Collateral Status at Single-Phase and Multiphase CT Angiography versus CT Perfusion for Outcome Prediction in Anterior Circulation Acute Ischemic Stroke.

Background Collateral status assessed with single- or multiphase CT angiography can be used to predict outcome in patients with acute ischemic stroke (AIS); however, little is known about whether these measures could be comparable with CT perfusion parameters. Purpose To compare the predictive ability of collateral score systems assessed with single- or multiphase CT angiography and CT perfusion parameters in determining clinical outcomes in patients with AIS. Materials and Methods In this retrospective study, data obtained from October 2017 to August 2018 in consecutive patients with AIS caused by isolated anterior circulation large artery occlusion and that were obtained within 24 hours after onset were reviewed. The collateral score was assessed by using established scoring systems described by Menon et al. The correlations between single- and multiphase collateral scores, hypoperfusion, and ischemic core volume and final infarct volume (FIV) determined by follow-up diffusion-weighted imaging or unenhanced CT were studied. Receiver operating characteristic curves and multivariable logistic regression analysis were performed to assess the predictive ability of scoring systems and CT perfusion parameters for a favorable clinical outcome. Results A total of 119 patients (median age, 75 years; interquartile range, 66-82 years; 74 men) were included. Both single- and multiphase Menon scores had a moderate negative correlation with FIV (r = -0.43, P < .001; r = -0.44, P < .001). Receiver operating characteristic curve analysis revealed the multiphase Menon score performed better than the single-phase Menon score (area under the curve [AUC], 0.72 vs 0.64; P = .045) in the prediction of a favorable 90-day modified Rankin scale score. There was no difference between multiphase Menon score and hypoperfusion volume (AUC, 0.72 vs 0.72; P = .97) or ischemic core volume (AUC, 0.72 vs 0.71; P = .94). Multivariable analysis showed multiphase Menon score was an independent predictor of good clinical outcomes (odds ratio = 3.04, P = .001). Conclusion Multiphase Menon score performed better than single-phase Menon score and was comparable with CT perfusion parameters in determining clinical outcomes in patients with acute ischemic stroke. © RSNA, 2020.

Changed Synaptic Plasticity in Neural Circuits of Depressive-Like and Escitalopram-Treated Rats.

BACKGROUND: Although progress has been made in the detection and characterization of neural plasticity in depression, it has not been fully understood in individual synaptic changes in the neural circuits under chronic stress and antidepressant treatment. METHODS: Using electron microscopy and Western-blot analyses, the present study quantitatively examined the changes in the Gray's Type I synaptic ultrastructures and the expression of synapse-associated proteins in the key brain regions of rats' depressive-related neural circuit after chronic unpredicted mild stress and/or escitalopram administration. Meanwhile, their depressive behaviors were also determined by several tests. RESULTS: The Type I synapses underwent considerable remodeling after chronic unpredicted mild stress, which resulted in the changed width of the synaptic cleft, length of the active zone, postsynaptic density thickness, and/or synaptic curvature in the subregions of medial prefrontal cortex and hippocampus, as well as the basolateral amygdaloid nucleus of the amygdala, accompanied by changed expression of several synapse-associated proteins. Chronic escitalopram administration significantly changed the above alternations in the chronic unpredicted mild stress rats but had little effect on normal controls. Also, there was a positive correlation between the locomotor activity and the maximal synaptic postsynaptic density thickness in the stratum radiatum of the Cornu Ammonis 1 region and a negative correlation between the sucrose preference and the length of the active zone in the basolateral amygdaloid nucleus region in chronic unpredicted mild stress rats. CONCLUSION: These findings strongly indicate that chronic stress and escitalopram can alter synaptic plasticity in the neural circuits, and the remodeled synaptic ultrastructure was correlated with the rats' depressive behaviors, suggesting a therapeutic target for further exploration.

[Influence of methylenetetrahydrofolate reductase gene polymorphisms on antidepressant response].

OBJECTIVE: To assess the influence of polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene on response to antidepressant treatment. METHODS: Two hundred and eight one Chinese Han patients have received single antidepressant drugs for at least 6 weeks, among whom 275 were followed up for 8 weeks. Hamilton depression scale 17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effects. Single nucleotide polymorphisms (SNPs) of the MTHFR gene were determined using gene chips. Associations of single loci and haplotypes with response to treatment were analyzed using an Unphased 3.0.13 software. RESULTS: No significant differences in gender, age, year of education, family history, episode times, and antidepressant agents were found between responders and non-responders (all P U+003E 0.05), while the baseline scores of HAMD-17 was significantly different(t=2.891, P=0.004). There was also no significant difference between age, years of education, family history, baseline scores of HAMD-17 and antidepressant agents between remitters and non-remitters (both P U+003E 0.05), while proportion of male patients was significantly higher in non-remission group than remission group (t=2.381, P=0.018), and episode times in non-remission group was significantly higher (t=-1.983, P=0.049). Single locus association analysis has found no significant association between SNPs rs1801131 and rs1801133 in the MTHFR gene with antidepressant response (P U+003E 0.05). On the other hand, haplotype A-C of MTHFR gene (rs1801131 and rs1801133) was significantly associated with antidepressant response in total group (U+03C7 2=11.39, P=0.0007), male subgroup (U+03C7 2=8.767, P=0.003) and serotonin noradrenaline reuptake inhibitors (SNRIs) subgroup (U+03C7 2=10.51, P=0.001). CONCLUSION: Particular haplotype of MTHFR gene may be related with antidepressant effect, in which the haplotype (rs1801131, rs1801133) A-C type may be associated with better antidepressant efficacy, particularly in males and patients receiving SNRIs drugs.

The combination of plasma glutamate and physical impairment after acute stroke as a potential indicator for the early-onset post-stroke depression.

OBJECTS: The present study aimed to investigate the relationship of plasma glutamate levels with the early-onset of post-stroke depression (PSD) and to further explore the prognostic value of plasma glutamate combined with clinical characteristics for the early-onset PSD in the acute ischemic stroke patients. METHODS: Seventy-four patients who admitted to the hospital within 24h of acute ischemic stroke were consecutively recruited and followed up for 2weeks. The Beck Depression Inventory (BDI) and 17-item Hamilton Depression Rating Scale (HAMD-17) were used to screen for depressive symptoms 14days after stroke. Diagnoses of depression were made in accordance with DSM-IV. Plasma glutamate levels were determined by High Performance Liquid Chromatography (HPLC) on days 1 and 14 after stroke for all patients. RESULTS: Plasma glutamate levels were significantly lower in PSD patients than those of non-PSD patients on day 1 after stroke. ROC curve analyses revealed an AUC (area under the ROC curve) of 0.724 (95% CI: 0.584-0.863, p=0.004) and of 0.669 (95% CI: 0.523-0.814, p=0.030) for National Institute of Health Stroke Scale (NIHSS) scores and plasma glutamate levels on day 1 respectively. Combined ROC analyses using the two factors revealed the highest AUC of 0.804 (95% CI: 0.685-0.922, P<0.0001). CONCLUSIONS: These results indicated an association between the early-onset PSD and a low plasma glutamate level following acute ischemic stroke. The combination of reduced plasma glutamate levels and physical impairment (determined by NIHSS) 1day after acute ischemic stroke was a potential diagnostic indicator for early-onset PSD.

Blood oxygen level-dependent signals via fMRI in the mood-regulating circuit using two animal models of depression are reversed by chronic escitalopram treatment.

BACKGROUND: People exposed to stressful experience are at increased risk of the development of depression. A number of functional imaging studies have found disturbances in the mood-regulating circuit of the stress-exposed depressed patients, although few animal imaging studies have been undertaken addressing the brain functional changes of depression. METHODS: Two rat models of depression: maternal separation (MS) and chronic unpredictable mild stress (CUMS), imitating early life stress and adult stress respectively, were administered with escitalopram. The differences in functional brain changes were determined by blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). RESULTS: Increased BOLD activation was observed in some brain regions of MS and CUMS animals, such as the bilateral hypothalamus, limbic system, hippocampus and frontal lobe, which were parts of mood-regulating circuit. Furthermore, the MS- and CUMS-induced increases in BOLD activation were partially attenuated by chronic escitalopram treatment. CONCLUSIONS: These results suggested hyperactivation of mood-regulating circuit at baseline in the depressed animals exposed to stressful experience, and escitalopram can at least partially reverse these effects.

Influence of genetic polymorphisms involved in the hypothalamic-pituitary-adrenal axis and their interactions with environmental factors on antidepressant response.

AIMS: To investigate the role of genetic polymorphisms in candidate genes associated with the HPA axis and their interactions with environmental stressors in antidepressant response. METHODS: The remission of depressive symptoms after 8 weeks of antidepressant treatment was tested against 21 single nucleotide polymorphisms (SNPs) in five candidate genes associated with the HPA axis in a Chinese Han sample suffering from unipolar depression (n = 273). Any history of childhood trauma and recent negative life events were measured using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) (n = 206) and the Life Event Scale (48 item, LES) (n = 207), respectively. Reporter gene assays were used to evaluate the possible effects of the most significant SNP on gene expression. RESULTS: A functional polymorphism at 3'UTR of the corticotropin-releasing hormone receptor 1 (CRHR1) gene (rs28364032) and three haplotypes containing it showed significant relationships with antidepressant remission. Further laboratory-based genomic studies showed that the G-to-A change of rs28364032 resulted in a 10-12% decrease in the intensity of luciferase activity. However, we failed to find association of environments and their interaction with HPA system-related genes with antidepressant remission. CONCLUSIONS: Our results support a definite role for CRHR1 in the pharmacogenetics of antidepressant drugs. This may contribute to interpatient differences in their responses to antidepressant drugs.