Neuropsychobiology最新文献

Background: Severe depressive episodes with suicidal ideation present major therapeutic challenges and often require interventions beyond standard antidepressant therapy. Electroconvulsive therapy (ECT) remains a cornerstone treatment for refractory depression, while ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has emerged as a rapid-acting antidepressant with potential benefits in reducing suicidal ideation. This study compares the efficacy, onset of action, and tolerability of intravenous ketamine and ECT as adjunctive treatments in severe major depressive disorder with active suicidal ideation.

Methods: A randomised controlled trial was conducted at a tertiary care psychiatry department in India, enrolling 64 patients aged 18-60 years with severe depression (HAM-D ≥ 19, SSI ≥ 4). Participants were randomly assigned to receive either intravenous ketamine (n = 31) or ECT (n = 33), alongside ongoing oral antidepressants. Both groups underwent six treatment sessions over two weeks. Outcomes were assessed at baseline, post-treatment, and four weeks after completion. Primary endpoints included changes in depression severity (HAM-D) and suicidal ideation (SSI), while secondary outcomes included response and remission rates, as well as safety and tolerability profiles.

Results: Both ECT and ketamine significantly reduced depressive symptoms and suicidal ideation (p < 0.001). HAM-D scores declined from 27 to 1 in the ECT group and from 26 to 2 in the ketamine group by the 4-week follow-up. SSI scores showed parallel improvement, from 12.1 to 1.2 with ECT and 12.6 to 2.0 with ketamine. Ketamine demonstrated a faster onset of clinical improvement, while ECT showed slightly greater durability of response. Side effects were mild in both groups, though ECT was associated with transient cognitive impairment, whereas ketamine produced minor dissociative and urinary symptoms.

Conclusion: Ketamine offers a faster reduction in suicidal ideation than ECT, making it a promising acute intervention. Both are effective, safe adjunctive therapies, with treatment choice guided by patient profile and tolerability.

Introduction: Sensory processing sensitivity (SPS) describes innate temperament, which consists of three characteristics: ease of excitation (EOE), low sensory threshold (LST) and aesthetic sensitivity (AES). There has been no research on SPS in bipolar disorder, nor the effect of treatment on these traits. Relations between temperament, personality and the course of bipolar disorder are complex and modify the effect of treatment. Long-term lithium treatment modifies course of the illness and excellent lithium responders (ELR) are known from their unique clinical characteristic. The aim of the study was to examine the relation between pharmacological treatment and sensory processing sensitivity in bipolar disorder patients.

Methods: The study group comprised of 35 patients (F/M=26/9) with bipolar disorder (BD), where 20 patients were diagnosed with BD type I and 15 patients with BD type II. Twenty patients were treated with lithium (16±13 years) and fifteen with other mood stabilizers (14±4 years). The comparison between groups included parameters: BD type, clinical characteristics (family history, suicidal attempts, duration of illness, duration of treatment), type of treatment and gender in relation to sensory sensitivity traits. The Highly Sensitive Person Scale (HSPS) including 27 items and distinguishing three parameters: EOE, LST and AES was used. To assess quality of lithium treatment the Alda Scale was implemented.

Results: Lithium-treated patients obtained significantly lower scores on HSPS total score (4.27 vs 4.98, p=0.009) and EOE (4.05 vs 5.23, p=0.002), compared to patients treated with other mood stabilizers. AES and LST remained on similar level in both groups (however the results are limited by insufficient statistical power). Also, the negative correlation between LST score and Alda Scale score was obtained (r = -0.484; p=0.031). There was no difference according to clinical characteristics between BD I and BD II, as well as between males and females.

Conclusions: Longitudinal treatment with lithium could reduce overall sensory processing sensitivity traits, and particularly "ease of excitation". However, it is possible that low intensity of these traits is a factor in good response to lithium. Also, lithium treatment may not reduce aesthetic sensitivity, parameter related to creativity. "Low sensory threshold" can be considered as negative predictor of lithium treatment outcome.

Background: Nutrition is an important determinant of health among people with mental disorders; however, barriers to dietary counselling exist. The Eating and Supplementation for Generalized Anxiety Disorder study ("EASe-GAD") was the first trial to assess the impact of these interventions on anxiety symptoms. The primary objective of the present companion qualitative study was to gather and analyze qualitative data about the acceptability, participant experience, impact, barriers and facilitators, strengths, and weaknesses of the EASe-GAD program while also identifying opportunities for improvement.

Methods: Participants were eligible for this study if they participated in the EASe-GAD trial. Data were collected using focus groups which followed a semi-structured interview approach with a set of pre-determined questions. The sessions were recorded and transcribed for data analysis. Data were analyzed by thematic analysis.

Results: Three focus groups were completed, involving a total of 12 women. They reported a range of components that they found helpful, such as increased self-efficacy, as well as positive outcomes that they attributed to the intervention, such as improved mental and physical health. They reported components of the program that were less enjoyable, such as having their body weight measured, and also suggested opportunities for improvement. Many participants reported that cost implications of a diet intervention were an important consideration.

Conclusion: This project provided valuable insight into the participant experience and impact of the pilot dietary counselling program. Participants reported benefits and opportunities for improvement for subsequent studies aimed at improving nutrition among people with anxiety disorders.

Introduction: Exportin-6 (XPO6) regulates nuclear export of actin and related proteins, processes essential for cytoskeletal integrity and synaptic function. Given the importance of these mechanisms in mood regulation, XPO6 dysregulation may contribute to the pathophysiology of major depressive disorder (MDD), yet its role remains largely unknown.

Method: XPO6 mRNA was measured in the peripheral blood of participants with MDD in an acute depressive episode (acute MDD group), MDD in remission, and healthy controls (screen by Chinese health questionnaire-12 and semi-structured interviews to exclude current or past psychiatric disorders) at baseline. XPO6 mRNA levels were measured after four weeks of antidepressant treatment in the acute MDD group. The 17-item Hamilton Depression Rating Scale was used to assess depression severity. XPO6 mRNA levels were quantified by quantitative reverse transcription polymerase chain reaction (RT-qPCR).

Results: We recruited 90 participants in the acute MDD group, 60 in the MDD in remission group, and 70 healthy controls. After adjusting for demographics, a significant difference in baseline XPO6 mRNA levels was found among the three groups (F=4.34, P=0.014). In the post-hoc analysis, a stepwise pattern in XPO6 mRNA levels was observed (acute MDD group > MDD in remission group > healthy controls). After antidepressant treatment in the acute MDD group, XPO6 mRNA levels significantly decreased (2.23±2.39 vs. 1.82±1.96, P=0.016).

Conclusion: XPO6 mRNA levels could be a potential biomarker for MDD, which is also associated with depression disease state and treatment response to antidepressants. Larger sample sizes are needed to confirm these results in the future.

Introduction: Current predictors of electroconvulsive therapy (ECT) effects rely on static measures. The prognostic value of anxiety evolution during ECT remains unestablished, which impedes personalized treatment. This study aims to investigate the dynamic evolution of anxiety during ECT and its predictive role in treatment effects.

Methods: We collected 1,053 data points from 117 patients with depression who were undergoing ECT, measuring both the Hamilton Anxiety Rating Scale (HAMA) and the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and at each of the first eight ECT sessions. K-means longitudinal (KML) clustering identified anxiety evolution patterns, while linear mixed-effects modeling (LMM) and survival analysis were used to assess associations with treatment outcomes.

Results: Three distinct anxiety trajectory phenotypes were identified: Rapid Anxiety Remitters (Cluster A: 47%), Gradual Anxiety Improvers (Cluster B: 41%), and Anxiety Non-Remitters (Cluster C: 12%). LMM analysis demonstrated significantly greater HAMD-17 reduction slopes in Cluster A (β = -1.32, p = 0.003) and Cluster B (β = -1.15, p = 0.007) compared to Cluster C. Kaplan-Meier analysis revealed a hierarchical response advantage (Cluster A > B > C; Log-Rank χ² = 32.15, p < 0.001). Multivariable Cox regression confirmed the superior predictive value of trajectories over baseline HAMA: Rapid Anxiety Remitters showed a 19.77-fold higher response likelihood than Anxiety Non-Remitters (95%CI 8.21-47.63), compared to only a 4% increased probability per HAMA point (hazard ratios = 1.04).

Conclusion: Dynamic anxiety trajectories are effective biomarkers for ECT response, offering enhanced predictive value over baseline HAMA scores and enabling personalized treatment strategies for depression.

Introduction: The role of chemokines in motor abnormalities (MAs) in first-episode psychosis (FEP) is underexplored. Investigating immune biomarker levels in FEP, their association with MAs, and their differences with individuals without FEP may reveal therapeutic targets.

Methods: Thirty-eight patients and thirty-four controls were included. Primary outcomes assessed group differences in chemokines related immune whole blood biomarkers, including innate (CCL2, CCL3, and CCL11), compensatory (PPARα, CXCL1, and CB2), natural immune chemotaxis biomarkers (CXCL2 and CXCR4), and growth factors (LPAR2, brain-derived neurotrophic factor [BDNF], and vascular endothelial growth factor [VEGF]). Our secondary aim was to examine their association with the total score of five motor scales: the Neurological Evaluation Scale (NES), Simpson Angus Scale (SAS), catatonia symptom of the Comprehensive Assessment of Symptoms and History (CASH), Barnes Akathisia Rating Scale, and Unified Parkinson's Disease Rating Scale (UPDRS).

Results: We found significantly higher levels of protein markers (CCL2, VEGF, and CXCL12) and mRNA expression (CXCR4, PPARα, CB2, and LPAR2) in FEP patients compared to the control group. We only observed positive and significant results for CCL2-UPDRS total and CXCR4-SAS associations in post hoc multivariate analyses (β = 0.401, p = 0.036 and β = 0.58, p = 0.001, respectively).

Conclusions: Elevated levels of potential neurotoxic (CCL2) and neuroprotective (PPARα and CB2) biomarkers were seen in FEP patients when compared to controls. Moreover, CCL2 levels seem to be directly associated with Parkinsonism in FEP patients, while CXCR4 may be protective against extrapyramidal symptoms. Further research should clarify immune differences between FEP and non-FEP groups, especially in chemotaxis and endocannabinoid pathways.

Introduction: Intrusive memories are a central identifying symptom of post-traumatic stress disorder (PTSD), and their development can be modelled in experimental settings with the trauma film paradigm. Neurosteroids and sex hormones, such as allopregnanolone and testosterone, respectively, have recently become potential targets for PTSD pharmacological treatment due to their influence on the stress response.

Methods: In the current study, 49 healthy female participants underwent stress induction and viewed a trauma film. Plasma allopregnanolone, testosterone, and cortisol responses to stress induction and the trauma film were recorded, and stress-induced responses were modelled as predictors of intrusive memory frequency using negative binomial regression models.

Results: Compared to baseline, plasma allopregnanolone and cortisol levels, along with subjective stress, were significantly higher after the stress induction. Plasma cortisol and subjective stress responses to the stress induction task significantly predicted intrusive memories. Allopregnanolone and testosterone did not predict intrusive memories, though allopregnanolone and cortisol stress responses were significantly correlated.

Conclusion: These findings expand our current understanding of the biochemical processes of intrusive memory formation under stress. Additionally, changes in allopregnanolone were observed in response to stress, which contributes towards the discussion of neurosteroids and sex hormones as potential pharmacological targets for the treatment of PTSD.

Introduction: Throughout time, there has always been a trend connecting stress and tangible damage to one's physical well-being. However, there's a lack of research that elucidates the physical and molecular traits of this stress on organ integrity. Chronic stress disrupts homeostasis, causing oxidative stress, mitochondrial dysfunction, inflammatory markers, and histological damage.

Methods: In this study, a repeated forced swim stress (FSS) was used to induce stress in the C57BL/6 mice model and analyzed its effects on the brain and liver at behavioral, biochemical, histology, and genetic marker levels.

Results: Behavioral analysis showed reduced mobility duration in experimental mice. This was further supplemented by histopathological data, which revealed mild brain deterioration and moderate liver damage. Biochemical analysis revealed upregulated levels of aminotransferase (ALT) and alkaline phosphatase (ALP) and decreased levels of mean corpuscular haemoglobin (MCH), pointing towards the existence of liver dysfunctionality due to stress. Moreover, we reported the gene expression analysis of stress biomarkers (Bdnf, Fkbp5, Npy, Comt, Ppm1f, Adra2b, and Slc6a4), with a particular focus on Fkbp5, which is associated with depression and cognitive impairment. Similarly, we also studied the expressions of Crp, Cyp2e1, and Irs-2 to gauge liver damage. Results revealed significantly upregulated expression of Npy, Fkbp5, and Ppm1f in stressed mice.

Conclusion: Our study identifies that chronic stress shows physical and molecular realizations. Additionally, this offers further incentive to look closely at Fkbp5, Npy, and Ppm1f under similar conditions and highlights their possible roles as markers of stress-induced damage.

Background: Bipolar disorder (BD) is a severe, recurrent mood disorder associated with mitochondrial and bioenergetic dysfunction, which may contribute to both symptom expression and variability in treatment response. Although lithium remains the gold standard treatment, a significant proportion of patients fail to achieve full benefit, and reliable predictive biomarkers are still lacking. Increasing evidence suggests that lithium exerts part of its therapeutic effects through modulation of mitochondrial function, including enhanced oxidative phosphorylation, regulation of mitochondrial dynamics, and reduction of oxidative stress.

Summary: In this state-of-the-art review, we synthesize the current literature on the relationship between lithium and mitochondrial function, with the aim of evaluating how this relationship may inform our understanding of lithium response in BD. We reviewed findings on mitochondrial bioenergetics, oxidative stress, and mitochondrial DNA alterations, and discussed the roles of key regulatory proteins such as Drp1, Opa1, MFN2, and Nrf2. In addition, we explore peripheral and epigenetic biomarkers, including mitochondrial DNA D-loop methylation, microRNAs, and a potential therapeutic target - mitochondrial transfer mechanism. In addition to synthesizing the existing literature, we identify key gaps that hinder progress, such as clinical studies being predominantly cross-sectional, lacking standardized mitochondrial assessments, and rarely employing longitudinal or genetically informed designs like mitochondrial twin studies.

Key messages: Future research requires unified protocols, integration of omics technologies, extracellular vesicle-based sampling strategies, and improved in vitro and in vivo models. A better understanding of mitochondrial signatures related to lithium may enable biomarker discovery and advance personalized treatment in BD.