Pub Date : 2020-03-01DOI: 10.1093/med-psych/9780190697266.003.0015
R. McCarty
A consistent finding from research on animal models of depression and PTSD is that some animals are highly susceptible to the effects of stressful stimulation, while others show few obvious effects. A relatively new of line of research on resilience has emerged and has directed attention to those animals that are resistant to the effects of chronic or traumatic stressors. By tracking animals that are resistant to the behavioral effects of these stressful paradigms, one can then explore the molecular underpinnings of resilience in the brains of these same animals. Using chronic social defeat stress, some investigators have focused their attention on the ventral tegmental area, nucleus accumbens, and the prefrontal cortex. Other systems that have been studied include signaling molecules of the immune system and communication pathways between the immune system and the brain. A related line of research has addressed the possibility that prior exposure to stressors may inoculate animals to the deleterious effects of later stressor exposure.
{"title":"Resilience","authors":"R. McCarty","doi":"10.1093/med-psych/9780190697266.003.0015","DOIUrl":"https://doi.org/10.1093/med-psych/9780190697266.003.0015","url":null,"abstract":"A consistent finding from research on animal models of depression and PTSD is that some animals are highly susceptible to the effects of stressful stimulation, while others show few obvious effects. A relatively new of line of research on resilience has emerged and has directed attention to those animals that are resistant to the effects of chronic or traumatic stressors. By tracking animals that are resistant to the behavioral effects of these stressful paradigms, one can then explore the molecular underpinnings of resilience in the brains of these same animals. Using chronic social defeat stress, some investigators have focused their attention on the ventral tegmental area, nucleus accumbens, and the prefrontal cortex. Other systems that have been studied include signaling molecules of the immune system and communication pathways between the immune system and the brain. A related line of research has addressed the possibility that prior exposure to stressors may inoculate animals to the deleterious effects of later stressor exposure.","PeriodicalId":251581,"journal":{"name":"Stress and Mental Disorders: Insights from Animal Models","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128682309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-03-01DOI: 10.1093/med-psych/9780190697266.003.0014
R. McCarty
Two especially valuable animal models of post-traumatic stress disorder (PTSD) have been developed, including brief exposure of laboratory rats to a predator (a cat) or its odor, and the single prolonged stress paradigm. In each of these models, laboratory animals are evaluated for behavioral changes several days to several weeks following the stressful experience and are compared to unstressed controls. In both of these models, stressed animals display behavioral changes consistent with a PTSD-like phenotype. Using these models, investigators have explored central and peripheral neural and endocrine changes associated with the onset of PTSD-like symptoms and approaches to prevent or block the effects of the traumatic stressor on behavioral changes. Two particularly effective treatments that have been described include administration of a protein synthesis inhibitor and intra-nasal administration of neuropeptide Y. Animal models also provide an opportunity to study transgenerational transmission of PTSD risk.
{"title":"Post-Traumatic Stress Disorder","authors":"R. McCarty","doi":"10.1093/med-psych/9780190697266.003.0014","DOIUrl":"https://doi.org/10.1093/med-psych/9780190697266.003.0014","url":null,"abstract":"Two especially valuable animal models of post-traumatic stress disorder (PTSD) have been developed, including brief exposure of laboratory rats to a predator (a cat) or its odor, and the single prolonged stress paradigm. In each of these models, laboratory animals are evaluated for behavioral changes several days to several weeks following the stressful experience and are compared to unstressed controls. In both of these models, stressed animals display behavioral changes consistent with a PTSD-like phenotype. Using these models, investigators have explored central and peripheral neural and endocrine changes associated with the onset of PTSD-like symptoms and approaches to prevent or block the effects of the traumatic stressor on behavioral changes. Two particularly effective treatments that have been described include administration of a protein synthesis inhibitor and intra-nasal administration of neuropeptide Y. Animal models also provide an opportunity to study transgenerational transmission of PTSD risk.","PeriodicalId":251581,"journal":{"name":"Stress and Mental Disorders: Insights from Animal Models","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129668262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-03-01DOI: 10.1093/med-psych/9780190697266.003.0002
R. McCarty
Genome-wide association studies (GWAS) have revolutionized the field of psychiatric genetics by examining genetic variation at millions of single-nucleotide polymorphisms (SNPs) in many thousands of individual genome using microarrays. The sample sizes for these studies range from tens of thousands on up. Results to date from GWAS have called into question the validity of current diagnostic categories in psychiatry. For example, there may be some level of genetic risk that is shared across many psychiatric disorders, with the final symptom clusters of a given disorder being shaped by other genetic, epigenetic, and environmental variables. Research findings on three mental disorders are evaluated to make the case that stressful life events play a crucial role in the etiology of mental disorders. The mental disorders discussed include schizophrenia, bipolar disorder, and depression. These findings set the stage for the remainder of the book.
{"title":"Making the Case","authors":"R. McCarty","doi":"10.1093/med-psych/9780190697266.003.0002","DOIUrl":"https://doi.org/10.1093/med-psych/9780190697266.003.0002","url":null,"abstract":"Genome-wide association studies (GWAS) have revolutionized the field of psychiatric genetics by examining genetic variation at millions of single-nucleotide polymorphisms (SNPs) in many thousands of individual genome using microarrays. The sample sizes for these studies range from tens of thousands on up. Results to date from GWAS have called into question the validity of current diagnostic categories in psychiatry. For example, there may be some level of genetic risk that is shared across many psychiatric disorders, with the final symptom clusters of a given disorder being shaped by other genetic, epigenetic, and environmental variables. Research findings on three mental disorders are evaluated to make the case that stressful life events play a crucial role in the etiology of mental disorders. The mental disorders discussed include schizophrenia, bipolar disorder, and depression. These findings set the stage for the remainder of the book.","PeriodicalId":251581,"journal":{"name":"Stress and Mental Disorders: Insights from Animal Models","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121624086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-03-01DOI: 10.1093/med-psych/9780190697266.003.0010
R. McCarty
Animal models of bipolar disorder (BD) should capture the switching of mood states from mania to depression and vice versa. Dopamine signaling pathways in brain, including variations in the dopamine transporter protein, have been a focus of many animal models of BD. Another aspect of BD in humans is reflected in circadian and seasonal changes in onset of symptoms. Other animal models of BD include the Myshkin and Madison mouse strains, both of which display mania-like behavior that is reversed by treatment with lithium or valproic acid. Another experimental approach has been to manipulate circadian clock genes and examine effects on dopamine signaling and behavior. Finally, manipulations of risk genes for BD in laboratory mice have advanced our understanding of the molecular mechanisms involved in extreme alterations in mood state.
{"title":"Stress and Bipolar Disorder","authors":"R. McCarty","doi":"10.1093/med-psych/9780190697266.003.0010","DOIUrl":"https://doi.org/10.1093/med-psych/9780190697266.003.0010","url":null,"abstract":"Animal models of bipolar disorder (BD) should capture the switching of mood states from mania to depression and vice versa. Dopamine signaling pathways in brain, including variations in the dopamine transporter protein, have been a focus of many animal models of BD. Another aspect of BD in humans is reflected in circadian and seasonal changes in onset of symptoms. Other animal models of BD include the Myshkin and Madison mouse strains, both of which display mania-like behavior that is reversed by treatment with lithium or valproic acid. Another experimental approach has been to manipulate circadian clock genes and examine effects on dopamine signaling and behavior. Finally, manipulations of risk genes for BD in laboratory mice have advanced our understanding of the molecular mechanisms involved in extreme alterations in mood state.","PeriodicalId":251581,"journal":{"name":"Stress and Mental Disorders: Insights from Animal Models","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131155373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-03-01DOI: 10.1093/med-psych/9780190697266.003.0006
R. McCarty
Darwin made a compelling case that studies of animals could provide insights into the behavior of humans. Early studies by Pavlov and Harlow paved the way for further developments of animal models of psychiatric disorders. Seligman and Maier’s learned helplessness model continues to be employed in laboratory studies of stress and depression. It has become clear that no single animal model can possibly reproduce all of the critical facets of a mental disorder in humans. However, animal models do provide an essential element in attempts to understand the mechanisms that underlie mental disorders and to reveal molecular targets for the development of new drug therapies. Concerns have been raised about the reproducibility of laboratory experiments with inbred strains of laboratory mice and rats. Any animal model should be evaluated based upon a battery of behavioral tests and the parameters of stressful stimulation employed in experiments should be chosen with care.
{"title":"Animal Models in Psychiatry","authors":"R. McCarty","doi":"10.1093/med-psych/9780190697266.003.0006","DOIUrl":"https://doi.org/10.1093/med-psych/9780190697266.003.0006","url":null,"abstract":"Darwin made a compelling case that studies of animals could provide insights into the behavior of humans. Early studies by Pavlov and Harlow paved the way for further developments of animal models of psychiatric disorders. Seligman and Maier’s learned helplessness model continues to be employed in laboratory studies of stress and depression. It has become clear that no single animal model can possibly reproduce all of the critical facets of a mental disorder in humans. However, animal models do provide an essential element in attempts to understand the mechanisms that underlie mental disorders and to reveal molecular targets for the development of new drug therapies. Concerns have been raised about the reproducibility of laboratory experiments with inbred strains of laboratory mice and rats. Any animal model should be evaluated based upon a battery of behavioral tests and the parameters of stressful stimulation employed in experiments should be chosen with care.","PeriodicalId":251581,"journal":{"name":"Stress and Mental Disorders: Insights from Animal Models","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114836456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-03-01DOI: 10.1093/med-psych/9780190697266.003.0011
R. McCarty
Much of the research relating to animal models of anxiety has been devoted to developing more effective drugs for the treatment of the various anxiety disorders. Using selective breeding of laboratory mice and rats, investigators have developed high-anxiety and low-anxiety lines that have been especially valuable for basic research purposes. Other approaches to enhance the expression of an anxiety-like phenotype have included prenatal or early postnatal exposure to stressors, maternal immune activation, or selecting offspring based upon differences in the maternal behaviors of their mothers. In addition, risk genes for anxiety disorders have been studied in animal models, including genes related to serotonin, neuropeptide Y, neuropeptide S, and corticotropin-releasing factor signaling in the brain. Finally, some infant rhesus monkeys display an anxious temperament and extreme behavioral inhibition when separated from their mothers. This nonhuman primate model affords many opportunities to explore brain mechanisms and interventions that may be effective in preventing the further development of an anxious phenotype as these monkeys mature.
{"title":"Stress and Anxiety Disorders","authors":"R. McCarty","doi":"10.1093/med-psych/9780190697266.003.0011","DOIUrl":"https://doi.org/10.1093/med-psych/9780190697266.003.0011","url":null,"abstract":"Much of the research relating to animal models of anxiety has been devoted to developing more effective drugs for the treatment of the various anxiety disorders. Using selective breeding of laboratory mice and rats, investigators have developed high-anxiety and low-anxiety lines that have been especially valuable for basic research purposes. Other approaches to enhance the expression of an anxiety-like phenotype have included prenatal or early postnatal exposure to stressors, maternal immune activation, or selecting offspring based upon differences in the maternal behaviors of their mothers. In addition, risk genes for anxiety disorders have been studied in animal models, including genes related to serotonin, neuropeptide Y, neuropeptide S, and corticotropin-releasing factor signaling in the brain. Finally, some infant rhesus monkeys display an anxious temperament and extreme behavioral inhibition when separated from their mothers. This nonhuman primate model affords many opportunities to explore brain mechanisms and interventions that may be effective in preventing the further development of an anxious phenotype as these monkeys mature.","PeriodicalId":251581,"journal":{"name":"Stress and Mental Disorders: Insights from Animal Models","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128596430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-03-01DOI: 10.1093/med-psych/9780190697266.003.0012
R. McCarty
Major depressive disorder is a significant contributor to the global burden of disease, and it appears to be a mental disorder that is strongly dependent upon exposure to stressful stimuli. A major concern related to the development of animal models of depression is to capture those variables that explain the much higher incidence of depression in human females compared to males. Several genetically selected animal models have been studied, including the Flinders sensitive strain and the WKY strain. In addition, a strain of rats has been selected that is highly susceptible to the development of learned helplessness. Two especially valuable animal models of depression involve exposure of inbred mice to chronic social defeat stress (CSDS) or to chronic unpredictable mild stress. Results from these animal models point to disruptions in dopamine circuits in the brain as critical for the expression of depressive symptoms.
{"title":"Stress and Depression","authors":"R. McCarty","doi":"10.1093/med-psych/9780190697266.003.0012","DOIUrl":"https://doi.org/10.1093/med-psych/9780190697266.003.0012","url":null,"abstract":"Major depressive disorder is a significant contributor to the global burden of disease, and it appears to be a mental disorder that is strongly dependent upon exposure to stressful stimuli. A major concern related to the development of animal models of depression is to capture those variables that explain the much higher incidence of depression in human females compared to males. Several genetically selected animal models have been studied, including the Flinders sensitive strain and the WKY strain. In addition, a strain of rats has been selected that is highly susceptible to the development of learned helplessness. Two especially valuable animal models of depression involve exposure of inbred mice to chronic social defeat stress (CSDS) or to chronic unpredictable mild stress. Results from these animal models point to disruptions in dopamine circuits in the brain as critical for the expression of depressive symptoms.","PeriodicalId":251581,"journal":{"name":"Stress and Mental Disorders: Insights from Animal Models","volume":"2012 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128077872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-03-01DOI: 10.1093/med-psych/9780190697266.003.0016
R. McCarty
Several exciting lines of research have emerged from the study of animal models of mental disorders. This chapter presents seven opportunities for enhancing the diagnosis and treatment of mental disorders. They include improvements to the system for diagnosis of mental disorders, use of induced pluripotent stem cells from patients to generate neuronal cultures for in vitro determination of effective drug therapies for those individuals, use of data-mining techniques for understanding patient variability, a commitment to a greater focus on the prevention of mental disorders, innovative uses of smartphones to track patients and individuals at high risk of developing a mental disorder, and developing next-generation therapies and delivery systems that target a specific area of the brain rather than the entire brain. A common theme in these seven thoughts for the future is a commitment to bringing precision medicine tools to the treatment of patients with mental disorders.
{"title":"Thoughts for the Future","authors":"R. McCarty","doi":"10.1093/med-psych/9780190697266.003.0016","DOIUrl":"https://doi.org/10.1093/med-psych/9780190697266.003.0016","url":null,"abstract":"Several exciting lines of research have emerged from the study of animal models of mental disorders. This chapter presents seven opportunities for enhancing the diagnosis and treatment of mental disorders. They include improvements to the system for diagnosis of mental disorders, use of induced pluripotent stem cells from patients to generate neuronal cultures for in vitro determination of effective drug therapies for those individuals, use of data-mining techniques for understanding patient variability, a commitment to a greater focus on the prevention of mental disorders, innovative uses of smartphones to track patients and individuals at high risk of developing a mental disorder, and developing next-generation therapies and delivery systems that target a specific area of the brain rather than the entire brain. A common theme in these seven thoughts for the future is a commitment to bringing precision medicine tools to the treatment of patients with mental disorders.","PeriodicalId":251581,"journal":{"name":"Stress and Mental Disorders: Insights from Animal Models","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127233437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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