World Journal of Biological Psychiatry最新文献

Objectives: Bipolar disorder (BD) has been repeatedly linked to immune dysregulation, yet the clinical specificity of neutrophil-based indices remains unclear. This brief report examined whether the neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR) vary across BD subtypes, mood states, and treatments, focusing on their potential as state-sensitive markers rather than direct indicators of inflammation.

Methods: We retrospectively analysed 54 inpatients with BD diagnosed per DSM-5. Complete blood counts were used to compute NLR and dNLR, alongside socio-demographic, clinical (subtype, mood state, psychosis), and pharmacological data. Non-parametric tests with effect-size estimates and a multivariable sensitivity model were applied. Illness severity was assessed with YMRS and HAM-D.

Results: NLR and dNLR were significantly higher in BD-I patients with psychotic mania than in BD-II patients in depression. Lithium treatment was associated with lower NLR/dNLR levels. No significant correlations emerged with YMRS or HAM-D scores. The apparent reduction in NLR among comorbid ADHD cases was exploratory only due to the very small subgroup (n = 2).

Conclusions: NLR and dNLR appear to act as state-dependent peripheral markers in BD, reflecting acute psychotic mania and lithium modulation rather than trait inflammation. These preliminary findings warrant confirmation in larger, longitudinal cohorts.

Objectives: Anxiety disorders are associated with dysfunction in key neurotransmitter systems like, GABAergic, serotonergic, dopaminergic, noradrenergic, and endocannabinoid, alongside oxidative stress, neuroinflammation, and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. Conventional pharmacotherapies offer symptomatic relief but often cause adverse effects and dependency. This review explores medicinal plants as alternative anxiolytic agents due to their multi-targeted mechanisms of action.

Methods: The review analyzes medicinal plants traditionally used for anxiety relief, focusing on their bioactive compounds, including flavonoids, alkaloids, saponins, terpenoids, and polyphenols. Mechanisms of action evaluated include GABA-A receptor activation, serotonergic modulation, neuroendocrine regulation, and antioxidant activity.

Results: Bioactive compounds from medicinal plants demonstrate anxiolytic effects through modulation of neurotransmitters, reduction of cortisol levels, and regulation of neuropeptides such as brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY). Additionally, several phytochemicals enhance endocannabinoid signaling, supporting their role in anxiety management.

Conclusions: Medicinal plants offer promising potential as alternative treatments for anxiety disorders by targeting multiple neurochemical and neuroendocrine pathways. However, challenges such as standardization, pharmacokinetic variability, and lack of clinical validation must be addressed. Future research should prioritize optimized formulations and large-scale clinical trials to ensure efficacy and safety.

Objectives: The gut-brain axis is a bidirectional communication network regulated by the immune, nervous, and endocrine systems, microbial metabolites, and environmental factors such as diet, stress, circadian rhythm, and drugs/chemicals. This review aims to examine current literature on the link between gut microbiota dysbiosis and major brain disorders, and to explore strategies for improving patient outcomes.

Methods: This narrative (non-systematic) review investigated the association between gut microbiota dysbiosis and psychiatric (schizophrenia, major depressive disorder, bipolar disorder, eating disorders), neurological (autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, migraine), and neurodegenerative disorders (Parkinson's disease, Alzheimer's disease, multiple sclerosis). It also considered potential microbiota- and neuroprotective interventions.

Results: The existing body of evidence consistently links gut dysbiosis with neuropsychiatric and neurodegenerative conditions through mechanisms including inflammation, impaired intestinal barriers, microbial production of neurotransmitters or toxins, and accumulation of α-synuclein or amyloid affecting neurogenesis and myelination. Balanced dietary patterns and the use of probiotics, prebiotics, or fermented foods are associated with healthier gut microbiota and improved neurological function.

Conclusions: Further research is needed to clarify whether gut dysbiosis causes or contributes to these disorders, and to develop evidence-based, gut-focused practical recommendations for their prevention and management.

Background: Anorexia nervosa (AN) is a debilitating eating disorder. To date, very few genes have been identified that predispose to AN.

Aim: An alternative to association studies is the characterisation of ultra-rare variants in familial forms of AN.

Methods: Here, we use this approach to identify molecular pathways that contribute to the development of AN by analysing one family with two members suffering from AN by trio whole-exome analysis.

Results: We identified an ultra-rare deleterious variant c.199 + 2T > G in the HCRTR1 gene in the two affected females in the family. The in vitro minigene assay confirmed that c.199 + 2T > C resulted in exon 3 skipping, leading to the loss of the start initiation codon.

Conclusion: This HCRTR1 gene, known to be involved in the regulation of feeding and physical activity, and already implicated in the reward pathway, may play a predisposing role in AN, at least in familial forms.

Core tip: Anorexia nervosa (AN) is a debilitating eating disorder. To date, only a few genes have been identified as predisposing to AN. The HCRTR1 gene is known to be involved in the regulation of feeding and physical activity. The identification of a rare loss-of-function variant in HCRTR1 strongly suggests that the orexin pathway may be involved in the predisposition to anorexia nervosa.

Background: Emerging evidence suggests that neuroinflammation may contribute to suicidal behaviour by altering immune responses and neural-pathways. Polymorphisms in cytokine gene promoter regions have been previously associated with depression and suicidal behaviour. Psychological autopsy is a thorough investigation method to investigate suicide. To date, there is no reported association study linking psychological autopsy outcomes with inflammatory markers. This cross-sectional post-mortem study aimed to investigate the relationship between psychosocial behaviour and inflammatory genetic patterns.

Material and methods: The Comprehensive Psychological Autopsy: Structured Interview Schedule was used to gather psychosocial data of suicide completers (n=234), and genotyping of polymorphic sites in the promoter regions of IL-1β, IL-4, IL-6, IL-10, and TNF-α genes was done.

Results: Our study found a consistent correlation between risk genotypes of all the understudy SNPs with the negative social behaviours. In linear regression analysis, IL-6(-174G/C) demonstrated a protective effect across emotional and negative behavioural traits, whereas TNF-α(-308G/A) was associated with the general behaviour domain.

Conclusion: Although it cannot be generalised at this point, the findings of this study highlight a definite pattern of correlation between genetic-psychosocial and behavioural descriptions of suicide completers, also backed by linear regression models. The findings can be further tested rigorously to confirm worldwide.

Objectives: Psychological factors such as well-being, stress, and depression can influence immune function, with dysregulated inflammation during pregnancy contributing to adverse outcomes. While the role of inflammatory markers has been studied in pregnancy complications like preterm birth and preeclampsia, few studies explore how psychological states impact cellular and serum immune responses in pregnant women. In this study, we investigated associations between psychological factors and inflammatory markers from peripheral blood mononuclear cells (PBMCs) and serum in early and late pregnancy.

Methods: This secondary analysis of 70 pregnant women from the MicrobeMom2 RCT investigated associations between psychological factors and inflammatory markers from peripheral blood mononuclear cells (PBMCs) and serum in early and late pregnancy. Wellbeing, stress, and depression risk were assessed using the WHO-5 Well-being Index, Perceived Stress Questionnaire, and Edinburgh Postnatal Depression Scale. Associations between immune markers and psychological factors were analysed using independent t-tests, ANOVA, and linear regression.

Results: Higher well-being correlated with lower leptin levels in late pregnancy serum. Higher stress scores were associated with decreased PBMC-secreted TNF-α in early pregnancy. Increased depression risk was associated with lower serum TNF-α and ICAM1 in early pregnancy and reduced IL17A in late pregnancy.

Conclusions: Well-being, stress, and depression risk are associated with an altered immune response during early and late pregnancy, which may contribute to the relationship between suboptimal psychological states and adverse pregnancy outcomes.

Background: The blood-brain barrier (BBB) is essential for maintaining normal brain function and is involved in the progression of major depressive disorder (MDD). This study investigated the abnormal expression and regulatory role of miR-24-3p in neuronal injury and BBB dysfunction during MDD pathogenesis.

Methods: The expression of miR-24-3p was examined in serum samples from patients with MDD and from chronic unpredictable mild stress and lipopolysaccharide mouse models, as well as in hippocampal tissue from mice. A loss-of-function assay was conducted to explore the role of miR-24-3p in brain injury, assessing neuronal cell viability, apoptosis, inflammatory response, oxidative stress, and astrocyte activation. Exosomes were then isolated to evaluate the regulatory role and function of miR-24-3p in BBB dysfunction. Behavioural tests were performed to assess depressive-like behaviours in mice.

Results: miR-24-3p was significantly upregulated in MDD samples. Inhibiting miR-24-3p suppressed LPS-induced neuronal apoptosis and inflammation, while promoting the secretion of neurofunctional factors. Further analysis revealed that inhibiting exosomal miR-24-3p alleviated depressive-like behaviour in MDD model mice, reduced BBB permeability, and improved BBB function.

Conclusion: miR-24-3p inhibition attenuated neuronal damage, reduced astrocyte activation, and enhanced BBB stability through exosome-mediated regulation, thereby alleviating neurobehavioural abnormalities and the progression of MDD.

Background: Melatonin emerged as a new potential therapeutic agent for the treatment of mood and anxiety disorders. Existing randomized controlled trials (RCTs) have predominantly focused on the immediate effects of melatonin, leaving a knowledge gap concerning its long-term effects.

Objectives: To conduct a scoping review of the literature in order to collect long-term (≥ 3 months) efficacy and tolerability data of melatonin (agonists) in children, adults, or the elderly with anxiety, depressive, or bipolar disorder.

Methods: A systematic literature search of PubMed, Embase, Web of Science, Scopus, and CENTRAL electronic databases was conducted for English or Dutch-language RCTs. Additionally, 3 electronic databases were screened for unpublished clinical trials.

Results: Six hundred sixty-one records were identified as possibly eligible. Of these, six met the inclusion criteria. Although some studies have demonstrated a significant positive long-term effect of melatonin on mood or anxiety symptoms, most have not. In general, the use of melatonin is associated with mild adverse events.

Conclusions: Long-term efficacy data of melatonin (agonists) in patients with mood or anxiety disorders are scarce and inconsistent. There is insufficient long-term data allowing a thorough evaluation of its safety profile.

Objectives: Non-suicidal self-injury (NSSI) is associated with pro-inflammatory states. The cholinergic anti-inflammatory reflex is a neural pathway, modulating the body's inflammatory response. This study aimed to investigate the cholinergic anti-inflammatory reflex in adolescents with and without NSSI in a first, cross-sectional observational study.

Methods: Heart rate variability (HRV; a proxy for vagus nerve activity), inflammatory markers (leukocytes, c-reactive protein (CRP), interleukin-6 (IL-6)) and several clinical measures were assessed in female adolescents with NSSI (n = 154) and healthy controls (n = 46). Statistical analyses tested for group differences and correlations between HRV, inflammatory markers and depression in patients and controls. Mediation analyses were conducted to test direct and indirect effects.

Results: The NSSI group showed greater depressive symptoms and leukocyte levels, but lower HRV compared to the control group. In the full sample, depression severity was positively correlated with leukocyte and CRP levels and negatively correlated with HRV. HRV was also negatively correlated with leukocyte and CRP levels. Depression severity mediated the association between leukocytes and HRV.

Conclusions: Overall, this study lends initial support that lower vagal activity is associated with increased inflammatory markers in a sample of adolescents with NSSI which suggests altered functioning of the cholinergic anti-inflammatory reflex.