Objective: To estimate the rate of response to divalproex sodium extended release in pediatric bipolar spectrum disorder in young children age 6 - 12. Methods: This was an 8-week, open-label treatment of youth with DS...Objective: To estimate the rate of response to divalproex sodium extended release in pediatric bipolar spectrum disorder in young children age 6 - 12. Methods: This was an 8-week, open-label treatment of youth with DSM-IV bipolar disorder with divalproex sodium extended release (ER) monotherapy. Severity of mania was assessed weekly with the Young Mania Rating Scale (YMRS). Results: The sample was 8.9 ± 2.0 years of age and predominantly male (83%). At study entry the mean YMRS score was 26.3 ± 4.5. Of the 18 subjects enrolled, 7 (39%) completed the 8 week course. We failed to find a clinically or statistically significant improvement with divalproex sodium ER. Pre-post comparisons at endpoint (LOCF) indicated an average response reduction of 6.1 ± 2.6 in the YMRS to a mean of 20.3 ± 8.1. Weight increased by 1.36 ± 0.7 kg (p = 0.08) from baseline to endpoint. Conclusion. Divalproex sodium ER monotherapy was associated with poor tolerability, was associated with clinically concerning weight gain but had modest therapeutic benefits in the management of symptoms of mania and depression in children with pediatric bipolar disorder.展开更多
Mood disorders/psychosis have been associated with dysfunctions in the default mode network(DMN).However,the relative contributions of DMN regions to state and trait disturbances in pediatric bipolar disorder(PBD)rema...Mood disorders/psychosis have been associated with dysfunctions in the default mode network(DMN).However,the relative contributions of DMN regions to state and trait disturbances in pediatric bipolar disorder(PBD)remain unclear.The aim of this study was to investigate the possible mechanisms of PBD through brain imaging and explore the influence of psychotic symptoms on functional alterations in PBD patients.Twenty-nine psychotic and 26 non-psychotic PBD patients,as well as 19 age-and sex-matched healthy controls underwent a restingstate functional MRI scan and the data were analyzed by independent component analysis.The DMN component from the fMRI data was extracted for each participant.Spearman's rank correlation analysis was performed between aberrant connectivity and clinical measurements.The results demonstrated that psychotic PBD was characterized by aberrant DMN connectivity in the anterior cingulate cortex/medial prefrontal cortex,bilateral caudate nucleus,bilateral angular gyri,and left middle temporal gyrus,while non-psychotic PBD was not,suggesting further impairment with the development of psychosis.In summary,we demonstrated unique impairment in DMN functional connectivity in the psychotic PBD group.These specific neuroanatomical abnormalities may shed light on the underlying pathophysiology and presentation of PBD.展开更多
Background Pediatric bipolar disorder(PBD)has been proven to be related to abnormal brain structural connectivity,but how the abnormalities in PBD correlate with gene expression is debated.Objective This study aims at...Background Pediatric bipolar disorder(PBD)has been proven to be related to abnormal brain structural connectivity,but how the abnormalities in PBD correlate with gene expression is debated.Objective This study aims at identification of cell-type-specific gene modules based on cortical structural differences in PBD.Methods Morphometric similarity networks(MSN)were computed as a marker of interareal cortical connectivity based on MRI data from 102 participants(59 patients and 43 controls).Partial least squares(PLS)regression was used to calculate MSN differences related to transcriptomic data in AHBA.The biological processes and cortical cell types associated with this gene expression profile were determined by gene enrichment tools.Results MSN analysis results demonstrated differences of cortical structure between individuals diagnosed with PBD and healthy control participants.MSN differences were spatially correlated with the PBD-related weighted genes.The weighted genes were enriched for“trans-synaptic signaling”and“regulation of ion transport”,and showed significant specific expression in excitatory and inhibitory neurons.Conclusions This study identified the genes that contributed to structural network aberrations in PBD.It was found that transcriptional changes of excitatory and inhibitory neurons might be associated with abnormal brain structural connectivity in PBD.展开更多
A pathophysiological relationship has been reported between inflammatory processes,decreased levels of neurotrophins,increased oxidative stress and psychiatric disorders in both juvenile and adult ages.Moreover,this r...A pathophysiological relationship has been reported between inflammatory processes,decreased levels of neurotrophins,increased oxidative stress and psychiatric disorders in both juvenile and adult ages.Moreover,this relationship remains unclear in juvenile bipolar disorder(BD).We performed a systematic literature review of studies reporting measurements of inflammatory markers,oxidative stress markers or neurotrophins in juvenile and young adult subjects with BD.Concordant findings showed that inflammatory markers are increased since the earlier stages of BD.A positive correlation between decreased levels of a peripheral brain-derived neurotrophic factor and juvenile BD is controversial suggesting that those changes might occur only during the late stage of BD.No changes in central glutathione levels were reported in young adult age BD indicating that oxidative stress may be an outcome of long illness duration and repeated affective episodes.In conclusion,preliminary findings indicate that a certain relationship exists between inflammatory process and juvenile BD but evidence are insufficient to support a causal relationship.Adequately powered and prospective studies are warranted to clarify the role of inflammation,neurotrophins and oxidative stress in juvenile BD.展开更多
文摘Objective: To estimate the rate of response to divalproex sodium extended release in pediatric bipolar spectrum disorder in young children age 6 - 12. Methods: This was an 8-week, open-label treatment of youth with DSM-IV bipolar disorder with divalproex sodium extended release (ER) monotherapy. Severity of mania was assessed weekly with the Young Mania Rating Scale (YMRS). Results: The sample was 8.9 ± 2.0 years of age and predominantly male (83%). At study entry the mean YMRS score was 26.3 ± 4.5. Of the 18 subjects enrolled, 7 (39%) completed the 8 week course. We failed to find a clinically or statistically significant improvement with divalproex sodium ER. Pre-post comparisons at endpoint (LOCF) indicated an average response reduction of 6.1 ± 2.6 in the YMRS to a mean of 20.3 ± 8.1. Weight increased by 1.36 ± 0.7 kg (p = 0.08) from baseline to endpoint. Conclusion. Divalproex sodium ER monotherapy was associated with poor tolerability, was associated with clinically concerning weight gain but had modest therapeutic benefits in the management of symptoms of mania and depression in children with pediatric bipolar disorder.
基金supported by National Natural Science Foundation of China (81171291, 81371531, 81571344, 81871344)the Natural Science Foundation of Jiangsu Province, China (BK20161109)+2 种基金the Key Program for Guangming Lu (BWS11J063, and 10z026)the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province, China (18KJB190003)the Postdoctoral Science Foundation of China (2014M552700)
文摘Mood disorders/psychosis have been associated with dysfunctions in the default mode network(DMN).However,the relative contributions of DMN regions to state and trait disturbances in pediatric bipolar disorder(PBD)remain unclear.The aim of this study was to investigate the possible mechanisms of PBD through brain imaging and explore the influence of psychotic symptoms on functional alterations in PBD patients.Twenty-nine psychotic and 26 non-psychotic PBD patients,as well as 19 age-and sex-matched healthy controls underwent a restingstate functional MRI scan and the data were analyzed by independent component analysis.The DMN component from the fMRI data was extracted for each participant.Spearman's rank correlation analysis was performed between aberrant connectivity and clinical measurements.The results demonstrated that psychotic PBD was characterized by aberrant DMN connectivity in the anterior cingulate cortex/medial prefrontal cortex,bilateral caudate nucleus,bilateral angular gyri,and left middle temporal gyrus,while non-psychotic PBD was not,suggesting further impairment with the development of psychosis.In summary,we demonstrated unique impairment in DMN functional connectivity in the psychotic PBD group.These specific neuroanatomical abnormalities may shed light on the underlying pathophysiology and presentation of PBD.
基金This study was supported by National Natural Science Foundation of China(81871344,81971289)Natural Science Foundation of Jiangsu Province(BK20191369)+1 种基金Qing Lan Project of the Higher Educations of Jiangsu ProvinceJiangsu Provincial Key Research and Development Program(BE2019609).
文摘Background Pediatric bipolar disorder(PBD)has been proven to be related to abnormal brain structural connectivity,but how the abnormalities in PBD correlate with gene expression is debated.Objective This study aims at identification of cell-type-specific gene modules based on cortical structural differences in PBD.Methods Morphometric similarity networks(MSN)were computed as a marker of interareal cortical connectivity based on MRI data from 102 participants(59 patients and 43 controls).Partial least squares(PLS)regression was used to calculate MSN differences related to transcriptomic data in AHBA.The biological processes and cortical cell types associated with this gene expression profile were determined by gene enrichment tools.Results MSN analysis results demonstrated differences of cortical structure between individuals diagnosed with PBD and healthy control participants.MSN differences were spatially correlated with the PBD-related weighted genes.The weighted genes were enriched for“trans-synaptic signaling”and“regulation of ion transport”,and showed significant specific expression in excitatory and inhibitory neurons.Conclusions This study identified the genes that contributed to structural network aberrations in PBD.It was found that transcriptional changes of excitatory and inhibitory neurons might be associated with abnormal brain structural connectivity in PBD.
基金It was supported by the Research Fellowship from Sapienza University of Rome to Dr.Giulia Serra.
文摘A pathophysiological relationship has been reported between inflammatory processes,decreased levels of neurotrophins,increased oxidative stress and psychiatric disorders in both juvenile and adult ages.Moreover,this relationship remains unclear in juvenile bipolar disorder(BD).We performed a systematic literature review of studies reporting measurements of inflammatory markers,oxidative stress markers or neurotrophins in juvenile and young adult subjects with BD.Concordant findings showed that inflammatory markers are increased since the earlier stages of BD.A positive correlation between decreased levels of a peripheral brain-derived neurotrophic factor and juvenile BD is controversial suggesting that those changes might occur only during the late stage of BD.No changes in central glutathione levels were reported in young adult age BD indicating that oxidative stress may be an outcome of long illness duration and repeated affective episodes.In conclusion,preliminary findings indicate that a certain relationship exists between inflammatory process and juvenile BD but evidence are insufficient to support a causal relationship.Adequately powered and prospective studies are warranted to clarify the role of inflammation,neurotrophins and oxidative stress in juvenile BD.
