Objective:To introduce the Australian Life Saving Drugs Program ( LSDP) and provide references for medical assistance system for the rare diseases in China. Methods:The main content and characteristics of LSDP were analyzed and compared with the Chinese status quo valuation. Results:Through the orphan drug designation and cost-effectiveness evaluation, eligible drugs are included in LSDP and funded to the rare disease patients. LSDP stip-ulated the strict funding criteria and conditions, established the Guidelines and Disease Advisory Committees, and processed the post-market reviews program in order to guarantee the medication requirements of the patients. Conclu-sions:The Australian experience is worth learning and China should implement a country-led management system for the rare disease and orphan drugs, and explore a medical assisstance system in line with the Chinese national condi-tion based on the catastrophic medical insurances.

Bipolar disorder (BD) is a chronic mental illness with high recurrence rate and disability. As one of the core symptoms, cognitive impairment may occurs at every stage of the disease. Evidence from the neuroimaging studies revealed that the abnormal brain volumes, the blood flow and oxygen saturation of key brain areas are related to executive impairment in patients with bipolar disorder. This article reviews current structural and functional neuroimaging studies about the executive impairment of patients with euthymic bipolar disorder and research progresses.

Objective To evaluate the efficacy of antidepressants plus cognitive-behavioral education and self-management preventing the recurrent or deterioration of depression.Methods Outpatients with non-episode depression,Hamilton Rating Scales of Depression 17 items (HAMD17 ≥3),entered openly intervention group (n =30) and control group (n =30),and were followed up one year.Patients in intervention group received intervention,including treatment as usual,group education of cognitive behavior,self-help group attendance and self-management of depressive mood.Patients in control group only received treatment as usual.The primary outcome was time to recurrent or deterioration of depression.Kaplan-Meier methodology was used to evaluate differences of survival curves between two different groups.Results There were significant differences for risk of recurrent or deterioration (x2 =5.70,P ＜ 0.05) and one-year rate of recurrent or deterioration (intervention group 27％ (8/30),control group 53％ (16/30),x2 =4.44,P ＜ 0.05) between two groups,but not for average time of recurrent or deterioration (intervention group (4.75 ± 2.49) months,control group (6.63 ± 3.10) months,t =-1.48,P ＞0.05).There were no significant differences for risk of drop-out (x2 =1.66,P ＞ 0.05),one-year rate of drop-out (intervention group 13％ (4/30),control group 23％ (7/30),x2 =1.00,P ＞ 0.05) and average time of drop-out (intervention group (7.25 ± 3.78) months,control group (4.00 ± 2.58) months,t =1.71,P ＞ 0.05) between two groups.Conclusion Antidepressants plus cognitive-behavioral education and self-management can effectively prevent the recurrent or deterioration of depression.

Objective To investigate the relationship between cognitive function of first-episode schizophrenic patients and dopamine D1 receptor gene. Methods A total of 112 first-episode schizophrenic patients and 60 healthy controls were evaluated with Wechsler adult intelligence scale ( WAIS-R), Wechsler memory scale (WMS) and Wisconsin card sort test (WCST) ,and genotyped one polymorphism (rs4532) within DRD1 gene using TaqMan SNP genotyping assay. Results There were no significant differences on the frequencies of the genotypes and alleles of rs4532 polymorphism between patients with schizophrenia and normal controls ( x2 =2.90, P=0.35; x2 = 0.01, P= 0. 93 ). There were significant differences in all index of WCST between two groups (P ＜0.01 ). Patients with rs4532G allele had worse WCST performance than those without G allele ((60.9 ± 13.2)%vs (44.9 ±21.3)%, t=4.79, P=0.00002). Conclusion Rs4532 polymorphism of DRD1 gene may be associated with executive function impairment in schizophrenic patients.

Objective To better understand the role of CREB signaling pathway in chronic mild stress (CMS), we investigated the alteration of CREB and p-CREB in CMS rats with and without fluoxetine hydrochloride. Methods Fifty adult male Sprague-Dawley rats were randomly divided into three groups:CMS group (26), fluoxtine group (12) and con-trol group (12). The rats in CMS group and fluoxtine group received 8 weeks of chronic mild stress. Rats in fluoxtine group were administered daily injections of fluoxetine 10mg/kg I.P. Sucrose preference tests and open-field test were car-ried out after the 8th week. Based on endpoint sucrose-intake, animals were further divided into 4 groups:CMS sensitive group, CMS resilient group, fluoxtine group and control group. Western blot was used to detect the expression levels of CREB and p-CREB in the hippocampus and prefrontal cortex. Results The sucrose consumption was significantly de-creased in CMS resilience group compared to sensitive group, control group and fluoxetine-intervention group (all P<0.05). Similarly, the numbers in total arm entries, percentage of entries into open arms and time spent in open arms was significantly lower in CMS resilience group compared to control group(all P<0.05), but not different compared to CMS sensitive group(all P<0.05). The p-CREB in the hippocampus was significantly lower in CMS sensitive rat compared to CMS resilience group, control group and fluoxetine-intervention group(all P<0.05), but CREB was not dfferent among the four groups(all P<0.05). Conclusions The elevated phosphorylation of CREB in the hippocampus and prefrontal cortex of resilience CMS rats may contribute to the mood alteration induced by stress.

Objective To explore the role of default mode network (DMN) in the pathophysiology of depression and the correlations between the functional connectivity (FC) of DMN and the clinical characteristics of depression through the resting-state fMRI scan in depressed patients. Methods Sixteen medication-na?ve patients with major depressive disorder and 15 healthy controls were recruited and underwent the resting-state MRI scan. Hamiliton depression rating scale (HAMD) was used to evaluate patients’symptom. The FC of DMN and its correlations with clinical features of pa-tients were analyzed. Results Compared with healthy controls, the FC within DMN in depressed patients is disturbed. There were negative correlations between the left mPFC-left hippocampus FC and HAMD total scores (r=-0.569, P=0.021) and subscale scores for sluggishness (r=-0.498, P=0.050). The left mPFC-right hippocampus FC in patients was negatively correlated with HAMD scores (r=-0.508, P=0.045). There were negative correlations between FC in the hippo-campus and HAMD subscale scores for cognitive impairment (r=-0.509, P=0.044). Conclusions The results suggest that there is abnormal FC within DMN in drug-na?ve patients with depression during resting state and some abnormal altera-tions of FC may be correlated with the clinical characteristics in depression.

Objective To compare the cost-effectiveness and cost-utility of venlafaxine and mirtazapine in patients with treatment-resistant major depression (TRD).Methods One hundred and five patients with TRD were enrolled in this study and grouped into venlafaxine treatment (n=50) and mirtazapine treatment (n=55) based on the double-blind randomization scheme generated by computer.The treatment costs of antidepressants during 8 weeks were calculated,the rates of clinical response and remission were taken as treatment effectiveness,and the quality-adjusted life years (QALYs) as treatment utility.The descriptive analysis and nonparametric test were used to compare the cost-effectiveness and cost-utility of different groups.Results During 8 weeks,the treatment cost of antidepressant was ￥ 1 396.44 for venlafaxine and ￥ 1 206.90 mirtazapine,and the difference between two groups was ￥ 189.54.The cost-effectiveness ratios between venlafaxine and mirtazapine were very close (differed ￥ 0.06 for remission rate and ￥ 1.08 for response rate respectively).There was no significant difference for cost-utility ratios between two groups (physical functioning Z=-0.15,P＞0.05 ; mental health Z=-0.54,P＞0.05).Conclusion Both cost-effectiveness and cost-utility of venlafaxine in patients with TRD are close between venlafaxine and mirtazapine.

Objective · To detect the vitamin D2 and D3 levels in the patients with moderate and severe depression. Methods · Eighty-five patientswho met the criteria for major depressive disorder were recruited (53 patients with moderate depression, 32 patients with severe depression). Fifty agematchedhealthy volunteers were recruited as controls. Serum 25 (OH) D2, 25 (OH) D3 and total 25 (OH) D2/D3 levels were detected by using liquidchromatography-tandem mass spectrometry (LC-MS/MS). The risk factors which might influence the severity of depression were screened by Logisticregression analysis. Results · The serum 25 (OH) D2, 25 (OH) D3 and total 25 (OH) D2/D3 levels in the case group was lower than those in the controlgroup (P=0.012, P=0.000, P=0.000). The patients with moderate depression presented significantly lower serum 25 (OH) D3 and total 25 (OH) D2/D3 levelsthan the controls did (P=0.000), although no significant difference in serum 25 (OH) D2 levels was found between these two groups. As well, the serum 25 (OH) D2, 25 (OH) D3 and total 25 (OH) D2/D3 levels in patients with severe depression were significantly lower than those in patients with moderate depression and controls (P<0.05). The body mass index of severe depression group was much higher than that of moderate depression group and control group (P=0.002). Both overweight/obesity and the concentration of vitamin D may be the major influencing factors of depression severity (P=0.034, P=0.011). Conclusion · Vitamin D2 and D3 deficiency in depressive patients, particularly in those patients with severe depression, was shown in the present study. In addition, overweight/obesity as well as the concentration of vitamin D may exert the significant influence on the severity of depression. Vitamin D supplementation and weight control may be needed to be considered in making therapeutic strategies of major depressive disorder.

Objective To investigate the changes in the prescriptions of antidepressants for inpatients with psychosis from 2005 to 2008. Methods The prescriptions of antidepressants for all the inpatients with psychosis in Shanghai Mental Health Center were investigated by one day survey on each June 1st from 2005 to 2008. The most common diseases treated with antidepressants, the most commonly used antidepressants, the average dosage of antidepressants and the combination use of antidepressants were analysed. Results The most common diseases treated with antidepressants were affective disorder, schizophrenia and neurosis. The prescription rate of tricyclic antidepressants declined year by year, and that of selective serotonin reuptake inhibitors (SSRIs) fluctuated moderately, while that of antidepressants of newer generation with the other transmitter mechanisms such as venlafaxine, mitrazapine and trazodone increased gradually. Single antidepressant prescription was common, while the combination use of antidepressants accounted for a small portion. Combination use of antidepressants with one psychotropics (antipsychotics, mood stabilizer, sedative hypnotics) was common, while with two were less frequently occurred. Conclusion Prescriptions of antidepressants for patients with psychosis hospitalized in Shanghai Mental Health Center from 2005 to 2008 are relatively safe and reasonable. Antidepressants of newer generation have been widely used in clinics, and SSRIs have been serving as the major antidepressants.

Objective To evaluate the effectiveness of different medicine treatment strategies on the social functions promotion on the patients with treatment-resistant depression (TRD). Methods 375 Patients with TRD were randomly grouped into 8 groups, and each group was received 8 weeks different treatment for paroxetine,venlafaxine, mirtazapine, paroxetine plus risperidone, paroxetine plus sodium valproate, paroxetine plus buspirone, paroxetine plus trazodone,or paroxetine plus thyroxine, respectively. The efficacy and social functions were evaluated with HAMD-17, SDSS and SF-36. Results There were significant difference in SDSS scores between 8th week and the baseline( P＜0.01 ) , and for social functions factor scores of SF-36 there was significant difference between 4th ,8th week and the baseline in each groups( P＜0.01 ). There were significant difference in social functions factor scores of SF-36 and subtracting scores between 4th and 8th week in all groups except group paroxetine and group venlafaxine(P ＜ 0.05 or P ＜ 0.01 ). There were significant difference in SDSS subtracting scores at 8th week among 8 groups( paroxetine plus risperidone group 7.05 ± 6.39, mirtazapine group 6.53 ± 4.75, paroxetine plusthyroxine group 5.14 ± 4.94, paroxetine group 5.13 ± 4.94 ,paroxetine plus trazodone group 5.00 ± 4.94, paroxetine plus sodium valproate group 4.60 ± 4.09, venlafaxine group 4.57 ± 4.18, paroxetine plus buspirone group 4.24 ± 4.95 ) ( Z = 2.076, P ＜ 0.05 ), between group paroxetine plus risperidone and group venlafaxine , group paroxetine plus sodium valproate, group paroxetine plus buspirone,as group mirtazapine and group paroxetine plus buspirone(P＜ 0.05 ), respectively. The influencing factors on improving social functions are the severity, improvement of depressive symptoms and latest onset time. Conclusions These 8 treatment strategies all can promote social functions on the patients with TRD. But the intensity and chronological order of improvement werent the same among 8 groups. The influencing factors on improving social functions are the severity, improvement of depressive symptoms and latest onset time.