World Journal of Biological Psychiatry最新文献

Objective: We investigated the mechanism of Dexmedetomidine (Dex) in infant rats with brain injury.

Methods: The infant rats underwent brain injury modelling. The motor function, spatial learning and memory abilities in rats, and the hippocampal CA1 region Nissl body level and apoptosis were evaluated by behavioural tests and histological stainings. Levels of the hippocampal CA1 region p-IRE1α, nuclear/cytoplasmic p65, CHOP, Bax and Bcl-2 proteins were determined by Western blot.

Results: Propofol anaesthesia caused brain injury in infant rats. Dex increased the hippocampal CA1 region Nissl body level, abated cell apoptosis, reduced p-IRE1α, ATF6, p-PERK/PERK and CHOP levels, decreased the Bax protein level, elevated the Bcl-2 protein level, and alleviated brain injury in infant rats. After ERS induction and the NF-κB pathway inhibition, the hippocampal CA1 region nuclear/cytoplasmic p65 ratio, CHOP level, and apoptosis were reduced in infant rats with brain injury treated with Dex, while the learning and memory abilities of rats were enhanced.

Conclusion: Dex reduced the hippocampal CA1 region cell apoptosis and enhanced learning and memory abilities by inhibiting the ERS-mediated IRE1α/NF-κB/CHOP pathway, thereby alleviating brain injury in infant rats.

Objective: Facial emotion recognition is central to successful social interaction. People with autism spectrum disorder (ASD) have difficulties in this area. However, neuroimaging evidence on facial emotion processing in ASD has been diverse. This study aims to identify common and consistent brain activity patterns during facial emotion processing in autism.

Methods: Following PRISMA guidelines, 22 fMRI studies (539 ASD, 502 typically developing participants (TD) were included.

Results: Both groups showed significant activation in the right fusiform gyrus (FG) and left fusiform face area (FFA). In addition, TD participants showed increased left amygdala activity. Compared to TD, ASD individuals had increased activation in the right cerebellum lobule VI and left secondary visual cortex. Age-based subgroup analysis showed that ASD children showed increased activity in bilateral FG, and ASD adults and TD children in the right FG. Finally, adults from both groups had increased activity in the right FG in the within-group and conjunction analyses.

Conclusions: These results suggest that ASD and TD engage core face processing areas similarly while TD may use core and an extended social brain network. Findings of this study underscore the role of fusiform face area in facial emotion processing along with more insights into the neural processing of facial emotions.

Objectives: The relationship between the gut microbiome and mental health, particularly depression, has gained significant attention. This review explores the connection between microbial metabolites, dysbiosis, and depression. The gut microbiome, comprising diverse microorganisms, maintains physiological balance and influences health through the gut-brain axis, a communication pathway between the gut and the central nervous system.

Methods: Dysbiosis, an imbalance in the gut microbiome, disrupts this axis and worsens depressive symptoms. Factors like diet, antibiotics, and lifestyle can cause this imbalance, leading to changes in microbial composition, metabolism, and immune responses. This imbalance can induce inflammation, disrupt neurotransmitter regulation, and affect hormonal and epigenetic processes, all linked to depression.

Results: Microbial metabolites, such as short-chain fatty acids and neurotransmitters, are key to gut-brain communication, influencing immune regulation and mood. The altered production of these metabolites is associated with depression. While progress has been made in understanding the gut-brain axis, more research is needed to clarify causative relationships and develop new treatments. The emerging field of psychobiotics and microbiome-targeted therapies shows promise for innovative depression treatments by harnessing the gut microbiome's potential.

Conclusions: Epigenetic mechanisms, including DNA methylation and histone modifications, are crucial in how the gut microbiota impacts mental health. Understanding these mechanisms offers new prospects for preventing and treating depression through the gut-brain axis.

Objective: The aetiology of epilepsy is known to have genetic contributions, yet results from genome-wide association studies (GWAS) have not always been consistent. We undertook a systematic review in order to identify risk variants for epilepsy.

Methods: This systematic review was conducted in accordance with the PRISMA protocol. The quality of each of the studies was evaluated using the Q-Genie tool.

Results: A total of 79 SNPs, located in 64 genes, were significantly associated with epilepsy at the genome-wide level. The majority of the variants were intronic and intergenic, with SCN1A as the most widely reported gene involved across studies. Two SNPs, rs2292096 and rs149212747, linked respectively to focal epilepsy (FE) and status epilepticus, were exclusively identified in individuals of Asian ancestry, alongside an Asian-exclusive synonymous variant (rs3782886) in BRAP and a missense variant (rs671) in ALDH2.

Conclusions: Genes, which encode for ion and transport channels, transcription factors, ubiquitin ligase and transporter proteins were identified as potentially involved in the aetiology of epilepsy. The review identified one missense and one synonymous variant which deserve further exploration. Future research should include populations of more diverse ancestries, which may reveal unique epilepsy-associated genes.

Objectives: While neuropsychological effects of conventional antidepressants are well-documented, more research is needed for rapid-acting antidepressants. This study examines the effects of esketamine on emotion processing and cognitive functioning, both acutely and sub-chronically.

Methods: Eighteen treatment-resistant depression (TRD) patients received repeated intravenous esketamine infusions. Mood state was reported daily, and the Facial Expression Recognition Task was administered 1h before and 4h after each infusion. Other assessments included the Digit Symbol Substitution Task.

Results: 66.7% participants who received at least five infusions (n = 12) showed significant improvement. Emotion recognition improved for all emotions except sadness, where accuracy decreased, particularly for low-intensity expressions (p = .007, d = -1.09). Misclassifications of other emotions as sad also decreased (p = .035, d = -0.79), indicating a reduced response bias towards sadness. This shift in bias emerged after the first infusion and then consolidated over time. In parallel, participants showed significant reductions in feelings of sadness (p = .015, d = -0.89) and irritability (p = .001, d = -1.35). Symptomatic improvement negatively correlated with accuracy for and misclassifications of sadness, and cognitive functioning also improved (p = .001, d = 1.62).

Conclusions: Improvement of TRD by esketamine may involve shifts in emotion processing and cognition, with the acute mood-lifting effects of esketamine being discernible from longer-lasting antidepressant response, which consolidates after repeated administration.

Background: Magnetic seizure therapy (MST) has emerged as a promising alternative to electroconvulsive therapy (ECT) for treatment-resistant depression. Previous systematic reviews and meta analysis already showed its primary results, however, there are no recent reviews updating these findings.

Objectives: This systematic review aimed to make an updated systematic review of MST on unipolar and bipolar depression.

Methods: We conducted a search considering databases (PubMed/MEDLINE, EMBASE, Web of Science, Scopus). Studies were included if they investigated MST in human subjects for unipolar or bipolar depression, and not restricting to year or language.

Results: Data resulted in 15 studies, corresponding to 300 participants that received MST. Most studies were pilot, open-label or secondary analyses (n = 12). Participants that received MST had a response and remission rates ranging from 26.9% to 72.2% and 11.1% to 61.1%, respectively. The most common stimulation regions were vertex and prefrontal cortex, with frequencies between 25-100 Hz and duration of 6-24 sessions (2-3 times a week). Few side effects were reported.

Conclusions: MST shows to be effective and well-tolerated treatment for depression. Larger, double-blinded RCTs with standardised mood, cognitive, and side effect assessments are needed to confirm these findings.

Objectives: This study investigates the effects of quercetin, an antioxidant and nitric oxide (NO) modulator, on depressive-like behaviours triggered by social isolation stress (SIS) in mice. SIS, known to harm psychosocial functioning and increase the risk of depression, involves oxidative stress and NO in its pathophysiology.

Methods: 72 male mice were divided into nine groups, including the social (SC) group as the control group (stress-free with normal saline intake). The isolation (IC) groups received normal saline, quercetin at doses of 10, 20, and 40 mg/kg, the nitric oxide synthetase inhibitor L-NAME at a dose of 5 mg/kg, the NO precursor L-arginine at a dose of 100 mg/kg, an ineffective dose of quercetin combined with L-NAME and an effective dose of quercetin combined with L-arginine. Behavioural tests (open-field, forced swimming, and splash tests) were conducted, followed by measuring hippocampal nitrite levels.

Results: Quercetin significantly reduced immobility in the forced swimming test, increased activity in the open-field test, and enhanced grooming behaviour, particularly at 40 mg/kg. Co-administration of an ineffective dose of quercetin (10 mg/kg) with L-NAME increased immobility and grooming activity time. Interestingly, co-administration of the effective dose of quercetin (40 mg/kg) with L-arginine increased immobility time in the FST. Additionally, administration of quercetin at doses of 20 and 40 mg/kg significantly reduced the nitrite level in the hippocampus of SIS mice. Furthermore, co-administration of L-NAME and L-arginine with ineffective and effective doses of quercetin decreased and increased nitrite levels in the hippocampus and increased immobility time in the FST compared to their respective counterparts administered alone.

Conclusions: These results suggest quercetin's potential in alleviating depression by modulating NO levels, pointing to its promise in treating depression associated with chronic stressors like social isolation.

Objectives: This study employed a chronic unpredictable mild stress (CUMS) model to examine the antidepressant properties of SEP-363856.

Methods: The sucrose preference test (SPT) was employed to evaluate anhedonia, the open field test (OFT) to measure locomotor activity and exploratory behaviour, the elevated plus-maze (EPM) to assess anxiety-like behaviour, and the tail suspension test (TST) and forced swimming test (FST) to determine despair behaviour. qRT-PCR was implemented to evaluate gene expression levels in the hippocampus. Western blot, and ELISA were implemented to evaluate hippocampal protein expression, and Nissl staining was implemented to identify hippocampal neuronal injury.

Results: The 10 mg/kg dosage of SEP-363856 and fluoxetine significantly improved depressive-like behaviours as assessed by the SPT, OFT, EPM, TST, and FST. This was associated with improved hippocampal neuronal damage, enhanced mRNA expression of brain-derived neurotrophic factor, synaptophysin, and postsynaptic density 95. SEP-363856 increased the levels of insulin-like growth factor-1 (IGF-1), IGF-1 receptor β, phospho-phosphatidylinositide 3-kinase, and phospho-protein kinase B in the brain.

Conclusions: The antidepressant-like effects of SEP-363856 are linked to increased hippocampal neurotrophic factors, decreased hippocampus neuronal lesions, and activation of the IGF-1Rβ/PI3K/AKT signalling pathway. The latter may serve as a novel drug target for the treatment of depression.

Objectives: The primary objective in managing depression is achieving full recovery, but some patients experience ongoing symptoms that affect daily life, with residual hypersomnia being notably prevalent. Understanding its extent, frequency, and potential treatments is limited.

Methods: This systematic review consolidates existing knowledge on the prevalence and treatment of residual hypersomnia in depression, drawing from PubMed, Web of Science, and Scopus databases. The protocol was registered in PROSPERO (CRD42023392062).

Results: Residual hypersomnia is highly prevalent in depression. Modafinil is the only pharmacological intervention studied, showing short-term effectiveness in randomised placebo-controlled trials. For patients with comorbid obstructive sleep apnoea (OSA), continuous positive airway pressure (CPAP) appears promising for reducing excessive sleepiness. Challenges arise from ambiguous definitions of 'residual symptoms', 'partial response', and 'hypersomnia', and the use of various scales to assess hypersomnia. The scarcity of placebo-controlled randomised trials complicates evaluating treatment efficacy and standardising management approaches.

Conclusions: Given its high prevalence, managing residual hypersomnia is a significant challenge with current treatments appearing ineffective long-term. Data suggest benefits from modafinil augmentation and CPAP treatment, but more research is needed.

Background: India currently accounts for a majority of global suicide deaths. Research in European ancestry has established that suicide mortality has a significant genetic component, and suggests that inflammation may play a crucial role in the pathophysiology of suicide. Inflammation is also highly relevant in regions of increased pollution exposure, such as the megacities of India. To address the existing gaps in genetic research on suicide and possible association with inflammatory biomarkers, we examined genetic polymorphism and clinical risk phenotypes in a population-based suicide-death cohort, India.

Material and methods: Genotyping of IL-1β(rs16944) & (rs1143627), IL-4(rs2070874), IL-6(rs1800795) and IL-10(rs1800896) was done in 234 post-mortem suicide-death cases and 256 post-mortem controls (N = 490) using PCR RFLP method.

Results: Our analyses identified three significant (p < 0.001) associations of cytokine variants with suicide death, including IL-1β(rs16944), OR = 0.627; IL-4(rs2070874), OR = 0.524; and IL-6(rs1800795), OR = 2.509. Cases were more likely female and were more likely to have a history of psychiatric illness, though rate of psychiatric illness was low in suicide cases(9%).

Conclusion: Our genetic results are generally consistent with previous research on risk for depression and suicidal behaviour, and both genetic and phenotypic results provide new insights into risk factors that may contribute to suicide in India.