Alpha psychiatry最新文献

Background: The objective of this study was to analyze the functional connectivity (FC) of the precentral gyrus (PCG) bilaterally in a sample of patients with schizophrenia experiencing chronic auditory verbal hallucinations (AVH) including a control cohort of healthy volunteers.

Methods: A total of 105 subjects underwent resting-state functional magnetic resonance imaging (MRI) scanning, including 63 healthy control individuals (HC) and 42 schizophrenia patients experiencing AVH. A comparative approach was used to analyze the FC of the PCG bilaterally.

Results: The present study detected increased resting-state FC (rsFC) involving the right PCG and three clusters distributed bilaterally across the frontal cortex, the supplementary motor area (SMA), paracingulate gyrus and the anterior cingulate gyrus (ACC), as well as hypoconnectivity between the right PCG and the lingual gyrus - bilaterally and the left occipital fusiform gyrus in schizophrenia as compared to HC. Furthermore, we observed hyperconnectivity between the left PCG and four clusters, including right paracingulate gyrus, ACC, right frontal pole (FP), precuneus, right pre- and postcentral gyri, right superior frontal gyrus (SFG), and right SMA. In addition, the patient group demonstrated hypoconnectivity between the left PCG and the right occipital pole, right lingual gyrus, right lateral occipital cortex, as well as the right cerebellar crus 1.

Conclusions: In the present study we observed a lateralized impairment in rsFC between the explored seeds and specific cortical and subcortical regions in schizophrenia. These alterations might contribute to the neurobiological pathways involved in schizophrenia pathogenesis with a focus on higher hallucination proneness.

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) and Major Depressive Disorder (MDD) both exhibit working memory (WM) impairments and frequently co-occur. However, the impact of comorbid MDD on WM in ADHD patients and the underlying mechanisms remain unclear.

Methods: The study included 409 adults, comprising 125 ADHD patients comorbid with MDD (ADHD+MDD), 145 ADHD patients without MDD (ADHD-MDD), and 139 healthy controls. In addition, functional connectivities (FCs) with the region of interest-the dorsolateral prefrontal cortex (DLPFC)-were analyzed in a subsample to explore the potential underlying neural mechanism.

Results: The WM scores of the ADHD+MDD group were higher than those of the ADHD-MDD group. In all ADHD patients, depression scores were positively correlated with the WM impairment scores and explained 3.6% of the variance in WM impairment. Mediation analysis detected a potential effect of ADHD diagnosis on WM impairment via depressive symptoms. WM-related FC was identified between the left DLPFC and the right supramarginal gyrus (FC_{[DLPFC/L - SMG/R]}), which partially mediated the relationship between the co-morbid status of MDD and WM.

Conclusions: MDD in adults with ADHD exacerbated WM impairment, which may be related to the FC alteration between the left DLPFC and the right supramarginal gyrus (SMG). This finding provides a scientific basis for a deeper understanding of the pathogenesis and brain biomarkers of ADHD+MDD patients.

Background: Depression relapse rates remain high after acute treatment; this study evaluates the efficacy of maintenance noninvasive brain stimulation in preventing relapse and identifies optimal treatment parameters.

Methods: This meta-analysis was conducted following PRISMA guidelines. We conducted a systematic search of PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO databases up to January 5, 2025. The primary outcome was relapse rate.

Results: A total of nine randomized controlled trials with 837 participants were included, six studies used electroconvulsive therapy (ECT) and three studies used repetitive transcranial magnetic stimulation (rTMS). Our findings indicate that ECT combined with pharmacotherapy or rTMS alone demonstrated superiority over pharmacotherapy alone in reducing the relapse of depression during 6, 9, 12-month maintenance treatment periods. Interestingly, ECT alone did not show significant results. In terms of stimulation parameters, the ECT combined with pharmacotherapy group mainly received right unilateral stimulation, while the ECT alone group had bitemporal stimulation. The stimulation frequency was similar between the two groups. In contrast, the rTMS-alone group had significantly higher stimulation frequencies than the ECT groups. We did not find any eligible studies on transcranial direct current stimulation, transcranial alternating current stimulation or magnetic seizure therapy, but they also showed potential in the maintenance treatment of depression, which warrants further investigation.

Conclusions: ECT combined with pharmacotherapy, or rTMS alone, is more effective than pharmacotherapy alone in preventing relapse of depression during 6 to 12 months of maintenance treatment. Future research should prioritize identifying the optimal treatment regimen and exploring the potential of combination therapies.

The prospero registration: CRD42023490546, https://www.crd.york.ac.uk/PROSPERO/view/CRD42023490546.

Accumulating evidence highlights the role of Vitamin B12 (VitB12) in the pathophysiology of affective disorders. However, its influence on brain function and the underlying mechanisms remain incompletely understood. In humans, VitB12 is obtained solely from dietary sources, primarily animal-based foods. VitB12 deficiency leads to the accumulation of homocysteine, a known contributor to emotional and behavioral dysregulation. VitB12 plays a critical role in maintaining neuron stability, synapsis plasticity, and regulating neuroinflammation by modulating key bioactive factors. These processes help to alleviate hippocampal damage, mitigate blood-brain barrier disruption, reduce oxidative stress, and enhance both structural and functional connectivity-collectively contributing to resilience against affective disorders. VitB12 from both diet and microbial sources is essential to gut homeostasis. Within the gut lumen, it stabilizes gut microbial communities, promotes short-chain fatty acid (SCFA) production, and supports neurotransmitter metabolism (e.g., serotonin and dopamine) via its role in S-adenosyl-l-methionine biosynthesis. Crucially, VitB12, gut microbiota, SCFAs, intestinal mucosa, and vagal nerve signaling interact synergistically within the gut-brain axis (GBA) to maintain gut microenvironment stability, protect the gut-blood barrier, and suppress neuroinflammatory cascades, eventually reducing the susceptibility to affective disorders. This review synthesizes current evidence on the involvement of VitB12 in the GBA, its association with mood regulation, and its potential as a nutritional adjunct in managing affective disorders. By elucidating this integrative mechanism, we provide new insights into targeting the GBA to improve clinical outcomes in affective disorders.

Background: Treatment-resistant depression (TRD) with comorbid anxiety affects up to 30% of patients and frequently fails to respond to conventional therapeutic approaches. The Seville Protocol is a novel, accelerated, high-dose, bilateral theta burst stimulation (TBS) paradigm combining intermittent TBS (iTBS) and continuous TBS (cTBS), specifically designed to address both depressive and anxiety symptoms in TRD.

Methods: This retrospective study was conducted at the Andalusian Institute of Brain Health (Seville, Spain). All participants received the Seville Protocol, consisting of neuronavigated iTBS applied to the left and cTBS to the right dorsolateral prefrontal cortex (DLPFC), delivered at high intensity (110-133.5% of the resting motor threshold) over 30 sessions within three weeks. Symptom severity was assessed at baseline and post-treatment using the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A). Treatment efficacy was analyzed using the Wilcoxon signed-rank test, and logistic regression models were applied to identify predictors of response and remission.

Results: A total of 64 patients diagnosed with TRD and comorbid anxiety were included in the analysis. The Seville Protocol led to significant improvements in both HAM-D and HAM-A scores (p < 0.001). Response rates were 45.3% for depression (95% Confidence Interval (CI) = 33.7-57.4) and 48.4% for anxiety (95% CI = 36.6-60.4), while remission rates were 29.7% for depression (95% CI = 19.9-41.8) and 23.4% for anxiety (95% CI = 14.7-35.1). Logistic regression analysis suggested that a positive family history of mental disorders was associated with a lower likelihood of depression response (β = -1.49, 95% CI = -2.98 to -0.18, p = 0.033); however, this association did not remain significant after false discovery rate (FDR) correction (adjusted p = 0.298).

Conclusions: The Seville Protocol appears to be a feasible, practical, and time-efficient neuromodulation approach for patients with TRD and comorbid anxiety. These findings support the potential utility of accelerated bilateral TBS in this population, although further studies are needed to validate the findings and assess their broader applicability.

Background: Patients with narcolepsy experience excessive daytime sleepiness (EDS) and cognitive impairment. However, studies on the circadian variability associated with cognitive impairment in narcolepsy patients are scarce. This study aimed to explore circadian cognitive performance in narcolepsy patients compared with patients with obstructive sleep apnea (OSA) and EDS (OSA-with-EDS).

Methods: A total of 62 participants, 29 with narcolepsy and 33 with OSA-with-EDS completed the study. The assessments were done using questionnaires, polysomnography (PSG), the multiple sleep latency test (MSLT), and cognitive-behavioral tasks at different time points (20:00, 08:00, 10:00, 12:00, 14:00, 16:00, and 18:00) including the psychomotor vigilance task (PVT), the Stroop color-word task, and the 2-back task to separately assess the circadian variations of vigilant attention, inhibitory control, and working memory respectively.

Results: Narcolepsy patients showed significant within-subject circadian variations in vigilant attention (p < 0.001), inhibitory control (p = 0.016), and working memory (p < 0.001) in the time domain. Overall, vigilant attention in narcolepsy patients presented a pattern with optimal performance observed at 20:00 on the previous night followed by deterioration in the morning (08:00~14:00) and improvement in the afternoon (14:00~18:00). Inhibitory control displayed a pattern of "enhancement in the morning (08:00~12:00) followed by a decline in the afternoon (12:00~18:00)", while working memory displayed a trend of improvement during daytime hours, with these two measures showing their poorest performance at 20:00 on the previous night.

Conclusions: Circadian variations were prominently observed in vigilant attention, inhibitory control, and working memory performance among patients with narcolepsy. Except for EDS, the intrinsic disease specificity may play an important role in the cognitive impairments associated with narcolepsy.

With the development of the brain-gut axis (GBA), the bidirectional communication between gut microbiota and the brain has become critical in emotion regulation research, and dopamine D2 receptors and gut microbiota play key roles in this process, especially in neurological and psychiatric disorders. This narrative review explores the impact of dopamine D2 receptors in the GBA, focusing on how gut microbiota modulates emotion and behavior via D2 receptors, analyzes their imbalance correlation, and looks forward to D2 receptor-based therapies.Comprehensive searches were conducted in PubMed, Web of Science, and Google Scholar (2000-2025) using keywords like "dopamine D2 receptor", "brain-gut axis", and "emotional disorders", including animal and clinical studies. Research shows gut microbiota affects dopamine system activity and D2 receptor function mainly via metabolites, especially short-chain fatty acids (SCFAs, such as butyric acid and propionic acid). SCFAs cross the blood-brain barrier, bind to G protein-coupled receptors (GPCRs) to regulate dopamine synthesis/release, enhance brain immune function by improving astrocyte activity and blood-brain barrier integrity, and thus promote D2 receptor signal transduction. Gut microbiota also indirectly influences D2 receptor expression/activity by regulating dopamine precursor (such as tyrosine) metabolism. Gut microbiota imbalance is closely associated with D2 receptor dysfunction. In depression, anxiety, schizophrenia, and Parkinson's disease, D2 receptor function is reduced or abnormally activated; gut dysbiosis (such as altered Firmicutes/Bacteroidetes ratio, increased Proteobacteria/Escherichia coli) disrupts gut metabolites (such as reduced SCFAs), aggravates systemic inflammation, and impairs the dopamine system. Overall, gut microbiota modulates D2 receptor activity through multiple mechanisms, exerting an important role in regulating emotion and behavior.

Background: In autism spectrum disorder (ASD), the human plasma metabolome is altered but the causal relationship between the levels of metabolites and ASD is unclear. We aimed to assess bidirectional causal associations between plasma metabolites and ASD.

Methods: We investigated potential causal associations between the genetic variation contributing to the levels of metabolites and ASD via Mendelian randomization (MR) analyses. Genome-wide association study (GWAS) summary datasets were used in the study, including ASD (n = 46,350) and 871 plasma metabolite (n = 8299) datasets. We used druggability analysis to prioritize metabolites with therapeutic potential.

Results: Our MR analysis identified 32 plasma metabolites whose levels were protective against the risk of ASD, including 5 alpha-androstan-3 alpha, 17 beta-diol disulfate (odds ratio (OR): 0.94, 95% CI: 0.90-0.97) and 11beta-hydroxyetiocholanolone glucuronide (OR: 0.95, 95% CI: 0.92-0.98). Additionally, 12 metabolites were found to be positively associated with the risk of ASD, including indoleacetylglutamine (OR: 1.04, 95% CI: 1.01-1.08) and sphingomyelin (d18:1/24:1, d18:2/24:0) (OR: 1.06, 95% CI: 1.01-1.11). Some metabolites may be regulated through drug intervention, including sphingomyelin, chiro-inositol, carotene diol (1)/(2), and glycerol. Genetic variation contributing to ASD may increase the abundance of five metabolites, including deoxycholic acid glucuronide (OR: 1.18, 95% CI: 1.03-1.34); meanwhile, the abundance of 27 metabolites, including stearoyl choline (OR: 0.80, 95% CI: 0.69-0.92) may be causally reduced.

Conclusions: Our MR analysis uncovered bidirectional causal associations between certain plasma metabolites and ASD, suggesting that these metabolites could be biomarkers for ASD and paving the way for novel therapeutic targets in ASD phenotypes.

Background: Previous studies have demonstrated a significant association between neuroinflammation and major depressive disorder (MDD). (6aS,10S,11aR,11bR,11cS)-10-methylamino-dodecahydro-3a,7a-diaza-benzo(de)anthracene-8-thione (MASM), a derivative of matrine, has recently been shown to display anti-inflammatory properties. However, its effects on lipopolysaccharide (LPS)-induced depression and the underlying mechanisms remain unexplored. This study aimed to assess the effects of MASM on depressive-like behaviors induced by LPS and to investigate the potential mechanisms involved.

Methods: Following intraperitoneal injection of LPS (0.83 mg/kg), MASM was administered. Depressive-like behaviors were assessed through the forced swim test (FST) and tail suspension test (TST). To further explore the mechanisms, LPS-induced BV2 microglial cell models were established. Enzyme-linked immunosorbent assay (ELISA) was used to quantify the expression of TNF-α and high mobility group box 1 (HMGB1), while immunoblotting was performed to assess heme oxygenase-1 (HO-1), sirtuin 1 (SIRT-1), p62, and microtubule-associated protein 1A/1B-light chain 3-phosphatidylethanolamine conjugate (LC3-II) expression. Reactive oxygen species (ROS) levels were evaluated using flow cytometry.

Results: MASM pretreatment markedly ameliorated acute depressive-like behaviors in LPS-treated mice and upregulated HO-1 expression in the hippocampus. In LPS-stimulated BV2 cells, MASM reduced the levels of proinflammatory markers TNF-α and HMGB1. Furthermore, MASM mitigated LPS-induced oxidative stress, as evidenced by increased ATP, HO-1, and SIRT-1 levels, along with decreased ROS levels. MASM also restored autophagic function, demonstrated by increased LC3-II expression and reduced p62 levels.

Conclusion: These findings suggests that MASM alleviates LPS-induced neuroinflammation and acute depressive-like behaviors, possibly by reducing oxidative stress and promoting autophagy.

Objective: To explore the effects of hypertension, uric acid (UA) level, and other physiological factors on blood lithium concentration/dose ratio (C/D; a measure of lithium pharmacokinetics) values in patients experiencing manic episodes.

Methods: A total of 644 patients with manic episodes were treated at the study hospital between January and June 2022. Patients were divided into groups according to their systolic and diastolic blood pressure (BP) as well as blood glucose, triglyceride, and UA levels. The effects of these factors on blood lithium C/D values after lithium carbonate treatment were examined.

Results: The mean blood lithium C/D value of all study participants was 0.832 ± 0.248 mmol·L^-1·g^-1·d. There was no significant difference in blood lithium C/D value between patients with abnormal and normal diastolic BP (p > 0.05). However, patients with an abnormal systolic BP (>130 mmHg) had lower lithium C/D values than those with normal systolic BP (p < 0.05). Systolic BP was negatively correlated with C/D value (r = -0.232; p = 0.001), as was UA level (r = -0.114; p = 0.013).

Conclusion: Hypertension and elevated UA levels can affect the blood lithium C/D value in patients with manic episodes. Personalized treatment approaches that take these physiological factors into account may help reduce treatment risks.