Neuropsychiatric disorders(NPDs) constitute a heavyburden on public health systems around the world and studies have demonstrated that the negative impact of NPDs is larger in Low and Middle Income Countries(LMICs). I...Neuropsychiatric disorders(NPDs) constitute a heavyburden on public health systems around the world and studies have demonstrated that the negative impact of NPDs is larger in Low and Middle Income Countries(LMICs). In recent decades, several studies have come to the understanding that genetic factors play a major role in the risk for a large number of NPDs. However, few neuropsychiatric genetics studies have been published from LMICs. In this Editorial, we discuss important issues impinging on advances in neuropsychiatric genetics research in LMICs. It is essential that scientists educate policymakers and officials of funding agencies on the importance of providing adequate funding for research in these areas. Development of local well-supported research programs focused on NPD genetics should be an important asset to develop; it would facilitate the establishment of sustainable research efforts that could lead to appropriate diagnosis and specific, affordable and feasible interventions in LMICs. It is important to point out that research into the biological basis of human NPDs is not only an academic effort reserved for a few elite institutions in economically developed countries, but it is vitally important for the mental health of people around the world.展开更多
We refute the controversial statement that addiction is not a brain disorder. Extensive peer-reviewed studies support the underlying neurobiological and neurogenetic basis of addiction’s “disease model”. In the 70s...We refute the controversial statement that addiction is not a brain disorder. Extensive peer-reviewed studies support the underlying neurobiological and neurogenetic basis of addiction’s “disease model”. In the 70s and 80s, a few clinical scientists suggested that it is possible to use behavioral training to teach controlled drinking. However, this controversial model failed drastically and increased labeling and stigmatization. Additionally, it was unhelpful in the search for treatment. Instead, we assert that addiction is a neuropsychiatric disorder characterized by a recurring desire to continue taking substances despite harmful physical and mental consequences. Work from our laboratory in 1995 supported the Reward Deficiency Syndrome (RDS) concept based on a common neurogenetic mechanism (hypodopaminergia) that underlies all substance and non-substance addictions. Non-substance addictions include behaviors like pathological gambling, internet addiction, and mobile phone addiction. Certain impulsive and compulsive behaviors or the acute intake of psychoactive substances result in heightened dopaminergic activity, while the opposite, hypodopaminergia, occurs following chronic abuse. Patients with Substance Use Disorder (SUD) can have a genetic predisposition compounded by stress or other epigenetic insults that can impact recovery. Relapse will occur post-short-term recovery if dopaminergic dysfunction remains untreated. Addiction, a brain disorder, requires treatment with DNA-directed pro-dopamine regulation and rehabilitation.展开更多
Tauopathies comprise a spectrum of genetic and sporadic neurodegenerative diseases mainly characterized by the presence of hyperphosphorylated TAU protein aggregations in neurons or glia.Gene therapy,in particular ade...Tauopathies comprise a spectrum of genetic and sporadic neurodegenerative diseases mainly characterized by the presence of hyperphosphorylated TAU protein aggregations in neurons or glia.Gene therapy,in particular adeno-associated virus(AAV)-based,is an effective medical approach for difficult-to-treat genetic diseases for which there are no convincing traditional therapies,such as tauopathies.Employing AAV-based gene therapy to treat,in particular,genetic tauopathies has many potential therapeutic benefits,but also drawbacks which need to be addressed in order to successfully and efficiently adapt this still unconventional therapy for the various types of tauopathies.In this Viewpoint,we briefly introduce some potentially treatable tauopathies,classify them according to their etiology,and discuss the potential advantages and possible problems of AAV-based gene therapy.Finally,we outline a future vision for the application of this promising therapeutic approach for genetic and sporadic tauopathies.展开更多
Complex genetic architecture is the major cause of heterogeneity in epilepsy,which poses challenges for accurate diagnosis and precise treatment.A large number of epilepsy candidate genes have been identified from cli...Complex genetic architecture is the major cause of heterogeneity in epilepsy,which poses challenges for accurate diagnosis and precise treatment.A large number of epilepsy candidate genes have been identified from clinical studies,particularly with the widespread use of next-generation sequencing.Validating these candidate genes is emerging as a valuable yet challenging task.Drosophila serves as an ideal animal model for validating candidate genes associated with neurogenetic disorders such as epilepsy,due to its rapid reproduction rate,powerful genetic tools,and efficient use of ethological and electrophysiological assays.Here,we systematically summarize the advantageous techniques of the Drosophila model used to investigate epilepsy genes,including genetic tools for manipulating target gene expression,ethological assays for seizure-like behaviors,electrophysiological techniques,and functional imaging for recording neural activity.We then introduce several typical strategies for identifying epilepsy genes and provide new insights into gene-gene interactions in epilepsy with polygenic causes.We summarize well-established precision medicine strategies for epilepsy and discuss prospective treatment options,including drug therapy and gene therapy for genetic epilepsy based on the Drosophila model.Finally,we also address genetic counseling and assisted reproductive technology as potential approaches for the prevention of genetic epilepsy.展开更多
Nervous systems endow animals with cognition and behavior. To understand how nervous systems control behavior, neural circuits mediating distinct functions need to be identified and characterized. With superior geneti...Nervous systems endow animals with cognition and behavior. To understand how nervous systems control behavior, neural circuits mediating distinct functions need to be identified and characterized. With superior genetic manipulability, Drosophila is a model organism at the leading edge of neural circuit analysis. We briefly introduce the state-of-the-art genetic tools that permit precise labeling of neurons and their interconnectivity and investigating what is happening in the brain of a behaving animal and manipulating neurons to determine how behaviors are affected. Brain-wide wiring diagrams, created by light and electron microscopy, bring neural circuit analysis to a new level and scale. Studies enabled by these tools advances our understanding of the nervous system in relation to cognition and behavior.展开更多
基金Supported by Research grants from VCTI-UAN and Colcienciasresearch grants from Universidad del Rosario
文摘Neuropsychiatric disorders(NPDs) constitute a heavyburden on public health systems around the world and studies have demonstrated that the negative impact of NPDs is larger in Low and Middle Income Countries(LMICs). In recent decades, several studies have come to the understanding that genetic factors play a major role in the risk for a large number of NPDs. However, few neuropsychiatric genetics studies have been published from LMICs. In this Editorial, we discuss important issues impinging on advances in neuropsychiatric genetics research in LMICs. It is essential that scientists educate policymakers and officials of funding agencies on the importance of providing adequate funding for research in these areas. Development of local well-supported research programs focused on NPD genetics should be an important asset to develop; it would facilitate the establishment of sustainable research efforts that could lead to appropriate diagnosis and specific, affordable and feasible interventions in LMICs. It is important to point out that research into the biological basis of human NPDs is not only an academic effort reserved for a few elite institutions in economically developed countries, but it is vitally important for the mental health of people around the world.
文摘We refute the controversial statement that addiction is not a brain disorder. Extensive peer-reviewed studies support the underlying neurobiological and neurogenetic basis of addiction’s “disease model”. In the 70s and 80s, a few clinical scientists suggested that it is possible to use behavioral training to teach controlled drinking. However, this controversial model failed drastically and increased labeling and stigmatization. Additionally, it was unhelpful in the search for treatment. Instead, we assert that addiction is a neuropsychiatric disorder characterized by a recurring desire to continue taking substances despite harmful physical and mental consequences. Work from our laboratory in 1995 supported the Reward Deficiency Syndrome (RDS) concept based on a common neurogenetic mechanism (hypodopaminergia) that underlies all substance and non-substance addictions. Non-substance addictions include behaviors like pathological gambling, internet addiction, and mobile phone addiction. Certain impulsive and compulsive behaviors or the acute intake of psychoactive substances result in heightened dopaminergic activity, while the opposite, hypodopaminergia, occurs following chronic abuse. Patients with Substance Use Disorder (SUD) can have a genetic predisposition compounded by stress or other epigenetic insults that can impact recovery. Relapse will occur post-short-term recovery if dopaminergic dysfunction remains untreated. Addiction, a brain disorder, requires treatment with DNA-directed pro-dopamine regulation and rehabilitation.
文摘Tauopathies comprise a spectrum of genetic and sporadic neurodegenerative diseases mainly characterized by the presence of hyperphosphorylated TAU protein aggregations in neurons or glia.Gene therapy,in particular adeno-associated virus(AAV)-based,is an effective medical approach for difficult-to-treat genetic diseases for which there are no convincing traditional therapies,such as tauopathies.Employing AAV-based gene therapy to treat,in particular,genetic tauopathies has many potential therapeutic benefits,but also drawbacks which need to be addressed in order to successfully and efficiently adapt this still unconventional therapy for the various types of tauopathies.In this Viewpoint,we briefly introduce some potentially treatable tauopathies,classify them according to their etiology,and discuss the potential advantages and possible problems of AAV-based gene therapy.Finally,we outline a future vision for the application of this promising therapeutic approach for genetic and sporadic tauopathies.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2022A1515111123(to JQ)。
文摘Complex genetic architecture is the major cause of heterogeneity in epilepsy,which poses challenges for accurate diagnosis and precise treatment.A large number of epilepsy candidate genes have been identified from clinical studies,particularly with the widespread use of next-generation sequencing.Validating these candidate genes is emerging as a valuable yet challenging task.Drosophila serves as an ideal animal model for validating candidate genes associated with neurogenetic disorders such as epilepsy,due to its rapid reproduction rate,powerful genetic tools,and efficient use of ethological and electrophysiological assays.Here,we systematically summarize the advantageous techniques of the Drosophila model used to investigate epilepsy genes,including genetic tools for manipulating target gene expression,ethological assays for seizure-like behaviors,electrophysiological techniques,and functional imaging for recording neural activity.We then introduce several typical strategies for identifying epilepsy genes and provide new insights into gene-gene interactions in epilepsy with polygenic causes.We summarize well-established precision medicine strategies for epilepsy and discuss prospective treatment options,including drug therapy and gene therapy for genetic epilepsy based on the Drosophila model.Finally,we also address genetic counseling and assisted reproductive technology as potential approaches for the prevention of genetic epilepsy.
基金supported by the National Natural Science Foundation of China (6531000063, 31571093, 31622028, 31471063, and 31671074)the Science Foundation of Jiangsu Province of China (BK20160025)Fundamental Research Funds for the Central Universities, China (2242016R20028 and 2017FZA7003)
文摘Nervous systems endow animals with cognition and behavior. To understand how nervous systems control behavior, neural circuits mediating distinct functions need to be identified and characterized. With superior genetic manipulability, Drosophila is a model organism at the leading edge of neural circuit analysis. We briefly introduce the state-of-the-art genetic tools that permit precise labeling of neurons and their interconnectivity and investigating what is happening in the brain of a behaving animal and manipulating neurons to determine how behaviors are affected. Brain-wide wiring diagrams, created by light and electron microscopy, bring neural circuit analysis to a new level and scale. Studies enabled by these tools advances our understanding of the nervous system in relation to cognition and behavior.
