Quantitative imaging for predicting hematoma expansion in intracerebral hemorrhage: A multimodel comparison.

BACKGROUND: Several studies report that radiomics provides additional information for predicting hematoma expansion in intracerebral hemorrhage (ICH). However, the comparison of diagnostic performance of radiomics for predicting revised hematoma expansion (RHE) remains unclear. METHODS: The cohort comprised 312 consecutive patients with ICH. A total of 1106 radiomics features from seven categories were extracted using Python software. Support vector machines achieved the best performance in both the training and validation datasets. Clinical factors models were constructed to predict RHE. Receiver operating characteristic curve analysis was used to assess the abilities of non-contrast computed tomography (NCCT) signs, radiomics features, and combined models to predict RHE. RESULTS: We finally selected the top 21 features for predicting RHE. After univariate analysis, 4 clinical factors and 5 NCCT signs were selected for inclusion in the prediction models. In the training and validation dataset, radiomics features had a higher predictive value for RHE (AUC = 0.83) than a single NCCT sign and expansion-prone hematoma. The combined prediction model including radiomics features, clinical factors, and NCCT signs achieved higher predictive performances for RHE (AUC = 0.88) than other combined models. CONCLUSIONS: NCCT radiomics features have a good degree of discrimination for predicting RHE in ICH patients. Combined prediction models that include quantitative imaging significantly improve the prediction of RHE, which may assist in the risk stratification of ICH patients for anti-expansion treatments.

Hydrocephalus Growth: Definition, Prevalence, Association with Poor Outcome in Acute Intracerebral Hemorrhage.

BACKGROUND/OBJECTIVES: To propose a novel definition for hydrocephalus growth and to further describe the association between hydrocephalus growth and poor outcome among patients with intracerebral hemorrhage (ICH). METHODS: We analyzed consecutive patients who presented within 6 h after ICH ictus between July 2011 and June 2017. Follow-up CT scans were performed within 36 h after initial CT scans. The degree of hydrocephalus were evaluated by the hydrocephalus score of Diringer et al. The optimal increase of the hydrocephalus scores between initial and follow-up CT scan was estimated to define hydrocephalus growth. Poor long-term outcome was defined as a modified Rankin Scale of 4-6 at 3 months. Multivariate logistic regression analysis was performed to investigate the hydrocephalus growth for predicting 30-day mortality, 90-day mortality, and poor long-term outcome. RESULTS: A total of 321 patients with ICH were included in the study. Of 64 patients with hydrocephalus growth, 34 (53.1%) patients presented with both concurrent hematoma expansion and intraventricular hemorrhage (IVH) growth. After adjusting for potential confounding factors, hydrocephalus growth independently predicted 30-day mortality, 90-day mortality, and 90-day poor long-term outcome in multivariate logistic regression analysis. Hydrocephalus growth showed higher accuracy for predicting 30-day mortality, 90-day mortality, and poor long-term outcome than IVH growth or hematoma expansion, respectively. CONCLUSIONS: Hydrocephalus growth is defined by strongly predictive of short- or long-term mortality and poor outcome at 90 days, and might be a potential indicator for assisting clinicians for clinical decision-making.

Expansion-Prone Hematoma: Defining a Population at High Risk of Hematoma Growth and Poor Outcome.

BACKGROUND: Noncontrast computed tomography (CT) markers are increasingly used for predicting hematoma expansion. The aim of our study was to investigate the predictive value of expansion-prone hematoma in predicting hematoma expansion and outcome in patients with intracerebral hemorrhage (ICH). METHODS: Between July 2011 and January 2017, ICH patients who underwent baseline CT scan within 6 h of symptoms onset and follow-up CT scan were recruited into the study. Expansion-prone hematoma was defined as the presence of one or more of the following imaging markers: blend sign, black hole sign, or island sign. The diagnostic performance of blend sign, black hole sign, island sign, and expansion-prone hematoma in predicting hematoma expansion was assessed. Predictors of hematoma growth and poor outcome were analyzed using multivariable logistical regression analysis. RESULTS: A total of 282 patients were included in our final analysis. Of 88 patients with early hematoma growth, 69 (78.4%) had expansion-prone hematoma. Expansion-prone hematoma had a higher sensitivity and accuracy for predicting hematoma expansion and poor outcome when compared with any single imaging marker. After adjustment for potential confounders, expansion-prone hematoma independently predicted hematoma expansion (OR 28.33; 95% CI 12.95-61.98) and poor outcome (OR 5.67; 95% CI 2.82-11.40) in multivariable logistic model. CONCLUSION: Expansion-prone hematoma seems to be a better predictor than any single noncontrast CT marker for predicting hematoma expansion and poor outcome. Considering the high risk of hematoma expansion in these patients, expansion-prone hematoma may be a potential therapeutic target for anti-expansion treatment in future clinical studies.

MINFIT: A Spreadsheet-Based Tool for Parameter Estimation in an Equilibrium Speciation Software Program.

Determination of equilibrium constants describing chemical reactions in the aqueous phase and at solid-water interface relies on inverse modeling and parameter estimation. Although there are existing tools available, the steep learning curve prevents the wider community of environmental engineers and chemists to adopt those tools. Stemming from classical chemical equilibrium codes, MINEQL+ has been one of the most widely used chemical equilibrium software programs. We developed a spreadsheet-based tool, which we are calling MINFIT, that interacts with MINEQL+ to perform parameter estimations that optimize model fits to experimental data sets. MINFIT enables automatic and convenient screening of a large number of parameter sets toward the optimal solutions by calling MINEQL+ to perform iterative forward calculations following either exhaustive equidistant grid search or randomized search algorithms. The combined use of the two algorithms can securely guide the searches for the global optima. We developed interactive interfaces so that the optimization processes are transparent. Benchmark examples including both aqueous and surface complexation problems illustrate the parameter estimation and associated sensitivity analysis. MINFIT is accessible at http://minfit.strikingly.com .

Effect of acidic polymers on the morphology of non-photochemical laser-induced nucleation of potassium bromide.

Non-photochemical laser-induced nucleation (NPLIN) in supersaturated potassium bromide (KBr) solutions with the addition of acidic polymers is reported here for the first time. Upon absorbing the incident laser, crystallites are immediately induced along the laser pathway in the solution, eventually growing into needle-shaped crystals of varying sizes. When comparing induction time, nucleation probability, and crystal habits with spontaneous nucleation, the results suggest that NPLIN creates a distinct morphological pathway, transforming cubic crystals into needle-like structures. Additionally, it improves crystallization probability and growth rate. This paper aims to realize control from crystal nucleation to crystal growth by adding acidic polymers to the process of laser-induced nucleation, potentially influencing crystal morphology modification in NPLIN. With 19 wt% acidic polymers added to the solution as additives, control over both crystal growth and morphological modifications was observed: cubic KBr crystals with square patterns were produced through laser irradiation, and there was a varying reduction in both the number and growth rate of the crystals. The influence of acidic polymers on the solution environment was analyzed to determine the reasons for the variations in crystal quantity and growth speed. The underlying mechanisms responsible for the changes in crystal shape were also discussed.

Altered neurometabolite levels in the brains of patients with depression: A systematic analysis of magnetic resonance spectroscopy studies.

BACKGROUND: Numerous magnetic resonance spectroscopy (MRS) studies have reported metabolic abnormalities in the brains of patients with depression, although inconsistent results have been reported. The aim of this study was to explore changes in neurometabolite levels in patients with depression across large-scale MRS studies. METHOD: A total of 307 differential metabolite entries associated with depression were retrieved from 180 MRS studies retrieved from the Metabolite Network of Depression Database. The vote-counting method was used to identify consistently altered metabolites in the whole brain and specific brain regions of patients with depression. RESULTS: Only few differential neurometabolites showed a stable change trend. The levels of total choline (tCho) and the tCho/N-acetyl aspartate (NAA) ratio were consistently higher in the brains of patients with depression, and that the levels of NAA, glutamate and glutamine (Glx), and gamma-aminobutyric acid (GABA) were lower. For specific brain regions, we found lower Glx levels in the prefrontal cortex and lower GABA concentrations in the occipital cortex. We also found lower concentrations of NAA in the anterior cingulate cortex and prefrontal cortex. The levels of tCho were higher in the prefrontal cortex and putamen. CONCLUSION: Our results revealed that most altered neurometabolites in previous studies lack of adequate reproducibility. Through vote-counting method with large-scale studies, downregulation of glutamatergic neurometabolites, impaired neuronal integrity, and disturbed membrane metabolism were found in the pathobiology of depression, which contribute to existing knowledge of neurometabolic changes in depression. Further studies based on a larger dataset are needed to confirm our findings.

Corrigendum: New Prediction Models of Functional Outcome in Acute Intracerebral Hemorrhage: The dICH Score and uICH Score.

[This corrects the article DOI: 10.3389/fneur.2021.655800.].

Integrated Multiomics Analysis Identifies a Novel Biomarker Associated with Prognosis in Intracerebral Hemorrhage.

Existing treatments for intracerebral hemorrhage (ICH) are unable to satisfactorily prevent development of secondary brain injury after ICH and multiple pathological mechanisms are involved in the development of the injury. In this study, we aimed to identify novel genes and proteins and integrated their molecular alternations to reveal key network modules involved in ICH pathology. A total of 30 C57BL/6 male mice were used for this study. The collagenase model of ICH was employed, 3 days after ICH animals were tested neurological. After it, animals were euthanized and perihematomal brain tissues were collected for transcriptome and TMT labeling-based quantitative proteome analyses. Protein-protein interaction (PPI) network, Gene Set Enrichment Analysis (GSEA), and regularized Canonical Correlation Analysis (rCCA) were performed to integrated multiomics data. For validation of hub genes and proteins, qRT-PCR and Western blot were carried out. The candidate biomarkers were further measured by ELISA in the plasma of ICH patients and the controls. A total of 2218 differentially expressed genes (DEGs) and 353 differentially expressed proteins (DEPs) between the ICH model group and control group were identified. GSEA revealed that immune-related gene sets were prominently upregulated and significantly enriched in pathways of inflammasome complex, negative regulation of interleukin-12 production, and pyroptosis during the ICH process. The rCCA network presented two highly connective clusters which were involved in the sphingolipid catabolic process and inflammatory response. Among ten hub genes screened out by integrative analysis, significantly upregulated Itgb2, Serpina3n, and Ctss were validated in the ICH group by qRT-PCR and Western blot. Plasma levels of human SERPINA3 (homologue of murine Serpina3n) were elevated in ICH patients compared with the healthy controls (SERPINA3: 13.3 ng/mL vs. 11.2 ng/mL, p = 0.015). Within the ICH group, higher plasma SERPINA3 levels with a predictive threshold of 14.31 ng/mL (sensitivity = 64.3%; specificity = 80.8%; AUC = 0.742, 95% CI: 0.567-0.916) were highly associated with poor outcome (mRS scores 4-6). Taken together, the results of our study exhibited molecular changes related to ICH-induced brain injury by multidimensional analysis and effectively identified three biomarker candidates in a mouse ICH model, as well as pointed out that Serpina3n/SERPINA3 was a potential biomarker associated with poor functional outcome in ICH patients.

Noncontrast Computed Tomography Markers as Predictors of Revised Hematoma Expansion in Acute Intracerebral Hemorrhage.

Background Noncontrast computed tomography (NCCT) markers are the emerging predictors of hematoma expansion in intracerebral hemorrhage. However, the relationship between NCCT markers and the dynamic change of hematoma in parenchymal tissues and the ventricular system remains unclear. Methods and Results We included 314 consecutive patients with intracerebral hemorrhage admitted to our hospital from July 2011 to May 2017. The intracerebral hemorrhage volumes and intraventricular hemorrhage (IVH) volumes were measured using a semiautomated, computer-assisted technique. Revised hematoma expansion (RHE) was defined by incorporating the original definition of hematoma expansion into IVH growth. Receiver operating characteristic curve analysis was used to compare the performance of the NCCT markers in predicting the IVH growth and RHE. Of 314 patients in our study, 61 (19.4%) had IVH growth and 93 (23.9%) had RHE. After adjustment for potential confounding variables, blend sign, black hole sign, island sign, and expansion-prone hematoma could independently predict IVH growth and RHE in the multivariate logistic regression analysis. Expansion-prone hematoma had a higher predictive performance of RHE than any single marker. The diagnostic accuracy of RHE in predicting poor prognosis was significantly higher than that of hematoma expansion. Conclusions The NCCT markers are independently associated with IVH growth and RHE. Furthermore, the expansion-prone hematoma has a higher predictive accuracy for prediction of RHE and poor outcome than any single NCCT marker. These findings may assist in risk stratification of NCCT signs for predicting active bleeding.

Early Perihematomal Edema Expansion: Definition, Significance, and Association with Outcomes after Intracerebral Hemorrhage.

OBJECTIVE: To investigate the association between early perihematomal edema (PHE) expansion and functional outcome in patients with intracerebral hemorrhage (ICH). METHODS: Patients with ICH who underwent initial computed tomography (CT) scans within 6 hours after the onset of symptoms and follow-up CT scans within 24 ± 12 hours were included. Absolute PHE increase was defined as the absolute increase in PHE volume from baseline to 24 hours. A receiver-operating characteristic (ROC) curve was generated to determine the cutoff value for early PHE expansion, which was operationally defined as an absolute increase in PHE volume of >6 mL. The outcome of interest was 3-month poor outcome defined as modified Rankin scale score of ≥4. A multivariable logistic regression procedure was used to assess the association between early PHE expansion and outcome after ICH. RESULTS: In 233 patients with ICH, 89 (38.2%) patients had poor outcome at 3-month follow-up. Early PHE expansion was observed in 56 of 233 (24.0%) patients. Patients with early PHE expansion were more likely to have poor functional outcome than those without (43.8% vs. 11.8%, p < 0.001). After adjusting for age, admission systolic blood pressure, admission Glasgow Coma Scale score, baseline ICH volume and the presence of intraventricular hemorrhage, and time from onset to CT, early PHE expansion was associated with poor outcome (adjusted odds ratio, 4.25; 95% confidence interval, 1.70-10.60; p = 0.002). CONCLUSIONS: The early PHE expansion was not uncommon in patients with ICH and was correlated with poor outcome following ICH.

New Prediction Models of Functional Outcome in Acute Intracerebral Hemorrhage: The dICH Score and uICH Score.

Objectives: The original intracerebral hemorrhage (oICH) score is the severity score most commonly used in clinical intracerebral hemorrhage (ICH) research but may be influenced by hematoma expansion or intraventricular hemorrhage (IVH) growth in acute ICH. Here, we aimed to develop new clinical scores to improve the prediction of functional outcomes in patients with ICH. Methods: Patients admitted to the First Affiliated Hospital of Chongqing Medical University with primary ICH were prospectively enrolled in this study. Hematoma volume was measured using a semiautomated, computer-assisted technique. The dynamic ICH (dICH) score was developed by incorporating hematoma expansion and IVH growth into the oICH score. The ultra-early ICH (uICH) score was developed by adding the independent non-contrast CT markers to the oICH score. Receiver operating characteristic curve analysis was used to compare performance among the oICH score, dICH score, and uICH score. Results: This study included 76 patients (23.3%) with hematoma expansion and 61 patients (18.7%) with IVH growth. Of 31 patients with two or more non-contrast computed tomography markers, 61.3% died, and 96.8% had poor outcomes at 90 days. After adjustment for potential confounding variables, we found that age, baseline Glasgow Coma Scale score, presence of IVH on initial CT, baseline ICH volume, infratentorial hemorrhage, hematoma expansion, IVH growth, blend sign, black hole sign, and island sign could independently predict poor outcomes in multivariate analysis. In comparison with the oICH score, the dICH score and uICH score exhibited better performance in the prediction of poor functional outcomes. Conclusions: The dICH score and uICH score were useful clinical assessment tools that could be used for risk stratification concerning functional outcomes and provide guidance in clinical decision-making in acute ICH.

Combination of ultra-early hematoma growth and blend sign for predicting hematoma expansion and functional outcome.

OBJECTIVE: Ultra-early hematoma growth (uHG) in acute intracerebral hemorrhage (ICH) has been well established and can improve spot sign in the prediction of hematoma expansion (HE) and poor outcome. This study aimed to investigate whether uHG can improve blend sign as a promising combining marker to stratify HE and poor outcome. PATIENTS AND METHODS: A consecutive cohort study in patients with primary ICH conducted in the First Affiliated Hospital of Chongqing Medical University. Demographic characteristics, medical history, clinical features and radiological characteristics were recorded. Univariate analysis and multivariate logistic regression analyses were used to identify independently risk factors of HE and poor outcome. ß coefficient was calculated for combining markers using the logistic regression. Receiver operating characteristic (ROC) curves were fitted to calculate predictive values for each variable and combining markers to stratify HE and poor outcome. RESULTS: Among 257 ICH patients in the study, there were 85 (33.1 %) patients with HE. Blend sign and uHG were independently associated with HE and poor outcome (P < 0.05). Age, admission GCS score, presence of IVH at baseline CT were also independently associated with poor outcome (P < 0.05). Combining marker including uHG and blend sign had the best AUC (0.846, 0.80-0.90), sensitivity (87.1 %), NPV (91.0 %), and -LR (0.2) than single variable to stratify HE. Combining marker including uHG, blend sign and risk clinical factors had the best AUC (0.800, 0.75-0.85), sensitivity (75.6 %), NPV (73.2 %), -LR (0.33) than single variable and the ICH score to stratify poor outcome. ICH score had the highest PPV (80.3 %) and + LR (3.68) to stratify poor outcome than other variables. CONCLUSION: The combination of both uHG and blend sign could be a simple and useful tool for better stratification of HE and poor outcome.

The slice score: A novel scale measuring intraventricular hemorrhage severity and predicting poor outcome following intracerebral hemorrhage.

OBJECTIVES: To quantify extent of intraventricular hemorrhage (IVH) following intracerebral hemorrhage (ICH) with a novel, simple IVH severity score, and to explore and compare its performance in predicting worse outcomes. PATIENTS AND METHODS: A new scoring system for IVH severity was proposed and termed Slice score. The Slice score features non-septum pellucidum section, internal capsule section, third ventricle occipital horn section, three standardized scans for scoring the lateral ventricles. 652 scans from 326 subjects were retrospectively analyzed. The correlations between measured IVH volume and Slice score, original Graeb, LeRoux, and IVH score (IVHS) were compared. The association between these scores and clinical outcomes were evaluated using logistic regression. We then identified clinical thresholds of Slice score by balancing the probability of prediction and accuracy. Primary outcome was defined as 90-day poor outcome (modified Rankin Scale score ≥ 4) and secondary outcome was 90-day mortality. RESULTS: Of 326 ICH patients, 122 (37.4%) had poor outcome and 59 (18.1%) died at 3 months. The Slice score showed the highest correlation with measured IVH volume (R = 0.73, R2 = 0.54, p < 0.001). The observed area under the curve were similar among the Slice, original Graeb, LeRoux score, and IVH score for poor outcome (0.633, 0.633, 0.632, 0.634, respectively), and for mortality (0.660, 0.660, 0.660, 0.656, respectively). All IVH scales were independently associated with 90-day poor outcome and mortality with close odds ratio in adjusted models (all odds ratio > 1.07, all p < 0.05). Multivariable Analyses of categorized Slice score revealed optimal thresholds of 6 and 12 for primary and secondary outcomes (odds ratio 4.20, 95% confidence interval 1.82-10.02, p = 0.001; odds ratio 5.41, 95% confidence interval 1.66-17.43, p = 0.005, respectively). CONCLUSIONS: The Slice score correlated highly with the IVH volume, was a reliable volumetric scale for measuring IVH severity, and could be an easy-to-use tool for predicting 90-day poor outcome and mortality in ICH.

Comparison of Satellite Sign and Island Sign in Predicting Hematoma Growth and Poor Outcome in Patients with Primary Intracerebral Hemorrhage.

OBJECTIVE: Satellite sign (SS) and island sign (IS) are novel noncontrast computed tomography (CT) predictors of hematoma growth. The aim of this study was to compare diagnostic performance of IS and SS in predicting hematoma growth and functional outcome in patients with intracerebral hemorrhage (ICH). METHODS: The study included patients with ICH who underwent baseline CT scan within 6 hours of symptom onset and follow-up CT scan within 36 hours after initial CT between July 2012 and April 2017. Sensitivity, specificity, positive predictive value, and negative predictive value of IS and SS in predicting hematoma growth and functional outcome were assessed. Accuracy of the 2 signs in predicting hematoma growth and functional outcome was analyzed using receiver operating characteristic analysis. Association between the presence of IS and SS and ICH growth was assessed using multivariate logistic regression. RESULTS: Of 307 patients with ICH, IS was observed in 46 patients (15.0%), and SS was observed in 151 patients (49.2%). Rates of hematoma growth were 40.4% in SS+ patients, 91.3% in IS+ patients, 18.4% in SS-IS- patients, 21.1% in SS+IS- patients, 100% in SS-IS+ patients, and 90.5% in SS+IS+ patients. After adjusting for potential confounders, IS remained an independent predictor for hematoma growth and poor functional outcome. The area under the curve of IS was significantly larger than the area under the curve of SS in predicting hematoma growth (P = 0.001). CONCLUSIONS: IS seems to be an optimal shape irregularity imaging marker for predicting hematoma growth and functional outcome in patients with ICH.

Benign Intracerebral Hemorrhage: A Population at Low Risk for Hematoma Growth and Poor Outcome.

Background To define benign intracerebral hemorrhage ( ICH ) and to investigate the association between benign ICH , hematoma expansion, and functional outcome. Methods and Results We analyzed a prospectively collected cohort of patients with ICH, who presented within 6 hours of symptom onset between July 2011 and February 2017 to a tertiary teaching hospital. Follow-up computed tomographic scanning was performed within 36 hours after initial computed tomographic scanning. Benign ICH was operationally defined as homogeneous and regularly shaped small ICH . The presence of benign ICH was judged by 2 independent reviewers (Q.L., W.Y.) on the basis of the admission computed tomographic scan. Functional independence was defined as a modified Rankin Scale score of 0 to 2 at 3 months. The associations between benign ICH , hematoma expansion, and functional outcome were assessed by using multivariable logistic regression analyses. A total of 288 patients with ICH were included. Benign ICH was found in 48 patients (16.7%). None of the patients with benign ICH had early hematoma expansion. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of benign ICH for predicting functional independence at 3 months were 30.7%, 96.6%, 90.0%, 60.0%, and 0.637, respectively. Conclusions Patients with benign ICH are at low risk of hematoma expansion and poor outcome. These patients may be safe for less intensive monitoring and are unlikely to benefit from therapies aimed at preventing ICH expansion.

Increased functional connectivity of the posterior cingulate cortex with the lateral orbitofrontal cortex in depression.

To analyze the functioning of the posterior cingulate cortex (PCC) in depression, we performed the first fully voxel-level resting state functional-connectivity neuroimaging analysis of depression of the PCC, with 336 patients with major depressive disorder and 350 controls. Voxels in the PCC had significantly increased functional connectivity with the lateral orbitofrontal cortex, a region implicated in non-reward and which is thereby implicated in depression. In patients receiving medication, the functional connectivity between the lateral orbitofrontal cortex and PCC was decreased back towards that in the controls. In the 350 controls, it was shown that the PCC has high functional connectivity with the parahippocampal regions which are involved in memory. The findings support the theory that the non-reward system in the lateral orbitofrontal cortex has increased effects on memory systems, which contribute to the rumination about sad memories and events in depression. These new findings provide evidence that a key target to ameliorate depression is the lateral orbitofrontal cortex.

Functional connectivity of the human amygdala in health and in depression.

To analyse the functioning of the amygdala in depression, we performed the first voxel-level resting state functional-connectivity neuroimaging analysis of depression of voxels in the amygdala with all other voxels in the brain, with 336 patients with major depressive disorder and 350 controls. Amygdala voxels had decreased functional connectivity (FC) with the orbitofrontal cortex, temporal lobe areas, including the temporal pole, inferior temporal gyrus and the parahippocampal gyrus. The reductions in the strengths of the FC of the amygdala voxels with the medial orbitofrontal cortex and temporal lobe voxels were correlated with increases in the Beck Depression Inventory score and in the duration of illness measures of depression. Parcellation analysis in 350 healthy controls based on voxel-level FC showed that the basal division of the amygdala has high FC with medial orbitofrontal cortex areas, and the dorsolateral amygdala has strong FC with the lateral orbitofrontal cortex and related ventral parts of the inferior frontal gyrus. In depression, the basal amygdala division had especially reduced FC with the medial orbitofrontal cortex, which is involved in reward; and the dorsolateral amygdala subdivision had relatively reduced FC with the lateral orbitofrontal cortex, which is involved in non-reward.

Insight into the metabolic mechanism of Diterpene Ginkgolides on antidepressant effects for attenuating behavioural deficits compared with venlafaxine.

Depression is a severe and chronic mental disorder, affecting about 322 million individuals worldwide. A recent study showed that diterpene ginkgolides (DG) have antidepressant-like effects on baseline behaviours in mice. Here, we examined the effects of DG and venlafaxine (VLX) in a chronic social defeat stress model of depression. Both DG and VLX attenuated stress-induced social deficits, despair behaviour and exploratory behaviour. To elucidate the metabolic changes underlying the antidepressive effects of DG and VLX, we investigated candidate functional pathways in the prefrontal cortex using a GC-MS-based metabolomics approach. Metabolic functions and pathways analysis revealed that DG and VLX affect protein biosynthesis and nucleotide metabolism to enhance cell proliferation, with DG having a weaker impact than VLX. Glutamate and aspartate metabolism played important roles in the antidepressant effects of DG and VLX. Tyrosine degradation and cell-to-cell signaling and interaction helped discriminate the two antidepressants. L-glutamic acid was negatively correlated, while hypoxanthine was positively correlated, with the social interaction ratio. Understanding the metabolic changes produced by DG and VLX should provide insight into the mechanisms of action of these drugs and aid in the development of novel therapies for depression.