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Objective: Heightened reactivity to stress is associated with poor treatment outcome in people with substance use disorders (SUDs). Behavioral strategies can reduce stress reactivity; however, these strategies are understudied in people with SUDs. The objective of this study was to test the effect of two behavioral strategies (cognitive reappraisal and affect labeling) on stress reactivity in people with SUDs., Method: Treatment-seeking adults with SUDs ( N = 119) were randomized to receive brief training in cognitive reappraisal, affect labeling, or a psychoeducational control, followed by a standardized stress induction. Markers of stress reactivity were collected before and following stress induction and included self-reported negative affect and substance craving, as well as salivary cortisol, and skin conductance response., Results: Analyses of covariance did not indicate a significant effect of treatment condition on negative affect, cortisol, or skin conductance response. Participants in the affect labeling condition had greater increase in craving than those in the cognitive reappraisal condition; neither condition differed from control., Conclusions: Results indicated that, although participants were able to implement behavioral skills following a brief training, training condition did not modify stress reactivity, on average, relative to control. Future directions include consideration of individual differences in response to training and determination of whether higher "dosing" of skills via multiple sessions or extended practice is needed to influence stress reactivity in people with SUDs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

In patients with out-of-hospital cardiac arrest (OHCA) who attain return of spontaneous circulation (ROSC), rearrest while in the prehospital setting represents a significant barrier to survival. To date, there are limited data to guide prehospital emergency medical services (EMS) management immediately following successful resuscitation resulting in ROSC and prior to handoff in the emergency department. Post-ROSC care encompasses a multifaceted approach including hemodynamic optimization, airway management, oxygenation, and ventilation. We sought to develop an evidenced-based, goal-directed bundle of care targeting specified vital parameters in the immediate post-ROSC period, with the goal of decreasing the incidence of rearrest and improving survival outcomes. Here, we describe the rationale and development of this goal-directed bundle of care, which will be adopted by several EMS agencies within California. We convened a group of EMS experts, including EMS Medical Directors, quality improvement officers, data managers, educators, EMS clinicians, emergency medicine clinicians, and resuscitation researchers to develop a goal-directed bundle of care to be applied in the field during the period immediately following ROSC. This care bundle includes guidance for prehospital personnel on recognition of impending rearrest, hemodynamic optimization, ventilatory strategies, airway management, and diagnosis of underlying causes prior to the initiation of transport., Competing Interests: James J. Menegazzi was supported in part by a grant from the National Heart, Lung, and Blood Institute, National Institutes of Health (NHLBI 1RO1HL117979‐01) and David G Dillon was supported in this work by NHLBI grant K38HL165363. They have three patents issued and has been loaned equipment for use in his lab. These are described in more detail in his conflicts of interest form. The other authors declare no conflicts of interest., (© 2024 The Author(s). Journal of the American College of Emergency Physicians Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Importance: The incidence of opioid-associated out-of-hospital cardiac arrest (OA-OHCA) has grown from less than 1% of OHCA in 2000 to between 7% and 14% of OHCA in recent years; American Heart Association (AHA) protocols suggest that emergency medical service (EMS) clinicians consider naloxone in OA-OHCA. However, it is unknown whether naloxone improves survival in these patients or in patients with undifferentiated OHCA., Objective: To evaluate the association of naloxone with clinical outcomes in patients with undifferentiated OHCA., Design, Setting, and Participants: Retrospective cohort study of EMS-treated patients aged 18 or older who received EMS treatment for nontraumatic OHCA in 3 Northern California counties between 2015 and 2023. Data were analyzed using propensity score-based models from February to April 2024., Exposure: EMS administration of naloxone., Main Outcomes and Measures: The primary outcome was survival to hospital discharge; the secondary outcome was sustained return of spontaneous circulation (ROSC). Covariates included patient and cardiac arrest characteristics (eg, age, sex, nonshockable rhythm, any comorbidity, unwitnessed arrest, and EMS agency) and EMS clinician determination of OHCA cause as presumed drug-related., Results: Among 8195 patients (median [IQR] age, 65 [51-78] years; 5540 male [67.6%]; 1304 Asian, Native Hawaiian, or Pacific Islander [15.9%]; 1119 Black [13.7%]; 2538 White [31.0%]) with OHCA treated by 5 EMS agencies from 2015 to 2023, 715 (8.7%) were believed by treating clinicians to have drug-related OHCA. Naloxone was administered to 1165 patients (14.2%) and was associated with increased ROSC using both nearest neighbor propensity matching (absolute risk difference [ARD], 15.2%; 95% CI, 9.9%-20.6%) and inverse propensity-weighted regression adjustment (ARD, 11.8%; 95% CI, 7.3%-16.4%). Naloxone was also associated with increased survival to hospital discharge using both nearest neighbor propensity matching (ARD, 6.2%; 95% CI, 2.3%-10.0%) and inverse propensity-weighted regression adjustment (ARD, 3.9%; 95% CI, 1.1%-6.7%). The number needed to treat with naloxone was 9 for ROSC and 26 for survival to hospital discharge. In a regression model that assessed effect modification between naloxone and presumed drug-related OHCA, naloxone was associated with improved survival to hospital discharge in both the presumed drug-related OHCA (odds ratio [OR], 2.48; 95% CI, 1.34-4.58) and non-drug-related OHCA groups (OR, 1.35; 95% CI, 1.04-1.77)., Conclusions and Relevance: In this retrospective cohort study, naloxone administration as part of EMS management of OHCA was associated with increased rates of ROSC and increased survival to hospital discharge when evaluated using propensity score-based models. Given the lack of clinical practice data on the efficacy of naloxone in OA-OHCA and OHCA in general, these findings support further evaluation of naloxone as part of cardiac arrest care.

Poor inhibitory control contributes to deficits in emotion regulation, which are often targeted by treatments for major depressive disorder (MDD), including cognitive behavioral therapy (CBT). Brain regions that contribute to inhibitory control and emotion regulation overlap; thus, inhibitory control might relate to response to CBT. In this study, we examined whether baseline inhibitory control and resting state functional connectivity (rsFC) within overlapping emotion regulation-inhibitory control regions predicted treatment response to internet-based CBT (iCBT). Participants with MDD were randomly assigned to iCBT (N = 30) or a monitored attention control (MAC) condition (N = 30). Elastic net regression was used to predict post-treatment Patient Health Questionnaire-9 (PHQ-9) scores from baseline variables, including demographic variables, PHQ-9 scores, Flanker effects (interference, sequential dependency, post-error slowing), and rsFC between the dorsal anterior cingulate cortex, bilateral anterior insula (AI), and right temporoparietal junction (TPJ). Essential prognostic predictor variables retained in the elastic net regression included treatment group, gender, Flanker interference response time (RT), right AI-TPJ rsFC, and left AI-right AI rsFC. Prescriptive predictor variables retained included interactions between treatment group and baseline PHQ-9 scores, age, gender, Flanker RT, sequential dependency effects on accuracy, post-error accuracy, right AI-TPJ rsFC, and left AI-right AI rsFC. Inhibitory control and rsFC within inhibitory control-emotion regulation regions predicted reduced symptom severity following iCBT, and these effects were stronger in the iCBT group than in the MAC group. These findings contribute to a growing literature indicating that stronger inhibitory control at baseline predicts better outcomes to psychotherapy, including iCBT., (© 2024. The Author(s).)

Background: In 2015, California passed AB 71 to create a state-wide Use of Force Incident Reporting Database (URSUS) to tabulate law enforcement-reported encounters that resulted in serious bodily injury, death or discharge of a firearm. We use these data to analyse encounters that resulted in fatal and non-fatal civilian injuries in California between 2016 and 2021., Methods: We performed a retrospective review of URSUS from January 2016 to December 2021. The main outcomes were the number of law enforcement encounters that involved civilian serious bodily injury or death and encounter-level characteristics., Results: URSUS recorded 3677 incidents between 2016 and 2021 resulting in 942 civilian fatalities and 2735 instances of serious civilian injuries. Injury rates were highest for civilians who identified as Hispanic (1.80 injuries per 100 000 population) or black (5.17 injuries per 100 000 population). Injuries involving a firearm were usually fatal (58.9% fatality rate; 1471 injuries), while non-firearm incidents were more likely to result in serious injuries (4.2% fatality rate; 2929 injuries). We did not find statistically significant trends in rates of civilian injuries per 100 000 population., Conclusion: Rates of law enforcement-related injuries were highest for Hispanic and black civilians in California between 2016 and 2021 and firearm-related injuries were overwhelmingly fatal. The URSUS database represents an important effort by law enforcement agencies to collect information on injuries and fatalities resulting from law enforcement encounters. Given similar databases exist in fewer than half of states, additional legislative efforts are needed to improve systematic national data collection on these encounters., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Deeper phenotyping may improve our understanding of depression. Because depression is heterogeneous, extracting cognitive signatures associated with severity of depressive symptoms, anhedonia, and affective states is a promising approach., Methods: Sequential sampling models decomposed behavior from an adaptive approach-avoidance conflict task into computational parameters quantifying latent cognitive signatures. Fifty unselected participants completed clinical scales and the approach-avoidance conflict task by either approaching or avoiding trials offering monetary rewards and electric shocks., Results: Decision dynamics were best captured by a sequential sampling model with linear collapsing boundaries varying by net offer values, and with drift rates varying by trial-specific reward and aversion, reflecting net evidence accumulation toward approach or avoidance. Unlike conventional behavioral measures, these computational parameters revealed distinct associations with self-reported symptoms. Specifically, passive avoidance tendencies, indexed by starting point biases, were associated with greater severity of depressive symptoms (R = 0.34, p = .019) and anhedonia (R = 0.49, p = .001). Depressive symptoms were also associated with slower encoding and response execution, indexed by nondecision time (R = 0.37, p = .011). Higher reward sensitivity for offers with negative net values, indexed by drift rates, was linked to more sadness (R = 0.29, p = .042) and lower positive affect (R = -0.33, p = .022). Conversely, higher aversion sensitivity was associated with more tension (R = 0.33, p = .025). Finally, less cautious response patterns, indexed by boundary separation, were linked to more negative affect (R = -0.40, p = .005)., Conclusions: We demonstrated the utility of multidimensional computational phenotyping, which could be applied to clinical samples to improve characterization and treatment selection., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Despite frequent treatment of alcohol withdrawal syndrome (AWS) in the emergency department (ED), evidence for phenobarbital (PB) as an ED alternative therapy is mixed. We conducted a systematic review and meta-analysis comparing safety and efficacy of PB to benzodiazepines (BZDs) for treatment of AWS in the ED., Methods: We searched articles and references published in English in PubMed, Web of Science, and Embase from inception through May 2022. We included randomized trials and cohort studies comparing treatment with PB to BZD controls and excluded studies focused on non-AWS conditions. Review was conducted by two blinded investigators and a third author; eight of 59 (13.6%) abstracts met inclusion criteria for review and meta-analysis using a random-effects model. Treatment superiority was evaluated through utilization, pharmacologic, and clinical outcomes. Primary outcomes for meta-analysis were the proportion of patients (1) admitted to the intensive care unit (ICU), (2) admitted to the hospital, (3) readmitted to the ED after discharge, and (4) who experienced adverse events., Results: Eight studies (two randomized controlled trials, six retrospective cohorts) comprised data from 1507 patients in 2012 treatment encounters for AWS. All studies were included in meta-analysis for adverse events, seven for hospital admission, five for ICU admission, and three for readmission to the ED after discharge. Overall methodological quality was low-moderate, risk of bias moderate-high, and statistical heterogeneity moderate. Pooled relative risk of ICU admission for those treated with PB versus BZD was 0.92 (95% confidence interval [CI] 0.54-1.55). Risk for admission to the hospital was 0.98 (95% CI 0.89-1.07) and for any adverse event was 1.1 (95% CI 0.78-1.57); heterogeneity prevented meta-analysis for ED readmission., Conclusions: The current literature base does not show that treatment with PB significantly reduces ICU admissions, hospital admissions, ED readmissions, or adverse events in ED patients with AWS compared with BZDs alone., (© 2024 The Authors. Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Introduction: Estimates of the prevalence of drug-related out of hospital cardiac arrest (OHCA) vary, ranging from 1.8% to 10.0% of medical OHCA. However, studies conducted prior to the recent wave of fentanyl deaths likely underestimate the current prevalence of drug-related OHCA. We evaluated recent trends in drug-related OHCA, hypothesizing that the proportion of presumed drug-related OHCA treated by emergency medical services (EMS) has increased since 2015., Methods: We conducted a retrospective analysis of OHCA patients treated by EMS providers in San Francisco, California between 2015 and 2023. Participants included OHCA cases in which resuscitation was attempted by EMS. The study exposure was the year of arrest. Our primary outcome was the occurrence of drug-related OHCA, defined as the EMS impression of OHCA caused by a presumed or known overdose of medication(s) or drug(s)., Results: From 2015 to 2023, 5044 OHCA resuscitations attended by EMS (average 561 per year) met inclusion criteria. The median age was 65 (IQR 50-79); 3508 (69.6%) were male. The EMS impression of arrest etiology was drug-related in 446/5044 (8.8%) of OHCA. The prevalence of presumed drug-related OHCA increased significantly each year from 1% in 2015 to 17.6% in 2023 (p-value for trend = 0.0001). After adjustment, presumed drug-related OHCA increased by 30% each year from 2015-2023., Conclusion: Drug-related OHCA is an increasingly common etiology of OHCA. In 2023, one in six OHCA was presumed to be drug related. Among participants less than 60 years old, one in three OHCA was presumed to be drug related., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Importance: Recent studies have demonstrated that people of color are more likely to be restrained in emergency department (ED) settings compared with other patients, but many of these studies are based at a single site or health care system, limiting their generalizability., Objective: To synthesize existing literature on risk of physical restraint use in adult EDs, specifically in reference to patients of different racial and ethnic backgrounds., Data Sources: A systematic search of PubMed, Embase, Web of Science, and CINAHL was performed from database inception to February 8, 2022., Study Selection: Included peer-reviewed studies met 3 criteria: (1) published in English, (2) original human participants research performed in an adult ED, and (3) reported an outcome of physical restraint use by patient race or ethnicity. Studies were excluded if they were conducted outside of the US, or if full text was unavailable., Data Extraction and Synthesis: Four independent reviewers (V.E., M.M., D.D., and A.H.) abstracted data from selected articles following Meta-Analysis of Observational Studies in Epidemiology guidelines. A modified Newcastle-Ottawa scale was used to assess quality. A meta-analysis of restraint outcomes among minoritized racial and ethnic groups was performed using a random-effects model in 2022., Main Outcome(s) and Measure(s): Risk of physical restraint use in adult ED patients by racial and ethnic background., Results: The search yielded 1597 articles, of which 10 met inclusion criteria (0.63%). These studies represented 2 557 983 patient encounters and 24 030 events of physical restraint (0.94%). In the meta-analysis, Black patients were more likely to be restrained compared with White patients (RR, 1.31; 95% CI, 1.19-1.43) and to all non-Black patients (RR, 1.27; 95% CI, 1.23-1.31). With respect to ethnicity, Hispanic patients were less likely to be restrained compared with non-Hispanic patients (RR, 0.85; 95% CI, 0.81-0.89)., Conclusions and Relevance: Physical restraint was uncommon, occurring in less than 1% of encounters, but adult Black patients experienced a significantly higher risk of physical restraint in ED settings compared with other racial groups. Hispanic patients were less likely to be restrained compared with non-Hispanic patients, though this observation may have occurred if Black patients, with a higher risk of restraint, were included in the non-Hispanic group. Further work, including qualitative studies, to explore and address mechanisms of racism at the interpersonal, institutional, and structural levels are needed.

Background: The efficacy of empiric calcium for patients with undifferentiated cardiac arrest has come under increased scrutiny, including a randomized controlled trial that was stopped early due to a trend towards harm with calcium administration. However, small sample sizes and non-significant findings have hindered precise effect estimates. In this analysis we evaluate the association of calcium administration with survival in a large retrospective cohort of patients with cardiac arrest treated in the emergency department (ED)., Methods: We conducted a retrospective review of medical records from two academic hospitals (one quaternary care center, one county trauma center) in San Francisco between 2011 and 2019. Inclusion criteria were patients aged greater than or equal to 18 years old who received treatment for cardiac arrest during their ED course. Our primary exposure was the administration of calcium while in the ED and the main outcome was survival to hospital admission. The association between calcium and survival to admission was estimated using a multivariable log-binomial regression, and also with two propensity score models., Results: We examined 781 patients with cardiac arrest treated in San Francisco EDs between 2011 and 2019 and found that calcium administration was associated with decreased survival to hospital admission (RR 0.74; 95% CI 0.66-0.82). These findings remained significant after adjustment for patient age, sex, whether the cardiac arrest was witnessed, and including an interaction term for shockable cardiac rhythms (RR 0.60; 95% CI 0.50-0.72) and non-shockable cardiac rhythms (RR 0.87; 95% CI 0.76-0.99). Risk ratios for the association between calcium and survival to hospital admission were also similar between two propensity score-based models: nearest neighbor propensity matching model (RR 0.79; 95% CI 0.68-0.89) and inverse propensity weighted regression adjustment model (RR 0.75; 95% CI 0.67-0.84)., Conclusions: Calcium administration as part of ED-directed treatment for cardiac arrest was associated with lower survival to hospital admission. Given the lack of statistically significant outcomes from smaller, more methodologically robust evaluations on this topic, we believe these findings have an important role to serve in confirming previous results and allowing for more precise effect estimates. Our data adds to the growing body evidence against the empiric use of calcium in cardiac arrest., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Variability in decision-making capacity and reward responsiveness may underlie differences in the ability to abstain from smoking. Computational modeling of choice behavior, as with the Hierarchical Drift Diffusion Model (HDDM), can help dissociate reward responsiveness from underlying components of decision-making. Here we used the HDDM to identify which decision-making or reward-related parameters, extracted from data acquired in a reward processing task, contributed to the ability of people who smoke that are not seeking treatment to abstain from cigarettes during a laboratory task., Methods: 80 adults who smoke cigarettes completed the Probabilistic Reward Task (PRT) - a signal detection task with a differential reinforcement schedule - following smoking as usual, and the Relapse Analogue Task (RAT) - a task in which participants could earn money for delaying smoking up to 50min - after a period of overnight abstinence. Two cohorts were defined by the RAT; those who waited either 0-min (n=36) or the full 50-min (n=44) before smoking., Results: PRT signal detection metrics indicated all subjects learned the task contingencies, with no differences in response bias or discriminability between the two groups. However, HDDM analyses indicated faster drift rates in 50-min vs. 0-min waiters., Conclusions: Relative to those who did not abstain, computational modeling indicated that people who abstained from smoking for 50min showed faster evidence accumulation during reward-based decision-making. These results highlight the importance of decision-making mechanisms to smoking abstinence, and suggest that focusing on the evidence accumulation process may yield new targets for treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Background: The orbitofrontal cortex (OFC) is essential for decision making, and functional disruptions within the OFC are evident in schizophrenia. Postnatal phencyclidine (PCP) administration in rats is a neurodevelopmental manipulation that induces schizophrenia-relevant cognitive impairments. We aimed to determine whether manipulating OFC glutamate cell activity could ameliorate postnatal PCP-induced deficits in decision making., Methods: Male and female Wistar rats ( n  = 110) were administered saline or PCP on postnatal days 7, 9, and 11. In adulthood, we expressed YFP (yellow fluorescent protein) (control), ChR2 (channelrhodopsin-2) (activation), or eNpHR 3.0 (enhanced halorhodopsin) (inhibition) in glutamate neurons within the ventromedial OFC (vmOFC). Rats were tested on the probabilistic reversal learning task once daily for 20 days while we manipulated the activity of vmOFC glutamate cells. Behavioral performance was analyzed using a Q-learning computational model of reinforcement learning., Results: Compared with saline-treated rats expressing YFP, PCP-treated rats expressing YFP completed fewer reversals, made fewer win-stay responses, and had lower learning rates. We induced similar performance impairments in saline-treated rats by activating vmOFC glutamate cells (ChR2). Strikingly, PCP-induced performance deficits were ameliorated when the activity of vmOFC glutamate cells was inhibited (halorhodopsin)., Conclusions: Postnatal PCP-induced deficits in decision making are associated with hyperactivity of vmOFC glutamate cells. Thus, normalizing vmOFC activity may represent a potential therapeutic target for decision-making deficits in patients with schizophrenia., (© 2023 The Authors.)

Background: Anhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study was to examine linkages between striatal DA, reward circuitry functioning, anhedonia, and, in an exploratory fashion, self-reported stress, in a transdiagnostic anhedonic sample., Methods: Participants with (n = 25) and without (n = 12) clinically impairing anhedonia completed a reward-processing task during simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging with [ 11 C]raclopride, a DA D2/D3 receptor antagonist that selectively binds to striatal DA receptors., Results: Relative to controls, the anhedonia group exhibited decreased task-related DA release in the left putamen, caudate, and nucleus accumbens and right putamen and pallidum. There were no group differences in task-related brain activation (fMRI) during reward processing after correcting for multiple comparisons. General functional connectivity (GFC) findings revealed blunted fMRI connectivity between PET-derived striatal seeds and target regions in the anhedonia group. Associations were identified between anhedonia severity and the magnitude of task-related DA release to rewards in the left putamen, but not mesocorticolimbic GFC., Conclusions: Results provide evidence for reduced striatal DA functioning during reward processing and blunted mesocorticolimbic network functional connectivity in a transdiagnostic sample with clinically significant anhedonia., Competing Interests: Declaration of Competing Interest Over the past 3 years, Dr. Pizzagalli has received consulting fees from Albright Stonebridge Group, Boehringer Ingelheim, Compass Pathways, Engrail Therapeutics, Neumora Therapeutics (formerly BlackThorn Therapeutics), Neurocrine Biosciences, Neuroscience Software, Otsuka, Sunovion, and Takeda; he has received honoraria from the Psychonomic Society (for editorial work) and from Alkermes; he has received research funding from the Brain and Behavior Research Foundation, the Dana Foundation, Millennium Pharmaceuticals, and NIMH; he has received stock options from Compass Pathways, Engrail Therapeutics, Neumora Therapeutics, and Neuroscience Software. No funding from these entities was used to support the current work, and all views expressed are solely those of the authors. The other authors have no conflicts of interest or relevant disclosures., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The ability to appropriately update the value of a given action is a critical component of flexible decision making. Several psychiatric disorders, including schizophrenia, are associated with impairments in flexible decision making that can be evaluated using the probabilistic reversal learning (PRL) task. The PRL task has been reverse-translated for use in rodents. Disrupting glutamate neurotransmission during early postnatal neurodevelopment in rodents has induced behavioral, cognitive, and neuropathophysiological abnormalities relevant to schizophrenia. Here, we tested the hypothesis that using the NMDA receptor antagonist phencyclidine (PCP) to disrupt postnatal glutamatergic transmission in rats would lead to impaired decision making in the PRL. Consistent with this hypothesis, compared to controls the postnatal PCP-treated rats completed fewer reversals and exhibited disruptions in reward and punishment sensitivity (i.e., win-stay and lose-shift responding, respectively). Moreover, computational analysis of behavior revealed that postnatal PCP-treatment resulted in a pronounced impairment in the learning rate throughout PRL testing. Finally, a deep neural network (DNN) trained on the rodent behavior could accurately predict the treatment group of subjects. These data demonstrate that disrupting early postnatal glutamatergic neurotransmission impairs flexible decision making and provides evidence that DNNs can be trained on behavioral datasets to accurately predict the treatment group of new subjects, highlighting the potential for DNNs to aid in the diagnosis of schizophrenia., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

The balance between exploration and exploitation is essential for decision-making. The present study investigated the role of ventromedial orbitofrontal cortex (vmOFC) glutamate neurons in mediating value-based decision-making by first using optogenetics to manipulate vmOFC glutamate activity in rats during a probabilistic reversal learning (PRL) task. Rats that received vmOFC activation during informative feedback completed fewer reversals and exhibited reduced reward sensitivity relative to rats. Analysis with a Q-learning computational model revealed that increased vmOFC activity did not affect the learning rate but instead promoted maladaptive exploration. By contrast, vmOFC inhibition increased the number of completed reversals and increased exploitative behavior. In a separate group of animals, calcium activity of vmOFC glutamate neurons was recorded using fiber photometry. Complementing our results above, we found that suppression of vmOFC activity during the latter part of rewarded trials was associated with improved PRL performance, greater win-stay responding and selecting the correct choice on the next trial. These data demonstrate that excessive vmOFC activity during reward feedback disrupted value-based decision-making by increasing the maladaptive exploration of lower-valued options. Our findings support the premise that pharmacological interventions that normalize aberrant vmOFC glutamate activity during reward feedback processing may attenuate deficits in value-based decision-making., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Social anxiety disorder (SAD) is common, first-line treatments are often only partially effective, and reliable predictors of treatment response are lacking. Here, we assessed resting state functional connectivity (rsFC) at pre-treatment and during early treatment as a potential predictor of response to a novel attention bias modification procedure, gaze-contingent music reward therapy (GC-MRT)., Methods: Thirty-two adults with SAD were treated with GC-MRT. rsFC was assessed with multi-voxel pattern analysis of fMRI at pre-treatment and after 2-3 weeks. For comparison, 20 healthy control (HC) participants without treatment were assessed twice for rsFC over the same time period. All SAD participants underwent clinical evaluation at pre-treatment, early-treatment (week 2-3), and post-treatment., Results: SAD and depressive symptoms improved significantly from pre-treatment to post-treatment. After 2-3 weeks of treatment, decreased connectivity between the executive control network (ECN) and salience network (SN), and increased connectivity within the ECN predicted improvement in SAD and depressive symptoms at week 8. Increased connectivity between the ECN and default mode network (DMN) predicted greater improvement in SAD but not depressive symptoms at week 8. Connectivity within the DMN decreased significantly after 2-3 weeks of treatment in the SAD group, while no changes were found in HC over the same time interval., Conclusion: We identified early changes in rsFC during a course of GC-MRT for SAD that predicted symptom change. Connectivity changes within the ECN, ECN-DMN, and ECN-SN may be related to mechanisms underlying the clinical effects of GC-MRT and warrant further study in controlled trials.

Healthy adults show better memory for low-arousal positive versus negative stimuli, but depression compromises this positive memory advantage. Existing studies are limited by small samples or analyses that provide limited insight into underlying mechanisms. Our study addresses these concerns by using a multistaged analysis, including diffusion modeling, to identify precise psychological processes underlying the positive memory advantage and its disruption by depression in a large sample. A total of 1,358 participants completed the BDI-II (Beck et al., 1996) and an emotional memory task. At encoding, participants judged whether positive and negative words were positive or self-descriptive. After a free recall test, participants viewed an equal mix of studied and unstudied words and judged whether each was "old" or "new"; if judged "old," they indicated whether the study source was a valence or self-reference judgment. We replicate the positive memory advantage and its decrease in depression in recall, recognition, and source accuracy. The hierarchical drift diffusion model (HDDM; Wiecki et al., 2013) revealed that higher BDI-II scores are associated with more efficient evidence accumulation for negative words in the recognition and source memory tasks. By contrast, evidence accumulation for positive words is unaffected by BDI-II during the recognition task but becomes less efficient with increased BDI-II during the source memory task. In conclusion, in a well-controlled design with a large sample, we find that depression reduces the positive memory advantage. HDDM analyses suggest that this reflects differential effects of depression on the speed of evidence accumulation during the retrieval of positive versus negative memories. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: A hyperactive default mode network (DMN) has been observed in people with major depressive disorder (MDD), and weak DMN suppression has been linked to depressive symptoms. However, whether dysregulation of the DMN contributes to blunted positive emotional experience in people with MDD is unclear., Methods: We recorded 128-channel electroencephalograms (EEGs) from 24 participants with MDD and 31 healthy controls in a resting state (RS) and an emotion-induction state (ES), in which participants engaged with emotionally positive pictures. We combined Granger causality analysis and data-driven decomposition to extract latent brain networks shared among states and groups, and we further evaluated their interactions across individuals., Results: We extracted 2 subnetworks. Subnetwork 1 represented a delta (δ)-band (1~4 Hz) frontal network that was activated more in the ES than the RS (i.e., task-positive). Subnetwork 2 represented an alpha (α)-band (8~13 Hz) parietal network that was suppressed more in the ES than the RS (i.e., task-negative). These subnetworks were anticorrelated in both the healthy control and MDD groups, but with different sensitivities: for participants with MDD to achieve the same level of task-positive (subnetwork 1) activation as healthy controls, more suppression of task-negative (subnetwork 2) activation was necessary. Furthermore, the anticorrelation strength in participants with MDD correlated with the severity of 2 core MDD symptoms: anhedonia and rumination., Limitations: The sample size was small., Conclusion: Our findings revealed altered coordination between 2 functional networks in MDD and suggest that weak suppression of the task-negative α-band parietal network contributes to blunted positive emotional responses in adults with depression. The subnetworks identified here could be used for diagnosis or targeted for treatment in the future., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

Although depression is associated with poor memory for positive material, the underlying mechanisms remain unclear. We used the Hierarchical Drift Diffusion Model (HDDM) to determine whether slow evidence accumulation at retrieval contributes to depressed individuals' difficulty remembering positive events. Participants completed the Beck Depression Inventory-II and were stratified into High BDI (HBDI; BDI-II > 20, n = 49) and Low BDI (LBDI; BDI-II < 6, n = 46) groups. Next, participants completed an oddball task in which neutral, negative, and positive pictures served as rare targets. One day later, recognition memory was tested by presenting the encoded ("old") pictures along with closely matched ("new") lures. Recognition accuracy was analyzed with a generalized linear model, and choice and response time data were analyzed with the HDDM. Recognition accuracy for old positive pictures was lower in HBDI versus LBDI participants, and the HDDM highlighted slow evidence accumulation during positive memory retrieval in the HBDI group. Impaired memory for positive material in depressed adults was related to slow evidence accumulation at retrieval. Because oddballs should elicit prediction errors that normally strengthen memory formation, these retrieval findings may reflect weak positive prediction errors, at encoding, in depressed adults., (© 2022. The Psychonomic Society, Inc.)

Option generation is a critical process in decision making, but previous studies have largely focused on choices between options given by a researcher. Consequently, how we self-generate options for behaviour remain poorly understood. Here, we investigated option generation in major depressive disorder and how dopamine might modulate this process, as well as the effects of modafinil (a putative cognitive enhancer) on option generation in healthy individuals. We first compared differences in self-generated options between healthy non-depressed adults [n = 44, age = 26.3 years (SD 5.9)] and patients with major depressive disorder [n = 54, age = 24.8 years (SD 7.4)]. In the second study, a subset of depressed individuals [n = 22, age = 25.6 years (SD 7.8)] underwent PET scans with 11C-raclopride to examine the relationships between dopamine D2/D3 receptor availability and individual differences in option generation. Finally, a randomized, double-blind, placebo-controlled, three-way crossover study of modafinil (100 mg and 200 mg), was conducted in an independent sample of healthy people [n = 19, age = 23.2 years (SD 4.8)] to compare option generation under different doses of this drug. The first study revealed that patients with major depressive disorder produced significantly fewer options [t(96) = 2.68, P = 0.009, Cohen's d = 0.54], albeit with greater uniqueness [t(96) = -2.54, P = 0.01, Cohen's d = 0.52], on the option generation task compared to healthy controls. In the second study, we found that 11C-raclopride binding potential in the putamen was negatively correlated with fluency (r = -0.69, P = 0.001) but positively associated with uniqueness (r = 0.59, P = 0.007). Hence, depressed individuals with higher densities of unoccupied putamen D2/D3 receptors in the putamen generated fewer but more unique options, whereas patients with lower D2/D3 receptor availability were likely to produce a larger number of similar options. Finally, healthy participants were less unique [F(2,36) = 3.32, P = 0.048, partial η2 = 0.16] and diverse [F(2,36) = 4.31, P = 0.021, partial η2 = 0.19] after taking 200 mg versus 100 mg and 0 mg of modafinil, while fluency increased linearly with dosage at a trend level [F(1,18) = 4.11, P = 0.058, partial η2 = 0.19]. Our results show, for the first time, that option generation is affected in clinical depression and that dopaminergic activity in the putamen of patients with major depressive disorder may play a key role in the self-generation of options. Modafinil was also found to influence option generation in healthy people by reducing the creativity of options produced., (© The Author(s) (2022). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The brain circuitry of depression and anxiety/fear is well-established, involving regions such as the limbic system and prefrontal cortex. We expand prior literature by examining the extent to which four discrete factors of anxiety (immediate state anxiety, physiological/panic, neuroticism/worry, and agitation/restlessness) among depressed outpatients are associated with differential responses during reactivity to and regulation of emotional conflict., Methods: A total of 172 subjects diagnosed with major depressive disorder underwent functional magnetic resonance imaging while performing an Emotional Stroop Task. Two main contrasts were examined using whole brain voxel wise analyses: emotional reactivity and emotion regulation. We also evaluated the association of these contrasts with the four aforementioned anxiety factors., Results: During emotional reactivity, participants with higher immediate state anxiety showed potentiated activation in the rolandic operculum and insula, while individuals with higher levels of physiological/panic demonstrated decreased activation in the posterior cingulate. No significant results emerged for any of the four factors on emotion regulation. When re-analyzing these statistically-significant brain regions through analyses of a subsample with (n = 92) and without (n = 80) a current anxiety disorder, no significant associations occurred among those without an anxiety disorder. Among those with an anxiety disorder, results were similar to the full sample, except the posterior cingulate was associated with the neuroticism/worry factor., Conclusions: Divergent patterns of task-related brain activation across four discrete anxiety factors could be used to inform treatment decisions and target specific aspects of anxiety that involve intrinsic processing to attenuate overactive responses to emotional stimuli., (Copyright © 2022. Published by Elsevier Ltd.)