copyright © 2016 John Wiley & Sons, Ltd.

Course of cognitive impairment following attempted suicide in older adults.

OBJECTIVE: Cognitive impairment has been associated with late-life suicidal behavior. Without longitudinal data it is unclear whether these are transient features of a depressive state or stable impairments. We examined longitudinally the course of cognitive impairment in older adults with depression and a history of suicide attempt. METHODS: We investigated the persistence of cognitive impairment over time in 198 depressed older adults (age >60); 91 suicide attempters, 39 depressed individuals with suicidal ideation (ideators), and 68 non-suicidal depressed adults assessed over a 2-year period at four time points. We used linear mixed effects modeling to examine group differences in trajectories of cognitive decline over 2 years, using the Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale (DRS), and Executive Interview (EXIT). RESULTS: Over the 2-year period, suicide attempters performed significantly worse than both suicide ideators and non-suicidal depressed older adults on the MMSE (mean difference: from ideators: -0.88, p = 0.02; from non-suicidal depressed: -1.52, p < 0.01), while on the EXIT and DRS, suicide attempters performed significantly worse than non-suicidal depressed older adults (mean difference: in EXIT: -1.75, p = 0.01; in DRS: 3.04, p < 0.01; in MMSE: 1.15, p < 0.01). Cognitive impairment in suicide attempters partly resolved, as indicated by a group × time interaction on the DRS (p = 0.039), but not the EXIT (p = 0.58) or the MMSE (p = 0.08). CONCLUSIONS: Cognitive impairment in late-life suicidal behavior appears to involve both a stable and a state-related component.

Insomnia is associated with suicide attempt in middle-aged and older adults with depression.

BACKGROUND: Insomnia increases in prevalence with age, is strongly associated with depression, and has been identified as a risk factor for suicide in several studies. The aim of this study was to determine whether insomnia severity varies between those who have attempted suicide (n = 72), those who only contemplate suicide (n = 28), and those who are depressed but have no suicidal ideation or attempt history (n = 35). METHODS: Participants were middle-aged and older adults (age 44-87, M = 66 years) with depression. Insomnia severity was measured as the sum of the early, middle, and late insomnia items from the Hamilton Rating Scale for Depression. General linear models examined relations between group status as the independent variable and insomnia severity as the dependent variable. RESULTS: The suicide attempt group suffered from more severe insomnia than the suicidal ideation and non-suicidal depressed groups (p < 0.05). Differences remained after adjusting for potential confounders including demographics, cognitive ability, alcohol dependence in the past month, severity of depressed mood, anxiety, and physical health burden. Moreover, greater insomnia severity in the suicide attempt group could not be explained by interpersonal difficulties, executive functioning, benzodiazepine use, or by the presence of post-traumatic stress disorder. CONCLUSIONS: Our results suggest that insomnia may be more strongly associated with suicidal behavior than with the presence of suicidal thoughts alone. Accordingly, insomnia is a potential treatment target for reducing suicide risk in middle-aged and older adults.

Reinforcement learning models and their neural correlates: An activation likelihood estimation meta-analysis.

Reinforcement learning describes motivated behavior in terms of two abstract signals. The representation of discrepancies between expected and actual rewards/punishments-prediction error-is thought to update the expected value of actions and predictive stimuli. Electrophysiological and lesion studies have suggested that mesostriatal prediction error signals control behavior through synaptic modification of cortico-striato-thalamic networks. Signals in the ventromedial prefrontal and orbitofrontal cortex are implicated in representing expected value. To obtain unbiased maps of these representations in the human brain, we performed a meta-analysis of functional magnetic resonance imaging studies that had employed algorithmic reinforcement learning models across a variety of experimental paradigms. We found that the ventral striatum (medial and lateral) and midbrain/thalamus represented reward prediction errors, consistent with animal studies. Prediction error signals were also seen in the frontal operculum/insula, particularly for social rewards. In Pavlovian studies, striatal prediction error signals extended into the amygdala, whereas instrumental tasks engaged the caudate. Prediction error maps were sensitive to the model-fitting procedure (fixed or individually estimated) and to the extent of spatial smoothing. A correlate of expected value was found in a posterior region of the ventromedial prefrontal cortex, caudal and medial to the orbitofrontal regions identified in animal studies. These findings highlight a reproducible motif of reinforcement learning in the cortico-striatal loops and identify methodological dimensions that may influence the reproducibility of activation patterns across studies.

Impulsive traits and unplanned suicide attempts predict exaggerated prefrontal response to angry faces in the elderly.

OBJECTIVE: Abnormal responses to social stimuli are seen in people vulnerable to suicidal behavior, indicating possible disruptions in the neural circuitry mediating the interpretation of socioemotional cues. These disruptions have not been empirically related to psychological and cognitive pathways to suicide. In the present study of older suicide attempters, we examined neural responses to emotional faces and their relationship to impulsivity, one of the components of the suicidal diathesis. METHODS: Using functional magnetic resonance imaging, we recorded neurohemodynamic responses to angry faces in a carefully characterized sample of 18 depressed elderly with history of suicide attempts, 13 depressed nonsuicidal patients, and 18 healthy individuals, all aged 60+. Impulsivity was assessed with the Social Problem Solving Inventory Impulsivity/Carelessness Style subscale and Barratt Impulsiveness Scale. The Suicide Intent Scale planning subscale was used to describe the degree of planning associated with the most lethal attempt. RESULTS: Depression and history of attempted suicide were not associated with neural responses to angry faces, failing to replicate earlier studies. Higher impulsivity, however, predicted exaggerated responses to angry faces in fronto-opercular and dorsomedial prefrontal cortex (pcorr <0.05). Poorly planned suicide attempts also predicted increased fronto-opercular responses. Results were robust to effects of medication exposure, comorbid anxiety and addiction, severity of depression, burden of physical illness, and possible brain injury from suicide attempts. CONCLUSION: Impulsive traits and history of unplanned suicide attempts partly explain the heterogeneity in neural responses to angry faces in depressed elderly. Displays of social emotion command excessive cortical processing in impulsive suicide attempters.

Cognitive inhibition in older high-lethality suicide attempters.

BACKGROUND: People who attempt suicide often display cognitive impairments, particularly poor cognitive control. Could poor cognitive control contribute to high suicide rates in old age? A component of cognitive control, cognitive inhibition-active suppression of task-irrelevant processing-is very sensitive to aging and has been linked to attempted suicide. We investigated cognitive inhibition in older high-lethality suicide attempters, closely resembling suicide victims, as well as low-lethality attempters, and control groups with and without depression and suicidal ideation. METHODS: A total of 102 participants aged 60 years and older (17 psychiatrically healthy control subjects, 38 depressed control subjects, 16 suicide ideators, 14 low-lethality suicide attempters, and 17 high-lethality suicide attempters) underwent comprehensive clinical and cognitive assessments. They completed the Delis-Kaplan Executive Function System Color-Word Interference Test, a validated modification of the Stroop test. RESULTS: High-lethality suicide attempters demonstrated a distinct pattern of cognitive inhibition deficits. Compared with psychiatrically healthy control subjects and suicide ideators, high-lethality attempters took longer to complete inhibition trials, even after accounting for potential confounding factors (age, education, Mini mental state examination score, information processing speed, and accuracy). Compared with non-suicidal depressed and healthy control subjects, low-lethality suicide attempters committed more uncorrected errors; however, this difference was not specific to the inhibition condition. CONCLUSIONS: Older suicide attempters are a cognitively heterogeneous group. Poor cognitive control in high-lethality attempters may undermine their ability to solve real-life problems, precipitating a catastrophic accumulation of stressors. Meanwhile, low-lethality attempters' poor performance may reflect a careless approach to the task or faulty monitoring.

Impaired Executive Function in Contemplated and Attempted Suicide in Late Life.

OBJECTIVE: Executive deficits may play an important role in late-life suicide. Yet, current evidence in this area is inconclusive and does not indicate whether these deficits are broadly associated with suicidal ideation or are specific to suicidal behavior. This study examined global cognition and specifically executive function impairments as correlates of suicidal ideation and suicidal behavior in depressed older adults, with the goal of extending an earlier preliminary study. DESIGN: Case-control study. SETTING: University-affiliated psychiatric hospital. PARTICIPANTS: All participants were age 60+: 83 depressed suicide attempters, 43 depressed individuals having suicidal ideation with a specific plan, 54 nonsuicidal depressed participants, and 48 older adults with no history of psychiatric disorders. MEASUREMENTS: Global cognitive function was assessed with Dementia Rating Scale (DRS) and executive function with Executive Interview (EXIT). RESULTS: Both suicide attempters and suicide ideators performed worse than the two comparison groups on the EXIT, with no difference between suicide attempters and suicide ideators. On the DRS total score, as well as on Memory and Attention subscales, suicide attempters and ideators and nonsuicidal depressed subjects performed similarly and were impaired relative to nonpsychiatric control subjects. Controlling for education, substance use disorders, and medication exposure did not affect group differences in performance on either the EXIT or the DRS. CONCLUSIONS: Executive deficits, captured with a brief instrument, are associated broadly with suicidal ideation in older depressed adults but do not appear to directly facilitate suicidal behavior. Our data are consistent with the idea that different vulnerabilities may operate at different stages in the suicidal process.

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.

Dynamics of narcissistic grandiosity and vulnerability in naturalistic and experimental settings.

Theoretical accounts of narcissism emphasize the dynamic shifting of self-states in response to social feedback. Status threats are thought to set narcissism's dynamics in motion. Naturalistic ecological momentary assessment (EMA) studies have characterized dynamics of narcissistic grandiosity and vulnerability in relation to perceptions of the interpersonal environment. Experimental studies have emphasized the behavioral responses of narcissistic individuals to putative threats to status. Naturalistic and experimental studies suffer from opposing limitations, namely, a potential for confounding variables to impact results versus ambiguous generalizability to real-life and longer time scales, respectively. Integrating naturalistic and experimental studies has the potential to provide a comprehensive model of how dynamics within narcissism unfold in response to status threat. The present study examined shifts in grandiosity and vulnerability in both naturalistic EMA and experimentally controlled (rigged tournament game) social interactions (N = 437). Grandiosity decreased and vulnerability increased in response to both naturalistic and experimental status threats. Further, the same people who responded with decreased grandiosity in response to status threat in daily life responded with similar decreases in grandiosity to experimental defeat. Trait narcissistic agency amplified many of the observed links between narcissism and status threat experimentally and naturalistically. Given that warmth (in addition to dominance) emerged as an important predictor of shifts in narcissism, implications for status-threatening environments are discussed. The present study elucidates important differences with respect to expressions of grandiosity and vulnerability across naturalistic and experimental methods. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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.

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.

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.