Anxiety disorders have become one of the most severe psychiatric disorders,and the incidence is increasing every year.They impose an extraordinary personal and socioeconomic burden.Anxiety disorders are influenced by ...Anxiety disorders have become one of the most severe psychiatric disorders,and the incidence is increasing every year.They impose an extraordinary personal and socioeconomic burden.Anxiety disorders are influenced by multiple complex and interacting genetic,psychological,social,and environmental factors,which contribute to disruption or imbalance in homeostasis and eventually cause pathologic anxiety.The selection of a suitable animal model is important for the exploration of disease etiology and pathophysiology,and the development of new drugs.Therefore,a more comprehensive understanding of the advantages and limitations of existing animal models of anxiety disorders is helpful to further study the underlying pathological mechanisms of the disease.This review summarizes animal models and the pathogenesis of anxiety disorders,and discusses the current research status to provide insights for further study of anxiety disorders.展开更多
Early-onset mental disorders are associated with disrupted neurodevelopmental processes during adolescence.The methylazoxymethanol acetate(MAM)animal model,in which disruption in neurodevelopmental processes is induce...Early-onset mental disorders are associated with disrupted neurodevelopmental processes during adolescence.The methylazoxymethanol acetate(MAM)animal model,in which disruption in neurodevelopmental processes is induced,mimics the abnormal neurodevelopment associated with early-onset mental disorders from an etiological perspective.We conducted longitudinal structural magnetic resonance imaging(MRI)scans during childhood,adolescence,and adulthood in MAM rats to identify specific brain regions and critical windows for intervention.Then,the effect of repetitive transcranial magnetic stimulation(rTMS)intervention on the target brain region during the critical window was investigated.In addition,the efficacy of this intervention paradigm was tested in a group of adolescent patients with early-onset mental disorders(diagnosed with major depressive disorder or bipolar disorder)to evaluate its clinical translational potential.The results demonstrated that,compared to the control group,the MAM rats exhibited significantly lower striatal volume from childhood to adulthood(all P<0.001).In contrast,the volume of the hippocampus did not show significant differences during childhood(P>0.05)but was significantly lower than the control group from adolescence to adulthood(both P<0.001).Subsequently,rTMS was applied to the occipital cortex,which is anatomically connected to the hippocampus,in the MAM models during adolescence.The MAM-rTMS group showed a significant increase in hippocampal volume compared to the MAM-sham group(P<0.01),while the volume of the striatum remained unchanged(P>0.05).In the clinical trial,adolescents with early-onset mental disorders showed a significant increase in hippocampal volume after rTMS treatment compared to baseline(P<0.01),and these volumetric changes were associated with improvement in depressive symptoms(r=−0.524,P=0.018).These findings highlight the potential of targeting aberrant hippocampal development during adolescence as a viable intervention for earlyonset mental disorders with neurodevelopmental etiology as well as the promise of rTMS as a therapeutic approach for mitigating aberrant neurodevelopmental processes and alleviating clinical symptoms.展开更多
基金National Natural Science Foundation of ChinaGrant/Award Number:82104793 and 82104836+5 种基金Natural Science Foundation of Hunan ProvinceGrant/Award Number:2023JJ60482Openof TCM First-class Disciplines in HNUCMGrant/Award Number:2022ZYX18Science and Technology talent promotion Project of Hunan ProvinceGrant/Award Number:2023TJ-N22。
文摘Anxiety disorders have become one of the most severe psychiatric disorders,and the incidence is increasing every year.They impose an extraordinary personal and socioeconomic burden.Anxiety disorders are influenced by multiple complex and interacting genetic,psychological,social,and environmental factors,which contribute to disruption or imbalance in homeostasis and eventually cause pathologic anxiety.The selection of a suitable animal model is important for the exploration of disease etiology and pathophysiology,and the development of new drugs.Therefore,a more comprehensive understanding of the advantages and limitations of existing animal models of anxiety disorders is helpful to further study the underlying pathological mechanisms of the disease.This review summarizes animal models and the pathogenesis of anxiety disorders,and discusses the current research status to provide insights for further study of anxiety disorders.
基金supported by the National Science Fund for Distinguished Young Scholars(81725005)the National Natural Science Foundation Regional Innovation and Development Joint Fund(U20A6005)+5 种基金the National Natural Science Foundation of China(82151315 and 62176129)the National Key Research and Development Program(2022YFC2405605)the Jiangsu Provincial Key Research and Development Program(BE2021617 and BE2022160)the Key Project supported by Medical Science and Technology Development Foundation,Jiangsu Commission of Health(ZD2021026)the Jiangsu Funding Program for Excellent Postdoctoral Talent(2023ZB818)the Postdoctoral Research Project of Changzhou Medical Center,Nanjing Medical University(CMCP202305).
文摘Early-onset mental disorders are associated with disrupted neurodevelopmental processes during adolescence.The methylazoxymethanol acetate(MAM)animal model,in which disruption in neurodevelopmental processes is induced,mimics the abnormal neurodevelopment associated with early-onset mental disorders from an etiological perspective.We conducted longitudinal structural magnetic resonance imaging(MRI)scans during childhood,adolescence,and adulthood in MAM rats to identify specific brain regions and critical windows for intervention.Then,the effect of repetitive transcranial magnetic stimulation(rTMS)intervention on the target brain region during the critical window was investigated.In addition,the efficacy of this intervention paradigm was tested in a group of adolescent patients with early-onset mental disorders(diagnosed with major depressive disorder or bipolar disorder)to evaluate its clinical translational potential.The results demonstrated that,compared to the control group,the MAM rats exhibited significantly lower striatal volume from childhood to adulthood(all P<0.001).In contrast,the volume of the hippocampus did not show significant differences during childhood(P>0.05)but was significantly lower than the control group from adolescence to adulthood(both P<0.001).Subsequently,rTMS was applied to the occipital cortex,which is anatomically connected to the hippocampus,in the MAM models during adolescence.The MAM-rTMS group showed a significant increase in hippocampal volume compared to the MAM-sham group(P<0.01),while the volume of the striatum remained unchanged(P>0.05).In the clinical trial,adolescents with early-onset mental disorders showed a significant increase in hippocampal volume after rTMS treatment compared to baseline(P<0.01),and these volumetric changes were associated with improvement in depressive symptoms(r=−0.524,P=0.018).These findings highlight the potential of targeting aberrant hippocampal development during adolescence as a viable intervention for earlyonset mental disorders with neurodevelopmental etiology as well as the promise of rTMS as a therapeutic approach for mitigating aberrant neurodevelopmental processes and alleviating clinical symptoms.
