Neural responses to facial emotions and subsequent clinical outcomes in difficult-to-treat depression.

BACKGROUND: Amygdala and dorsal anterior cingulate cortex responses to facial emotions have shown promise in predicting treatment response in medication-free major depressive disorder (MDD). Here, we examined their role in the pathophysiology of clinical outcomes in more chronic, difficult-to-treat forms of MDD. METHODS: Forty-five people with current MDD who had not responded to ⩾2 serotonergic antidepressants (n = 42, meeting pre-defined fMRI minimum quality thresholds) were enrolled and followed up over four months of standard primary care. Prior to medication review, subliminal facial emotion fMRI was used to extract blood-oxygen level-dependent effects for sad v. happy faces from two pre-registered a priori defined regions: bilateral amygdala and dorsal/pregenual anterior cingulate cortex. Clinical outcome was the percentage change on the self-reported Quick Inventory of Depressive Symptomatology (16-item). RESULTS: We corroborated our pre-registered hypothesis (NCT04342299) that lower bilateral amygdala activation for sad v. happy faces predicted favorable clinical outcomes (rs[38] = 0.40, p = 0.01). In contrast, there was no effect for dorsal/pregenual anterior cingulate cortex activation (rs[38] = 0.18, p = 0.29), nor when using voxel-based whole-brain analyses (voxel-based Family-Wise Error-corrected p < 0.05). Predictive effects were mainly driven by the right amygdala whose response to happy faces was reduced in patients with higher anxiety levels. CONCLUSIONS: We confirmed the prediction that a lower amygdala response to negative v. positive facial expressions might be an adaptive neural signature, which predicts subsequent symptom improvement also in difficult-to-treat MDD. Anxiety reduced adaptive amygdala responses.

Virtual reality-assessment of social interactions and prognosis in depression.

BACKGROUND: Freud proposed that excessive self-blame-related motivations such as self-punishing tendencies play a key role in depression. Most of the supporting evidence, however, is based on cross-sectional studies and questionnaire measures. METHODS: In this pre-registered (NCT04593537) study, we used a novel Virtual Reality (VR) task to determine whether maladaptive self-blame-related action tendencies prospectively identify a subgroup of depression with poor prognosis when treated as usual over four months in primary care. Ninety-eight patients with depression (Patient Health Questionnaire-9 ≥ 15), screening negatively for bipolar and alcohol/substance use disorders, completed the VR-task at baseline (n = 93 completed follow-up). RESULTS: Our pre-registered statistical/machine learning model prospectively predicted a cross-validated 19 % of variance in depressive symptoms. Contrary to our specific predictions, and in accordance with Freud's observations, feeling like punishing oneself emerged as prognostically relevant rather than feeling like hiding or creating a distance from oneself. Using a principal components analysis of all pre-registered continuous measures, a factor most strongly loading on feeling like punishing oneself for other people's wrongdoings (ß = 0.23, p = 0.01), a baseline symptom factor (ß = 0.30, p = 0.006) and Maudsley Staging Method treatment-resistance scores (ß = 0.28, p = 0.009) at baseline predicted higher depressive symptoms after four months. LIMITATIONS: Patients were not assessed with a diagnostic interview. CONCLUSIONS: Independently and apart from known clinical variables, feeling like punishing oneself emerged as a distinctly relevant prognostic factor and should therefore be assessed and tackled in personalised care pathways for difficult-to-treat depression.

The Role of Subgenual Resting-State Connectivity Networks in Predicting Prognosis in Major Depressive Disorder.

Background: A seminal study found higher subgenual frontal cortex resting-state connectivity with 2 left ventral frontal regions and the dorsal midbrain to predict better response to psychotherapy versus medication in individuals with treatment-naïve major depressive disorder (MDD). Here, we examined whether these subgenual networks also play a role in the pathophysiology of clinical outcomes in MDD with early treatment resistance in primary care. Methods: Forty-five people with current MDD who had not responded to ≥2 serotonergic antidepressants (n = 43, meeting predefined functional magnetic resonance imaging minimum quality thresholds) were enrolled and followed over 4 months of standard care. Functional magnetic resonance imaging resting-state connectivity between the preregistered subgenual frontal cortex seed and 3 previously identified left ventromedial, ventrolateral prefrontal/insula, and dorsal midbrain regions was extracted. The clinical outcome was the percentage change on the self-reported 16-item Quick Inventory of Depressive Symptomatology. Results: We observed a reversal of our preregistered hypothesis in that higher resting-state connectivity between the subgenual cortex and the a priori ventrolateral prefrontal/insula region predicted favorable rather than unfavorable clinical outcomes (rs39 = -0.43, p = .006). This generalized to the sample including participants with suboptimal functional magnetic resonance imaging quality (rs43 = -0.35, p = .02). In contrast, no effects (rs39 = 0.12, rs39 = -0.01) were found for connectivity with the other 2 preregistered regions or in a whole-brain analysis (voxel-based familywise error-corrected p < .05). Conclusions: Subgenual connectivity with the ventrolateral prefrontal cortex/insula is relevant for subsequent clinical outcomes in current MDD with early treatment resistance. Its positive association with favorable outcomes could be explained primarily by psychosocial rather than the expected pharmacological changes during the follow-up period.

Evidence has shown that connectivity of the subgenual cortex, a frontal midline brain region, with 3 other brain regions can predict whether people with never-treated depression benefit more from psychological or medication-based treatments. Here, using resting-state fMRI, we show that subgenual connections with one of these regions, the left ventrolateral prefrontal/insula, also predict future average depression levels in people with difficult-to-treat depression. These data suggest that functional connectivity between these regions may be linked to clinical outcomes in major depressive disorder.

Self-blame-selective hyper-connectivity between anterior temporal and subgenual cortices predicts prognosis in major depressive disorder.

BACKGROUND: Self-blame-related fMRI measures were shown to predict subsequent recurrence in remitted major depressive disorder (MDD). Their role in current MDD, however, is unknown. We hypothesised that these neural signatures reflect a highly recurrent but remitting course of MDD and therefore predict favourable outcomes over a four-month follow-up period in current MDD. METHODS: Forty-five participants with current MDD and non-responders to at least two serotonergic antidepressants, were encouraged to optimise their medication and followed up after receiving four months of primary care treatment-as-usual. Prior to their medication review, participants completed an fMRI paradigm in which they viewed self- and other-blame emotion-evoking statements. Thirty-nine participants met pre-defined fMRI data minimum quality thresholds. Psychophysiological interaction analysis was used to determine baseline connectivity of the right superior anterior temporal lobe (RSATL), with an a priori BA25 region-of-interest for self-blaming vs other-blaming emotions, using Quick Inventory of Depressive Symptomatology (16-item) percentage change as a covariate. RESULTS: We corroborated our pre-registered hypothesis that a favourable clinical outcome was associated with higher self-blame-selective RSATL-BA25 connectivity (Family-Wise Error-corrected p <.05 over the a priori BA25 region-of-interest; rs(34) = -0.47, p =.005). This generalised to the sample including participants with suboptimal fMRI quality (rs(39) = -0.32, p =.05). CONCLUSIONS: This study shows that neural signatures of overgeneralised self-blame are relevant for prognostic stratification of current treatment-resistant MDD. Future studies need to confirm whether this neural signature indeed represents a trait-like feature of a fully remitting subtype of MDD, or whether it is also modulated by depressive state and related to treatment effects.

Antidepressant Advisor (ADeSS): a decision support system for antidepressant treatment for depression in UK primary care - a feasibility study.

OBJECTIVES: To develop and probe the first computerised decision-support tool to provide antidepressant treatment guidance to general practitioners (GPs) in UK primary care. DESIGN: A parallel group, cluster-randomised controlled feasibility trial, where individual participants were blind to treatment allocation. SETTING: South London NHS GP practices. PARTICIPANTS: Ten practices and eighteen patients with treatment-resistant current major depressive disorder. INTERVENTIONS: Practices were randomised to two treatment arms: (a) treatment-as-usual, (b) computerised decision support tool. RESULTS: Ten GP practices participated in the trial, which was within our target range (8-20). However, practice and patient recruitment were slower than anticipated and only 18 of 86 intended patients were recruited. This was due to fewer than expected patients being eligible for the study, as well as disruption resulting from the COVID-19 pandemic. Only one patient was lost to follow-up. There were no serious or medically important adverse events during the trial. GPs in the decision tool arm indicated moderate support for the tool. A minority of patients fully engaged with the mobile app-based tracking of symptoms, medication adherence and side effects. CONCLUSIONS: Overall, feasibility was not shown in the current study and the following modifications would be needed to attempt to overcome the limitations found: (a) inclusion of patients who have only tried one Selective Serotonin Reuptake Inhibitor, rather than two, to improve recruitment and pragmatic relevance of the study; (b) approaching community pharmacists to implement tool recommendations rather than GPs; (c) further funding to directly interface between the decision support tool and self-reported symptom app; (d) increasing the geographic reach by not requiring detailed diagnostic assessments and replacing this with supported remote self-report. TRIAL REGISTRATION NUMBER: NCT03628027.

Remote virtual reality assessment elucidates self-blame-related action tendencies in depression.

BACKGROUND: Action tendencies are implicit cognitive and motivational states before an action is taken, such as feeling like hiding when experiencing shame or guilt, independent of the actions people decide to take. Such "action tendencies" are key to understanding the maladaptive impact of self-blame in depression. For example, feeling like "hiding" in a text-based task was previously associated with recurrence risk in remitted depression. Despite their functional importance, action tendencies have not been systematically investigated in current depression, which was the aim of this pre-registered study. METHODS: We developed and validated the first virtual reality (VR) assessment of blame-related action tendencies and compared current depression (n = 98) with control participants (n = 40). The immersive VR-task, pre-programmed on devices sent to participants' homes, used hypothetical social interactions, in which either participants (self-agency) or their friend (other-agency) were described to have acted inappropriately. RESULTS: Compared with controls, people with depression showed a maladaptive profile: particularly in the other-agency condition, rather than feeling like verbally attacking their friend, they were prone to feeling like hiding, and punishing themselves. Interestingly, feeling like punishing oneself was associated with a history of self-harm but not suicide attempts. CONCLUSIONS: Current depression and self-harm history were linked with distinctive motivational signatures, paving the way for remote VR-based stratification and treatment.

Higher Depressive Symptoms Predict Lower Social Adaptive Functioning in Children and Adolescents with ASD.

Objective: Despite the frequent occurrence of depressive symptoms in children and adolescents with autism spectrum disorder (ASD), few studies have investigated the relationship between depressive symptoms and adaptive functioning. The present study explored the impact of depressive symptoms on different domains of adaptive functioning in children and adolescents with ASD.Methods: Depressive symptoms and adaptive functioning were analyzed in 62 children and adolescents with ASD (20 females) and 36 children and adolescents (15 females) with typical development between 5 and 18 years of age.Results: After controlling for IQ, age and sex, higher depressive symptoms predicted lower functioning in the social domain among children and adolescents with ASD. Depressive symptoms did not significantly predict communication or daily living skills.Conclusions: These findings highlight the relevance of depression in social adaptive function in ASD and emphasize the importance of assessing depressive symptomatology when evaluating social skills and planning treatment for children and adolescents with ASD.

Neurocognitive Measures of Self-blame and Risk Prediction Models of Recurrence in Major Depressive Disorder.

BACKGROUND: Overgeneralized self-blaming emotions, such as self-disgust, are core symptoms of major depressive disorder and prompt specific actions (i.e., action tendencies), which are more functionally relevant than the emotions themselves. We have recently shown, using a novel cognitive task, that when feeling self-blaming emotions, maladaptive action tendencies (feeling like hiding and feeling like creating a distance from oneself) and an overgeneralized perception of control are characteristic of major depressive disorder, even after remission of symptoms. Here, we probed the potential of this cognitive signature, and its combination with previously employed functional magnetic resonance imaging (fMRI) measures, to predict individual recurrence risk. For this purpose, we developed a user-friendly hybrid machine/statistical learning tool, which we make freely available. METHODS: A total of 52 medication-free patients with remitted major depressive disorder, who had completed the action tendencies task and our self-blame fMRI task at baseline, were followed up clinically over 14 months to determine recurrence. Prospective prediction models included baseline maladaptive self-blame-related action tendencies and anterior temporal fMRI connectivity patterns across a set of frontolimbic a priori regions of interest, as well as including established clinical and standard psychological predictors. Prediction models used elastic net regularized logistic regression with nested 10-fold cross-validation. RESULTS: Cross-validated discrimination was highly promising (area under the receiver-operating characteristic curve ≥ 0.86), and positive predictive values over 80% were achieved when including fMRI in multimodal models, but only up to 71% (area under the receiver-operating characteristic curve ≤ 0.74) when solely relying on cognitive and clinical measures. CONCLUSIONS: This study shows the high potential of multimodal signatures of self-blaming biases to predict recurrence risk at an individual level and calls for external validation in an independent sample.

Maladaptive blame-related action tendencies are associated with vulnerability to major depressive disorder.

Biases towards self-blaming emotions, such as self-contempt/disgust, were previously associated with vulnerability to major depressive disorder (MDD). Self-blaming emotions are thought to prompt specific action tendencies (e.g. "feeling like hiding"), which are likely to be more important for psychosocial functioning than the emotions themselves. Systematic investigations, however, of these action tendencies in MDD are lacking. Here, we investigated the role of blame-related action tendencies for MDD vulnerability and their relationship with blame-related emotions. 76 participants with medication-free remitted MDD and 44 healthy control (HC) participants without a history of MDD completed the value-related moral sentiment task, which measured their blame-related emotions during hypothetical social interactions and a novel task to assess their blame-related action tendencies (feeling like hiding, apologising, creating a distance from oneself, attacking oneself, creating a distance from other, attacking other, no action). As predicted, the MDD group showed a maladaptive profile of action tendencies: a higher proneness to feeling like hiding and creating a distance from themselves compared with the HC group. In contrast, feeling like apologising was less common in the MDD than the HC group. Apologising for one's wrongdoing was associated with all self-blaming emotions including shame, guilt, self-contempt/disgust and self-indignation. Hiding was associated with both shame and guilt. Our study shows that MDD vulnerability was associated with specific maladaptive action tendencies which were independent of the type of emotion, thus unveiling novel cognitive markers and neurocognitive treatment targets.

Development and validation of the Maudsley Modified Patient Health Questionnaire (MM-PHQ-9).

BACKGROUND: The Patient Health Questionnaire-9 (PHQ-9) is a widely used measure of depression in primary care. It was, however, originally designed as a diagnostic screening tool, and not for measuring change in response to antidepressant treatment. Although the Quick Inventory of Depressive Symptomology (QIDS-SR-16) has been extensively validated for outcome measurement, it is poorly adopted in UK primary care, and, although free for clinicians, has licensing restrictions for healthcare organisation use. AIMS: We aimed to develop a modified version of the PHQ-9, the Maudsley Modified PHQ-9 (MM-PHQ-9), for tracking symptom changes in primary care. We tested the measure's validity, reliability and factor structure. METHOD: A sample of 121 participants was recruited across three studies, and comprised 78 participants with major depressive disorder and 43 controls. MM-PHQ-9 scores were compared with the QIDS-SR-16 and Clinical Global Impressions improvement scale, for concurrent validity. Internal consistency of the scale was assessed, and principal component analysis was conducted to determine the items' factor structure. RESULTS: The MM-PHQ-9 demonstrated good concurrent validity with the QIDS-SR-16, and excellent internal consistency. Sensitivity to change over a 14-week period was d = 0.41 compared with d = 0.61 on the QIDS-SR-16. Concurrent validity between the paper and mobile app versions of the MM-PHQ-9 was r = 0.67. CONCLUSIONS: These results indicate that the MM-PHQ-9 is a valid and reliable measure of depressive symptoms in paper and mobile app format, although further validation is required. The measure was sensitive to change, demonstrating suitability for use in routine outcome assessment.

Attention-deficit/ hyperactivity disorder symptoms and suicidal ideation among college students: A structural equation modeling approach.

OBJECTIVE: Suicidal ideation (SI) among college students is frequently reported. However, the mediating roles of depressive and anxiety symptoms between attention-deficit/hyperactivity disorder (ADHD) symptoms and SI has yet to be explored among college students. METHOD: A cross-sectional survey of college freshmen in China was conducted between October 2018 and December 2018. Standardized questionnaires were used to collect information on basic sociodemographic characteristics, including SI, ADHD symptoms, and anxiety and depressive symptoms. A structural equation model (SEM) was then constructed. RESULTS: A total of 904 college freshmen were included in the analysis. The prevalence of ADHD symptoms and lifetime SI were 11.9% (95% CI: 9.9%-14.2%) and 29.2% (95% CI: 26.3%-32.2%), respectively. The SEM revealed that there were no direct paths from inattention, executive dysfunction, and hyperactivity to SI. Under the mediating role of anxiety and depressive symptoms, executive dysfunction (ß = 0.011, p < 0.05) and hyperactivity (ß = 0.015, p < 0.05) had indirect relationships with the risk of SI, and the role of inattention was not identified. Depressive and anxiety symptoms had direct influences on increasing SI. There also were indirect effects from anxiety symptoms to SI, which were mediated by depressive symptoms (ß = 0.023, p < 0.001). CONCLUSIONS: The current study indicated the indirect relationships between ADHD symptoms and SI among college freshmen. The findings could provide useful clues for clinical treatment and school-based prevention that aims to improve college students' mental well-being.

Developing a Text Messaging Intervention to Reduce Deliberate Self-Harm in Chinese Adolescents: Qualitative Study.

BACKGROUND: Deliberate self-harm is common during adolescence and can have detrimental consequences for the well-being of adolescents. Although it is sometimes difficult to engage adolescents in traditional psychotherapies for deliberate self-harm, SMS text messaging has been shown to be promising for cost-effective and low-intensity interventions. OBJECTIVE: This study aimed to investigate the views of Chinese adolescents with deliberate self-harm about SMS text messaging interventions in order to develop an acceptable and culturally competent intervention for adolescents with deliberate self-harm. METHODS: Semistructured interviews were conducted with 23 adolescents who had experience with deliberate self-harm. The transcripts of the interviews were analyzed using thematic analysis. RESULTS: Four themes were identified: beneficial perception of receiving messages, short frequency and duration of messages, caring content in messages, and specific times for sending messages. Most of the participants perceived SMS text messaging interventions to be beneficial. The key factors that emerged for the content of the intervention included encouragement and company, feeling like a virtual friend, providing coping strategies, and individualized messages. In addition, the preferred frequency and duration of the SMS text messaging intervention were identified. CONCLUSIONS: Our study will help in the development of a culturally appropriate SMS text messaging intervention for adolescents with deliberate self-harm. It has the potential to decrease deliberate self-harm instances by providing acceptable support for adolescents with deliberate self-harm who may be reluctant to seek face-to-face psychotherapies.

Bullying victimization, bullying witnessing, bullying perpetration and suicide risk among adolescents: A serial mediation analysis.

INTRODUCTION: Prior work suggests that involvement in bullying was associated with a higher suicide risk among adolescents. However, the mechanisms of this association remain unclear. The present study aimed to understand the relationship between direct and indirect involvement in bullying (bullying victimization, bullying perpetration and bullying witnessing) and suicide risk by examining the serial mediation of negative coping styles and depressive symptoms. METHODS: 12,354 Chinese adolescents (mean age = 15.00, 54% male) were recruited from December 2018 to January 2019 in 18 secondary schools. Participants completed questionnaires that measured their direct and indirect involvement in bullying, negative coping styles, depressive symptoms, and suicide risk. RESULTS: The relationship between involvement in bullying and suicide risk was mediated by negative coping styles, depressive symptoms, and also serially mediated by negative coping styles and depressive symptoms. Similar findings were obtained for both direct and indirect involvement in bullying. LIMITATIONS: The present study is limited by a cross-sectional design. Future studies could examine longitudinal changes in the outcome measures CONCLUSIONS: Given the urgent need to reduce the high suicide rate among adolescents in China, our findings suggest that having a less negative coping style is an important protective factor. These results provide direction for the development of prevention strategies and targeted interventions within this population. Additionally, it is essential to develop prevention strategies and interventions not only for those who have been a victim or perpetrator of bullying, but also for those who have witnessed bullying.

The relationship between mobile phone use and suicide-related behaviors among adolescents: The mediating role of depression and interpersonal problems.

BACKGROUND: This study examined (a) the relationship that interpersonal problems and depression share with the intensity of mobile phone use and (b) their effects on suicide-related behaviors (SRBs) and self-harming behaviors among adolescents. METHODS: In this cross-sectional study, adolescents were recruited from 11 middle and high schools in Shenzhen, China. They completed self-reported measures that assessed mobile phone use, their history of SRBs (i.e., suicidal ideation, suicidal planning, and attempted suicide) and self-harming behaviors, depression, and interpersonal problems. RESULTS: Interpersonal problems and depression mediated the relationship between high-intensity mobile phone use and the risk for SRBs and self-harming behaviors among Chinese adolescents. CONCLUSIONS: The findings delineate the pathways through which interpersonal problems and depression increase the risk for SRBs and self-harming behaviors among adolescents who report high-intensity mobile phone use. Future studies should develop interventions that alleviate interpersonal problems and depressive symptoms to reduce the risk for SRBs and self-harming behaviors among adolescents who report high-intensity mobile phone use.

The relationship between childhood trauma and Internet gaming disorder among college students: A structural equation model.

BACKGROUND: The aim of this study was to investigate the mechanisms of Internet gaming disorder (IGD) and the associated interaction effects of childhood trauma, depression and anxiety in college students. METHODS: Participants were enrolled full-time as freshmen at a University in the Hunan province, China. All participants reported their socio-demographic characteristics and undertook a standardized assessment on childhood trauma, anxiety, depression and IGD. The effect of childhood trauma on university students' internet gaming behaviour mediated by anxiety and depression was analysed using structural equation modelling (SEM) using R 3.6.1. RESULTS: In total, 922 freshmen participated in the study, with an approximately even male-to-female ratio. A mediation model with anxiety and depression as the mediators between childhood trauma and internet gaming behaviour allowing anxiety and depression to be correlated was tested using SEM. The SEM analysis revealed that a standardised total effect of childhood trauma on Internet gaming was 0.18, (Z = 5.60, 95% CI [0.02, 0.05], P < 0.001), with the direct effects of childhood trauma on Internet gaming being 0.11 (Z = 3.41, 95% CI [0.01, 0.03], P = 0.001), and the indirect effects being 0.02 (Z = 2.32, 95% CI [0.00, 0.01], P = 0.020) in the pathway of childhood trauma-depression-internet gaming; and 0.05 (Z = 3.67, 95% CI [0.00, 0.02], P < 0.001) in the pathway of childhood trauma-anxiety-Internet gaming. In addition, the two mediators anxiety and depression were significantly correlated (r = 0.50, Z = 13.54, 95% CI [3.50, 5.05], P < 0.001). CONCLUSIONS: The study revealed that childhood trauma had a significant impact on adolescents' Internet gaming behaviours among college students. Anxiety and depression both significantly mediated the relationship between childhood trauma and internet gaming and augmented its negative influence. Discussion of the need to understand the subtypes of childhood traumatic experience in relationship to addictive behaviours is included.

A meta-analysis on the relationship between interoceptive awareness and alexithymia: Distinguishing interoceptive accuracy and sensibility.

Alexithymia-a trait associated with difficulties understanding one's own emotions-is theorized to stem from deficits in interoceptive awareness, or the ability to detect, accurately monitor, and regulate internal bodily processes. The present meta-analysis analyzed all studies that empirically examined the relationship between alexithymia and interoceptive awareness. Across 66 independent samples (N = 7,146), alexithymia had a small, negative correlation with interoceptive awareness (r = -.162, p = .001, 95% CI [-.252, -.068]), but additional analyses revealed that the strength and directionality of this association was heavily influenced by the specific interoceptive awareness components measured (e.g., interoceptive accuracy vs. sensibility) and the methods used to measure interoceptive awareness (e.g., objective vs. self-report measures). The strength of this relationship was also moderated by diagnosis of participants such that alexithymia was moderately associated with interoceptive awareness in samples with psychiatric and developmental disorders, but the relationship was nonsignificant in healthy, typically developing samples. Results suggest interoception may represent a shared transdiagnostic vulnerability that underlies atypical emotional processing in a variety of disparate clinical populations but that current operationalization and measurement of interoceptive awareness continues to create confusion and inconsistency in the literature. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Rhodioloside ameliorates depressive behavior via up-regulation of monoaminergic system activity and anti-inflammatory effect in olfactory bulbectomized rats.

Rhodioloside, a major constituent from roots of Rhodiola rosea, has been previously confirmed to alleviate the hyperactivity in olfactory bulbectomized (OBX) rats exposed to the open field and to decrease the immobility time in the forced swimming test (FST) and tail suspension test (TST). However, its antidepressant effects and mechanisms remain unclear. This study aimed to evaluate the antidepressant effect and the potential mechanisms of rhodioloside in OBX rats. ELISA kits, HPLC-MS and western blot analysis were applied to explore the underlying antidepressant mechanisms of rhodioloside. Rhodioloside (20, 40mg/kg) significantly reversed OBX-induced reduction in sucrose consumption. It was also observed that administration of rhodioloside (20, 40mg/kg) decreased pro-inflammatory cytokines interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) levels and inhibits nuclear factor-kappa B (NF-κB) activation, as well as normalized the monoaminergic system changes in prefrontal cortex (PFC) of OBX rats. These results confirmed the antidepressant-like effect of rhodioloside, which might be primarily based on its up-regulation of the monoaminergic system activity and anti-inflammatory effect.