Objective:To investigate the associations of brain white matter integrity deficits, and to explore the association of fractional anisotropy (FA) abnormality with clinical symptoms and cognitive impairments, as well as the prediction effect of the FA alterations on symptoms and cognitive function outcomes in the acute stage of schizophrenia from the whole brain level based on magnetic resonance diffusion tensor imaging (DTI).Methods:From November 2019 to December 2020, thirty-eight patients with first-episode schizophrenia and 38 healthy controls were recruited in this study. Wisconsin card classification test (WCST), digit span test (DST forward/backward), verbal fluency test, Stroop (A/B/C), trail making test (TMT-A/B), as well as positive and negative syndrome scale (PANSS) were utilized to evaluate patients' cognitive function and clinical symptoms both before and after 8 weeks of risperidone monotherapy. T1-weighted images and DTI data of all the subjects were collected . FSL and SPM8 were used to preprocess MRI data and compare the between-group differences of FA. Support vector machine (SVM) analysis was used to evaluate the accuracy of abnormal FA values in differentiating schizophrenic patients from healthy controls. Finally, stepwise multiple regression analysis or generalized linear models were used to explore the associations between white matter integrity and symptoms or cognition.Results:Before treatment, patients' FA values of right medial temporal lobe (mTL), cuneus, anterior cingulate gyrus (ACG) and inferior parietal lobe (IPL) were significantly lower than those in healthy controls ( P<0.01, GRF corrected), and patients' FA values of bilateral middle cingulate gyrus (mCG) were significantly higher than those in the control group ( P<0.01, GRF corrected). SVM analysis showed that four combinations could distinguish the patients from the control with the most accurate rate of 89.47%. Patients' baseline decreased FA values in the right IPL were positively associated with their increased total response time in WCST ( β=0.489, P=0.003, FDR corrected), correct response time in WCST ( β=0.450, P=0.008, FDR corrected), error response time in WCST ( β=0.435, P=0.008, FDR corrected), TMT-B ( β=0.296, P=0.042, FDR corrected), Stroop-C ( β=0.345, P=0.035, FDR corrected), and PANSS-P ( β=0.321, P=0.042, FDR corrected). Reduced FA values in the right mTL in patient group were significantly negatively related to the total time spent on the TMT-A ( β=-0.425, P=0.009, FDR corrected) and TMT-B ( β=-0.325, P=0.026 with FDR correction). Increased FA values in right mCG in patient group demonstrated positive associations with total response time in the WCST ( β=0.585, P=0.002, FDR corrected), correct response time in WCST ( β=0.524, P=0.003, FDR corrected), error response time in WCST ( β=0.536, P=0.003, FDR corrected) and total time consuming in TMT-B ( β=0.484, P=0.004, FDR corrected), as well as negative associations with DST-forward ( β=-0.319, P=0.042, FDR corrected). After treatment, patients' percentage changes in total response time of WCST ( β=0.715, P<0.001, FDR corrected), correct response time of WCST ( β=0.752, P<0.001, FDR corrected), as well as total time-consuming of TMT-A ( β=1.333, P=0.001, FDR corrected) showed positive correlations with baseline increased FA values in the left mCG. Percentage alteration of Stroop-B was negatively correlated with baseline FA values in the right cuneus ( β=-0.745, P=0.015, FDR corrected). Conclusions:The combination of abnormal FA values in multiple brain regions may be potential biomarkers to distinguish schizophrenic patients from healthy volunteers. There was regional dependence in the associations of the impairment of white matter integrity with the cognitive impairment, the severity of psychopathological symptoms as well as the prognosis of patients in the acute stage.

Vortioxetine was approved by the US FDA in 2013 and by China Food and Drug Administration in November 2017 for the treatment of major depressive disorder (MDD) in adults. Vortioxetine exerts antidepressant effects by inhibiting 5-HT transporter-mediated 5-HT reuptake and regulating the activity of multiple 5-HT receptors. Vitro and animal studies have shown that, in addition to increasing 5-HT concentrations, vortioxetine elevates dopamine, norepinephrine, acetylcholine, histamine, and glutamate neurotransmission and decreases GABA neurotransmission in some brain areas associated with MDD. Clinical studies indicate that vortioxetine can relieve multidimensional symptoms, improve cognitive functions, and promote the recovery of social function in MDD patients. This article comprehensively reviews vortioxetine for the treatment of depression in aspects of the mechanism of action, clinical efficacy and safety, real-world studies, and clinical application.

Vortioxetine was approved by the US FDA in 2013 and by China Food and Drug Administration in November 2017 for the treatment of major depressive disorder (MDD) in adults. Vortioxetine exerts antidepressant effects by inhibiting 5-HT transporter-mediated 5-HT reuptake and regulating the activity of multiple 5-HT receptors. Vitro and animal studies have shown that, in addition to increasing 5-HT concentrations, vortioxetine elevates dopamine, norepinephrine, acetylcholine, histamine, and glutamate neurotransmission and decreases GABA neurotransmission in some brain areas associated with MDD. Clinical studies indicate that vortioxetine can relieve multidimensional symptoms, improve cognitive functions, and promote the recovery of social function in MDD patients. This article comprehensively reviews vortioxetine for the treatment of depression in aspects of the mechanism of action, clinical efficacy and safety, real-world studies, and clinical application.

Objective To examine the association between the polymorphisms of apolipoprotein E gene (APOE) and geriatric depression (GD),and then conduct an exploratory investigation to analyse whether the APOE polymorphisms would relate to the depressive syndrome severity,the cognitive function,or the level of serum lipid in patients.Methods Participants,including 120 GD patients and 120 normal controls were enrolled to detect the two single nucleotide polymorphisms of APOE,rs7412 and rs429358 using the technology of SNP site testing.The frequency differences of genotype and allele were compared between the two groups.Then the association between APOE polymorphisms and clinical or demographic data of patients were clarified.The relationship between clinical or demographic data,and the cognitive function of GD patients were investigated using the Logistic multiple regression analysis.Results The frequency of APOE genotype and allele showed no significant difference between the two groups(P＞0.05).Patients carrying e4 allen had significantly lower total scores of Man-Machine System Engineering((22.38±2.22) vs (25.28±2.28),t=3.091,P＜0.01) and higher levels of TC (t=2.225,P＜ 0.05) and LDL(t=2.728,P＜0.01) compared with those without ε4 allen.The specific symptoms of patients carrying e4 allen were cognitive impairment(load 0.902) and retardant factors(load 0.695),while patients without ε4 allen had characteristic symptoms of anxiety(load 0.990) and weight factors(load 0.864).Ranked by the effect power,the risk factors of cognitive impairment of GD patients are ε4(b'=1.097) and then TCTC (b'=0.401).Conclusions APOE may not modulate the susceptibility to GD.Patients carrying ε4 allen have severer cognitive impairment and higher levels of serum lipid.The different genotypes may lead to different clinical symptoms.

Objective To explore the alterations of ultrastructure of neuron and synapse in rat hippocampus induced by the expression changes of phospho cAMP response element-binding protein 1 (p-CREB1),and the effect of venlafaxine on the expression of p-CREB1 and relative neuronal and synaptic plasticity.Methods Fifty-four rats were randomly divided into 4 groups:normal group (n =12),depression model matched group (n =14),saline group (n =14),and venlafaxine medication group (n =14).Sucrose water consumption test and open field test were performed to observe the behavior of animals.To investigate the learning and memory ability,rats were tested by Morris water maze.The expression of p-CREB1 protein was detected by immunohistochemistry and the CREB1 mRNA was measured by RT-PCR.The ultrastructure of neuron and synapse were observed with electron microscope.Correlation analysis was used to measure the associations among the number of p-CREB1 positive cells,the parameters of Morris water maze and synaptic morphology.Results (1) The sucrose consumption in depression model matched group (7.4 ± 1.0) ml/100 g and saline group (7.5 ± 1.0) ml/100 g were significantly less than that in normal group (9.6 ± 0.3) ml/100 g and medication group (9.4 ± 0.8) ml/100 g,(F =17.851,P ＜ 0.01).Morris water maze showed that the escape latent period in depression model matched group (61.1 ± 10.5) s and saline group (59.0 ± 10.6) s were more than that in normal group (29.8 ± 10.1) s and medication group ((35.0 ± 8.5) s;F =30.559,P ＜ 0.01),which demonstrated the learning and memory ability of depression rats were decreased.(2) The positive cell number of p-CREB1 in the hippocampus of depression model matched group (21.07 ±5.99) and saline group (24.57 ±6.97) were lower than that in normal group (29.70 ± 6.21) and medication group (41.50 ± 11.95;F =16.497,P ＜ 0.01).(3) The CREB1 mRNA expression in the hippocampus of depression model matched group (0.58 ± 0.47) and saline group (0.45 ± 0.24) were less than that in normal group (1.03 ± 0.89) and medication group (1.10 ± 0.45;F =6.669,P ＜ 0.01).(4) There were pathologic alterations in the ultrastructure of neurons and synapses in the hippocampus of depression rats,which were improved by pharmacological intervention.(5) The number of p-CREB1 positive cells was related to the parameters of Morris water maze and synaptic morphology.Conclusion p-CREB1 expression is correlated with neuronal and synaptic plasticity,and venlafaxine may be effective through influencing the expression of p-CREB1 and neuronal and synaptic plasticity.

Objective To explore the alterations of ultrastructure of neuron and synapse in rat hippocampus induced by the expression changes of phospho cAMP response element-binding protein 1 (p-CREB1),and the effect of venlafaxine on the expression of p-CREB1 and relative neuronal and synaptic plasticity.Methods Fifty-four rats were randomly divided into 4 groups:normal group (n =12),depression model matched group (n =14),saline group (n =14),and venlafaxine medication group (n =14).Sucrose water consumption test and open field test were performed to observe the behavior of animals.To investigate the learning and memory ability,rats were tested by Morris water maze.The expression of p-CREB1 protein was detected by immunohistochemistry and the CREB1 mRNA was measured by RT-PCR.The ultrastructure of neuron and synapse were observed with electron microscope.Correlation analysis was used to measure the associations among the number of p-CREB1 positive cells,the parameters of Morris water maze and synaptic morphology.Results (1) The sucrose consumption in depression model matched group (7.4 ± 1.0) ml/100 g and saline group (7.5 ± 1.0) ml/100 g were significantly less than that in normal group (9.6 ± 0.3) ml/100 g and medication group (9.4 ± 0.8) ml/100 g,(F =17.851,P ＜ 0.01).Morris water maze showed that the escape latent period in depression model matched group (61.1 ± 10.5) s and saline group (59.0 ± 10.6) s were more than that in normal group (29.8 ± 10.1) s and medication group ((35.0 ± 8.5) s;F =30.559,P ＜ 0.01),which demonstrated the learning and memory ability of depression rats were decreased.(2) The positive cell number of p-CREB1 in the hippocampus of depression model matched group (21.07 ±5.99) and saline group (24.57 ±6.97) were lower than that in normal group (29.70 ± 6.21) and medication group (41.50 ± 11.95;F =16.497,P ＜ 0.01).(3) The CREB1 mRNA expression in the hippocampus of depression model matched group (0.58 ± 0.47) and saline group (0.45 ± 0.24) were less than that in normal group (1.03 ± 0.89) and medication group (1.10 ± 0.45;F =6.669,P ＜ 0.01).(4) There were pathologic alterations in the ultrastructure of neurons and synapses in the hippocampus of depression rats,which were improved by pharmacological intervention.(5) The number of p-CREB1 positive cells was related to the parameters of Morris water maze and synaptic morphology.Conclusion p-CREB1 expression is correlated with neuronal and synaptic plasticity,and venlafaxine may be effective through influencing the expression of p-CREB1 and neuronal and synaptic plasticity.