Major depressive disorder (MDD) is a highly heterogeneous disease. Further classification may characterize its heterogeneity. The purpose of this study was to examine whether metabolomic variables could differentiate traditional Chinese medicine (TCM) diagnostic subtypes of MDD. Fifty medication-free patients who were experiencing a recurrent depressive episode were classified into Liver Qi Stagnation (LQS, n = 30) and Heart and Spleen Deficiency (HSD, n = 20) subtypes according to TCM diagnosis. Healthy volunteers (n = 28) were included as controls. Gas chromatography-mass spectrometry (GC–MS) was used to examine serum and urinary metabolomic profiles. Twenty-eight metabolites were identified for good separations between TCM subtypes and healthy controls in serum samples. Both TCM subtypes had similar profiles in proteinogenic branched-chain amino acids (BCAAs) (valine, leucine, and isoleucine) and energy metabolism-related metabolites that were differentiated from healthy controls. The LQS subtype additionally differed from healthy controls in multiple amino acid metabolites that are involved in biosynthesis of monoamine and amino acid neurotransmitters, including phenylalanine, 3-hydroxybutric acid, o-tyrosine, glycine, l-tryptophan, and N-acetyl-l-aspartic acid. Threonic acid, methionine, stearic acid, and isobutyric acid are differentially associated with the two subtypes. While both TCM subtypes are associated with aberrant BCAA and energy metabolism, the LQS subtype may represent an MDD subpopulation characterized by abnormalities in the biosynthesis of monoamine and amino acid neurotransmitters and closer associations with stress-related pathophysiology. The metabolites differentially associated with the two subtypes are promising biomarkers for predicting TCM subtype-specific antidepressant response [registered at http://www.clinicaltrials.gov (NCT02346682) on January 27, 2015].

Major depressive disorder (MDD) is a severe and devastating condition. However, the anatomical basis behind the affective symptoms, cognitive symptoms, and somatic-vegetative symptoms of MDD is still unknown. To explore the mechanism behind the depressive symptoms in MDD, we used diffusion tensor imaging (DTI)–based structural brain connectivity analysis to investigate the network difference between MDD patients and healthy controls (CN), and to explore the association between network metrics and patients’ clinical symptoms. Twenty-six patients with MDD and 25 CN were included. A baseline 24-item Hamilton rating scale for depression (HAMD-24) score ≥ 21 and seven factors (anxiety/somatization, weight loss, cognitive disturbance, diurnal variation, retardation, sleep disturbance, hopelessness) scores were assessed. When compared with healthy subjects, significantly higher characteristic path length and clustering coefficient as well as significantly lower network efficiencies were observed in patients with MDD. Furthermore, MDD patients demonstrated significantly lower nodal degree and nodal efficiency in multiple brain regions including superior frontal gyrus (SFG), supplementary motor area (SMA), calcarine fissure, middle temporal gyrus (MTG), and inferior temporal gyrus (ITG). We also found that the characteristic path length of MDD patients was associated with weight loss. Moreover, significantly lower global efficiency of MDD patients was correlated with higher total HAMD score, anxiety somatization, and cognitive disturbance. The nodal degree in SFG was also found to be negatively associated with disease duration. In conclusion, our results demonstrated that MDD patients had impaired structural network features compared to CN, and disruption of optimal network architecture might be the mechanism behind the depressive symptoms and emotion disturbance in MDD patients.

Depression is one of the major mental disorders, which seriously endangers human health, brings a serious burden to patients’ families. In this study, we intended to further explore the antidepressant-like effect and possible molecular mechanisms of Salidroside (SAL). We built corticosterone (CORT)-induced depressive mice model and used behavioural tests to evaluate depression behaviour. To explore the molecular mechanisms of SAL, we employed a variety of methods such as immunofluorescence, western blot, pharmacological interference, etc. The results demonstrated that SAL both at 25 mg/kg and 50 mg/kg can reduce immobility time in the tail suspension test (TST). At the same time, SAL treatment could restore the reduced sugar water intake preference in the sucrose preference test (SPT) in CORT-induced depressive mice and reduce the immobility time in TST and forced swimming experiments (FST). In addition, SAL treatment reversed the reduction in the number of Ki-67, BrdU, and NeuN in the hippocampus due to CORT treatment. SAL treatment also restored the expression of SIRT1, PGC-1α, brain-derived neurotrophic factor (BDNF) and other proteins in the hippocampus. In addition, after blocking SIRT1 signalling with EX527, we found that the treatment with SAL failed to reduce the immobility time in TST and FST, the level of SIRT1 and PGC-1α activity were correspondingly downregulated, and the expression of DCX and Ki-67 in the hippocampus failed to be activated. These findings suggested that SAL exerts antidepressant-like effects by promoting hippocampal neurogenesis through the SIRT1/PGC-1α signalling pathway.

Background: Major depressive disorder (MDD) is highly heterogeneous in pathogenesis and manifestations. Further classification may help characterize its heterogeneity. We previously have shown differential metabolomic profiles of traditional Chinese medicine (TCM) diagnostic subtypes of MDD. We further determined brain connectomic associations with TCM subtypes of MDD. Methods: In this naturalistic study, 44 medication-free patients with a recurrent depressive episode were classified into liver qi stagnation (LQS, n = 26) and Heart and Spleen Deficiency (HSD, n = 18) subtypes according to TCM diagnosis. Healthy subjects (n = 28) were included as controls. Whole-brain white matter connectivity was analyzed on diffusion tensor imaging. Results: The LQS subtype showed significant differences in multiple network metrics of the angular gyrus, middle occipital gyrus, calcarine sulcus, and Heschl’s gyrus compared to the other two groups. The HSD subtype had markedly greater regional connectivity of the insula, parahippocampal gyrus, and posterior cingulate gyrus than the other two groups, and microstructural abnormalities of the frontal medial orbital gyrus and middle temporal pole. The insular betweenness centrality was strongly inversely correlated with the severity of depression and dichotomized the two subtypes at the optimal cutoff value with acceptable sensitivity and specificity. Conclusions: The LQS subtype is mainly characterized by aberrant connectivity of the audiovisual perception-related temporal-occipital network, whereas the HSD subtype is more closely associated with hyperconnectivity and microstructural abnormalities of the limbic-paralimbic network. Insular connectivity may serve a biomarker for TCM-based classification of depression. Trial registration Registered at http://www.clinicaltrials.gov (NCT02346682) on January 27, 2015

Introduction: Hydrocephalus is a form of communication hydrocephalus syndrome characterized by ventricular enlargement and normal intraventricular pressure. The primary clinical manifestations include gait disturbances, cognitive dysfunction, urinary incontinence, and either elevated or normal intracranial pressure. This paper presents a case of a mental disorder resulting from inadequate drainage following a ventriculoperitoneal shunt procedure for hydrocephalus. The case report aims to enhance clinicians’ understanding of such organic brain lesions, which are prone to misdiagnosis and inappropriate treatment, thereby improving differential diagnostic skills.Case presentation: This case report describes a 34-year-old male with a 16-year history of depressive disorder, previously managed with 150 mg of venlafaxine daily, 7.5 mg of zopiclone every night, and 2.4 g of piracetam every day. The patient underwent a ventriculoperitoneal shunt procedure for hydrocephalus, leading to the development of a mental disorder attributable to poor drainage from the shunt tube. Initial symptoms consisted of low mood, decreased interest, and cognitive impairment. Despite psychiatric consultation and antidepressant treatment, there was no improvement in his condition. The final diagnosis was an organic mental disorder. Following an increase in shunt drainage and the administration of a low dose of olanzapine, the patient’s psychiatric symptoms showed significant improvement.Conclusion: Reporting this case seeks to enhance clinicians’ awareness of the psychiatric manifestations of organic brain lesions, expand the differential diagnostic approach for psychiatrists, and improve diagnostic accuracy. Additionally, it emphasizes the need for cautious use of psychiatric medications, appropriate symptomatic management, and timely referral when necessary.

Post-traumatic stress disorder (PTSD) is associated with immune and autonomic disturbances, but molecular programs linking PTSD-related blood transcriptional signals with autonomic–cardiac biology remain incompletely characterized. The public Gene Expression Omnibus (GEO) cohorts analyzed here did not directly measure palpitations or autonomic dysfunction. Peripheral-blood transcriptomes from GSE81761 and GSE63878 were integrated with a prespecified pathway-derived autonomic–cardiac gene set constructed from Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Genes overlapping the curated pathway set were assessed using functional enrichment and protein–protein interaction (PPI) analyses. Multi-algorithm comparison and a separate random-forest/SHapley Additive exPlanations (SHAP) analysis were performed for internal model assessment and biological prioritization. GSE64813 and GSE97356 were analyzed using targeted single-gene analyses and cohort-specific multivariable logistic models. Model performance was examined using repeated nested cross-validation, a fully nested sensitivity analysis, and locked-transfer testing to GSE64813 and GSE97356. Interleukin 15 (IL15) and protein phosphatase 2 scaffold subunit Aalpha (PPP2R1A) were evaluated using external-cohort analyses, immune-cell deconvolution, and descriptive postmortem hippocampal single-nucleus data. Among 1679 nominally significant PTSD-associated candidate genes, 92 overlapped the curated pathway set and were enriched for cytokine signaling, chemotaxis, apoptosis, calcium transport, and PP2A-related functions. PPI analysis yielded 37 recurrent candidate hub genes. The original model comparison ranked support-vector machine (SVM) the highest across the merged and source-cohort summaries [mean area under the receiver-operating-characteristic curve (AUC) 0.853], but these estimates represent internal discovery-stage performance. IL15 was recurrently prioritized by network-based analyses, whereas PPP2R1A was a component of an enriched phosphatase-related module. IL15 and PPP2R1A showed modest single-gene effects in GSE64813 (AUC 0.566 and 0.612) and GSE97356 (AUC 0.558 and 0.593). Cohort-specific refitted models showed apparent AUC values of 0.834 and 0.749, respectively. Repeated nested cross-validation conditional on the preselected 29-gene feature set identified L2-regularized logistic regression as the best-performing algorithm (mean AUC = 0.690). Importantly, a more stringent fully nested sensitivity analysis, in which differential-expression screening and pathway intersection were repeated within each outer training fold, yielded a mean repeated outer-cross-validated AUC of 0.593 [standard deviation (SD) = 0.033; range, 0.541–0.625], indicating limited predictive performance. Locked-transfer AUCs were 0.664 in GSE64813 and 0.534 in GSE97356. Single-nucleus summaries suggested donor- and nucleus-type-dependent expression patterns for IL15 and PPP2R1A. These findings identify IL15-related cytokine signaling and PPP2R1A-related phosphatase regulation as candidate molecular programs linking PTSD-associated transcriptional variation with pathway-derived autonomic–cardiac biology. The results should therefore be interpreted as hypothesis-generating rather than direct molecular evidence for unmeasured palpitation symptoms. Prospective validation in independent, clinically well-characterized cohorts with standardized autonomic and cardiac phenotyping is warranted.