A meta-analysis of electrophysiological biomarkers of reward and error monitoring in substance misuse.

Substance use disorders are characterized by marked changes in reward and error processing. The primary objective of this meta-analysis was to estimate effect sizes for the reward positivity (RewP) and error-related negativity (ERN), two event-related potential indicators of outcome monitoring, in substance users compared to controls. The secondary objective was to test for moderation by demographic, substance type, and EEG experiment parameters. Final PubMed searches were performed in August 2023. Inclusion criteria were substance use disorder/dependence or validated self-report of substance misuse, RewP/ERN means available, healthy control comparison group, non-acute drug study, peer-reviewed journal, English language, and human participants. Selection bias was tested through modified Egger's regression and exploratory 3-parameter selection model tests. The RewP results (19 studies, 1641 participants) did not support an overall effect (Hedges' g = 0.07, 95% CI [-0.44, 0.58], p = .777) and nor effect of any moderators. The ERN results (20 studies, 1022 participants) indicated no significant overall effect (g = 0.41, 95%CI [-0.05, 0.88]). Subgroup analyses indicated that cocaine users had a blunted ERN compared to controls (g = 1.12, 95%CI [0.77, 1.47]). There was limited evidence for publication/small study bias. Although the results indicate a potential dissociation between substance types, this meta-analysis revealed the need for additional research on the RewP/ERN in substance using populations and for better designed experiments that adequately address research questions.

Alterations in brain synaptic proteins and mRNAs in mood disorders: a systematic review and meta-analysis of postmortem brain studies.

The pathophysiological mechanisms underlying bipolar (BD) and major depressive disorders (MDD) are multifactorial but likely involve synaptic dysfunction and dysregulation. There are multiple synaptic proteins but three synaptic proteins, namely SNAP-25, PSD-95, and synaptophysin, have been widely studied for their role in synaptic function in human brain postmortem studies in BD and MDD. These studies have yielded contradictory results, possibly due to the small sample size and sourcing material from different cortical regions of the brain. We performed a systematic review and meta-analysis to understand the role of these three synaptic proteins and other synaptic proteins, messenger RNA (mRNA) and their regional localizations in BD and MDD. A systematic literature search was conducted and the review is reported in accordance with the MOOSE Guidelines. Meta-analysis was performed to compare synaptic marker levels between BD/MDD groups and controls separately. 1811 papers were identified in the literature search and screened against the preset inclusion and exclusion criteria. A total of 72 studies were screened in the full text, of which 47 were identified as eligible to be included in the systematic review. 24 of these 47 papers were included in the meta-analysis. The meta-analysis indicated that SNAP-25 protein levels were significantly lower in BD. On average, PSD-95 mRNA levels were lower in BD, and protein levels of SNAP-25, PSD-95, and syntaxin were lower in MDD. Localization analysis showed decreased levels of PSD-95 protein in the frontal cortex. We found specific alterations in synaptic proteins and RNAs in both BD and MDD. The review was prospectively registered online in PROSPERO international prospective register of systematic reviews, registration no. CRD42020196932.

The Association between Potentially Traumatic Events and Cocaine, Cannabis, and Alcohol Use Differs by Race.

Background: Although exposure to potentially traumatic events (PTEs) for Black and Latinx may be comparable or lower than their White counterparts, type of trauma experiences differ such as more interpersonal trauma and violence reported by Black people, who also experience higher rates of PTSD. In this retrospective study, we examined the association between use of particular substances and various PTEs and the race/ethnicity-group differences for this association. Methods: One-hundred seventy-nine participants recruited from an outpatient substance use disorder program from February 2018 to October 2020 completed measures on lifetime trauma history and current/past cocaine, cannabis, and alcohol misuse. Bayesian generalized linear modeling with horseshoe prior was used to predict substance misuse using 17 PTEs, then PTEs were ranked and examined by racial/ethnic group. Results: No PTEs were associated with substance misuse across all four r/e groups. Transportation accident, natural disaster, war exposure, and other stressful events were associated with substance misuse across two or three r/e groups. Notably, the three PTEs involving interpersonal violence in our study (weapon assault, physical assault, and sexual assault) were only associated with substance misuse (posterior probability ≥70%) for Latinx participants. Conclusion: The relational nature of interpersonal/violent traumas may make them particularly salient for Latinx people where interpersonal relationships are prioritized. These types of traumas may also be viewed as an extension of discrimination and exclusion, two longstanding, intractable issues for people of color in the US, making them even more damaging. Furthermore, lack of resources may limit options for coping, resulting in substance use problems.

Initial development of a brief assessment of cocaine demand.

Cocaine demand is a behavioral economic measure assessing drug reward value and motivation to use drug. The purpose of the current study was to develop a brief assessment of cocaine demand (BACD). Results from the BACD were compared with self-report measures of cocaine use. Participants consisted of treatment-seeking individuals with cocaine use disorder (N = 22). Results revealed that indices of brief demand were significantly associated with various self-report measures of cocaine use. Overall, these results support the utility of a BACD for assessing cocaine demand.

Exenatide Adjunct to Nicotine Patch Facilitates Smoking Cessation and May Reduce Post-Cessation Weight Gain: A Pilot Randomized Controlled Trial.

INTRODUCTION: Approved pharmacological treatments for smoking cessation are modestly effective, underscoring the need for improved pharmacotherapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate the rewarding effects of nicotine in preclinical studies. We examined the efficacy of extended-release exenatide, a GLP-1R agonist, combined with nicotine replacement therapy (NRT, patch) for smoking cessation, craving, and withdrawal symptoms, with post-cessation body weight as a secondary outcome. METHODS: Eighty-four prediabetic and/or overweight smokers were randomized (1 : 1) to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received NRT (21 mg) and brief smoking cessation counseling. Seven-day point prevalence abstinence (expired CO level ≤5 ppm), craving, withdrawal, and post-cessation body weight were assessed following 6 weeks of treatment. A Bayesian approach for analyzing generalized linear models yielded posterior probabilities (PP) to quantify the evidence favoring hypothesized effects of treatment on the study outcomes. RESULTS: Exenatide increased the risk for smoking abstinence compared to placebo (46.3% and 26.8%, respectively), (risk ratio [RR] = 1.70; 95% credible interval = [0.96, 3.27]; PP = 96.5%). Exenatide reduced end-of-treatment craving in the overall sample and withdrawal among abstainers. Post-cessation body weight was 5.6 pounds lower in the exenatide group compared to placebo (PP = 97.4%). Adverse events were reported in 9.5% and 2.3% of participants in the exenatide and placebo groups, respectively. CONCLUSIONS: Exenatide, in combination with the NRT improved smoking abstinence, reduced craving and withdrawal symptoms, and decreased weight gain among abstainers. Findings suggest that the GLP-1R agonist strategy is worthy of further research in larger, longer duration studies. IMPLICATIONS: Despite considerable progress in tobacco control, cigarette smoking remains the leading cause of preventable disease, disability, and death. In this pilot study, we showed that extended-release exenatide, a glucagon-like peptide-1 receptor agonist, added to the nicotine patch, improved abstinence and mitigated post-cessation body weight gain compared to patch alone. Further research is needed to confirm these initial positive results.

Opioid Risk Tool, in-hospital opioid exposure, and opioid demand predict pain outcomes following traumatic injury.

Prescribed opioids are a mainstay pain treatment after traumatic injury, but a subgroup of patients may be at risk for continued opioid use. We evaluated the predictive utility of a traditional screening tool, the Opioid Risk Tool (ORT), and two other measures: average in-hospital milligram morphine equivalents (MME) per day and an assessment of opioid demand in predicting pain outcomes. Assessments of pain-related outcomes (pain intensity, interference, injury-related stress, and need for additional pain treatment) were administered at 2 weeks and 12 months post-discharge in a sample of 34 patients hospitalized for traumatic injury. Bayesian linear models were used to evaluate changes in responses over time as a function of predictors. High-risk ORT, higher MME per day, and greater opioid demand predicted less change in outcomes over time. This report provides first evidence that malleable factors of opioid and opioid demand have utility in predicting pain outcomes following traumatic injury.

Safety of multiple intravenous infusions of adipose-derived mesenchymal stem cells for hospitalized cases of COVID-19: a randomized controlled trial.

Objective: The purpose of the study was to assess the safety of allogeneic, Hope Biosciences Adipose Derived Mesenchymal Stem Cells (HB-adMSCs) for the treatment of hospitalized subjects with COVID-19. Methods: N = 48 patients were randomly assigned to HB-adMSC (100 MM) or placebo group. Four intravenous infusions of HB-adMSCs or saline were administered at days 0, 3, 7, 10. The primary safety endpoint was incidence of adverse and serious adverse events (AE/SAEs); secondary endpoints were incidence of specific AEs and alterations in hematology, biochemistry, and coagulation parameters. Results: Majority of AEs were mild in severity. HB-adMSC group showed a higher incidence of cardiopulmonary failure, anemia, anxiety, and diarrhea, while placebo group showed a higher incidence of headaches, fatigue, and chest discomfort (posterior probabilities ≥80%). Deaths were attributed to severe complications due to COVID-19 and were unrelated to study drug. No AEs were attributed to the treatment. Hematology and coagulation panel alterations were not associated with HB-adMSCs. Analyses of inflammatory markers showed increased levels of interleukin-6 and C-reactive protein over time in HB-adMSC group (posterior probabilities ≥78%). Conclusion: Multiple infusions of 100MM allogeneic HB-adMSCs were considered safe for the study population. More research is needed to determine the safety of MSC therapy. Clinical trial registration: (www.ClinicalTrials.gov) identifier NCT04362189.

Types of Traumatic Experiences in Drug Overdose-Related Deaths: An Exploratory Latent Class Analysis.

Aim: Drug overdose related-deaths in the US are increasing, with over 100,000 deaths occurring in 2020, an increase of 30% from the previous year and the highest number recorded in a single year. It is widely known that experiences of trauma and substance use very often co-occur, but little is known about the role of trauma in the context of drug overdose-related deaths. Latent class analysis (LCA) was used to classify drug overdose-related deaths based on type of traumatic experiences and individual, social, and substance use characteristics. Methods: Psychological autopsy data were obtained from the University of Texas Health Science Center at Houston (UTHealth) Brain Collection. A total of 31 drug overdose-related deaths collected from January 2016 through March 2022 were included in this study. LCA was used to identify latent factors via experience of four trauma categories (illness/accidents, sexual/interpersonal violence, death/trauma to another, other situations where life was in danger). Generalized linear modeling (GLM) was used to explore differences on demographic, social, substance use, and psychiatric variables between the latent classes in separate models. Results: LCA identified 2 classes: C1 ( n =12; 39%) was characterized by higher incidence of overall trauma exposure as well as variation in trauma type; C2 ( n =19; 61%) had lower levels of overall trauma exposure with sexual/interpersonal violence as the most frequent. GLMs indicated that C1 membership was associated with higher incidence of polysubstance use, being married, and having suicidal ideation compared to C2 membership ( p s<0.05). Conclusion: Among individuals who died by drug overdose, the exploratory LCA identified two distinct subgroups that differed in type of trauma experienced and substance use pattern, the first group having more "typical" characteristics of drug overdoses cases, the other group less typical. This suggests that those at risk of drug overdose may not always exhibit high-risk characteristics.

Assessing cocaine motivational value: Comparison of brain reactivity bias toward cocaine cues and cocaine demand.

The behavioral economic measure drug demand and the neural measure late positive potential (LPP) are two measures of motivational value that have been associated with drug relapse risk and treatment outcomes. Despite having overlapping themes, no studies have directly compared drug demand and LPP. Participants (N = 59) included treatment-seeking individuals with cocaine use disorder that had completed both a baseline cocaine demand task and an electroencephalogram (EEG) picture-viewing task of drug-related and pleasant picture cues. Associations between the LPP difference score amplitude (drug-pleasant) and five demand indices (Q0, essential value [EV], Omax, Pmax, and breakpoint [BP]) were evaluated via Bayesian generalized linear modeling. Positive associations (posterior probabilities ≥ 75%) were found between LPP amplitude and four demand indices (Q0, EV, Omax, BP). These results suggest that individuals who attach greater relevance to cocaine cues also exhibit greater valuation of cocaine reward. Implications for incorporating methodology from behavioral science and brain imaging are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

An opioid-minimizing multimodal pain regimen reduces opioid exposure and pain in trauma-injured patients at high risk for opioid misuse: Secondary analysis from the mast trial.

BACKGROUND: Screening to identify patients at risk for opioid misuse after trauma is recommended but not commonly used to guide perioperative opioid management interventions. The Multimodal Analgesic Strategies for Trauma trial demonstrated that an opioid-minimizing multimodal pain regimen reduced opioid exposure in a heterogeneous trauma patient population. Here, we assess the efficacy of the Multimodal Analgesic Strategies for Trauma multimodal pain regimen in a critical patient subgroup who screened at high risk for opioid misuse. METHODS: The Multimodal Analgesic Strategies for Trauma trial compared an opioid-minimizing multimodal pain regimen (oral acetaminophen, naproxen, gabapentin, lidocaine patch, as-needed opioid) against an original multimodal pain regimen (intravenous followed by oral acetaminophen, 48-hour celecoxib and pregabalin, followed by naproxen and gabapentin, scheduled tramadol, as-needed opioid), in a randomized trial conducted from April 2018 to March 2019. A total of 631 enrolled patients were classified either as low- or high-risk via the Opioid Risk Tool. Bayesian analyses evaluated the moderating influence of Opioid Risk Tool risk (high/low) on the effect of Multimodal Analgesic Strategies for Trauma multimodal pain regimen (versus original) on opioid exposure (morphine milligram equivalents/day), opioids prescribed at discharge, and pain scores. RESULTS: Multimodal Analgesic Strategies for Trauma multimodal pain regimen effectively reduced morphine milligram equivalents/day in low- and high-Opioid Risk Tool risk groups. Moderation was observed for opioids at discharge and pain scores; Multimodal Analgesic Strategies for Trauma multimodal pain regimen was effective in the high-risk group only (opioids at discharge: 63% vs 77%, relative risk = 0.86, 95% Bayesian credible interval [0.66-1.08], posterior probability (relative risk <1) = 90%; pain scores: b = 3.8, 95% Bayesian credible interval [3.2-4.4] vs b = 4.0, 95% Bayesian credible interval [3.4-4.6], posterior probability (b <0) = 87%). CONCLUSION: This study is the first to show the moderating influence of opioid misuse risk on the effectiveness of an opioid-minimizing multimodal pain regimen. The Opioid Risk Tool was useful in identifying high-risk patients for whom the Multimodal Analgesic Strategies for Trauma multimodal pain regimen is recommended for perioperative pain management.

Electrophysiological responses to emotional and cocaine cues reveal individual neuroaffective profiles in cocaine users.

Smokers with stronger neuroaffective responses to drug-related cues compared to nondrug-related pleasant images (C > P) are more vulnerable to compulsive smoking than individuals with the opposite brain reactivity profile (P > C). However, it is unknown if these neurobehavioral profiles exist in individuals abusing other drugs. We tested whether individuals with cocaine use disorder (CUD) show similar neuroaffective profiles to smokers. We also monitored eye movements to assess attentional bias toward cues and we further performed exploratory analyses on demographics, personality, and drug use between profiles. Participants with CUD (n = 43) viewed pleasant, unpleasant, cocaine, and neutral images while we recorded electroencephalogram. For each picture category, we computed the amplitude of the late positive potential (LPP), an event-related potential component that reflects motivational relevance. k-means clustering classified participants based on their LPP responses. In line with what has been observed in smokers, clustering participants using LPP responses revealed the presence of two groups: one with larger LPPs to pleasant images compared to cocaine images (P > C) and one group with larger LPPs to cocaine images compared to pleasant images (C > P). Individuals with the C > P reactivity profile also had higher attentional bias toward drug cues. The two groups did not differ on demographic and drug use characteristics, however individuals with the C > P profile reported lower distress tolerance, higher anhedonia, and higher posttraumatic stress symptoms compared to the P > C group. This is the first study to report the presence of these neuroaffective profiles in individuals with CUD, indicating that this pattern may cut across addiction populations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Late positive potential as a candidate biomarker of motivational relevance in substance use: Evidence from a meta-analysis.

The objective of the current meta-analysis was to assess the effect size of the Late Positive Potential (LPP) to drug and emotional cues in substance users compared to controls. The secondary objective was to test for moderation by: age, gender, years of use, use status, and substance type. Search was performed in August 2021 using PubMed. Inclusion criteria were: substance use disorder/dependence or validated self-report, LPP means, healthy control comparison, non-acute drug study, data available, peer-reviewed journal, English, and human participants. Selection bias was tested through modified Egger's regression and exploratory 3-parameter selection model tests. Results (k = 11) indicated LPP to drug cues was larger in substance use compared to control group, with a large effect size (Hedges' g=1.66, 95%CI [0.64,2.67], p = 0.005). There were no overall differences for emotional cues. Though threats of selection bias were not severe, inclusion of more studies with larger sample sizes in future meta-analyses will allow more robust tests of publication bias and more accurate measures of effect size.

Experience Affects EEG Event-Related Synchronization in Dancers and Non-dancers While Listening to Preferred Music.

EEGs were analyzed to investigate the effect of experiences in listening to preferred music in dancers and non-dancers. Participants passively listened to instrumental music of their preferred genre for 2 min (Argentine tango for dancers, classical, or jazz for non-dancers), alternate genres, and silence. Both groups showed increased activity for their preferred music compared to non-preferred music in the gamma, beta, and alpha frequency bands. The results suggest all participants' conscious recognition of and affective responses to their familiar music (gamma), appreciation of the tempo embedded in their preferred music and emotional arousal (beta), and enhanced attention mechanism for cognitive operations such as memory retrieval (alpha). The observed alpha activity is considered in the framework of the alpha functional inhibition hypothesis, in that years of experience listening to their favorite type of music may have honed the cerebral responses to achieve efficient cortical processes. Analyses of the electroencephalogram (EEG) activity over 100s-long music pieces revealed a difference between dancers and non-dancers in the magnitude of an initial alpha event-related desynchronization (ERD) and the later development of an alpha event-related synchronization (ERS) for their preferred music. Dancers exhibited augmented alpha ERD, as well as augmented and uninterrupted alpha ERS over the remaining 80s. This augmentation in dancers is hypothesized to be derived from creative cognition or motor imagery operations developed through their dance experiences.

Citalopram for treatment of cocaine use disorder: A Bayesian drop-the-loser randomized clinical trial.

BACKGROUND: Medication development research for cocaine use disorder (CUD) has been a longstanding goal in addiction research, but has not resulted in an FDA-approved treatment. Rising cocaine use rates underscore the need for efficient adaptive designs. This study compared differences between two doses of the selective serotonin reuptake inhibitor (SSRI) citalopram (versus placebo) on duration of cocaine abstinence and applied adaptive decision rules to select the 'best efficacy' dose. METHODS: A double-blind, placebo-controlled, randomized Bayesian drop-the-loser (DTL) trial with three arms compared placebo to citalopram 20 mg and 40 mg. Adults (N = 107) with CUD attended thrice-weekly clinic visits for 9 weeks. The primary outcome was longest duration of abstinence (LDA), based on continuous cocaine-negative urine drug screens (UDS). The secondary outcome was probability of cocaine-negative UDS during treatment. A planned interim analysis performed at approximately 50% of recruitment dropped the least-effective active medication. Bayesian inference was used for all analyses with a pre-specified posterior probability (PP) threshold PP ≥ 95% considered statistically reliable evidence RESULTS: Citalopram 40 mg satisfied interim efficacy criteria and was retained for the second half of the trial. For LDA, analyses indicated PP = 82% and PP = 65% of benefit for 40 mg and 20 mg, respectively (each relative to placebo). The odds of having cocaine-negative UDS decreased in all groups over 9 weeks but remained higher for 40 mg (PP = 97.4%) CONCLUSIONS: Neither dose met the 95% PP threshold for the primary outcome; however, 40 mg provided moderate-to-strong evidence for positive effects on LDA and cocaine-negative UDS. The 40 mg dose was declared the "winner" in this DTL trial.

Prescription fill patterns for benzodiazepine and opioid drugs during the COVID-19 pandemic in the United States.

BACKGROUND: COVID-19 and resulting mitigation measures in the United States (US) brought about limited access to medical care that has been linked to increases in mental health problems, excessive substance use, and drug overdoses. The increase in co-prescription of benzodiazepines and opioids may indicate population-level changes in health behaviors that can be exacerbated by limited access, hence necessitating the tracking of these drugs during COVID-19. We evaluated the impact of the declaration of COVID-19 as a US national emergency on prescription patterns in 2020. METHODS: Prescriptions of benzodiazepines and opioids were analyzed using data aggregated on a weekly basis across 38 states over the January 2019-December 2020 period. Data were from Bamboo Health Prescription Drug Monitoring Program and covered all individuals regardless of insurance status. Generalized additive models estimated the effects of the March 13, 2020 declaration on proportion of prescriptions to all controlled substances by comparing volumes before to after the week of March 13 in 2020 (range: January 27-May 24) and comparing this trend to its 2019 counterpart. RESULTS: When comparing the January 27-March 9 period to the March 16-May 24 period in 2020, there was a statistically significant 2.0% increase in the proportion of benzodiazepine dispensations to all controlled substances, and a significant 1.7% mean decrease in proportion of opioid dispensations to all controlled substances. A significant return approaching pre-declaration levels was observed only for opioids (beginning week of May 18, 2020). CONCLUSIONS: The results suggest significant impacts of the COVID-19 pandemic on dispensations of benzodiazepines and opioids across the US. Continued monitoring of prescription trends and maintenance of adequate and accessible access to mental healthcare are important for understanding public health crises related to substance use.

Decreased cocaine demand following contingency management treatment.

A hypothetical cocaine purchasing task (CocPT) was used to assess changes in cocaine demand in the context of contingency management (CM) treatment for cocaine use disorder (CUD). Participants (N = 89) were treatment-seeking individuals with CUD receiving 4 weeks of abstinence-based, high-magnitude CM. Treatment response (vs. non-response) was operationally defined as the submission of 6 consecutive cocaine-negative urine samples across two weeks. The CPT was assessed at baseline, week 2, and week 5. Demand data were well described by the exponentiated demand model, and baseline demand indices (Q0, Pmax, breakpoint, essential value) were significantly associated with self-report measures of cocaine use. The probability of being a zero-responder reporting zero cocaine consumption at all prices significantly increased over the course of treatment, and was greater among treatment responders vs. non-responders. Among non-zero demand data, decreases in Omax, Pmax, breakpoint, and essential value were observed over the course of CM treatment, favoring responders. To our knowledge, this is the first study to assess change in cocaine demand in the context of CM treatment targeting cocaine abstinence. Our results support the utility of cocaine demand as a measure for both identifying individuals with greater treatment need and tracking relapse risk over the course of treatment.

Cocaine-specific speed-accuracy trade-off during anti-saccade testing differentiates patients with cocaine use disorder who achieve initial abstinence during treatment.

BACKGROUND: The response time speed-accuracy trade-off (SATO) is an established index of information processing ability, but rarely examined as a variable in association with treatment of substance use disorder (SUD). AIM: The purpose of this study was to test baseline information-processing ability differences between individuals who respond to treatment for cocaine use disorder v. those who do not. METHODS: Eighty patients enrolled in a clinical trial for cocaine use disorder completed a baseline drug-specific eye-tracking (anti-saccade) assessment prior to treatment, which included trials with both cocaine-related and neutral stimuli. SATO functions were computed for treatment responders v. non-responders. RESULTS: Unexpectedly, responders demonstrated statistically different SATO functions, showing poorer accuracy when executing faster response times. This difference was present on trials that presented cocaine stimuli only. CONCLUSIONS: SATO during performance of an eye-movement task may be useful for predicting differential response to substance use disorder treatment. However, in the present study, results were specific to cocaine cues rather than an overall SATO performance decrement.

Revisiting monoamine oxidase inhibitors for the treatment of depressive disorders: A systematic review and network meta-analysis.

BACKGROUND: Monoamine oxidase inhibitors (MAOIs) were the first class of modern antidepressants; however, they are under-utilized as compared to the newer antidepressants. METHODS: In this systematic review, network meta-analysis was used to investigate the comparative efficacy and acceptability of MAOIs for depressive disorders. Overall, the network meta-analysis included 52 double-blind, randomized controlled trials (RCTs) that compared 14 antidepressants or placebo. Across studies, the mean arm size was n = 58 participants from a total N = 6462 (5309 active drug; 1153 placebo). RESULTS: Except fluvoxamine, all antidepressants demonstrated superior efficacy to placebo, and none demonstrated substantially better or worse all-cause dropout rates. Phenelzine demonstrated superior evidence for efficacy compared to all other treatments, and clomipramine demonstrated superior evidence for acceptability compared to all other treatments. LIMITATIONS: The study is primarily limited by low estimate precision due to a relative paucity of studies for some of the included treatment conditions. Further evidence is required to study the relative efficacy of MAOIs against newer antidepressants. CONCLUSIONS: The results of this analysis largely support the re-evaluation of the use of MAOIs as antidepressant agents in the treatment algorithm of depression.

Effect of immune activation on the kynurenine pathway and depression symptoms - A systematic review and meta-analysis.

Dysregulated kynurenine (KYN) pathway has been implicated in the pathophysiology of depression. In this systematic review, we examined the relationship between kynurenine pathway metabolites (KYN, kynurenic acid KYNA, tryptophan TRP, quinolinic acid QUIN, KYN/TRP ratio) and depression symptoms in the context of pro-inflammatory activation and immune response. Out of 5,082 articles, fifteen studies were suitable; ten studies (N = 315 medically ill patients treated with interferon-alpha IFN-α) reported baseline and post-intervention plasma KYN, TRP and KYN/TRP ratios which were included in quantitative meta-analysis. Data from five studies were summarized (IFN-α, interferon-beta IFN-ß, and lipopolysaccharide LPS). We found that IFN-α treatment in patients with chronic illnesses was associated with decreased TRP, increased levels of KYN and KYN/TRP ratio and depression scores from baseline to follow-up at both 4 and 24 weeks. Our findings suggest that increased risk of depression observed after immune-activating agents in patients with chronic medical illnesses is likely mediated by the kynurenine pathway. Further prospective studies are required to investigate the exact pathophysiology of the KYN pathway in depression.

The role of the neural reward system in attention selection.

The prefrontal cortex may play a role in attention selection using motivational information from the mesotelencephalic dopamine system, a neural system that responds to reward prediction violations. If so, neural indices of attention selection and reward prediction violation should have overlapping spatiotemporal distributions. Attention selection elicits a frontal event-related potential component around 200-300 ms, the frontal selection positivity. A component with similar spatiotemporal characteristics, the reward positivity is elicited in reward prediction designs to outcomes that are better than expected. The current study used dense sensor array recording in a sample of 41 participants performing visual oddball (attention) and a reward prediction 'slot machine-like' design to compare the spatiotemporal distributions of the frontal selection positivity and the reward positivity. The components did not differ in their peak latencies and had overlapping scalp topographies, supporting the hypothesis that these positivities represent attachment of incentive salience to perceptual representations in the prefrontal cortex.