Tag: Depression

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Disruption of a GalR2–mitochondrial axis in the ventral hippocampus contributes to depression-like phenotypes after prenatal stress

BackgroundPrenatal stress (PS) is a major risk factor for depression later in life, yet the cellular mechanisms linking early-life adversity to long-term affective vulnerability remain incompletely understood. Neuropeptide receptors have emerged as important modulators of stress-related psychopathology, but their roles in mitochondrial regulation within limbic circuits remain largely unexplored.MethodsA rat model of PS was established to assess depression-like behaviors in adulthood. Mitochondrial ultrastructure, ATP production, and the expression of Galanin receptor 2 (GalR2) and key components of the PINK1/Parkin mitochondrial quality control machinery were examined in the ventral hippocampus (vHPC). The effects of intranasal administration of the GalR2 agonist AR-M1896 on behavioral and mitochondrial alterations were evaluated in vivo. To directly test whether the vHPC mediates these effects, we performed unilateral intra−vHPC infusion of AR−M1896. In vitro, glucocorticoid exposure and pharmacological manipulation of GalR2 were used to assess their impact on mitochondrial function and PINK1/Parkin signaling.ResultsPS induced persistent anhedonia-like behavior and behavioral despair phenotypes in adult offspring, accompanied by marked mitochondrial structural abnormalities, reduced ATP production, and downregulation of GalR2 and PINK1/Parkin-associated mitochondrial quality control signaling in the vHPC. Intranasal AR-M1896 partially normalized reward-related behavioral deficits and ameliorated mitochondrial dysfunction. Importantly, direct intra−vHPC infusion of AR−M1896 elevated ATP, PINK1 and Parkin levels in the ipsilateral vHPC, providing causal evidence that the vHPC is a critical site for GalR2−mediated PINK1/Parkin-related mitophagy−restoring effects. In cell-based assays, glucocorticoid exposure suppressed, whereas GalR2 activation enhanced, mitochondrial membrane potential and PINK1/Parkin-related signaling.ConclusionThese findings identify a GalR2–mitochondrial axis in the ventral hippocampus that is disrupted by PS and associated with vulnerability to depression-like phenotypes. The complementary intra−vHPC infusion experiments establish a causal role for vHPC GalR2 signaling in rescuing mitochondrial deficits, directly demonstrating that intranasal AR−M1896 acts at least in part via the vHPC. This receptor–organelle pathway may represent a neurobiological mechanism linking early-life adversity to long-term affective dysfunction.
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Integrative mechanisms and intervention targets of the microbiota–gut–brain axis in depressive disorders: advances across immune, endocrine, and central nervous system pathways

Depressive disorders are highly heterogeneous syndromes characterized not only by depressed mood but also by cognitive impairment, sleep–circadian rhythm disturbances, altered appetite, somatic discomfort, and metabolic or gastrointestinal comorbidities. In recent years, the microbiota–gut–brain axis (MGBA) has been increasingly recognized as an integrative biological framework linking abnormalities in mood regulation, immune responses, endocrine function, metabolism, and neuroplasticity. This review provides a systematic synthesis of gut microbial ecology and host phenotypic features associated with depressive disorders, with particular emphasis on the depletion of short-chain fatty acid-producing commensals, the enrichment of potentially pro-inflammatory taxa, and the functional remodeling of key metabolic pathways, including the tryptophan–kynurenine pathway, short-chain fatty acids, bile acids, and trimethylamine N-oxide. We further discuss how bidirectional gut-to-brain and brain-to-gut communication may contribute to the onset and progression of depressive disorders through intestinal barrier disruption, low-grade systemic inflammation, hypothalamic–pituitary–adrenal axis activation, vagal signaling, and dysregulation of neurotransmitter and neurotrophic pathways. Current interventional evidence suggests that dietary and lifestyle modification, psychobiotics, and fecal microbiota transplantation may exert antidepressant potential in selected populations; however, the overall effect sizes remain limited and between-study heterogeneity is substantial. Patients with prominent gastrointestinal symptoms, metabolic abnormalities, or low-grade inflammatory states may represent priority candidates for MGBA-targeted interventions; nevertheless, a putative microbiota-responsive phenotype should not be simply equated with high stress exposure alone, and its definition requires prospective validation integrating stress burden, host responses, and microbial/metabolic readouts. Overall, MGBA research is gradually moving beyond descriptive profiling of microbial composition toward functional integration and clinical translation; however, causal inference, multi-omics standardization, and the identification of stratification biomarkers remain major challenges. Future studies should incorporate phenotype-based stratification, strengthened functional readouts, and precision intervention designs to determine which patients are most likely to benefit from microbiota-targeted therapies.
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Feasibility study examining the short-term effects of Sonic Augmentation Technology™

BackgroundThe current study evaluated Sonic Augmentation Technology™ (SAT), a novel, Polyvagal-informed probe that incorporates continuously varying and acoustic features modeled on patterns of autonomic regulation into musical soundscapes. Specifically, the study examined whether SAT led to improvements in self-reported biobehavioral state (e.g. relaxation, breathing slowly, interoceptive clarity), and whether individuals with poorer baseline functioning (i.e., increased autonomic reactivity and anxiety/depression symptoms) reported greater improvements in biobehavioral state following SAT. It also sought to determine whether there would be changes in endogenous oxytocin level, and whether individuals who exhibit larger gains in biobehavioral state would show greater increases in oxytocin.MethodsThe current study examined data obtained from four samples, with 72 participants providing data virtually and 41 participants providing data in-person. Participants completed self-report measures of biobehavioral state, autonomic reactivity, and psychiatric symptomatology (i.e. anxiety and depression). Salivary oxytocin (pg/mL) was assessed via enzyme immunoassay in the participants who completed the study in person, with samples collected pre-and post-SAT.ResultsFollowing SAT, participants reported significant improvements in total biobehavioral state and the low and high arousal subscales. We also found that participants scoring above the cutoff for autonomic reactivity, anxiety, and depression reported greater increases in total biobehavioral state and decreases in the high arousal subscale. Greater decreases in the low arousal subscale were observed in the participants with increased anxiety. The subset of participants with salivary oxytocin samples exhibited increases in salivary oxytocin.ConclusionsThus, our results support the potential of SAT as a low-cost, non-invasive auditory probe for improving wellbeing, especially for clinical populations experiencing autonomic dysregulation and psychiatric difficulties, such as anxiety and depression.Clinical trial registrationClinicalTrials.gov, identifiers NCT06710886, NCT06902506, NCT06580119, and NCT07065227.
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Evaluating an Abbreviated Internet-Delivered Stress Recovery Intervention for Health Care Workers: Pre-Post Feasibility Study of Outcomes, Usability, and Acceptability

<strong>Background:</strong> Health care workers face numerous occupational stressors that place them at heightened risk for burnout and poor mental health. Internet-delivered interventions have shown promise in reducing stress and related symptoms, yet adherence is often low, and users do not complete programs. Abbreviated interventions may help address engagement barriers such as high workload, limited time, and varying user preferences. There is a need to evaluate brief, accessible formats of internet-delivered programs for this population. <strong>Objective:</strong> This study aimed to examine the initial outcomes, usability, and acceptability of a 4-week abbreviated internet-delivered stress recovery intervention for health care workers. Specifically, it evaluated changes in stress recovery, perceived stress, depression and anxiety symptoms, and psychological well-being. The study also sought to understand participants’ experiences with the brief format to determine whether it meets their needs. <strong>Methods:</strong> This single-arm pre-post study examined a 4-week abbreviated version of the online guided cognitive behavioral therapy-based stress recovery program FOREST among self-enrolled health care workers recruited through professional networks (N=52; mean age 39.31, SD 11.31 years; 49/52, 94.2% women). Outcomes included stress recovery (the Recovery Experience Questionnaire), perceived stress (the Perceived Stress Scale-4), depression and anxiety symptoms (the Patient Health Questionnaire-4), psychological well-being (the World Health Organization Well-being Index), and usability and acceptability ratings. <strong>Results:</strong> We found that after the abbreviated version of the FOREST intervention participants showed moderate improvements in stress recovery (<i>d</i>=0.54, 95% CI 0.25-0.83); reductions in stress (<i>d</i>=–0.43, 95% CI –0.72 to –0.14), anxiety and depression symptoms (<i>d</i>=–0.51, 95% CI –0.80 to –0.22); and increase in psychological well-being (<i>d</i>=0.39, 95% CI 0.08-0.70). The majority (37/52, 71.2%) accessed all 6 modules. Users reported high satisfaction with the abbreviated program. <strong>Conclusions:</strong> While preliminary and limited by the pre-post design, these findings indicate that abbreviated internet-based stress recovery programs are a promising and practical tool for supporting the mental health of health care workers. Future research should examine the long-term effects, compare the abbreviated and standard versions, and explore implementation in routine practice. <strong>Trial Registration:</strong>
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Personality functioning in adolescents with depression: links with childhood maltreatment, psychopathology, self-harm and suicidal ideation

BackgroundAdolescence represents a critical developmental period marked by significant vulnerability to depression, a condition with heterogeneous presentations that complicate clinical management. The co-occurrence of personality dysfunction with depression is known to indicate greater severity and poorer prognosis, yet specific features of this comorbidity in adolescent clinical samples require further delineation. This study aimed to compare clinical and psychosocial correlates in depressed adolescents with and without impaired personality functioning.MethodsThe clinical sample comprised 73 adolescents (aged 12–17; 83.6% female) diagnosed with depression or reporting clinically significant depressive symptoms. Participants completed self-report measures assessing personality functioning (LoPF-Q 12–18), childhood maltreatment (CEQ), psychopathology (YSR 11-18), mentalizing capacity (RFQY-8), borderline traits (BPFS-C), and self-harm behavior. Based on LoPF-Q 12-18 T-scores, participants were categorized into two subgroups: depression without personality dysfunction (T ≤ 64; n=20) and depression with personality dysfunction (T ≥ 65; n=53).ResultsResults indicated that adolescents with co-occurring depression and personality dysfunction exhibited significantly lower functioning across all personality domains compared to those with depression alone. This subgroup also reported an earlier onset and higher frequency of self-harm, more severe suicidal ideation, elevated borderline traits, and greater impairments in mentalizing. Furthermore, they demonstrated higher levels of internalizing, affective, conduct, and PTSD symptoms, alongside greater exposure to emotional neglect.ConclusionImpaired personality functioning in depressed adolescents is associated with elevated and multifaceted patterns of symptoms, including subjective distress and risky behaviors. These findings underscore the necessity of routinely assessing personality functioning in adolescents with clinically significant depressive symptoms to enable early identification and the development of tailored, integrated interventions for this high-risk subgroup.
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Waiting between war and loss: a qualitative study on the experience of ambiguous loss among Syrian refugees

IntroductionAmbiguous loss refers to individuals’ lack of knowledge about the whereabouts or fate of loved ones due to traumatic events such as war or natural disasters. It is associated with significant economic, social, and psychological consequences, including grief, depression, and identity confusion.MethodsWe examined the psychological impact of ambiguous loss among 15 refugees displaced by the Syrian civil war. Participants (22 -53 years old; 9 women, 6 men) had experienced the disappearance or prolonged uncertainty regarding the fate of their spouse, child, sibling, or relative and had lived with uncertainty regarding the fate of their loved one for 4 to 13 years (in some cases, the uncertainty resolved after the interviews). We collected the data through semi-structured interviews and analyzed them using inductive thematic analysis.ResultsFindings revealed emotional oscillation between hope and hopelessness, social isolation, and difficulties adapting to changing roles. Although beliefs and collective rituals served as coping resources, inadequate support and stigma intensified distress.DiscussionThe results indicate that ambiguous loss is embedded in sociocultural contexts and underscore the need for culturally sensitive, family- and community-based psychosocial interventions and supportive national policies.