Transcranial direct current stimulation for auditory verbal hallucinations:a systematic review of clinical trials

Transcranial direct current stimulation(tDCS)has been reportedly beneficial for different neurodegenerative disorders.tDCS has been reported as a potential adjunctive or alternative treatment for auditory verbal hallucination(AVH).This study aims to review the effects of tDCS on AVH in patients with schizophrenia through combining the evidence from randomized clinical trials(RCTs).The databases of PsycINFO(2000–2019),PubMed(2000–2019),EMBASE(2000–2019),CINAHL(2000–2019),Web of Science(2000–2019),and Scopus(2000–2019)were systematically searched.The clinical trials with RCT design were selected for final analysis.A total of nine RCTs were eligible and included in the review.Nine RCTs were included in the final analysis.Among them,six RCTs reported a significant reduction of AVH after repeated sessions of tDCS,whereas three RCTs did not show any advantage of active tDCS over sham tDCS.The current studies showed an overall decrease of approximately 28%of AVH after active tDCS and 10%after sham tDCS.The tDCS protocols targeting the sensorimotor frontal-parietal network showed greater treatment effects compared with the protocols targeting other regions.In this regard,cathodal tDCS over the left temporoparietal area showed inhibitory effects on AVHs.The most effective tDCS protocol on AVHs was twice-daily sessions(2 mA,20-minute duration)over 5 consecutive days(10 sessions)with the anode over the left dorsolateral prefrontal cortex and the cathode over the left temporal area.Some patient-specific and diseasespecific factors such as young age,nonsmoking status,and higher frequencies of AVHs seemed to be the predictors of treatment response.Taken together,the results of tDCS as an alternative treatment option for AVH show controversy among current literatures,since not all studies were positive.However,the studies targeting the same site of the brain showed that the tDCS could be a promising treatment option to reduce AVH.Further RCTs,with larger sample sizes,should be conducted to reach a conclusion on the efficacy of tDCS for AVH and to develop an effective therapeutic protocol for clinical setting.

Construction of lentiviral vector carrying Rab9 gene and its expression in mouse brain

Rab proteins and their effectors facilitate ves-icular transport by tethering donor vesicles to their respec-tive target membranes.Rab9 mediates late endosome to trans-Golgi-network trafficking.To explore the possibility of Rab9-related gene therapy for neurodegenerative diseases,we packed lentivirus encoding Rab9 cDNA.The expressing plasmid pCDH1-MCF1-Rab9-EF1-copGFP was constructed by using molecular biological techniques.The lentivirus encoding Rab9 cDNA was packed by Lifectamine-2000 mediated co-transfection of the plasmid pPACKH1-GAG,pPACKH1-REV and pVSV-G into 293T cells.DNA sequencing proved the successful construction of pCDH1-MCF1-Rab9-EF1-copGFP.After 72 h,the expression of GFP could be detected in BV-2 cells.Western blotting revealed that the Rab9 gene expression in BALB/c mice brain was up-regulated significantly 4 weeks after injection with lentivirus encoding Rab9 cDNA,which evidenced a satisfactory increasing effect of this virus.Administration of lenti-Rab9 to postnatal day 3 Niemann-Pick disease type C(NPC)mice reduced motor defects and prevented the weight loss associated with female NPC mice,as well as modulated the death rate of Purkinje neurons.It is concluded that the packaging of lentivirus encoding Rab9 cDNA was successful.lentivirus encoding Rab9 can increase the expression of Rab9 cDNA gene effectively,which might offer a novel means for the treatment of neurodegenerative diseases.