Efficacy and safety of repetitive transcranial magnetic stimulation for generalised anxiety disorder: A metaanalysis

Background Pharmacological and conventional nonpharmacological treatments are only moderately effective in treatingeneralised anxiety disorder(GAD).Recently,repetitive transcranial magnetic stimulation(rTMS)has attracted interest because of its potential therapeutic value.Aim To investigate the efficacy and safety of rTMS treatment for GAD.Methods Literature studies published in English or Chinese were screened in 10 electronic databases up to 5 December 2018.The included studies'bias risk was assessed using Cochrane risk of bias assessment tool.Meta-analysis was performed to compute the standardised mean difference(SMD)and risk ratio(RR)along with its 95%Cis through using RevMan V.5.3.Heterogeneity was inspected by I2 and the χ2 test.We performed subgroup analysis and meta-regression to investigate heterogeneity.We used funnel plot to assess publication bias.We used the GRADE approach to assess the whole quality of evidence.Results Twenty-one studies,with a total sample size of 1481,were analysed.The risk of bias in most studies included is moderate,the majority of which are lacking of blinding methods of treatment allocation.The treatment had beneficial effects in the rTMS group compared with the control group in mean anxiety score(SMD=-0.68;95%Cl-0.89 to-0.46).None of the 21 studies included here reported severe adverse events.As for dropout rates,there are no statistically significant differences between the two groups(RR 1.14,95%Cl 0.72 to 1.82)or adverse events(RR 0.95,95%Cl 0.77 to 1.18).No particular influence on the heterogeneity of any variable was observed.The risk of publication bias was low.According to the GRADE approach,the evidence levels of primary outcome(treatment effects)and secondary outcomes(acceptability and safety)were rated as‘medium’.Conclusion The use of rTMS combined with medication treatment may have a significant positive anti-anxiety effect on patients with GAD.However,we should interpret the results cautiously due to the relatively high heterogeneity of the meta-analysis.Future high-quality clinical trials are needed to confirm our results.

Altered heartbeat perception sensitivity associated with brain structural alterations in generalised anxiety disorder

Background Palpitation is a common complaint in generalised anxiety disorder(GAD).Brain imaging studies have Investigated the neural mechanism of heartbeat perception in healthy volunteers.This study explored the neuroanatomical differences of altered heartbeat perception in patients with GAD using structural MRI.Aims Based on the strong somatic-interoceptive symptoms in GAD,we explored the regional structural brain abnormalities involved in heartbeat perception in patients with GAD.Methods This study was applied to the a priori regions using neuroanatomical theories of heartbeat perception,including the insula,anterior cingulate cortex,supplementary motor area and prefrontal cortex.A total of 19 patients with GAD and 19 healthy control subjects were enrolled.We used the FMRIB Software Library voxel-based morphometry software for estimating the grey matter volume of these regions of interest and analysed the correlation between heartbeat perception sensitivity and the volume of abnormal grey matter.Results Patients with GAD showed a significantly decreased volume of grey matter in their left medial prefrontal cortex,right orbital frontal cortex and anterior cingulate cortex.The grey matter volume of the left medial prefrontal cortex negatively correlated with heartbeat perception sensitivity in patients with GAD.Conclusions It should be the first study that shows heartbeat perception is associated with brain structure in GAD.Our findings suggest that the frontal region may play an important role in aberrant heartbeat perception processing in patients with GAD,and this may be an underlying mechanism resulting in the abnormal cardiovascular complaints in GAD.This is hypothesised as a'top-down'deficiency,especially in the medial prefrontal cortex.This will provide the foundation for a more targeted region for neuromodulation intervention in the future.

Reduced temporal activation during a verbal fluency test in clinical high risk of psychosis: a functional near-infrared spectroscopy-based study

Background Clinical high risk(CHR)of psychosis is a state in which positive symptoms cause the subjects distress but do not approach a severity level that fulfils the criteria for a psychotic episode.CHR exhibits cognitive deficits;however,the underlying neurobiological mechanisms remain unclear.This study aimed to investigate whether brain activation measured by the levels of oxygenated hemoglobin(oxy-Hb)in CHR subjects could be correlated with cognitive deficits.Methods Fifty-eight CHR individuals who fulfilled the criteria for attenuated positive syndrome as specified in the Structured Interview for Prodromal Syndrome(SIPS)and the Scale of Prodromal Syndrome(SOPS)and 58 age-and sex-matched healthy participants were included in the study.All subjects completed the Measurement and Treatment Research to Improve Cognition in Schizophrenia(MATRICS)Consensus Cognitive Battery(MCCB)that includes tests measuring attention,verbal memory,verbal fluency,executive function,and general intelligence.Functional near-infrared spectroscopy(fNIRS)was used to measure the level of oxy-Hb in the dorsolateral prefrontal and frontotemporal cortices.Results We observed significantly decreased oxy-Hb levels in channel 32(located in the right superior temporal gyrus,rSTG)within the CHR individuals compared with that in the healthy controls(HCs)(t=−3.44,Bonferroni-corrected p=0.002),indicating lower brain activity.A significant positive correlation was observed between task-relatedβvalues and working memory in the CHR group(r=0.35,p=0.008).Conclusions The brain activation of rSTG is abnormal among subjects at clinicial high risk for psychosis.This abnormality is probably associated with the neural mechanisms of deficits in the working memory during the early stage of psychosis.

Relationships between selfreflectiveness and clinical symptoms in individuals during pre-morbid and early clinical stages of psychosis

Background Self-reflectiveness,one dimension of cognitive insight,plays a protective role in an individual’s mental state.Both high and low levels of self-reflectiveness have been reported in patients with schizophrenia and individuals at clinical high risk for the illness.Aims This study aimed to explore the relationship patterns between self-reflectiveness and clinical symptoms in individuals during the pre-morbid and early clinical stages of psychosis.Methods A total of 181 subjects,including individuals with attenuated positive symptoms(APS,n=122)and patients with first-episode psychosis(FEP,n=59),completed the Beck Cognitive Insight Scale and were evaluated using the Schedule of Assessment of Insight and Positive and Negative Syndrome Scale.All subjects were classified into three groups according to their level of selfreflectiveness:low level(LSR,n=59),medium level(MSR,n=67)and high level(HSR,n=55).Both linear and nonlinear relationships between self-reflectiveness and clinical symptoms were explored.Results More individuals with APS were classified into the MSR group,while more patients with FEP were classified into the LSR group.The LSR group demonstrated less awareness of illness than the MSR and HSR groups,more stereotyped thinking and poorer impulse control but less anxiety than the MSR group,and lower levels of blunted affect and guilt feelings than the HSR group.The MSR group demonstrated lower stereotyped thinking than the HSR group.Compared to the LSR group,the MSR group had increased selfreflectiveness,improved awareness of illness,decreased stereotyped thinking,and better impulse control,but increased feelings of guilt.The HSR group showed increased stereotyped thinking when compared to the MSR group,but the other variables did not change significantly between these two groups.Overall,self-reflectiveness demonstrated an approximately inverse S-shaped relationship with the awareness of illness,a U-shaped relationship with stereotyped thinking and poor impulse control,and an almost linear relationship with anxiety and guilt feelings.Conclusions Self-reflectiveness demonstrates complex relationships with clinical symptoms and fails to exert significant positive effects when reaching a certain high level.

精神病临床高危综合征认知功能损伤的功能磁共振成像研究进展

精神病临床高危综合征以弱化的精神病性症状和认知功能损伤为特征, 随访时转化为精神分裂症的患者往往表现出更严重的认知功能损伤。近年来, 任务态功能磁共振成像研究为揭示不同认知功能损伤的神经生物学基础提供了客观特征, 为预测精神病高转化风险的人群提供了生物学标志, 并为发展早期干预提供了潜在靶点。本文对精神病临床高危综合征认知功能损伤的功能磁共振成像研究进展进行综述, 包括认知功能相关的脑区活动异常特征、与临床症状的关联等, 并对利用功能磁共振成像特征预测转化风险进行展望。