Efficacy of repeated intravenous esketamine in adolescents with anxious versus non-anxious depression

Background Patients with anxious major depressive disorder(MDD)are more likely to have poorer outcomes than those with non-anxious MDD.However,the effect of esketamine on adolescents with anxious versus non-anxious MDD has remained unknown.Aims We compared the efficacy of esketamine in adolescents with MDD and suicidal ideation,both anxious and non-anxious.Methods Fifty-four adolescents with anxious(n=33)and non-anxious(n=21)MDD received three infusions of esketamine 0.25mg/kg or active-placebo(midazolam 0.045 mg/kg)over 5 days,with routine inpatient care and treatment.Suicidal ideation and depressive symptoms were assessed using the Columbia Suicide Severity Rating Scale and the Montgomery-Asberg Depression Rating Scale.Multiple-sample proportional tests were used to compare the differences between groups on treatment outcomes 24 hours after the final infusion(day 6,primacy efficacy endpoint)and throughout the 4-week post-treatment(days 12,19 and 33).Results In subjects who received esketamine,a greater number of patients in the non-anxious group than the anxious group achieved antisuicidal remission on day 6(72.7%vs 18.8%,p=0.015)and day 12(90.9%vs 43.8%,p=0.013),and the non-anxious group had a higher antidepressant remission rate compared with the anxious group on day 33(72.7%vs 26.7%,p=0.045).No significant differences in treatment outcomes were observed between the anxious and non-anxious groups at other time points.Conclusions Three infusions of esketamine as an adjunct to routine inpatient care and treatment had a greater immediate post-treatment antisuicidal effect in adolescents with non-anxious MDD than in those with anxious MDD;however,this benefit was temporary and was not maintained over time.

Face and object visual working memory deficits in first-episode schizophrenia correlate with multiple neurocognitive performances

Background Working memory(WM)deficit is considered a core feature and cognitive biomarker in patients with schizophrenia.Several studies have reported prominent object WM deficits in patients with schizophrenia,suggesting that visual WM in these patients extends to non-spatial domains.However,whether non-spatial WM is similarly affected remains unclear.Aim This study primarily aimed to identify the processing of visual object WM in patients with first-episode schizophrenia.Methods The study included 36 patients with first-episode schizophrenia and 35 healthy controls.Visual object WM capacity,including face and house WM capacity,was assessed by means of delayed matching-to sample visual WM tasks,in which participants must distribute memory so that they can discriminate a target sample.We specifically examined their anhedonia experience by the Temporal Experience of Pleasure Scale and the Snaith-Hamilton Pleasure Scale.Cognitive performance was measured by the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS).Results Both face and house WM capacity was significantly impaired in patients with schizophrenia.For both tasks,the performance of all the subjects was worse under the high-load condition than under the low-load condition.We found that WM capacity was highly positively correlated with the performance on RBANS total scores(r=−0.528,p=0.005),RBANS delayed memory scores(r=−0.470,p=0.013),RBANS attention scores(r=−0.584,p=0.001),RBANS language scores(r=−0.448,p=0.019),Trail-Making Test:Part A raw scores(r=0.465,p=0.015)and simple IQ total scores(r=−0.538,p=0.005),and correlated with scores of the vocabulary test(r=−0.490,p=0.011)and scores of the Block Diagram Test(r=−0.426,p=0.027)in schizophrenia.No significant correlations were observed between WM capacity and Positive and Negative Syndrome Scale symptoms.Conclusions Our research found that visual object WM capacity is dramatically impaired in patients with schizophrenia and is strongly correlated with other measures of cognition,suggesting a mechanism that is critical in explaining a portion of the broad cognitive deficits observed in schizophrenia.

Mutation analysis of ATP13A2 in early-onset parkinsonism patients

BACKGROUND： A recent study has found that ATP13A2 is the causative gene for PARK9-linked autosomal recessive early-onset parkinsonism, described previously in Jordanian and Chilean families （Kufor-Rakeb syndrome）. OBJECTIVE： To screen eastern Asian patients with early-onset parkinsonism for mutations in ATP13A2 and to describe positron emission tomography （PET） findings of PARK9-linked parkinsonism. DESIGN, TIME AND SETTING： In total, 117 patients were selected from the Department of Neurology, Juntendo University, from February 2003 to October 2006, for this molecular genetics and case-control study. PARTICIPANTS： The patients with parkinsonism consist of two cohorts. Ninety four patients with onset age of less than 30 years were selected for the first cohort. They included 49 males and 44 females, comprising 73 Japanese, 9 Korean, 8 Taiwan Residents, and 4 Mainland Chinese. Eleven patients had parkinsonism complicated with dementia, 15 patients had family histories of parkinsonism （including 2 families）, and 5 patients were from consanguineous parents （including one family）. The second cohort of 23 patients was composed of patients with consanguineous parents （n = 15） or who had affected siblings （n = 6） or both （n = 2）, but the age at onset ranged from 30 to 50 years. METHODS： In 117 patients with parkinsonism, direct sequencing of ATP13A2 exons 13, 16, and 26, in which mutations had been reported previously, were performed. Sequencing was also performed in all 29 exons, including splice sites, in 28 probands who showed homozygosity at the PARK9 locus by haplotype analysis. Mutation analysis was also performed in 150 normal people. Linkage analysis was performed on all 3 parkinsonism families using short tandem repeat markers flanking the PARK9 locus. For patients who had ATP13A2 mutation, we performed brain MRI and ^18F-dopa PET scans. MAIN OUTCOME MEASURES： ATP13A2 DNA sequence, ^18F-dopa PET scan and brain MRI findings. RESULTS： A novel F182L mutation in a consanguineous Japanese family was identified. The patient was homozygous for the F182L mutation and her unaffected parents and two unaffected siblings were heterozygous for the F182L mutation. The patient developed early-onset atypical parkinsonism, which resembled the originally reported Kufor-Rakeb syndrome. MRI examination showed spinal cord atrophy and ^18F-dopa PET scan findings were similar to those of Parkinson＇s disease. CONCLUSION： Detection of the new PARK9 mutation, together with the previously reported cases of PARK9-linked parkinsonism, expand the clinical phenotypic spectrum of levodopa-responsive parkinsonism.

Differences in olfactory functional connectivity in early-onset depression and late-onset depression

Background:Late-onset depression(LOD)and early-onset depression(EOD)exhibit different pathological mechanisms and clinical phenotypes,including different extents of olfactory dysfunction.However,the brain abnormalities underlying the differences in ol-factory dysfunction between EOD and LOD remain unclear.Objective:The aim of this study was to compare the functional connectivity(FC)patterns of olfactory regions between EOD patients and LOD patients and examine their relationship with cognitive function.Methods:One hundred and five patients with EOD,101 patients with LOD and 160 normal controls(NCs)were recruited for the present study.Participants underwent clinical assessment,olfactory testing,cognitive assessments,and magnetic resonance imaging.Eight regions of the primary and secondary olfactory regions were selected to investigate olfactory FC.Results:Patients with LOD exhibited decreased odor identification(OI)compared with patients with EOD and NCs.The LOD group exhibited decreased FC compared with the EOD and NC groups when primary and secondary olfactory regions were selected as the regions of interest(the piriform cortex,lateral entorhinal cortex,and orbital-frontal cortex).Additionally,these abnormal olfactory FCs were associated with decreased cognitive function scores and OI,and the FC between the left orbital-frontal cortex and left amygdala was a partial mediator of the relationship between global cognitive scores and OI.Conclusion:Overall,patients with LOD exhibited decreased FC in both the primary and secondary olfactory cortices compared with patients with EOD,and abnormal olfactory FC was associated with OI dysfunction and cognitive impairment.The FC between the orbital-frontal cortex and amygdala mediated the relationship between global cognitive function and OI.

Improvement of thermal stability of ZrSiON based solar selective absorbing coating

Solar selective absorbing coatings(SSACs)are required to have not only excellent optical property but also outstanding thermal stability for high temperature applications.The optical properties of Mo/ZrSiN/ZrSiON/SiO_(2) SSAC had been optimized successfully before.Herein,we are focusing on the evaluation and mechanism of thermal stability of this multilayer coating for its potential applications in concentrated solar power(CSP)systems.Fortunately,the coating exhibits excellent thermal stability after aging at 400℃ for 1500 h in vacuum.At aging temperature of 500℃ for 1000 h or 600℃ for 300 h in vacuum,the slight inter-diffusion between Mo layer and stainless steel(SS)substrate occurs.At higher aging temperature of 700℃ for 100 h in vacuum,the serious inter-diffusion between Mo layer and SS substrate leads to invalidation of the coating,which has been evidenced by Rutherford backscattering spectrometry(RBS)and X-ray diffraction(XRD)technologies.Additionally,this coating also has an outstanding thermal stability after aging at 400℃for 300 h in air.A heating-cooling cycling(HCC)treatment evidences the good thermal stability of this coating working in cold environment(60℃).The results reveal that this coating can be a promising candidate not only for CSP system in high temperatures but also for usage in cold environment.