Translational Psychiatry最新文献

Metabolomics may reveal non-invasive biomarkers for early diagnosis in Alzheimer's disease (AD) and provide new insights into the disease mechanisms to develop effective treatments. Here, we comprehensively analyzed the blood plasma metabolomes from a Chinese cohort of 447 individuals, including 188 AD, 181 MCI (mild cognitive impairment), and 78 NC (normal control). Differential analysis identified altered metabolites, followed by forward feature selection to prioritize a panel of key metabolites, and construction of a diagnostic model using logistic regression. Key metabolite-enriched pathways were identified and quantified for comparison across different groups, which was then validated through external datasets. We observed extensive metabolic dysregulation in AD compared to age-matched NC, with 25% of the differential metabolites also significantly dysregulated in MCI in the same directions. A panel of 22 key metabolites was prioritized, where triglycerides (TG) and phosphatidylethanolamines (PE) ranked top in importance. With these key metabolites, we trained a diagnostic model that classified AD from NC accurately (Area Under the Curve [AUC] = 0.935 in the replication cohort). Pathway quantification analysis showed significant changes in lipid metabolism in AD, which were validated in two external cohorts. We presented a precise and robust blood metabolic diagnostic model for AD, which may help promote early diagnosis and deepen the understanding of AD mechanisms.

Anxiety disorders are a prevalent public health burden that significantly impair daily functioning and decrease quality of life. A growing body of research suggests DNA methylation (DNAm), an epigenetic modification that can impact gene expression, may be altered in anxiety disorders. The current review used a systematic approach to identify and synthesize the literature regarding epigenome-wide association studies (EWASs) of anxiety disorders in humans. We screened 804 articles returned by a search in PubMed in May 2025 and identified 12 studies for inclusion. All included studies examined DNAm in blood. In total, 2023 DNAm sites corresponding to 985 genes were significantly associated with anxiety disorders. Three DNAm sites significantly replicated across studies and four nominally replicated, meeting methylome-wide significance in one study and nominal significance (p < 0.05) in at least one other. This low replicability is likely a result of phenotypic heterogeneity, small sample sizes, the use of different multiple testing correction methods, and inconsistent adjustment for relevant comorbidities. Findings suggest DNAm associated with anxiety disorders may promote dysregulation of immune and inflammatory processes, some possibly sex-dependent. Collectively, the findings from studies included in this review provide preliminary evidence of DNAm alterations related to anxiety in whole blood and multiple blood cell-types. Future EWASs of anxiety disorders could benefit from using more ethnically diverse participants and longitudinal study designs.

Papers that dispute the neurobiological basis of depression and the usefulness of antidepressants keep emerging; therefore, a thorough review is necessary to register pro and con arguments. The current paper formulated 10 questions and tried to provide evidence-based answers. Depression is not a functional stress reaction to life events; it is a dysfunction in mood, affect, and emotion regulation, which results in dysfunctional responses. The reductionism of the biomedical model has no alternative if a scientific pathway is to be followed. Psychosocial approaches find it very difficult to meet the falsification criterion, while methodological shortcomings in pharmacological trials leave room for unsubstantiated discussion of the role of non-biological factors in the response to medication. The dispute over the efficacy of antidepressants has long been resolved and the argument that antidepressants exert their efficacy through a generic emotional numbness was rejected. Psychotherapies probably act through a generic pathway, including simple, practical interventions and relationship compassion. Inevitably, the advances promised by neurosciences, biological psychiatry, and psychopharmacology will eventually pave the way for better outcomes. A profound culture change is essential to ensure that our field is ready to embrace new findings as they emerge. However, a strong psychosocial element and psychoeducation techniques will probably be of prime importance in the future; patients and their families need education and persuasion, otherwise any scientific breakthrough would have little effect on their lives.

Studies have shown that reward-related feedback is processed by distinct brain networks. Neuronal oscillations, particularly theta and beta rhythms, play a key role in facilitating communications within these networks. This study investigated how modulating brain oscillations at theta and beta frequencies using transcranial alternating current stimulation (tACS) influences activation in brain regions involved in feedback processing. In three separate sessions, 28 healthy participants received either theta (5 Hz), beta (25 Hz), or sham tACS over the left dorsolateral prefrontal cortex (DLPFC) while performing a gambling task. fMRI data were recorded simultaneously with tACS to measure BOLD activations associated with gain and loss feedback. Results showed that theta stimulation enhanced activity in brain regions related to sensory processing, error monitoring, cognitive control, and emotion regulation during loss feedback. On the other hand, beta stimulation modulated activation in areas associated with reward sensitivity and emotional processing during gain feedback. These findings demonstrate the distinct roles of theta and beta oscillations in negative and positive feedback processing.

The context-dependent behavior serves as a core behavioral manifestation of intrusive traumatic memory flashbacks in PTSD, its neural circuit and underlying brain regions remain incompletely understood. Although pituitary adenylate cyclase-activating polypeptide (PACAP) has been implicated as a key pathological factor in PTSD pathogenesis, its role in PTSD-like contextual behavioral responses has not yet been elucidated. In this study, we demonstrated that chronic social defeat stress (CSDS) induced locomotor hyperactivity in male mice, but only when they were re-exposed to the stress-associated chamber. Notably, neurons in the paraventricular thalamus (PVT) showed significant activation following the expression of above context-dependent behavior. Chronic optogenetic activation of PVT neurons was sufficient to recapitulate PTSD-like contextual behavior in naïve mice. Furthermore, anterograde and retrograde tracing revealed that the ventral hippocampus (vHip) sends monosynaptic and glutamatergic projections to the PVT. Chronic inhibition of PVT-projecting vHip neurons selectively suppressed PTSD-like context-dependent locomotion hyperactivity without affecting other stress-induced behavioral alterations. In contrast, chronic inhibition of vHip recipient PVT neurons attenuated most CSDS-induced PTSD-like behaviors. Moreover, CSDS led to upregulated expression of the PAC1 receptor in PVT neurons. Local pharmacological blockade of the PAC1 receptor in the PVT during the CSDS paradigm prevented the development of both context-dependent hyperactivity and other PTSD-like behavioral phenotypes. Collectively, our findings identify a vHip-PVT circuit and PVT PACAP/PAC1 signaling in the pathophysiology of PTSD-like contextual behavior and highlight the PVT as a potential therapeutic target for treating PTSD-related context-dependent symptoms.

Acupuncture is an ancient practice that was developed within the framework of traditional Chinese medicine. While acupuncture has been recently proposed as a therapy for Alzheimer's disease (AD), acupuncture effects are not well understood in terms of neural mechanisms. Here, we review and examine the studies that used AD mouse models and analyze the experiments where researchers administered electroacupuncture (EA) to AD mice to assess the potential therapeutic impact of acupuncture on disease pathology and cognitive function in controlled laboratory settings. We analyzed 29 relevant PubMed articles published between January 2014 and July 2025. Our results reveal that EA significantly reduces both amyloid-beta (Aβ) and phosphorylated tau (p-tau) levels and neuroinflammatory biomarkers, including molecular signatures for activated microglia and astrocytes in the brain. EA also enhances cognitive functions. While no study directly compared acupoint strategies, the indirect comparisons in our network analysis suggest that GV20 has potential as a therapeutic target for AD. Our present meta-analysis and review of literature add to the evidence of integrative health practices for acupuncture-based Alzheimer's disease treatment.

Identifying reliable biomarkers of treatment response is central to advancing personalized psychiatry. While whole-brain functional connectivity models have shown promise in predicting clinical outcomes, especially for broad-spectrum interventions like cognitive-behavioral therapy, targeted treatments may benefit from more specific neuromarkers. In social anxiety disorder (SAD), Gaze-Contingent Music Reward Therapy (GC-MRT) is a novel attention bias modification (ABM) intervention designed to reduce preferential attentional allocation to socially threatening stimuli. Given the dorsal attention network's (DAN) key role in top-down attentional control, we tested whether resting-state intra-network DAN connectivity could serve as a neural predictor of response to GC-MRT. Participants with SAD were randomized to either receive GC-MRT (n = 22) or to a waitlist control condition (n = 24). Resting-state fMRI data were collected before and after the intervention. Intra-DAN connectivity at baseline and post-treatment were associated with post-treatment symptom severity in the GC-MRT group. Post-treatment intra-DAN connectivity significantly differed in the GC-MRT group relative to controls. These findings suggest that intra-network connectivity within the DAN may have the potential to function both as a predictive biomarker and as a neural marker of successful intervention. Our findings highlight the role of the DAN in attention-based clinical interventions and show that network-specific connectivity metrics may offer a more precise understanding of how targeted neuromodulation affects symptom change in SAD.

Objective: This study aims to systematically investigate activation in brain regions during early-stage motor sequence learning (MSL) and to identify convergent neural activation patterns, thereby advancing our understanding of the neural mechanisms underlying MSL.

Methods: This meta-analysis integrated functional magnetic resonance imaging (fMRI) data from 12 studies (219 participants) using the serial reaction time task (SRTT) paradigm, applying anisotropic effect-size seed-based d mapping (AES-SDM) to identify common brain activation regions underlying MSL. After the primary meta-analysis, subgroup analyses were conducted on the young adult group, implicit learning group, and bimanual/right-hand task group to investigate the specific effects of age and task type on brain region activation in MSL. Additionally, an independent fMRI dataset from 64 healthy participants performing SRTT was used to validate the meta-analysis results.

Results: We identified convergent activations during SRTT in cortico-basal ganglia-cerebellar circuit, encompassing the supplementary motor area (SMA), precentral gyrus (PreCG), rolandic operculum (ROL), and other cortical regions, alongside basal ganglia and cerebellum, collectively underscoring their critical roles in early-stage MSL. Subgroup analyses revealed age- and task-related modulation of neural activation patterns. Results were largely replicated in the independent validation dataset.

Conclusions: Our findings provide reliable evidence for the involvement of a cortico-basal ganglia-cerebellar circuit in MSL.

Significance: Our meta-analysis contributes to unraveling the brain activation patterns underlying early-stage MSL, offering insights for clinical interventions in motor dysfunction rehabilitation.