To examine the influence of postpartum exercise on maternal depression and anxiety.

Systematic review with random effects meta-analysis and meta-regression.

Online databases up to 12 January 2024, reference lists, recommended studies and hand searches.

Randomised controlled trials (RCTs) and non-randomised interventions of any publication date or language were included if they contained information on the Population (postpartum people), Intervention (subjective or objective measures of frequency, intensity, duration, volume, type, or mode of delivery of exercise), Comparator (no exercise or different exercise measures), and Outcome (postpartum depression, anxiety prevalence, and/or symptom severity).

A total of 35 studies (n=4072) were included. Moderate certainty evidence from RCTs showed that exercise-only interventions reduced the severity of postpartum depressive symptoms (19 RCTs, n=1778, SMD: -0.52, 95% CI -0.80 to -0.24, I2=86%, moderate effect size) and anxiety symptoms (2 RCTs, n=513, SMD: -0.25, 95% CI -0.43 to -0.08, I2=0%, small effect size), and the odds of postpartum depression by 45% (4 RCTs, n=303 OR 0.55, 95% CI 0.32 to 0.95, I2=0%) compared with no exercise. No included studies assessed the impact of postpartum exercise on the odds of postpartum anxiety. To achieve at least a moderate reduction in the severity of postpartum depressive symptoms, postpartum individuals needed to accumulate at least 350 MET-min/week of exercise (eg, 80 min of moderate intensity exercise such as brisk walking, water aerobics, stationary cycling or resistance training).

Postpartum exercise reduced the severity of depressive and anxiety symptoms and the odds of postpartum depression.

This investigation aims to examine the connection between the aggregate index of systemic inflammation (AISI) and depression, using data from the National Health and Nutrition Examination Survey (NHANES) database.

We conducted a cross-sectional study using data from the NHANES collected between 2005 and 2018. Depression was assessed via the patient health questionnaire-9. To investigate the connection between AISI and the prevalence of depression, we employed weighted multivariable logistic regression models as well as restricted cubic spline (RCS) models. This study also performed subgroup and interaction analyses to further explore these associations. Additionally, threshold effect and saturation effect analyses were conducted to identify potential inflection points for AISI and depression. Finally, we compared the area under the curve (AUC) values from receiver operating characteristic (ROC) analyses to assess the diagnostic capability of the optimal model for depression.

This study initially recruited 29,092 individuals, of whom 2596 had depression. After adjusting for potential confounders, we discovered a higher AISI was significantly linked with an higher risk of depression when comparing the highest to the lowest quantile of AISI (odds ratio: 1.205; 95 % confidence interval: 1.019-1.424; P = 0.032). Marital status interacted with AISI to influence the prevalence of depression (P for trend = 0.0275). The curve for participants was U-shaped, with an optimal AISI value of 828.8, and a non-linear relationship was found between AISI and depression (P for log-likelihood ratio test <0.001). ROC analysis indicated that AISI had a stronger discriminative ability and accuracy in predicting depression compared to other inflammatory biomarkers.

The AISI level exhibited a U-shaped association with depression, indicating that maintaining AISI within a reasonable range may help reduce the prevalence of depression.

Anxiety and depression are highly comorbid with each other, warranting a need to better understand transdiagnostic mechanisms. Anhedonia has been hypothesized as a transdiagnostic mechanism but has often been investigated as a unidimensional factor. Thus, the current study examined how anticipatory and consummatory anhedonia, including how they interact with anxiety, predict next-week depression. Participants (N = 101) completed weekly assessments of anxiety, depression, and anhedonia. Using an iterative approach, we constructed four models to investigate independent and interactive effects of prior-week anxiety and anhedonia on next-week depression, as well as the effects of depression and anhedonia on anxiety. Our results indicate that anticipatory anhedonia is associated with next-week depression, and the association between anxiety and depression is greater when anticipatory anhedonia is high. The current findings provide insight into the transdiagnostic nature of anticipatory anhedonia between anxiety and depression. Future work should investigate how these associations may unfold over shorter time periods.

This article describes change in health status by analyzing key health domains at two time points before and during the COVID-19 pandemic among a sample of American Indian/Alaska Native (AI/AN) adolescents living outside of tribal land (n = 114) throughout California.

Data were analyzed from a longitudinal study, Native American Youth Sleep Health and Wellness (NAYSHAW). To test changes in health from baseline (March 2018-March 2020) to follow-up (December 2020-June 2022), we ran a series of linear regression models for continuous measures and repeated measures logistic regression models for dichotomous measures for physical health, behavioral health, and cultural contexts of health and well-being.

For physical health, body mass index percentile significantly decreased (p = 0.02), and both systolic and diastolic blood pressure significantly increased (p < 0.001 for both), although both measures remained within the normal range for adolescents. For behavioral health, depression and anxiety significantly increased (p = 0.005 and 0.008, respectively), although they remained within subclinical levels, and no significant changes were observed with alcohol and cannabis use. For cultural contexts of health and well-being, both cultural identity and sense of historical loss significantly increased (p < 0.001 and p = 0.03, respectively).

We observed a mix of positive and negative health changes among AI/AN adolescents living outside of tribal land before and during COVID-19. Findings highlight that enhanced cultural identity during adolescence may have helped foster resilience during this difficult period.

Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) are debilitating stress-related psychiatric disorders that can develop following exposure to traumatic events or chronic stress in some individuals. The neurobiological processes leading to disease remain largely unknown. Among others, these disorders are characterized by a dysregulated hypothalamic-pituitary-adrenal axis, which is regulated by the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). This leads to altered downstream corticosteroid-induced gene expression. In vitro models are promising tools to investigate specific neurobiological underpinnings of the stress response in the brain. Here, we investigated the suitability of SH-SY5Y-derived neurons as a cost-efficient system to study the role of GR and MR in the neuronal stress response. SH-SY5Y-derived neurons were characterized, exposed to corticosteroids, and analyzed on transcriptomic and proteomic levels. We show that (i) these neurons express sufficient and seemingly functional GR and MR to allow the study of corticosteroid-induced transcription, (ii) three corticosteroids cortisol, dexamethasone, and aldosterone, induced similar transcriptomic effects, (iii) the antagonist spironolactone mildly attenuated the effects of dexamethasone in FKBP5, DUSP1, and SUPV3L1. Mifepristone did not significantly alter the effect of aldosterone. (iv) Integrating transcriptomic alterations of these corticosteroid-exposed neurons with those of iPSC-derived neurons exposed to dexamethasone showed concordant corticosteroid-induced effects in the two in vitro systems. To determine translational validity, we compared the gene expression in these neurons with the transcriptome of postmortem brain samples from individuals with PTSD and MDD, yielding stronger negative correlations of corticosteroid effects in SH-SY5Y-derived neurons with PTSD signatures than with MDD signatures. Upon further refinement and validation, SH-SY5Y-derived neurons may serve as a simplistic tool to study neuronal corticosteroid-induced gene expression and the implicated molecular networks around GR and MR. Strengthening our insight into these receptors' functions improves our understanding of the hypothalamic-pituitary-adrenal axis, which is commonly altered in stress-related psychiatric disorders such as PTSD and MDD.

Major depressive disorder (MDD), a psychiatric disorder characterized by functional brain deficits, poses considerable diagnostic and treatment challenges, especially in adolescents owing to varying clinical presentations. Biomarkers hold substantial clinical potential in the field of mental health, enabling objective assessments of physiological and pathological states, facilitating early diagnosis, and enhancing clinical decision-making and patient outcomes. Recent breakthroughs combine neuroimaging with machine learning (ML) to distinguish brain activity patterns between MDD patients and healthy controls, paving the way for diagnostic support and personalized treatment. However, the accuracy of the results depends on the selection of neuroimaging features and algorithms. Ensuring privacy protection, ML model accuracy, and fostering trust are essential steps prior to clinical implementation. Future research should prioritize the establishment of comprehensive legal frameworks and regulatory mechanisms for using ML in MDD diagnosis while safeguarding patient privacy and rights. By doing so, we can advance accuracy and personalized care for MDD.

Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective therapy for treatment-resistant depression (TRD). A crucial next step in improving rTMS therapy is to identify response predictors to inform patient selection criteria. Brain-derived neurotrophic factor (BDNF) exerts influence over TRD treatment modalities. BDNF polymorphism, Val66Met, has shown altered cortical plasticity after single-session rTMS in healthy subjects and clinical response in noninvasive brain stimulation methods in major depressive disorder, stroke, Alzheimer's, and cerebral palsy. We sought to evaluate the effect of this BDNF polymorphism on clinical response in a standard course of rTMS therapy for TRD.

In this naturalistic study, 75 patients with TRD completed a standard course of rTMS with weekly clinical assessments via the Inventory of Depressive Symptomatology Self-Report (IDS-SR). BDNF polymorphisms were retrospectively compared in respect to treatment response and remission, baseline and final scores, percent change scores, and scores across the 6-week treatment course.

As expected, rTMS significantly decreased depressive symptoms as measured by IDS-SR scores. No difference was found in baseline, final, or percent change IDS-SR scores between polymorphism types. There was no difference between polymorphisms in IDS-SR scores across the treatment course. Response and remission rates did not differ between genotypes.

In contrast to previous research highlighting differential response between BDNF polymorphisms to motor plasticity and clinical rTMS outcomes, our data suggest that BDNF polymorphism status may not influence the response to a standard course of 10-Hz rTMS for major depressive disorder. Differences in TMS protocol, target, or BDNF serum levels may underlie our results.

Retrospective Cohort.

We investigate whether duration of symptoms a patient experiences prior to lumbar microdiscectomy affects pain, lifestyle, and return to work metrics after surgery.

A retrospective review of patients with a diagnosis of lumbar radiculopathy undergoing microdiscectomy was conducted using a statewide registry. Patients were grouped based on self-reported duration of symptoms prior to surgical intervention (Group 1: symptoms less than 3 months; Group 2: symptoms between 3 months and 1 year; and Group 3: symptoms greater than 1 year). Radicular pain scores, PROMIS PF Physical Function measure (PROMIS PF), EQ-5D scores, and return to work rates at 90 days, 1 year, and 2 years after surgery were compared using univariate and multivariate analysis.

There were 2408 patients who underwent microdiscectomy for lumbar disc herniation for radiculopathy with 532, 910, and 955 in Groups 1, 2, and 3, respectively. Postoperative leg pain was lower for Group 1 at 90 days, 1 year, and 2 years compared to Groups 2 and 3 (P < .05). Postoperative PROMIS PF and EQ-5D scores were higher for Group 1 at 90 days, 1 year, and 2 years compared to Groups 2 and 3 (P < .05).

Patients with prolonged symptoms prior to surgical intervention experience smaller improvements in postoperative leg pain, PROMIS PF, and EQ-5D than those who undergo surgery earlier. Patients undergoing surgery within 3 months of symptom onset have the highest rates of return to work at 1 year after surgery.

Device-based treatments exist in psychiatry for decades, but are usually operated by clinicians and require multiple office visits. Near-infrared transcranial photobiomodulation (tPBM) is a safe neurostimulation modality with potential antidepressant and hypnotic effects. We investigated the feasibility and efficacy of adjunctive tPBM treatment, self-administered by a wearable headband.

We randomized 48 outpatients with major depressive disorder (MDD) into tPBM or sham with 1:1 ratio. All participants were advised to receive the device-based intervention for at least 20 min daily at their preferred time and place for 8 weeks. The compliance and adverse events were monitored throughout the trial. The Hamilton Depression Rating Scale (HAMD), Beck's Depression Inventory (BDI) and Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the symptoms from baseline until week-12.

Participants reported this self-administered intervention well-tolerated. Treatment compliance was equally good between various group-comparisons, and the adverse effects were minimal and transient. Post-treatment, the HAMD and BDI scores of patients in both tPBM group and sham group significantly decreased compared to baseline, with no between-group difference. However, a significant PSQI score reduction was only found in tPBM group from week-2 onward compared with baseline, with significant between-group difference lasting until week-12 (F1,46 = 6.16, p = 0.017).

This smaller sample size and short treatment and follow-up durations.

Self-administered wearable tPBM appears to be a feasible and well-tolerated in MDD patients. The low-level dosimetry appeared insufficient to produce an antidepressant effect but effective in improving sleep quality. Further studies should investigate different dosimetry and intervention time. CLINICAL TRIALS REGISTRATION NUMBER IN CLINICALTRIAL.GOV: NCT04619121.

Electroconvulsive therapy (ECT) is recognized as one of the most efficacious interventions for depression. However, it is associated with impairments in learning and memory functions. Ketamine has demonstrated potential in mitigating cognitive deficits. Notably, the metabotropic glutamate system is hypothesized to play a pivotal role in cognitive process regulation. Nevertheless, the involvement of the metabotropic glutamate system in esketamine-mediated alleviation of electroconvulsive shock (ECS, an animal analogue of ECT)-induced memory impairment remains to be elucidated. In this study, a depressive rat model was established using chronic unpredictable mild stress. The depressive-like behavior and cognitive performance of the rats were evaluated using the sucrose preference test, the open field test, and the Morris water maze test, respectively. The expression levels of type-5 metabotropic glutamate receptor (mGluR5) and N-methyl-d-aspartate receptor 1 (NMDAR1) were quantified through immunofluorescence and real-time PCR techniques. Long-term potentiation (LTP) of hippocampal Schaffer collateral (SC)-CA1 synapses was observed in electrophysiological experiments. The results of this investigation revealed that a low dose of esketamine administration upregulated the expression of mGluR5 and NMDAR1 in the hippocampus of stressed rats, alleviated ECS-induced cognitive impairment, and ameliorated depressive-like behavior. Conversely, the mGluR5 antagonist MTEP effectively reversed esketamine-mediated changes in the rat hippocampus and counteracted its protective effect on learning and memory functions following ECS. In conclusion, the findings of this study support the hypothesis that esketamine upregulates mGluR5 and NMDAR1 expression, thereby enhancing NMDAR activation in the hippocampus. This mechanism may be responsible for the protective effects on spatial learning and memory function observed in depressed rats subjected to ECS.

This study aimed to investigate oxidative stress markers in the oral mucosal cells of individuals diagnosed with major depressive disorder (MDD).

A case-control design was used, including twenty patients diagnosed with MDD, based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, and twenty healthy controls. Oral exfoliated cells were collected from all participants. Intracellular levels of reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), caspase-3 and -7 activity, and reduced glutathione (GSH) were measured in Arbitrary Fluorescence Units (AFU).

The MDD group demonstrated significantly elevated intracellular ROS levels (p = 0.0012) and caspase-3 and -7 activity (p = 0.0171) in comparison to the control group. Additionally, a decrease in ΔΨm expression was observed in the oral cells of MDD patients (p = 0.0265), whereas GSH expression levels did not differ significantly between the two groups (p = 0.8908).

The findings indicate heightened oxidative stress in the oral exfoliated cells of individuals with MDD. This study supports the potential use of oral cells as a non-invasive biomarker source for assessing oxidative stress in depressive disorders.

Optogenetics and chemogenetics are emerging neuromodulation techniques that have attracted significant attention in recent years. These techniques enable the precise control of specific neuronal types and neural circuits, allowing researchers to investigate the cellular mechanisms underlying depression. The advancement in these techniques has significantly contributed to the understanding of the neural circuits involved in depression; when combined with other emerging technologies, they provide novel therapeutic targets and diagnostic tools for the clinical treatment of depression. Additionally, these techniques have provided theoretical support for the development of novel antidepressants. This review primarily focuses on the application of optogenetics and chemogenetics in several brain regions closely associated with depressive-like behaviors in rodent models, such as the ventral tegmental area, nucleus accumbens, prefrontal cortex, hippocampus, dorsal raphe nucleus, and lateral habenula and discusses the potential and challenges of optogenetics and chemogenetics in future research. Furthermore, this review discusses the potential and challenges these techniques pose for future research and describes the current state of research on sonogenetics and odourgenetics developed based on optogenetics and chemogenetics. Specifically, this study aimed to provide reliable insights and directions for future research on the role of optogenetics and chemogenetics in the neural circuits of depressive rodent models.

Gender differences in glucose metabolism disorders in patients with major depressive disorder (MDD) have been rarely studied. In this study we investigated gender differences in the prevalence of glucose metabolism disorders and associated factors in first-episode and drug naïve (FEDN) MDD patients in a Chinese Han population. In this cross-sectional study, a total of 1718 FEDN MDD outpatients were recruited, and demographic and clinical data were collected. All subjects were scored using the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and the Positive and Negative Syndrome Scale (PANSS) positive subscale to assess clinical symptoms. Female MDD patients were older, present with symptoms at an older age, were more likely to be married and had more psychotic symptoms than male MDD patients. There was no significant difference in the prevalence of glucose metabolism disorders between female patients (14.16%) and male patients (12.59%) (p > 0.05). In both male and female groups, patients with glucose metabolism disorders had higher HAMD score, HAMA score, suicide attempts, and psychotic symptoms than patients without glucose metabolism disorders (all p < 0.05). However, only in female group, patients with glucose metabolism disorders had more severe anxiety symptoms than patients without glucose metabolism disorders. Furthermore, binary logistic regression analysis showed that psychotic symptoms and suicide attempts were independently associated with glucose metabolism disorders in male MDD patients, while suicide attempts and HAMD score was independently associated with glucose metabolism disorders in female MDD patients. Our findings showed no gender differences in the prevalence of glucose metabolism disorders in patients with FEDN MDD. However, there were gender difference in the clinical correlates of glucose metabolism disorders in FEDN MDD patients.

Mental health assessment is typically carried out via a series of conversation sessions with medical professionals, where the overall aim is the diagnosis of mental illnesses and well-being evaluation. Despite its arguable socioeconomic significance, national health systems fail to meet the increased demand for such services that has been observed in recent years. To assist and accelerate the diagnosis process, this work proposes an AI-based tool able to provide interpretable predictions by automatically processing the recorded speech signals. An explainability-by-design approach is followed, where audio descriptors related to the problem at hand form the feature vector (Mel-scaled spectrum summarization, Teager operator and periodicity description), while modeling is based on Hidden Markov Models adapted from an ergodic universal one following a suitably designed data selection scheme. After extensive and thorough experiments adopting a standardized protocol on a publicly available dataset, we report significantly higher results with respect to the state of the art. In addition, an ablation study was carried out, providing a comprehensive analysis of the relevance of each system component. Last but not least, the proposed solution not only provides excellent performance, but its operation and predictions are transparent and interpretable, laying out the path to close the usability gap existing between such systems and medical personnel.

Depression is common in patients with gliomas, but few studies focused on the association between depression and glioma laterality.

This study was purposed to investigate depression difference and prognostic value between patients with left-hemispheric gliomas and right-hemispheric gliomas.

This study included 212 patients with left-hemispheric gliomas and 218 patients with right-hemispheric gliomas. Hospital Anxiety and Depression Scale (HADS) and Zung self-rating depression scale (SDS) were independently performed before surgery, 3 months and 6 months after surgery. All patients were followed up to death or 36 months. Overall survival (OS) and progression-free survival (PFS) were performed to evaluate the survival of glioma patients.

The preoperative prevalence and scores of depression in patients with left-hemispheric gliomas were higher than those in patients with right-hemispheric gliomas. But there were no differences in postoperative prevalence and scores of depression between patients with left-hemispheric gliomas and right-hemispheric gliomas. In patients with left-hemispheric gliomas or with right-hemispheric gliomas, the preoperative scores of depression were higher than postoperative scores of depression, whereas there was no difference in depression score between 3 months after surgery and 6 months after surgery. In addition, patients with right-hemispheric gliomas had better PFS and OS than patients with left-hemispheric gliomas.

Patients with left-hemispheric gliomas are more likely to bring about depression than patients with right-hemispheric gliomas. Besides, patients with right-hemispheric gliomas are more likely to have better survival than patients with left-hemispheric gliomas. Surgery is considered as a useful treatment to alleviate depression of glioma patients.

Depression frequently occurs among individuals suffering from chronic kidney disease (CKD), diminishing life quality considerably while accelerating the disease course. This study aims to create a predictive model to identify patients with CKD at high risk for depression.

Analysis of cross-sectional data.

US National Health and Nutrition Examination Survey (2007-2014).

A total of 2303 patients with CKD (weighted=17 422 083) with complete data were included in the analysis.

We used the least absolute shrinkage and selection operator regression for variable selection and constructed a weighted logistic regression model through stepwise backward elimination based on minimisation of the Akaike information criterion, visualised with a nomogram. Internal validation was conducted using 1000 bootstrap resamples. Model discrimination was assessed using receiver operating characteristic curves, calibration was evaluated using the Hosmer-Lemeshow test and calibration curves, and net benefits and clinical impact were analysed using decision curve analysis and comparative impact chart curves.

The final model included 10 predictors: age, gender, poverty income ratio, body mass index, smoking, sleep time, sleep disorder, chest pain, diabetes and arthritis. The model achieved an area under the curve of 0.776 (95% CI 0.745 to 0.806) with good fit (Hosmer-Lemeshow p=0.805). Interventions within the 0.1-0.6 probability range showed significant benefits.

We have crafted a predictive model with good discriminative power that could potentially help clinicians identify patients with CKD at high risk for depression, thereby facilitating early intervention and improving the prognosis of these patients.

Major depressive disorder (MDD) and bipolar disorder (BD) share various clinical behaviors and have confounded clinical diagnoses. Converging studies have suggested MDD and BD as disorders with abnormal communication among functional brain networks involved in mental activity and redirection. However, whether MDD and BD show disease-specific alterations in network information interaction remains unclear. This study collected resting-state functional MRI data of 98 patients with MDD, 55 patients with BD, and sex-, age-, and education-matched 95 healthy controls. Spectral dynamic causal model (spDCM) was used to investigate effective connectivities among three large-scale intrinsic functional networks including the default mode network (DMN), salience network (SN), and dorsal attention network (DAN). Effective connectivities showing disease-specific changes were then used as input features of support vector models to predict clinical symptoms and classify individuals with MDD and BD. Compared with healthy controls, both the MDD and BD groups showed increased DAN → SN connectivity. However, within-network connectivities of DMN and DAN showed opposite effects on the diseases. Notably, MDD and BD also showed different alterations on a connectivity loop of SN → DAN → DMN → SN, which could be used to predict the clinical symptom severity of either MDD or BD. Individuals with MDD and BD could be further classified by using connectivities showing opposite disease effects. Our findings reveal common and unique alterations of network interactions in MDD and BD, and further suggest disease-specific neuroimaging markers for clinical diagnosis.

The current study aimed to explore participants' views on the acceptability, impact and mechanisms of change of Augmented Depression Therapy (ADepT), a novel wellbeing-focused and recovery-oriented psychological therapy for depression.

A semi-structured qualitative interview design was used, with data analysed using the framework approach.

20 participants with anhedonic depression who had received up to 20 sessions of ADepT, sampled from a pilot randomised controlled trial of ADepT versus Cognitive Behavioural Therapy (CBT).

A primary care psychological therapy clinic in Devon, UK, with interviews occurring between May 2018 and February 2020.

Participants found the wellbeing focus of ADepT acceptable. Helpful aspects of therapy were a positive therapeutic bond, the structure and flow of therapy scaffolding the learning journey, the tools and techniques of therapy helping building wellbeing and booster sessions supporting long-term recovery. Negative aspects for some participants were therapy feeling too intense and triggering feelings of failure. Participants reported significant positive impacts of treatment on wellbeing, functioning and hope. Perceived mechanisms of change were reorienting to the positive, engaging with valued goals, taking a proactive life stance, gaining confidence and motivation for change, breaking down tasks into small steps, cultivating self-care and self-compassion, enhancing help seeking and interpersonal effectiveness, changing the relationship to depression, and rediscovering the self beyond depression.

Findings suggest that the wellbeing focus of ADepT is acceptable and leads to positive impacts, supports the logic model underpinning the intervention, and warrants continuation to a definitive trial.

ISRCTN85278228.

In the present study authors studied the effect of caffeic acid (CA) in chronic unpredictable mild stress (CUMS) and dexamethasone (DEXA) model of depression. CUMS (21 days) and DEXA (1.5 mg/kg × 21 days) was used for the induction of depression and anxiety related behavior. Locomotor activity was determined using actophotometer. Depression related behavior was determined using tail suspension test (TST) and forced swim test (FST) whereas for the determination of anxiety related behavior elevated plus maze (EPM) test was used. Following behavioral studies, mice were sacrificed by decapitation method. Hippocampus was dissected and was used for the neurochemical assays including 5-HT (serotonin), glutamate, nitrite and gamma-aminobutyric acid (GABA). The results obtained suggested that the CA (25-100 mg/kg, i.p.) did not affect the activity count in CUMS exposed and DEXA treated mice. CA (50 mg/kg) evoked anxiogenic reactions in CUMS model by increasing the hippocampal nitrite and glutamate level while CA (50 mg/kg) exerted anxiolysis in DEXA model by reducing the level of 5-HT. In CUMS model, CA exerted antidepressant like effect by increasing the hippocampal nitric oxide (NO) level, in DEXA model CA exerted antidepressant like effect by reducing the hippocampal glutamate level. CA failed to reverse DEXA mediated nNOS inhibition and therefore decreases hippocampal glutamate level to exert antidepressant like effect. Thus, CA modulate anxiety and depression related neurobehavioral alterations in both CUMS and DEXA models.

Contact between mother and child is essential for the proper development of an infant's physiological systems, brain maturation and behavioural outcomes. Early life stress (ELS), which includes factors such as inadequate parental care and childhood abuse, significantly increases the risk of developing neuropsychiatric disorders, including anxiety and depression. This review examines the impact of maternal separation (MS) on depression, anxiety and pain behaviour, with a particular emphasis on neuroinflammatory pathways. Experiences of ELS can adversely affect the maturation of neurotransmitter systems and associated neural circuits that are crucial for processing painful stimuli and regulating anxiety and depression. Stressful experiences trigger inflammatory processes in the brain, initiating immune responses in neural cells and stimulating the production of pro-inflammatory cytokines. In mammals, MS serves as a significant stressor that activates the hypothalamic-pituitary-adrenal (HPA) axis and other stress-related systems, leading to increased immune challenges and heightened pain sensitivity in adulthood due to systemic inflammation. Key inflammatory mediators, such as IL-1β, IL-6 and TNF-α, play critical roles in the development of pathological pain, while the activation of microglia releases inflammatory mediators that contribute to neurological dysfunction and the pathophysiology of stress, depression and anxiety. Moreover, therapeutics targeting oxidative stress and inflammation have shown promise in alleviating affective disorders following MS. This review discusses potential pathways, with a primary focus on neuroinflammatory mechanisms and the therapeutic strategies that may mitigate the adverse effects of MS. There is a pressing need for further research to elucidate the underlying pathways and identify effective interventions to improve mental health outcomes in individuals affected by MS.

As individuals age, they often face deteriorating health and significant lifestyle changes, including retirement. While retirement can alter individuals' economic and social roles, potentially increasing the risk of depression, involvement in volunteer activities has been found to be beneficial for retirees. Using data from the Health and Retirement Study, we apply the parametric g-formula to simulate an intervention aimed at estimating the effect of volunteering on depression, and to assess the mediating role of limitations in activities of daily living. Our results show that engagement in volunteering reduces the probability of depression by approximately 5% in the whole population, with larger gains among early retirees. The results hold irrespective of gender, and indicate that the benefits are greater for women. Our findings show that about 10% of the positive impact of volunteering on depression operates via a reduction in the likelihood of experiencing limitations in activities of daily living. Therefore, we conclude that the benefits of volunteering extend to improving the overall health of both individuals and the population. Our simulated intervention targeting early retirees may be a viable public health strategy for protecting individuals against depression, while also enabling them to contribute to the public good.

Depression and comorbid pain are frequently encountered clinically, and the comorbidity complicates the overall medical management. However, the mechanism whereby depression triggers development of pain needs to be further elucidated. Here, by using the chronic restraint stress (CRS) mouse model of depression and comorbid pain, we showed that CRS hyperactivated the glutamatergic neurons in the anterior cingulate cortex (ACC), as well as increasing the dendrite complexity and number. Chemogenetic activation of these neurons can induce depression and pain, while chemogenetic blockade can reverse such depression-induced pain. Moreover, we utilized translating ribosome affinity purification (TRAP) in combination with c-Fos-tTA strategy and pharmacological approaches and identified SIGMAR1 as a potential therapeutic molecular target. These results revealed a previously unknown neural mechanism for depression and pain comorbidity and provided new mechanistic insights into the antidepressive and analgesic effects of the disease.

The recurrence and treatment resistance of depression remain significant issues, primarily due to an inadequate understanding of its pathogenesis. Recent scientific evidence indicates that gut microbiota influence estradiol metabolism and are associated with the development of depression in nonpremenopausal women. Integrating existing studies on the regulation of estradiol metabolism by microorganisms in nature and the relevance of its degradation products to depression, recent scientific explorations have further elucidated the key mechanisms by which gut microbiota catabolize estradiol through specific metabolic pathways. These emerging scientific findings suggest that the unique metabolic effects of gut microbiota on estradiol may be one of the central drivers in the onset and course of depression in non-menopausal women.

The phenotypic expression of mental health (MH) conditions among people with HIV (PWH) in Uganda and worldwide are heterogeneous. Accordingly, there has been a shift toward identifying MH phenotypes using data-driven methods capable of identifying novel insights into mechanisms of divergent MH phenotypes among PWH. We leverage the analytic strengths of machine learning combined with inferential methods to identify novel MH phenotypes among PWH and the underlying explanatory features.

A total of 277 PWH (46% female, median age = 44; 93% virally suppressed [<50copies/mL]) were included in the analyses. Participants completed the Patient Health Questionnaire (PHQ-9), Beck Anxiety Inventory (BAI), and the PTSD Checklist-Civilian (PCL-C). A clustering pipeline consisting of dimension reduction with UMAP followed by HBDScan was used to identify MH subtypes using total symptom scores. Inferential statistics compared select demographic (age, sex, education), viral load, and early life adversity between clusters.

We identified four MH phenotypes. Cluster 1 (n = 76; PTSD phenotype) endorsed clinically significant PTSD symptoms (average PCL-C total score > 33). Clusters 2 (n = 32; anxiety phenotype) and 3 (n = 130; mixed anxiety/depression phenotype) reported minimal PTSD symptoms, with modest BAI (Cluster 2) and PHQ-9 (Cluster 3) elevations. Cluster 4 (n = 39; minimal symptom phenotype) reported no clinical MH symptom elevations. Comparisons revealed higher rates of sexual abuse during childhood among the PTSD phenotype vs. the minimal symptom phenotype (p = 0.03).

We identified unique MH phenotypes among PWH and confirmed the importance of early life adversity as an early risk determinant for unfavorable MH among PWH in adulthood.

Impairments in the ability to carry out social activities commonly co-occur alongside depression. Improving social functioning is often overlooked in treatment. This is despite the high value placed by patients on social functioning and the potential for interventions focused on social functioning to have additional benefits in reducing depressive symptoms. In older adults the relationship between depressive symptoms and social functioning during treatment is poorly understood.

We analysed data across the first four treatment sessions of 3260 older adults receiving psychological therapy for depression at eight NHS Talking Therapies for anxiety and depression services in England. Random-intercept cross-lagged panel models were estimated, modelling bi-directional change between depressive symptoms, and impairments in (a) social leisure activities, and (b) close relationships, controlling for gender and diagnosis.

Over treatment sessions, depressive symptoms and impairments in social functioning decreased. A bi-directional relationship was observed whereby depressive symptoms were associated with future impairments in social functioning and vice versa. Changes in depressive symptoms appeared to have a greater association with future social functioning, compared to the reverse.

Patients lived in Greater London and findings may not translate to other settings. We included older adults that attended at least four treatment sessions, and had no missing data at the first assessment, potentially biasing the sample and results.

Older adults receiving psychological therapy experience reductions in depressive symptoms and impairment in social functioning early in treatment. Treating core depressive symptoms and impairments in social functioning may benefit one another, and improve outcomes.

Major depressive disorder (MDD) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) frequently occur together; yet their causal relationship remains unclear. To investigate the potential genetic causal link between these conditions, we conducted a two-sample Mendelian randomization (MR) analysis. Summary data from Genome-Wide Association Studies (GWAS) for MDD were sourced from the UK Biobank and the Psychiatric Genomics Consortium, while GWAS data for ME/CFS were retrieved from the UK Biobank. Inverse-variance weighting (IVW), the MR-Egger method, and weighted median, simple and weighted modes were used to perform the MR analysis. In addition, Cochrane's Q-test was used to detect heterogeneity among the MR results. Horizontal pleiotropy was detected using the MR-Egger intercept and the MR pleiotropy residual sum and outlier (MR-PRESSO) tests. Leave-one-out analysis was performed to investigate the sensitivity of the association between MDD and ME/CFS. The results of the MR analysis revealed no causal relationship between MDD and ME/CFS. The pleiotropy test revealed that causality bias was improbable, and no evidence of heterogeneity was found among the genetic variants. Finally, the leave-one-out test confirmed the stability and robustness of our findings.

Insomnia and depression often receive inadequate attention regarding their association with common menopausal gynecological disorders (GDs), and there is a lack of longitudinal epidemiological evidence. Furthermore, the specific disorders that exhibit the strongest correlation with depression, as well as the potential mediating role of insomnia, remain poorly understood.

Using data from the Study of Women's Health Across the Nation (SWAN) spanning 1996 to 2008, this study analyzed a sample of 2217 racially diverse premenopausal women (aged 42 to 53 at baseline). Longitudinal trajectory analysis, employing latent class mixture models (LCMM), was used to identify optimal patterns for insomnia and depression. Logistic regression explored associations between pelvic pain, pelvic prolapse or relaxation, abnormal bleeding, and insomnia/depression trajectories. A causal mediation model investigated whether insomnia mediated the link between gynecological disorders and depression.

The analysis included 2217 participants for insomnia trajectories and 1767 for depression trajectories. Insomnia and depression showed similar patterns, with a single high and low trajectory and minimal fluctuations. Logistic regression revealed a significant positive correlation between pelvic pain, abnormal bleeding, number of GDs, and an increased risk of high insomnia and depression trajectories. Insomnia trajectories mediated 23.6%, 14.3%, and 11.9% of the association between pelvic pain, abnormal bleeding, and number of GDs, respectively, with depression trajectories.

This study found the significant associations between pelvic pain, abnormal bleeding, and comorbidity with an elevated risk of insomnia and depression during the menopausal transition.

A unique pool of immature glutamatergic neurons in the primate amygdala, known as the paralaminar nucleus (PL), are maturing between infancy and adolescence. The PL is a potential substrate for the steep growth curve of amygdala volume during this developmental period. A microglial component is also embedded among the PL neurons and likely supports local neuronal maturation and emerging synaptogenesis. Microglia may alter neuronal growth following environmental perturbations such as stress. Using multiple measures in rhesus macaques, we found that microglia in the infant primate PL had relatively large somas and a small arbor size. In contrast, microglia in the adolescent PL had a smaller soma and a larger dendritic arbor. We then examined microglial morphology in the PL after a novel maternal separation protocol, to examine the effects of early life stress. After maternal separation, the microglia had increased soma size, arbor size, and complexity. Surprisingly, strong effects were seen not only in the infant PL, but also in the adolescent PL from subjects who had experienced the separation many years earlier. We conclude that under normal maternal-rearing conditions, PL microglia morphology tracks PL neuronal growth, progressing to a more "mature" phenotype by adolescence. Maternal separation has long-lasting effects on microglia, altering their normal developmental trajectory, and resulting in a "hyper-ramified" phenotype that persists for years. We speculate that these changes have consequences for neuronal development in young primates.

Understanding health-related quality of life (HRQoL) dynamics is essential for assessing and improving treatment experiences; however, clinical and observational studies struggle to capture their full complexity. We use simulation modeling and the case of Chimeric Antigen Receptor T-cell therapy-a type of cancer immunotherapy that can prolong survival, but carries life-threatening risks-to study HRQoL dynamics.

We developed an exploratory system dynamics model with mathematical equations and parameter values informed by literature and expert insights. We refined its feedback structure and evaluated its dynamic behavior through iterative interviews. Model simulated HRQoL from treatment approval through six months post-infusion. Two strategies-reducing the delay to infusion and enhancing social support-were incorporated into the model. To dynamically evaluate the effect of these strategies, we developed four metrics: post-treatment HRQoL decline, recovery time to pre-treatment HRQoL, post-treatment HRQoL peak, and durability of the peak.

Model captures key interactions within HRQoL, providing a nuanced analysis of its continuous temporal dynamics, particularly physical well-being, psychological well-being, tumor burden, receipt and efficacy of treatment, side effects, and their management. Model analysis shows reducing infusion delays enhanced HRQoL across all four metrics. While enhanced social support improved the first three metrics for patients who received treatment, it did not change durability of the peak.

Simulation modeling can help explore the effects of strategies on HRQoL while also demonstrating the dynamic interactions between its key components, offering a powerful tool to investigate aspects of HRQoL that are difficult to assess in real-world settings.

An excess of exosomes, nanovesicles released from all cells and key regulators of brain plasticity, is an emerging therapeutic target for stress-related mental illnesses. The effects of chronic stress on exosome levels are unknown; even less is known about molecular drivers of exosome levels in the stress response.

We used our state-of-the-art protocol with 2 complementary strategies to isolate neuronal exosomes from plasma, ventral dentate gyrus, basolateral amygdala, and olfactory bulbs of male mice to determine the effects of chronic restraint stress (CRS) on exosome levels. Next, we used RNA sequencing and bioinformatic analyses to identify molecular drivers of exosome levels.

We found that CRS leads to an increase in the levels of neuronal exosomes but not total (i.e., not neuronally enriched) exosome levels assayed in plasma and the ventral dentate gyrus, whereas CRS leads to a decrease in neuronal exosome levels but not total exosome levels in the basolateral amygdala. There was a further specificity of effects as shown by a lack of changes in the levels of neuronal exosomes assayed in the olfactory bulbs. In pursuit of advancing translational applications, we showed that acetyl-L-carnitine administration restores the CRS-induced increase in neuronal exosome levels assayed in plasma (the most accessible specimen). Furthermore, the CRS-induced changes in neuronal exosome levels in the ventral dentate gyrus and basolateral amygdala mirrored the opposite pattern of CRS-induced transcriptional changes in these key brain areas, with β-estradiol signaling as a potential upstream driver of neuronal exosome levels.

This study provides a foundation for future studies of new forms of local and distant communication in stress neurobiology by demonstrating specific relationships between neuronal exosome levels assayed in plasma and the brain and providing new candidate targets for the normalization of exosome levels.

This umbrella review aims to consolidate the evidence concerning the influence of exercise on depressive symptoms and cognitive performance in adults diagnosed with depression.

An umbrella review of systematic reviews with meta-analyses investigating the effect of exercise on depression and cognition was performed. Databases (PubMed, Cochrane Library, Web of Science, Embase) were searched from inception until February 2024 for reviews of randomized controlled trials. Overlap within included reviews was assessed using the corrected covered area method (CCA). A random effects model was used to calculate overall pooled effect size with sub-analyses.

This study included 27 reviews, encompassing 190 experiments. In patients with depression, compared to the control group, exercise demonstrated a moderate effect size in reducing depressive symptoms (SMD = -0.67; SE = 0.04; p < 0.0001), with a Number Needed to Treat (NNT) of 2.78. When analyses were limited to data from studies with a low risk of bias, the effect on depressive symptoms was smaller (SMD = -0.38; SE = 0.07; p < 0.0001; NNT = 4.72). Exercise had a small effect on cognitive functions (SMD = 0.12; SE = 0.03; p < 0.0001), with an NNT for cognitive function treatment of 14.79.

All forms of exercise benefit patients with depression. However, for optimal intervention outcomes, it is essential to customize the intensity and type of exercise according to the specific characteristics of the patient's depressive symptoms and cognitive functions. It is recommended to implement a phased treatment approach for patients based on the intensity of exercise.

To examine whether patients with obsessive-compulsive disorder (OCD) are adequately treated with pharmacotherapy before referral to a specialized center for OCD.

We performed a retrospective chart review of patients with OCD who were seen for intake at an academic outpatient center in The Netherlands between 2016 and 2023. We collected data on age, gender, illness severity using the Yale-Brown Obsessive-Compulsive Scale, duration of illness, comorbidity and past pharmacotherapy and psychotherapy. Following the international treatment guidelines, we calculated percentages of patients treated with one SSRI, two or more SSRIs, clomipramine and/or antipsychotic augmentation treatments. Using multiple regression, we analyzed if patient and illness characteristics influenced the adequacy of treatment.

We included 673 patients with an average YBOCS score of 27. 76 % had taken at least one SSRI, and 35 % at least two SSRIs before admission. Only 29 % received a high SSRI-dose and 4 % had taken at least two SSRIs in high dose. Clomipramine and antipsychotics augmentation had been taken by less than one-third of patients. Only 3 % of referred patients followed all guideline-recommended treatment steps. Although the vast majority of patients had received some form of psychotherapy, a minority had received exposure and response prevention treatment. Multiple regression showed that illness duration and having received psychotherapy were independent moderators of the adequacy of pharmacological treatment.

Patients with OCD are not being treated adequately according to the pharmacological guidelines. Poor pharmacological treatment may lead to increased duration of illness, suboptimal recovery and unnecessary societal costs. Further research could clarify barriers for patients and caregivers, and facilitate improvement of pharmacological treatment for OCS.

The Hospital Anxiety and Depression Scale (HADS) is commonly used to detect depressive or anxious states, but its 14-item questionnaire is time-consuming. Visual analog scales (VAS) are easy to use and quick to implement. Although the VAS has been validated to assess pain and occupational stress, VAS scores for anxiety and mood have never been evaluated in the workplace. We aimed to validate the use of visual analog scales (VAS) for anxiety and mood compared to HADS in workers. A HADS self-reported questionnaire associated with VAS assessing perceived anxiety and mood on a horizontal line of 100 mm was administered to 182 workers, with a second test (retest) proposed one week later. Sociodemographic, characteristics of work, sleep, well-being, and stress were also assessed. VAS anxiety and mood correlated with the HADS sub-scores (0.70 and 0.65, respectively). The test-retest reliability was good. Optimal VAS cut-offs were ≥ 60/100 for anxiety and ≤ 60/100 for mood, to define at-risk patients. The VAS is quick to perform, easy to use, and reliable for screening depression and anxiety in occupational medicine. We recommend validated questionnaires for at-risk patients.

gov: NCT02596737. Available at: https://www.

gov/ct2/show/NCT02596737.

Major depressive disorder (MDD) often goes undiagnosed due to the absence of clear biomarkers. We sought to identify voice biomarkers for MDD and separate biomarkers indicative of MDD predisposition from biomarkers reflecting current depressive symptoms. Using a two-stage meta-analytic design to remove confounds, we tested the association between features representing vocal pitch and MDD in a multisite case-control cohort study of Chinese women with recurrent depression. Sixteen features were replicated in an independent cohort, with absolute association coefficients (beta values) from the combined analysis ranging from 0.24 to 1.07, indicating moderate to large effects. The statistical significance of these associations remained robust, with P values ranging from 7.2 × 10-6 to 6.8 × 10-58. Eleven features were significantly associated with current depressive symptoms. Using genotype data, we found that this association was driven in part by a genetic correlation with MDD. Significant voice features, reflecting a slower pitch change and a lower pitch, achieved an AUC-ROC of 0.90 (sensitivity of 0.85 and specificity of 0.81) in MDD classification. Our results return vocal features to a more central position in clinical and research work on MDD.

The construction industry faces a significant crisis with rising suicide rates and mental health issues among workers. Addressing these challenges requires both systemic changes in work practices and improved access to mental wellness resources. However, there is limited research on the perceptions of both workers and senior management towards proposed solutions to reducing psychological distress experienced in occupational settings. Understanding these perceptions is crucial to determining the needs and acceptability of different wellness interventions. Thus, this study aimed to uncover preferences for validated wellness interventions in occupational settings by exploring the attitudes of 12 senior managers and 15 frontline workers using Q-Methodology. Findings revealed that frontline workers favored personalized wellness interventions tailored to their unique situations. Additionally, notable differences were identified between frontline workers and senior managers in their views on policies and practices aimed at reducing workload pressures and enhancing accountability and communication. The data also showed that current contracting and work practices potentially hinder the implementation of interventions perceived to be most beneficial by workers and senior managers. These results provide valuable insights for future research and offer guidance to organizations on designing, implementing, and communicating effective wellness interventions.

This study investigates acculturative stress and its impact on psychological distress among Mexican immigrant women in the United States, with a particular focus on contextual factors shaping these acculturative stress experiences. It also seeks to provide actionable insights to address Mexican immigrant women's mental health needs.

Using the data from a total of 257 Mexican immigrant women in the National Latino Asian American Survey (NLAAS), path analysis was conducted to examine the relationships between acculturative stress, psychological distress, and various contextual factors.

Acculturative stress was found to significantly contribute to psychological distress among Mexican immigrant women. Key factors affecting acculturative stress include contentment with the decision to move to the United States, English language proficiency, experiences of racial discrimination, difficulties associated with visiting family abroad, religiosity, and age at immigration. Critical determinants of psychological distress in the studied cohort, according to the results, are familismo values and racial discrimination.

The results of this study underscore the need to consider contextual factors in understanding and addressing acculturative stress and psychological distress among Mexican immigrant women. Practical and policy implications include the necessity to develop culturally sensitive interventions, enhance educational opportunities, improve access to mental health services, and implement anti-discrimination policies. By adopting these strategies, mental health professionals and policymakers can foster resilience, wellbeing, and successful integration of Mexican immigrant women in the U.S. society.

Obesity, depressive symptoms, and periodontitis are major worldwide health concerns. Despite separate studies on both illnesses, no research has directly examined the link between depressive symptoms and periodontitis in obese people. Given the close correlation between obesity and chronic illnesses, as well as the possibility of a bidirectional impact between depressive symptoms and periodontitis, this study aims to investigate the link between depressive symptoms and periodontitis in an obese population.

This study analyzed data from the NHANES database (2009-2014), including 4,820 persons aged 30 years or older with a BMI over 30. The severity of periodontitis was assessed by clinical attachment loss and probing depth, while symptoms of depressive symptoms were measured using the PHQ-9 questionnaire. After gender, age, race, education, ratio of family income to poverty, sleep duration, diabetes, and cardiovascular illnesses were controlled for, the independent connection between depressive symptoms and periodontitis was investigated using multivariable logistic regression.

The modified models indicated a significant negative correlation between depressive symptoms and periodontitis (effect size: -0.13, 95% CI: -0.24 to -0.01, p = 0.0266), indicating that depressive symptoms may operate as a protective factor against periodontitis. Interaction studies did not indicate substantial impact modification by factors like age, gender, or education level.

This study is the first investigation demonstrating a negative link between depressive symptoms and periodontitis in obese persons, indicating a significant interaction between mental health and dental health in this demographic. The results highlight the importance of comprehensive psychological and oral health care in obese individuals, providing a new avenue for future research and therapeutic applications.

As a population at high risk for psychological distress, healthcare workers typically experience varying degrees of anxiety, depression, and burnout. Studies have found that depression and anxiety have a negative impact on the mental health domain of burnout in healthcare workers. However, little is known about the symptom-to-symptom interactions between these psychological outcomes. This study aims to elucidate the characteristics of depression, anxiety, and burnout networks among healthcare workers.

We recruited 846 healthcare workers from March to April 2023 from three hospitals. A total of 826 healthcare workers completed the General Information Scale, the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16), the Self-rating Anxiety Scale (SAS), and the Burnout Clinical Subtype Questionnaire (BCSQ)-36. The network models were constructed using network analysis. The expected influence and the bridge expected influence of nodes were calculated. The stability and accuracy of the network was assessed.

The results showed that the core symptoms in the symptom network mainly included QIDS8 (Energy/Fatigability), SAS3 (Easily upset or frightened), SAS11 (Dizzy), SAS8 (Tiredness), SAS10 (Tachycardia) and BCSQ3 (Worn-out), and the key nodes connecting these symptoms were QIDS2 (Sad mood), SAS20 (Have nightmares), BCSQ3 (Worn-out), SAS8 (Tiredness), QIDS8 (Energy/Fatigability), QIDS4 (Concentration/decision-making) and SAS4 (Madness).

Unique pathways of association between burnout, depression, and anxiety were found to exist. Interventions targeting core symptoms can maximize the improvement of depression, anxiety, and burnout, provide a deeper understanding of the relationship between the three conditions, and provide a target and basis for psychological interventions to improve the emotional wellbeing of healthcare workers and enhance their mental health.

Depression in male and female are commonly associated with different prevalence, severity, and, in some cases, distinct syndromes or subtypes. However, only a small amount of research has been conducted to completely understand the underlying neuroanatomical mechanisms. The goal of the current study was to provide neural markers for specific depression therapies by demonstrating the differences in aberrant prefrontal activity between male and female depressed subjects during an emotional autobiographical memory test. The study included 127 young adults who were randomly assigned to one of two groups: male depression (62 participants) or female depression (65 participants). The average oxyhemoglobin levels in the dorsolateral prefrontal cortex throughout the emotional autobiographical memory task were assessed utilizing 53-channel functional near-infrared spectroscopy imaging equipment. The oxy-Hb activation in the left dorsolateral prefrontal cortex (lDLPFC) and right dorsolateral prefrontal cortex (rDLPFC) had no significant interaction between groups and emotional valences. A significant main effect was found between male and female, with female depression groups showing lower oxy-Hb activity in lDLPFC and rDLPFC than male depression groups. Male and female depression patients showed distinct brain activation in the DLPFC during an emotional autobiographical memory test, suggesting potential specific neurological indicators for varied somatic symptoms in male and female depression patients. These distinctions should be taken into account while creating preventive measures.

Jiawei-Xiaoyao Pill (JWX), a classic formula in traditional Chinese medicine, is derived from Xiaoyao Pill by adding significant amounts of Gardeniae Fructus (GF) and Moutan Cortex (MC). It is frequently used for the treatment of depression. JWX has been demonstrated to uniquely elicit rapid antidepressant-like effects within the prescribed dosage range. To date, GF has been shown to have rapid antidepressant-like effects, but a much higher dose is required than its proportion in JWX. It is assumed that the synergism of GF with a minimum number of other herbs in JWX serves as a refined formula that exerts these rapid antidepressant-like effects. Identification of a refined formula is important for prioritizing the herbs and ingredients to optimize the quality control of JWX. However, such a refined formula for JWX has not been identified yet.

Here we aimed to identify a refined formula derived from JWX for optimized rapid antidepressant-like effects. Since the neuroinflammation mechanism involving in depression treatment has not been previously investigated for JWX, we tested the mechanism for both JWX and the refined formula.

Individual herbs (MC; ASR, Angelica Sinensis Radix; Bupleuri Radix; Paeonia Radix Alba) that show antidepressant-like responses were mixed with GF at the proportional dosage in JWX to identify the refined formula. Rapid antidepressant-like effects were assessed by using NSF (Novelty Suppressed Feeding Test) and other behavioral tests following a single administration. The identified formula was further tested in a lipopolysaccharide (LPS)-induced depressive model, and the molecular signaling mechanisms were investigated using Western blot analysis, immunofluorescence, and pharmacological inhibition of mTOR signaling. Scopolamine (Scop) was used as a positive control for induction of rapid antidepressant effects.

A combination of GF, MC and ASR (GMA) at their dosages proportional to JWX induced behavioral signs of rapid antidepressant-like responses in both normal and LPS-treated mice, with the antidepressant-like effects sustained for 5 d. Similar to JWX or Scop, GMA rapidly reduced the neuroinflammation signaling of Iba-1-NF-кB, enhanced neuroplasticity signaling of CaMKII-mTOR-BDNF, and attenuated the upregulated expressions of the NMDAR sub-units GluN1 and GluN2B in the hippocampus of LPS-treated mice. GMA, JWX and Scop rapidly restored the number of BDNF-positive cells reduced by LPS treatment in the CA3 region of the hippocampus. Furthermore, rapamycin, a selective inhibitor of mTOR, blunted the rapid antidepressant-like effects and hippocampal BDNF signaling upregulation by GMA.

GMA may serve as a refined formula from JWX, capable of inducing rapid antidepressant-like effects. In the LPS-induced depression model, the effects of GMA were mediated via rapidly alleviating neuroinflammation and enhancing neuroplasticity.