Emotion Regulation Flexibility (ERF) is defined as an individual's ability to adaptively respond to changing situations and goals. Deficits in the adaptiveness of ERF have been linked to depression, suggesting a critical relationship between emotional processing and mental health. The objective of the present study was to investigate how variations in situational and goal-related contexts influence the association between ERF adaptiveness and depression. We employed functional magnetic resonance imaging (fMRI) and behavioral tasks to explore this relationship. Participants completed tasks designed to provoke changing situations and changing goals, while fMRI captured neural activity. Our findings revealed a significant negative correlation between depression scores and ERF adaptiveness. Specifically, during changing-situations, activation was observed in temporal and limbic regions, while changing-goals engaged prefrontal and parietal regions. Correlation analyses indicated that the adaptiveness of ERF was supported by distinct neural contributions: the temporoparietal junction (TPJ) in the changing-situations condition and the dorsolateral prefrontal cortex (dlPFC) in the changing-goals condition. Furthermore, the functional coupling between the dlPFC and the ventromedial prefrontal cortex (vmPFC) mediated the relationship between ERF adaptiveness and depression during changing-goals, but not during changing-situations. These findings elucidate the neural mechanisms of ERF adaptiveness and its implications for understanding and addressing depression.

A recent neurodevelopmental rat model, utilizing lactational exposure to polyriboinosinic-polyribocytidilic acid (Poly I:C) leads to mimics of behavioral phenotypes resembling schizophrenia-like symptoms in male offspring and depression-like symptoms in female offspring.

To identify mechanisms of neuronal abnormalities in lactational Poly I:C offspring using quantitative MRI (qMRI) tools.

Prospective.

Twenty Poly I:C rats and 20 healthy control rats, age 130 postnatal day.

7 T. Multiflip-angle FLASH protocol for T1 mapping; multi-echo spin-echo T2-mapping protocol; echo planar imaging protocol for diffusion tensor imaging.

Nursing dams were injected with the viral mimic Poly I:C or saline (control group). In adulthood, quantitative maps of T1, T2, proton density, and five diffusion metrics were generated for the offsprings. Seven regions of interest (ROIs) were segmented, followed by extracting 10 quantitative features for each ROI.

Random forest machine learning (ML) tool was employed to identify MRI markers of disease and classify Poly I:C rats from healthy controls based on quantitative features.

Poly I:C rats were identified from controls with an accuracy of 82.5 ± 25.9% for females and 85.0 ± 24.0% for males. Poly I:C females exhibited differences mainly in diffusion-derived parameters in the thalamus and the medial prefrontal cortex (MPFC), while males displayed changes primarily in diffusion-derived parameters in the corpus callosum and MPFC.

qMRI shows potential for identifying sex-specific brain abnormalities in the Poly I:C model of neurodevelopmental disorders.

NA TECHNICAL EFFICACY: Stage 2.

Non-suicidal self-injury (NSSI) is a prevalent mental problem among children and adolescents, cutting across psychiatric disorders. Studies in specific disorders such as depression and ADHD have revealed associations with alterations in brain regions responsible for reward processing and emotion regulation. However, it remains largely unknown whether such associations are shared among different disorders. Here, we aimed to examine brain structural and functional associations with NSSI in a transdiagnostic psychiatric cohort of children and adolescents. A total of 386 patients (age = 10.72 ± 3.53, range = 5.04 to 21.22) diagnosed primarily with ADHD, autism and generalized anxiety disorder from the Healthy Brain Network study were included. Using linear regression models, we examined brain volumes (N = 386) and functional connectivities (N = 277) associated with NSSI and whether potential alterations could moderate/mediate the links between internalizing/externalizing symptoms and NSSI. We found that increased severity of NSSI was associated with decreased bilateral putamen volumes, and reduced connectivities of the left putamen with bilateral regions of temporoparietal junction and of the right putamen with the left temporoparietal junction, demonstrating the role of putamen in NSSI behavior. Moreover, some of these associations played moderating roles: in patients with lower putamen volumes or weaker functional connectivities, increased internalizing/externalizing symptoms were associated with higher NSSI severity. Our findings suggest that transdiagnostic NSSI is linked to structural alterations and functional dysfunctions in putamen, highlighting that putamen may serve as a neural marker of NSSI and as a potential target for neuromodulation treatments across mental conditions.

Depression has been postulated to relate to alterations in both anticipatory (i.e., motivation) and consummatory (i.e., hedonic pleasure) stages of reward processing. However, few studies have concurrently examined the various processes of these stages. Furthermore, little attention has been paid to whether these associations are sex-specific, despite increasing evidence of the sex specificity of neural markers of internalizing disorders. The current study examines event-related potentials (ERPs) of reward processing recorded during a monetary incentive delay task among a community sample of n = 309 emerging adults in relation to self-reported symptoms of depression. Regression modeling indicated that greater depressive symptom scores were associated with reduced responsivity to reward feedback and increased responsivity to non-reward feedback (as indexed by the Feedback-P3) but only for participants who were identified as female at birth. Individual differences in anticipatory processes (as indexed by both the Cue-P3 and CNV) were not associated with depressive symptoms for either sex. Results of these models suggest that depressive symptoms appear to be associated with consummatory reward processing for young women. It is possible that other dimensions of negative affect could be more poignant for male participants or may provide an additional description of the relationship between reward processing and depressive symptoms.

One of the primary challenges in metabolic psychiatry is that the disrupted brain functions that underlie psychiatric conditions arise from a complex set of downstream and feedback processes that span multiple spatiotemporal scales. Importantly, the same circuit can have multiple points of failure, each of which results in a different type of dysregulation, and thus elicits distinct cascades downstream that produce divergent signs and symptoms. Here, we illustrate this challenge by examining how subtle differences in circuit perturbations can lead to divergent clinical outcomes. We also discuss how computational models can perform the spatially heterogeneous integration and bridge in vitro and in vivo paradigms. By leveraging recent methodological advances and tools, computational models can integrate relevant processes across scales (e.g., tricarboxylic acid cycle, ion channel, neural microassembly, whole-brain macrocircuit) and across physiological systems (e.g., neural, endocrine, immune, vascular), providing a framework that can unite these mechanistic processes in a manner that goes beyond the conceptual and descriptive to the quantitative and generative. These hold the potential to sharpen our intuitions toward circuit-based models for personalized diagnostics and treatment.

We aimed to review clinical research on the safety profiles of antidepressant drugs and associations with maternal depression and neonatal outcomes. We focused on neuroendocrine changes during pregnancy and their effects on antidepressant pharmacokinetics. Pregnancy-induced alterations in drug disposition and metabolism impacting mothers and their fetuses are discussed. We considered evidence for the risks of antidepressant use during pregnancy. Teratogenicity associated with ongoing treatment, new prescriptions during pregnancy, or pausing medication while pregnant was examined. The Food and Drug Administration advises caution regarding prenatal exposure to most drugs, including antidepressants, largely owing to a dearth of safety studies caused by the common exclusion of pregnant individuals in clinical trials. We contrasted findings on antidepressant use with the lack of treatment where detrimental effects to mothers and children are well researched. Overall, drug classes such as selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors appear to have limited adverse effects on fetal health and child development. In the face of an increasing prevalence of major mood and anxiety disorders, we assert that individuals should be counseled before and during pregnancy about the risks and benefits of antidepressant treatment given that withholding treatment has possible negative outcomes. Moreover, newer therapeutics, such as ketamine and κ-opioid receptor antagonists, warrant further investigation for use during pregnancy. SIGNIFICANCE STATEMENT: The safety of antidepressant use during pregnancy remains controversial owing to an incomplete understanding of how drug exposure affects fetal development, brain maturation, and behavior in offspring. This leaves pregnant people especially vulnerable, as pregnancy can be a highly stressful experience for many individuals, with stress being the biggest known risk factor for developing a mood or anxiety disorder. This review focuses on perinatal pharmacotherapy for treating mood and anxiety disorders, highlighting the current knowledge and gaps in our understanding of consequences of treatment.

Serotonin (5-HT) plays an essential role in reward processing, however, the possibilities to investigate 5-HT action in humans during emotional stimulation are particularly limited. Here we demonstrate the feasibility of assessing reward-specific dynamics in 5-HT synthesis using functional PET (fPET), combining its molecular specificity with the high temporal resolution of blood oxygen level dependent (BOLD) fMRI. Sixteen healthy volunteers underwent simultaneous fPET/fMRI with the radioligand [11C]AMT, a substrate for tryptophan hydroxylase. During the scan, participants completed the monetary incentive delay task and arterial blood samples were acquired for quantifying 5-HT synthesis rates. BOLD fMRI was recorded as a proxy of neuronal activation, allowing differentiation of reward anticipation and feedback. Monetary gain and loss resulted in substantial increases in 5-HT synthesis in the ventral striatum (VStr, +21% from baseline) and the anterior insula (+41%). In the VStr, task-specific 5-HT synthesis was further correlated with BOLD signal changes during reward feedback (ρ = -0.65), but not anticipation. Conversely, 5-HT synthesis in the anterior insula correlated with BOLD reward anticipation (ρ = -0.61), but not feedback. In sum, we provide a robust tool to identify task-induced changes in 5-HT action in humans, linking the dynamics of 5-HT synthesis to distinct phases of reward processing in a regionally specific manner. Given the relevance of altered reward processing in psychiatric disorders such as addiction, depression and schizophrenia, our approach offers a tailored assessment of impaired 5-HT signaling during cognitive and emotional processing.

Depression is associated with functional brain impairments, although comprehensive studies remain limited. This study reviews neural mechanisms underlying cognitive impairment in depression and identifies associated activation abnormalities in brain regions. The study also explores the underlying neural processes of cognitive benefits of exercise intervention for depression. Executive function impairments, including working memory, inhibitory control and cognitive flexibility are associated with frontal cortex and anterior cingulate areas, especially dorsolateral prefrontal cortex. Depression is associated with certain neural impairments of reward processing, especially orbitofrontal cortex, prefrontal cortex, nucleus accumbens and other striatal regions. Depressed patients exhibit decreased activity in the hippocampus during memory function. Physical exercise has been found to enhance memory function, executive function, and reward processing in depression patients by increasing functional brain regions and the brain-derived neurotrophic factor (BDNF) as a nutritional factor also plays a key role in exercise intervention. The study documents neurophysiological mechanisms behind exercise intervention's improved functions. In summary, the study provides insights into neural mechanisms underlying cognitive impairments in depression and the effectiveness of exercise as a treatment.

Depressive disorders are associated with alterations in brain function, affecting processes such as affective and reward processing and emotion regulation. However, the influence of Cognitive Behavioral Therapy (CBT) on the neuronal patterns remains inadequately understood. Therefore, this review systematically summarizes longitudinal fMRI brain activity changes in depressive patients treated with CBT and their association with symptom remission.

This systematic review was conducted according to the PRISMA statement. Out of 2149 results of the literature search, N = 14 studies met the inclusion criteria (e.g., diagnosis of a current depressive disorder, assessment of longitudinal task-based fMRI, and the analysis of functional changes before and after CBT).

The findings reveal (1) diminished limbic reactivity following CBT across various tasks, (2) increased striatal activity during reward processing, but decreased activity during affective processing and future thinking, and (3) alterations in cingulate and prefrontal cortex activity across tasks. Partially, these results are associated with symptom remission, especially in the subgenual anterior cingulate cortex.

There are heterogenous results especially in cortical areas that might partially be due to methodological issues like differences across the studies in terms of task content, statistical evaluation, and interventions. Thus, future research should focus on the standardization of methodologies.

The results indicate that CBT partially normalizes the neural patterns of depressive patients, particularly within regions involved in affective and reward processing and the development of negative cognitive biases. Overall, potential neural mechanisms underlying CBT were identified, underscoring its effectiveness on an objective neurobiological basis.

Anhedonia-a core symptom of major depressive disorder (MDD)-is closely related to diminished reward sensitivity. Nonetheless, the psychopathological and computational mechanism underlying anhedonia in young patients with MDD remains unclear. Therefore, this study aims to investigate reward sensitivity in adolescents and young adults with MDD using computational modelling.

Overall, 70 patients with MDD and 54 age- and sex-matched healthy controls (HC) completed a probabilistic reward task (PRT) to assess their general behavioral inclination towards more frequently reinforced stimuli (i.e., "response bias"). Bayesian hierarchical drift diffusion modeling (HDDM) was employed to determine changes in reward sensitivity and computational process during decision-making.

Adolescents with depression showed a trend toward reduced response bias compared to those in HC. HDDM analysis revealed wider decision thresholds in both adolescents and young adults with MDD group. Adolescents with MDD exhibited significantly lower drift rates and reduced starting point bias compared to those in HC. Higher anhedonia levels were linked to lower drift rates and wider decision thresholds. Additionally, increased discriminability correlated with higher drift rates, while higher response bias was linked to larger starting points.

Our findings suggest that reduced reward sensitivity and slower evidence accumulation during reward learning may serve as potential indicators of anhedonia in adolescents with MDD. These findings provided crucial insights into the dysregulated positive affect model, underscoring a dysfunctional reward system as a key factor in anhedonia developmental psychopathology in depression.

Early experiences of stress and adversity are associated with blunted reward sensitivity and altered reward learning. Meanwhile, anhedonia is characterized by impairments in reward processing, including motivation, effort, and pleasure. Early life stress (ELS) and anhedonia share psychological, behavioral, and neurobiological correlates, and the system-level interactions that give rise to anhedonia have yet to be fully appreciated. The proposed framework uses a multilevel, multisystem approach to aid in understanding neural-immune interactions that link ELS and anhedonia. The interactions linking anhedonia and ELS presented here include reduced reward sensitivity, alterations in hypothalamic-pituitary-adrenal (HPA) axis response, elevated inflammatory cytokines or physiological markers of stress, and blunted reward circuitry functioning along the mesocorticolimbic pathway. The clinical implications and areas for future research are also discussed. Ultimately, this research may inform the development of more specific and individualized treatments for anhedonia.

Depression is usually characterized by impairments in reward function, and shows altered motivation to reward in reinforcement learning. This study further explored whether task difficulty affects reinforcement learning in college students with and without depression symptom.

The depression symptom group (20) and the no depression symptom group (26) completed a probabilistic reward learning task with low, medium, and high difficulty levels, in which task the response bias to reward and the discriminability of reward were analyzed. Additionally, electrophysiological responses to reward and loss feedback were recorded and analyzed while they performed a simple gambling task.

The depression symptom group showed more response bias to reward than the no depression symptom group when the task was easy and then exhibited more quickly decrease in response bias to reward as task difficulty increased. The no depression symptom group showed a decrease in response bias only in the high-difficulty condition. Further regression analyses showed that, the Feedback-related negativity (FRN) and theta oscillation could predict response bias change in the low-difficulty condition, the FRN and oscillations of theta and delta could predict response bias change in the medium and high-difficulty conditions.

The electrophysiological responses to loss and reward were not recorded in the same task as the reinforcement learning behaviors.

College students with depression symptom are more sensitive to task difficulty during reinforcement learning. The FRN, and oscillations of theta and delta could predict reward leaning behavior.

Depression is a significant public health concern. Identifying biopsychosocial risk factors for depression is important for developing targeted prevention. Studies have demonstrated that blunted striatal activation during reward processing is a risk factor for depression; however, few have prospectively examined whether adolescent reward-related resting-state functional connectivity (rsFC) predicts depression symptoms in adulthood and how this relates to known risk factors (e.g., childhood trauma).

At baseline, 66 adolescents (mean age = 14.7, SD = 1.4, 68 % female) underwent rsFC magnetic resonance imaging and completed the Children's Depression Inventory (CDI). At follow-up (mean time between adolescent scan and adult follow-up = 10.1 years, SD = 1.6, mean adult age = 24.8 years, SD = 1.7), participants completed the Childhood Trauma Questionnaire (CTQ) and Beck Depression Inventory- Second Edition (BDI-2). Average rsFC was calculated between nodes in mesocorticolimbic reward circuitry: ventral striatum (VS), rostral anterior cingulate cortex (rACC), medial orbitofrontal cortex, and ventral tegmental area. Linear regressions assessed associations between rsFC, BDI-2, and CTQ, controlling for adolescent CDI, sex assigned at birth, and scan age (Bonferroni corrected).

Greater childhood trauma was associated with higher adulthood depression symptoms. Stronger VS-rACC rsFC during adolescence was associated with greater depression symptoms in adulthood and greater childhood trauma.

The small sample size, limited depression severity, and seed-based approach are limitations.

The associations between adolescent striatal-cingulate rsFC and childhood trauma and adult depression symptoms suggest this connectivity may be an early neurobiological risk factor for depression and that early life experience plays an important role. Increased VS-rACC connectivity may represent an over-regulatory response on the striatum, commonly reported in depression, and warrants further investigation.

Major Depressive Disorder (MDD) is a complex, heterogeneous condition affecting millions worldwide. Computational neuropsychiatry offers potential breakthroughs through the mechanistic modeling of this disorder. Using the Kolmogorov theory (KT) of consciousness, we developed a foundational model where algorithmic agents interact with the world to maximize an Objective Function evaluating affective valence. Depression, defined in this context by a state of persistently low valence, may arise from various factors-including inaccurate world models (cognitive biases), a dysfunctional Objective Function (anhedonia, anxiety), deficient planning (executive deficits), or unfavorable environments. Integrating algorithmic, dynamical systems, and neurobiological concepts, we map the agent model to brain circuits and functional networks, framing potential etiological routes and linking with depression biotypes. Finally, we explore how brain stimulation, psychotherapy, and plasticity-enhancing compounds such as psychedelics can synergistically repair neural circuits and optimize therapies using personalized computational models.

A growing body of evidence supports the comorbidity between depression (DEP) and obesity, yet the genetic mechanisms underlying this association remain unclear. Our study explored the shared genetic architecture and causal associations of DEP with BMI.

We investigated the multigene overlap and genetic correlation between DEP (N > 1.3 million) and BMI (N = 806,834) based on genome-wide association studies (GWAS) and using the bivariate causal mixture model and linkage disequilibrium score regression (LDSC). The causal association was explored by bi-directional Mendelian randomization (MR). Common risk loci were identified through cross-trait meta-analyses. Stratified LDSC and multi-marker gene annotation analyses were applied to investigate single-nucleotide polymorphisms enrichment across tissue types, cell types, and functional categories. Finally, we explored shared functional genes by Summary Data-Based Mendelian Randomization (SMR) and further detected differential expression genes (DEG) in brain tissues of individuals with depression and obesity.

We found a positive genetic correlation between DEP and BMI (rg = 0.19, P = 4.07 × 10-26), which was more evident in local genomic regions. Cross-trait meta-analyses identified 16 shared genetic loci, 5 of which were newly identified, and they had influence on both diseases in the same direction. MR analysis showed a bidirectional causal association between DEP and BMI, with comparable effect sizes estimated in both directions. Combined with gene expression information, we found that genetic correlations between DEP and BMI were enriched in 6 brain regions, predominantly in the nucleus accumbens and anterior cingulate cortex. Moreover, 6 specific cell types and 23 functional genes were found to have an impact on both DEP and BMI across the brain regions. Of which, NEGR1 was identified as the most significant functional gene and associated with DEP and BMI at the genome-wide significance level (P < 5 × 10-8). Compared with healthy controls, the expression levels of NEGR1 gene were significant lower in brain tissues of individuals with depression and obesity.

Our study reveals shared genetic basis underpinnings between DEP and BMI, including genetic correlations and common genes. These insights offer novel opportunities and avenues for future research into their comorbidities.

Applying effort-based decision-making tasks provides insights into specific variables influencing choice behaviors. The current review summarizes the structural and functional neuroanatomy of effort-based decision-making. Across 39 examined studies, the review highlights the ventromedial prefrontal cortex in forming reward-based predictions, the ventral striatum encoding expected subjective values driven by reward size, the dorsal anterior cingulate cortex for monitoring choices to maximize rewards, and specific motor areas preparing for effort expenditure. Neuromodulation techniques, along with shifting environmental and internal states, are promising novel treatment interventions for altering neural alterations underlying decision-making. Our review further articulates the translational promise of this construct into the development, maintenance and treatment of psychiatric conditions, particularly those characterized by reward-, effort- and valuation-related deficits.

Previous task-related functional magnetic resonance imaging (task-fMRI) investigations have documented abnormal brain activation associated with subclinical depression (SD), defined as a clinically relevant level of depressive symptoms that does not meet the diagnostic criteria for major depressive disorder. However, these task-fMRI studies have not reported consistent conclusions. Performing a voxel-based meta-analysis of task-fMRI studies may yield reliable findings.

We extracted the peak coordinates and t values of included studies and analyzed brain activation between individuals with SD and healthy controls (HCs) using anisotropic effect-size signed differential mapping (AES-SDM).

A systematic literature search identified eight studies, including 266 individuals with SD and 281 HCs (aged 14 to 25). The meta-analysis showed that individuals with SD exhibited significantly greater activation in the right lenticular nucleus and putamen according to task-fMRI. The meta-regression analysis revealed a negative correlation between the proportion of females in a group and activation in the right striatum.

The recruitment criteria for individuals with SD, type of tasks and MRI acquisition parameters of included studies were heterogeneous. The results should be interpreted cautiously due to insufficient included studies.

Our findings suggest that individuals with SD exhibit increased activation in the right lenticular nucleus, putamen and striatum, which may indicate a compensatory increase in response to an impairment of insular and striatal function caused by depression. These results provide valuable insights into the potential pathophysiology of brain dysfunction in SD.

Depression is a highly prevalent and debilitating mental disorder that often begins in adolescence. However, it remains unclear whether adults and adolescents with depression exhibit common or distinct brain dysfunctions during reward processing. We aimed to identify common and separable neurofunctional alterations during receipt of rewards and brain structure in adolescents and adults with depression. A coordinate-based meta-analysis was employed using Seed-based d mapping with permutation of subject images (SDM-PSI). Compared with healthy controls, both age groups exhibited common activity decreases in the right striatum (putamen, caudate) and subgenual ACC. Adults with depression showed decreased reactivity in the right putamen and subgenual ACC, while adolescents with depression showed decreased activity in the left mid cingulate, right caudate but increased reactivity in the right postcentral gyrus. This meta-analysis revealed shared (caudate) and separable (putamen and mid cingulate cortex) reward-related alterations in adults and adolescents with depression. The findings suggest age-specific neurofunctional alterations and stress the importance of adolescent-specific interventions that target social functions.

To identify the spatial-temporal pattern variation of whole-brain functional connectivity (FC) during reward processing in melancholic major depressive disorder (MDD) patients, and to determine the clinical correlates of connectomic differences.

61 MDD patients and 32 healthy controls were enrolled into the study. During magnetoencephalography (MEG) scanning, all participants completed the facial emotion recognition task. The MDD patients were further divided into two groups: melancholic (n = 31) and non-melancholic (n = 30), based on the Mini International Neuropsychiatric Interview (M.I.N.I.) assessment. Melancholic symptoms were examined by using the 6-item melancholia subscale from the Hamilton Depression Rating Scale (HAM-D6). The whole-brain orthogonalized power envelope connections in the high-beta band (20-35 Hz) were constructed in each period after the happy emotional stimuli (0-200 ms, 100-300 ms, 200-400 ms, 300-500 ms, and 400-600 ms). Then, the network-based statistic (NBS) was used to determine the specific abnormal connection patterns in melancholic MDD patients.

The NBS identified a sub-network difference at the mid-late period (300-500 ms) in response to happy faces among the three groups (corrected P = 0.035). Then, the post hoc and correlation analyses found five FCs were decreased in melancholic MDD patients and were related to HAM-D6 score, including FCs of left fusiform gyrus-right orbital inferior frontal gyrus (r = -0.52, P < 0.001), left fusiform gyrus-left amygdala (r = -0.26, P = 0.049), left posterior cingulate gyrus-right precuneus (r = -0.32, P = 0.025), left precuneus-right precuneus (r = -0.27, P = 0.049), and left precuneus-left inferior occipital gyrus (r = -0.32, P = 0.025).

In response to happy faces, melancholic MDD patients demonstrated a disrupted functional connective pattern (20-35 Hz, 300-500 ms), which involved brain regions in visual information processing and the limbic system. The aberrant functional connective pattern in reward processing might be a biomarker of melancholic MDD.

Individuals with low social status are at heightened risk of major depressive disorder (MDD), and MDD also influences social status. While the interrelationship between MDD and social status is well-defined, the behavioral causality between these two phenotypes remains unexplored. Here, we investigated the behavioral relationships between depressive and dominance behaviors in male mice exposed to chronic restraint stress and the role of medial prefrontal cortex (mPFC) astrocytes in these behaviors. Chronic restraint stress induced both depressive and submissive behaviors. Chemogenetic mPFC astrocyte activation significantly enhanced dominance in chronic stress-induced submissive mice by increasing the persistence of defensive behavior, although it did not affect depressive behaviors. Notably, repetitive winning experiences following mPFC astrocyte stimulation exerted anti-depressive effects in chronic restraint stress-induced depressive mice. These data indicate that mPFC astrocyte-derived winning experience renders anti-depressive effects, and may offer a new strategy for treating depression caused by low status in social hierarchies by targeting mPFC astrocytes.

Major Depressive Disorder (MDD) is frequently associated with social dysfunction and impaired decision-making, but its impact on social decisions remains unclear. Thus, we conducted a series of meta-analyses to examine the effects of MDD on key social decision phenomena, including trust, altruistic punishment, and cooperation. We searched Web of Science, PubMed, PsycINFO, and Embase up to December 2023, using Hedges' g to compare social decision-making between MDD patients and healthy controls (HCs). Meta-analytic results showed that MDD patients exhibited a significant reduction in trust (Hedges' g = -0.347, p < 0.001), no significant difference in altruistic punishment (Hedges' g = 0.232, p = 0.149), and an increase in cooperative behaviors (Hedges' g = 0.361, p = 0.002) compared to HCs. The moderation analysis revealed that age (p = 0.039) and region (p = 0.007) significantly moderated altruistic punishment, with older MDD patients and those from Asian and European regions having larger MDD-HC contrast than others. Regarding cooperation, moderation analysis indicated that age (p = 0.028), years of education (p = 0.054), and treatment coverage (p = 0.042) were significant moderators, indicating larger MDD-HC contrast in older, less-educated and better-treated people. These findings suggest MDD has different impacts on different social decisions, highlighting the need for fine-tuned therapeutic interventions that address these differences. The data also underscores the importance of considering demographic and treatment-related variables in managing MDD, which could inform personalized treatment strategies and improve social functionality and patient outcomes.

The ability to successfully remember past events is critical to our daily lives, yet the neural mechanisms underlying the motivation to retrieve is unclear. Although reward-system activity and feedback-related signals have been observed during memory retrieval, whether this signal reflects intrinsic reward or goal-attainment is unknown. Adjudicating between these two alternatives is crucial for understanding how individuals are motivated to engage in retrieval and how retrieval supports later remembering. To test these two accounts, we conducted between-subjects recognition memory tasks on human participants undergoing scalp electroencephalography and varied test-phase goals (recognize old vs. detect new items). We used an independently validated feedback classifier to measure positive feedback evidence. We find positive feedback following successful retrieval regardless of task goals. Together, these results suggest that successful retrieval is intrinsically rewarding. Such a feedback signal may promote future retrieval attempts as well as bolster later memory for the successfully retrieved events.

Stress resilience is the phenomenon that some people maintain their mental health despite exposure to adversity or show only temporary impairments followed by quick recovery. Resilience research attempts to unravel the factors and mechanisms that make resilience possible and to harness its insights for the development of preventative interventions in individuals at risk for acquiring stress-related dysfunctions. Biological resilience research has been lagging behind the psychological and social sciences but has seen a massive surge in recent years. At the same time, progress in this field has been hampered by methodological challenges related to finding suitable operationalizations and study designs, replicating findings, and modeling resilience in animals. We embed a review of behavioral, neuroimaging, neurobiological, and systems biological findings in adults in a critical methods discussion. We find preliminary evidence that hippocampus-based pattern separation and prefrontal-based cognitive control functions protect against the development of pathological fears in the aftermath of singular, event-type stressors [as found in fear-related disorders, including simpler forms of posttraumatic stress disorder (PTSD)] by facilitating the perception of safety. Reward system-based pursuit and savoring of positive reinforcers appear to protect against the development of more generalized dysfunctions of the anxious-depressive spectrum resulting from more severe or longer-lasting stressors (as in depression, generalized or comorbid anxiety, or severe PTSD). Links between preserved functioning of these neural systems under stress and neuroplasticity, immunoregulation, gut microbiome composition, and integrity of the gut barrier and the blood-brain barrier are beginning to emerge. On this basis, avenues for biological interventions are pointed out.

Psychological processes have a crucial role in the recovery from acute myocardial infarction (AMI), yet the underlying mechanisms of these effects remain elusive. Here we demonstrate the impact of the reward system, a brain network associated with motivation and positive expectations, on the clinical outcomes of AMI in mice. Chemogenetic activation of dopaminergic neurons in the reward system improved the remodeling processes and vascularization after AMI, leading to enhanced cardiac performance compared to controls. These effects were mediated through several physiological mechanisms, including alterations in immune activity and reduced adrenergic input to the liver. We further demonstrate an anatomical connection between the reward system and the liver, functionally manifested by altered transcription of complement component 3, which in turn affects vascularization and recovery from AMI. These findings establish a causal connection between a motivational brain network and recovery from AMI, introducing potential therapeutic avenues for intervention.

Behavioral activation (BA) is a well-established method of evidence-based treatment for depression. There are clear links between the neural mechanisms underlying reward processing and BA treatment for depressive symptoms, including anhedonia; however, integrated interpretations of these two domains are lacking. Here we examine brain imaging studies involving BA treatments to investigate how changes in brain networks, including the reward networks, mediate the therapeutic effects of BA, and whether brain circuits are predictors of BA treatment responses. Increased activation of the prefrontal and subcortical regions associated with reward processing has been reported after BA treatment. Activation of these regions improves anhedonia. Conversely, some studies have found decreased activation of prefrontal regions after BA treatment in response to cognitive control stimuli in sad contexts, which indicates that the therapeutic mechanism of BA may involve disengagement from negative or sad contexts. Furthermore, the decrease in resting-state functional connectivity of the default-mode network after BA treatment appears to facilitate the ability to counteract depressive rumination, thereby promoting enjoyable and valuable activities. Conflicting results suggest that an intact neural response to rewards or defective reward functioning is predictive of the efficacy of BA treatments. Increasing the benefits of BA treatments requires identification of the unique individual characteristics determining which of these conflicting findings are relevant for the personalized treatment of each individual with depression.

The brain can be represented as a network, with nodes as brain regions and edges as region-to-region connections. Nodes with the most connections (hubs) are central to efficient brain function. Current findings on structural differences in Major Depressive Disorder (MDD) identified using network approaches remain inconsistent, potentially due to small sample sizes. It is still uncertain at what level of the connectome hierarchy differences may exist, and whether they are concentrated in hubs, disrupting fundamental brain connectivity.

We utilized two large cohorts, UK Biobank (UKB, N = 5104) and Generation Scotland (GS, N = 725), to investigate MDD case-control differences in brain network properties. Network analysis was done across four hierarchical levels: (1) global, (2) tier (nodes grouped into four tiers based on degree) and rich club (between-hub connections), (3) nodal, and (4) connection.

In UKB, reductions in network efficiency were observed in MDD cases globally (d = -0.076, pFDR = 0.033), across all tiers (d = -0.069 to -0.079, pFDR = 0.020), and in hubs (d = -0.080 to -0.113, pFDR = 0.013-0.035). No differences in rich club organization and region-to-region connections were identified. The effect sizes and direction for these associations were generally consistent in GS, albeit not significant in our lower-N replication sample.

Our results suggest that the brain's fundamental rich club structure is similar in MDD cases and controls, but subtle topological differences exist across the brain. Consistent with recent large-scale neuroimaging findings, our findings offer a connectomic perspective on a similar scale and support the idea that minimal differences exist between MDD cases and controls.

Childhood trauma plays a crucial role in the dysfunctional reward circuitry in major depressive disorder (MDD). We sought to explore the effect of abnormalities in the globus pallidus (GP)-centric reward circuitry on the relationship between childhood trauma and MDD.

We conducted seed-based dynamic functional connectivity (dFC) analysis among people with or without MDD and with or without childhood trauma. We explored the relationship between abnormal reward circuitry, childhood trauma, and MDD.

We included 48 people with MDD and childhood trauma, 30 people with MDD without childhood trauma, 57 controls with childhood trauma, and 46 controls without childhood trauma. We found that GP subregions exhibited abnormal dFC with several regions, including the inferior parietal lobe, thalamus, superior frontal gyrus (SFG), and precuneus. Abnormal dFC in these GP subregions showed a significant correlation with childhood trauma. Moderation analysis revealed that the dFC between the anterior GP and SFG, as well as between the anterior GP and the precentral gyrus, modulated the relationship between childhood abuse and MDD severity. We observed a negative correlation between childhood trauma and MDD severity among patients with lower dFC between the anterior GP and SFG, as well as higher dFC between the anterior GP and precentral gyrus. This suggests that reduced dFC between the anterior GP and SFG, along with increased dFC between the anterior GP and precentral gyrus, may attenuate the effect of childhood trauma on MDD severity.

Cross-sectional designs cannot be used to infer causality.

Our findings underscore the pivotal role of reward circuitry abnormalities in MDD with childhood trauma. These abnormalities involve various brain regions, including the postcentral gyrus, precentral gyrus, inferior parietal lobe, precuneus, superior frontal gyrus, thalamus, and middle frontal gyrus.

ChiCTR2300078193.

Psychosocial treatments targeting the positive valence system (PVS) in depression and anxiety demonstrate efficacy in enhancing positive affect (PA), but response to treatment varies. We examined whether individual differences in neural activation to positive and negative valence incentive cues underlies differences in benefitting from a PVS-targeted treatment. Individuals with clinically elevated depression and/or anxiety (N = 88, ages 18 to 55) participated in one of two randomized, waitlist-controlled trials of Amplification of Positivity (AMP; NCT02330627, NCT03196544), a cognitive and behavioral intervention targeting the PVS. Participants completed a monetary incentive delay (MID) task during fMRI acquisition at baseline measuring neural activation to the possibility of gaining or losing money. Change in PA from before to after treatment was assessed using the Positive and Negative Affect Schedule. No significant associations were observed between baseline neural activation during gain anticipation and AMP-related changes in PA in regions of interest (striatum and insula) or whole-brain analyses. However, higher baseline striatal and insula activation during loss anticipation was associated with greater increases in PA post-AMP. This study provides preliminary evidence suggesting neural reactivity to negative valence cues may inform who stands to benefit most from treatments targeting the PVS.

Binge eating is characterized as eating a large amount of food and feeling a loss of control while eating. However, the neurobiological mechanisms associated with the onset and maintenance of binge eating are largely unknown. Recent neuroimaging work has suggested that increased responsivity within reward regions of the brain to the anticipation or receipt of rewards is related to binge eating; however, limited longitudinal data has precluded understanding of the role of reward responsivity in the development of binge eating. The current study used data from the Adolescent Brain and Cognitive Development® (ABCD) longitudinal study dataset to assess whether heightened neural responses to different phases of reward processing (reward anticipation and receipt) (1) differentiated individuals with binge eating from matched controls, and (2) predicted the onset of binge eating in an "at risk" sample. Consistent with hypotheses, heightened neural responsivity in the right caudate and bilateral VS during reward anticipation differentiated youth with and without binge eating. Moreover, greater VS response to reward anticipation predicted binge eating two years later. Neural responses to reward receipt also were consistent with hypotheses, such that heightened VS and OFC responses differentiated youth with and without binge eating and predicted the presence of binge eating two years later. Findings from the current study suggest that hypersensitivity to rewards may contribute to the development of binge eating during early adolescence.

Major depressive disorder (MDD) is a major cause of poor quality of life and disability and is highly prevalent worldwide. Various pathological mechanisms are implicated in MDD, including the reward system. The human brain is equipped with a reward system that is involved in aspects such as motivation, pleasure, and learning. Several studies including a meta-analysis have been reported on the reward system network and MDD. However, to our knowledge, no studies have examined the relationship between the reward system network of drug-naïve, first-episode MDD patients and the detailed symptoms of MDD or age. The fronto-striato network (FSN) is closely related to the reward system network. The present study primarily aimed to elucidate this point.

A total of 89 drug-naïve first-episode MDD patients and 82 healthy controls (HCs) patients were enrolled in the study. The correlation between the FSN and age and the interaction between age and illness in the FSN were investigated in 75 patients in the MDD group and 79 patients in the HC group with available information on the FSN and age. In addition, the association between the FSN and the total scores on the 17-item Hamilton Rating Scale for Depression (HAMD-17) and scores in each symptom item was analyzed in 76 MDD subjects with information on the FSN and HAMD-17. The significance of each result was evaluated according to a p-value of <0.05.

Age was inversely correlated with the FSN (p=2.14e-11) in the HC group but not in the MDD group (p=0.79). FSN varied with the presence of MDD and with age, particularly showing an interaction with MDD and age (p=1.04e-08). Specifically, age and the presence or absence of MDD each affected FSN, but the effect of age on FSN changed in the presence of depression. FSN did not correlate with total HAMD-17 scores or scores in each item.

The reward system may be dysfunctional in patients with MDD. In addition, the effect could be greater in younger patients. Meanwhile, there is no correlation between the function of the reward system and the severity of MDD or the severity of each symptom. Thus, the reward system network may be an important biological marker of MDD, although careful consideration should be given to age and its association with the severity of the disorder.

The reward system function is decreased in MDD patients, and this decrease may be more pronounced in younger patients, although further research is still needed.

During task-based functional magnetic resonance imaging (t-fMRI) patients with depressive disorder (DD) have shown abnormal caudate nucleus activation. There have been no meta-analyses that are conducted on the caudate nucleus using Activation Likelihood Estimation (ALE) in patients with DD, and the relationships between abnormal caudate activity and different behavior domains in patients with DD remain unclear. There were 24 previously published t-fMRI studies included in the study with the caudate nucleus as the region of interest. Meta-analyses were performed using the method of ALE. Included five ALE meta-analyses: (1) the hypoactivated caudate nucleus relative to healthy controls (HCs); (2) the hyper-activated caudate nucleus; (3) the abnormal activation in the caudate nucleus in the emotion domain; (4) the abnormal activation in cognition domain; (5) the abnormal activation in the affective cognition domain. Results revealed that the hypo-/hyper-activity in the caudate subregions is mainly located in the caudate body and head, while the relationships between abnormal caudate subregions and different behavior domains are complex. The hypoactivation of the caudate body and head plays a key role in the emotions which indicates there is a positive relationship between the decreased caudate activity and depressed emotional behaviors in patients with DD.

How phenomenal experience and behavior are related to neural activity in physiology and psychopathology represents a fundamental question in neuroscience and psychiatry. The phenomenal-behavior patterns may be deconstructed into basic dimensions, i.e., psychomotricity, affectivity, and thought, which might have distinct neural correlates. This work provides a data overview on the relationship of these phenomenal-behavioral dimensions with brain activity across physiological and pathological conditions (including major depressive disorder, bipolar disorder, schizophrenia, attention-deficit/hyperactivity disorder, anxiety disorders, addictive disorders, Parkinson's disease, Tourette syndrome, Alzheimer's disease, and frontotemporal dementia). Accordingly, we propose a three-dimensional model of neural activity and phenomenal-behavioral patterns. In this model, neural activity is organized into distinct units in accordance with connectivity patterns and related input/output processing, manifesting in the different phenomenal-behavioral dimensions. (1) An external neural unit, which involves the sensorimotor circuit/brain's sensorimotor network and is connected with the external environment, processes external inputs/outputs, manifesting in the psychomotor dimension (processing of exteroception/somatomotor activity). External unit hyperactivity manifests in psychomotor excitation (hyperactivity/hyperkinesia/catatonia), while external unit hypoactivity manifests in psychomotor inhibition (retardation/hypokinesia/catatonia). (2) An internal neural unit, which involves the interoceptive-autonomic circuit/brain's salience network and is connected with the internal/body environment, processes internal inputs/outputs, manifesting in the affective dimension (processing of interoception/autonomic activity). Internal unit hyperactivity manifests in affective excitation (anxiety/dysphoria-euphoria/panic), while internal unit hypoactivity manifests in affective inhibition (anhedonia/apathy/depersonalization). (3) An associative neural unit, which involves the brain's associative areas/default-mode network and is connected with the external/internal units (but not with the environment), processes associative inputs/outputs, manifesting in the thought dimension (processing of ideas). Associative unit hyperactivity manifests in thought excitation (mind-wandering/repetitive thinking/psychosis), while associative unit hypoactivity manifests in thought inhibition (inattention/cognitive deficit/consciousness loss). Finally, these neural units interplay and dynamically combine into various neural states, resulting in the complex phenomenal experience and behavior across physiology and neuropsychiatric disorders.

Reward processing dysfunctions are considered a candidate mechanism underlying anhedonia and apathy in depression. Neuroimaging studies have documented that neurofunctional alterations in mesocorticolimbic circuits may neurally mediate these dysfunctions. However, common and distinct neurofunctional alterations during motivational and hedonic evaluation of monetary and natural rewards in depression have not been systematically examined. Here, we capitalized on pre-registered neuroimaging meta-analyses to (1) establish general reward-related neural alterations in depression, (2) determine common and distinct alterations during the receipt and anticipation of monetary v. natural rewards, and, (3) characterize the differences on the behavioral, network, and molecular level. The pre-registered meta-analysis (https://osf.io/ay3r9) included 633 depressed patients and 644 healthy controls and revealed generally decreased subgenual anterior cingulate cortex and striatal reactivity toward rewards in depression. Subsequent comparative analyses indicated that monetary rewards led to decreased hedonic reactivity in the right ventral caudate while natural rewards led to decreased reactivity in the bilateral putamen in depressed individuals. These regions exhibited distinguishable profiles on the behavioral, network, and molecular level. Further analyses demonstrated that the right thalamus and left putamen showed decreased activation during the anticipation of monetary reward. The present results indicate that distinguishable neurofunctional alterations may neurally mediate reward-processing alterations in depression, in particular, with respect to monetary and natural rewards. Given that natural rewards prevail in everyday life, our findings suggest that reward-type specific interventions are warranted and challenge the generalizability of experimental tasks employing monetary incentives to capture reward dysregulations in everyday life.

Parent-adolescent interactions, particularly parental criticism and praise, have previously been identified as factors relevant to self-concept development and, when negative, to adolescent depression. Yet, whether adolescents with depression show aberrant emotional and neural reactivity to parental criticism and praise is understudied.

Adolescents with depression (n = 20) and healthy controls (n = 59) received feedback supposedly provided by their mother or father in the form of negative ('untrustworthy'), neutral ('chaotic'), and positive ('respectful') personality evaluations while in an MRI-scanner. After each feedback word, adolescents reported their mood. Beforehand, adolescents had rated whether these personality evaluations matched their self-views.

In both groups, mood decreased after criticism and increased after praise. Adolescents with depression reported blunted mood responses after praise, whereas there were no mood differences after criticism. Neuroimaging analyses revealed that adolescents with depression (v. healthy controls) exhibited increased activity in response to criticism in the subgenual anterior cingulate cortex, temporal pole, hippocampus, and parahippocampal gyrus. Praise consistent with adolescents' self-views improved mood independent of depression status, while criticism matching self-views resulted in smaller mood increases in adolescents with depression (v. healthy controls). Exploratory analyses indicated that adolescents with depression recalled criticism (v. praise) more.

Adolescents with depression might be especially attentive to parental criticism, as indexed by increased sgACC and hippocampus activity, and memorize this criticism more. Together with lower positive impact of praise, these findings suggest that cognitive biases in adolescent depression may affect how parental feedback is processed, and may be fed into their self-views.

Exposure to stressful events is associated with a range of negative physical and mental health outcomes, including depression. It is critical to understand the mechanisms through which stress impacts mental health to identify promising targets for prevention and intervention efforts. Low-reward responsiveness is thought to be a mechanism of effects of stress on negative health outcomes and can be reliably measured at the neurophysiological level by using event-related potentials (ERPs), such as the reward positivity (RewP) component. The goal of this systematic review and preliminary meta-analysis was to examine evidence of associations between stress and alterations in reward responsiveness measured using ERPs. Through a systematic review of the literature, 23 studies examining the effects of laboratory-induced stressors and naturalistic stressors or perceived stress on reward responsiveness met study criteria, 13 of which were included in the meta-analysis. Most studies were conducted in undergraduate and community samples, with three selected for specific conditions, and primarily in adults. The systematic review supported evidence of associations between laboratory-induced stressors and blunted reward responsiveness as measured by the RewP but there were more mixed results when considering direct associations between naturalistic stressors/perceived stress and reward-related ERPs. Given that all studies examined the RewP, the meta-analysis focused on this component and indicated that there was a weak, nonsignificant negative association between stress and RewP. Results emphasize the complex nature of relations between stress and reward-related ERPs and the need to consider alternative models in future research. We also provide reporting recommendations for ERP researchers to facilitate future meta-analyses.

Anhedonia, which is defined as the inability to feel pleasure, is considered a core symptom of major depressive disorder (MDD). It can lead to several adverse outcomes in adolescents, including heightened disease severity, resistance to antidepressants, recurrence of MDD, and even suicide. Specifically, patients who suffer from anhedonia may exhibit a limited response to selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT). Previous researches have revealed a link between anhedonia and abnormalities within the reward circuitry, making the nucleus accumbens (NAc) a potential target for treatment. However, since the NAc is deep within the brain, repetitive transcranial magnetic stimulation (rTMS) has the potential to modulate this specific region. Recent advances have enabled treatment technology to precisely target the left dorsolateral prefrontal cortex (DLPFC) and modify the functional connectivity (FC) between DLPFC and NAc in adolescent patients with anhedonia. Therefore, we plan to conduct a study to explore the safety and effectiveness of using resting-state functional connectivity magnetic resonance imaging (fcMRI)-guided rTMS to alleviate anhedonia in adolescents diagnosed with MDD.

The aim of this article is to provide a study protocol for a parallel-group randomized, double-blind, placebo-controlled experiment. The study will involve 88 participants who will be randomly assigned to receive either active rTMS or sham rTMS. The primary object is to measure the percentage change in the severity of anhedonia, using the Snaith-Hamilton Pleasure Scale (SHAPS). The assessment will be conducted from the baseline to 8-week post-treatment period. The secondary outcome includes encompassing fMRI measurements, scores on the 17-item Hamilton Rating Scale for Depression (HAMD-17), the Montgomery Asberg Depression Rating Scale (MADRS), the Chinese Version of Temporal Experience of Pleasure Scale (CV-TEPS), and the Chinese Version of Beck Scale for Suicide Ideation (BSI-CV). The Clinical Global Impression (CGI) scores will also be taken into account, and adverse events will be monitored. These evaluations will be conducted at baseline, as well as at 1, 2, 4, and 8 weeks.

If the hypothesis of the current study is confirmed, (fcMRI)-guided rTMS could be a powerful tool to alleviate the core symptoms of MDD and provide essential data to explore the mechanism of anhedonia.

ClinicalTrials.gov NCT05544071. Registered on 16 September 2022.

Predicting mood disorders in adolescence is a challenge that motivates research to identify neurocognitive predictors of symptom expression and clinical profiles. This study used machine learning to test whether neurocognitive variables predicted future manic or anhedonic symptoms in two adolescent samples risk-enriched for lifetime mood disorders (Sample 1, n = 73, ages = 13-25, M [SD] = 19.22 [2.49] years, 68% lifetime mood disorder) or familial mood disorders (Sample 2, n = 154, ages = 13-21, M [SD] = 16.46 [1.95] years, 62% first-degree family history of mood disorder). Participants completed cognitive testing and functional magnetic resonance imaging at baseline, for behavioral and neural measures of reward processing and executive functioning. Next, participants completed a daily diary procedure for 8-16 weeks. Penalized mixed-effects models identified neurocognitive predictors of future mood symptoms and stress-reactive changes in mood symptoms. Results included the following. In both samples, adolescents showing ventral corticostriatal reward hyposensitivity and lower reward performance reported more severe stress-reactive anhedonia. Poorer executive functioning behavior was associated with heightened anhedonia overall in Sample 1, but lower stress-reactive anhedonia in both samples. In Sample 1, adolescents showing ventral corticostriatal reward hypersensitivity and poorer executive functioning reported more severe stress-reactive manic symptoms. Clustering analyses identified, and replicated, five neurocognitive subgroups. Adolescents characterized by neural or behavioral reward hyposensitivities together with average-to-poor executive functioning reported unipolar symptom profiles. Adolescents showing neural reward hypersensitivity together with poor behavioral executive functioning reported a bipolar symptom profile (Sample 1 only). Together, neurocognitive phenotypes may hold value for predicting symptom expression and profiles of mood pathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Negative emotions such as depression have been associated with increased absenteeism and presenteeism, contributing to substantial economic loss. However, no study has investigated if positive emotions such as happiness influence absenteeism and presenteeism.

Using data from the Japan COVID-19 and Society Internet Survey (JACSIS), a nationwide survey conducted in September-October 2022 (n = 19,214), we investigated if two major, representative positive emotions (happiness and gratitude) are associated with absenteeism and presenteeism. Absenteeism was defined as reporting more than one day of sick leave in the past one month. Presenteeism was measured with the Work Functioning Impairment Scale. Logistic regression was used to estimate odds ratios.

12.4 % and 21.8 % of subjects reported absenteeism and presenteeism, respectively. Logistic regression estimated that after adjusting covariates, happiness was associated with lower odds of absenteeism (OR = 0.792, 95 % CI [0.706, 0.888]) and presenteeism (OR = 0.531, 95 % CI [0.479, 0.588]) while gratitude was associated with lower odds of presenteeism only (OR = 0.705, 95 % CI [0.643, 0.774]). Furthermore, simultaneous presence of both happiness and gratitude was associated with further lower odds of presenteeism (OR = 0.385, 95%CI [0.338, 0.439]), indicating a synergetic relation.

This study is the first to investigate the association between positive emotions and absenteeism and presenteeism. Given the substantial economic loss due to absenteeism and presenteeism, strategies to enhance positive emotions are necessary.

The incidence of adolescent depressive disorder is globally skyrocketing in recent decades, albeit the causes and the decision deficits depression incurs has yet to be well-examined. With an instrumental learning task, the aim of the current study is to investigate the extent to which learning behavior deviates from that observed in healthy adolescent controls and track the underlying mechanistic channel for such a deviation.

We recruited a group of adolescents with major depression and age-matched healthy control subjects to carry out the learning task with either gain or loss outcome and applied a reinforcement learning model that dissociates valence (positive v. negative) of reward prediction error and selection (chosen v. unchosen).

The results demonstrated that adolescent depressive patients performed significantly less well than the control group. Learning rates suggested that the optimistic bias that overall characterizes healthy adolescent subjects was absent for the depressive adolescent patients. Moreover, depressed adolescents exhibited an increased pessimistic bias for the counterfactual outcome. Lastly, individual difference analysis suggested that these observed biases, which significantly deviated from that observed in normal controls, were linked with the severity of depressive symoptoms as measured by HAMD scores.

By leveraging an incentivized instrumental learning task with computational modeling within a reinforcement learning framework, the current study reveals a mechanistic decision-making deficit in adolescent depressive disorder. These findings, which have implications for the identification of behavioral markers in depression, could support the clinical evaluation, including both diagnosis and prognosis of this disorder.