Pub Date : 2019-09-01DOI: 10.31887/DCNS.2019.21.3/trobbins
T. Robbins
Evidence for pharmacological remediation of cognitive deficits in three major psychiatric disorders—attention deficit- hyperactivity disorder (ADHD), schizophrenia, and depression—is reviewed. ADHD is effectively treated with the stimulant medications methylphenidate and d-amphetamine, as well as nonstimulants such as atomoxetine, implicating cognitive enhancing effects mediated by noradrenaline and dopamine. However, the precise mechanisms underlying these effects remains unclear. Cognitive deficits in schizophrenia are less effectively treated, but attempts via a variety of neurotransmitter strategies are surveyed. The possibility of treating cognitive deficits in depression via antidepressant medication (eg, selective serotonin reuptake inhibitors) and by adjunctive drug treatment has only recently received attention because of confounding, or possibly interactive, effects on mood. Prospects for future advances in this important area may need to take into account transdiagnostic perspectives on cognition (including neurodegenerative diseases) as well as improvements in neuropsychological, neurobiological, and clinical trial design approaches to cognitive enhancement.
{"title":"Pharmacological treatment of cognitive deficits in nondementing mental health disorders\u2029","authors":"T. Robbins","doi":"10.31887/DCNS.2019.21.3/trobbins","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.3/trobbins","url":null,"abstract":"Evidence for pharmacological remediation of cognitive deficits in three major psychiatric disorders—attention deficit- hyperactivity disorder (ADHD), schizophrenia, and depression—is reviewed. ADHD is effectively treated with the stimulant medications methylphenidate and d-amphetamine, as well as nonstimulants such as atomoxetine, implicating cognitive enhancing effects mediated by noradrenaline and dopamine. However, the precise mechanisms underlying these effects remains unclear. Cognitive deficits in schizophrenia are less effectively treated, but attempts via a variety of neurotransmitter strategies are surveyed. The possibility of treating cognitive deficits in depression via antidepressant medication (eg, selective serotonin reuptake inhibitors) and by adjunctive drug treatment has only recently received attention because of confounding, or possibly interactive, effects on mood. Prospects for future advances in this important area may need to take into account transdiagnostic perspectives on cognition (including neurodegenerative diseases) as well as improvements in neuropsychological, neurobiological, and clinical trial design approaches to cognitive enhancement.\u2029","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":"21 1","pages":"301 - 308"},"PeriodicalIF":8.3,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46399727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-01DOI: 10.31887/DCNS.2019.21.3/fthibaut
Sonia Acuna-Vargas, F. Thibaut
Cognition has attracted a growing interest in psychiatry. Since the 1990s, cognition as a whole has become an important determinant in the outcome of psychosis. Despite recent progress in the genetics of cognition, the development of new pharmacological compounds in order to improve cognition has not progressed as quickly. This issue will review and discuss the main areas of clinical and basic research in this domain.
{"title":"Cognition in psychiatry\u2029","authors":"Sonia Acuna-Vargas, F. Thibaut","doi":"10.31887/DCNS.2019.21.3/fthibaut","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.3/fthibaut","url":null,"abstract":"Cognition has attracted a growing interest in psychiatry. Since the 1990s, cognition as a whole has become an important determinant in the outcome of psychosis. Despite recent progress in the genetics of cognition, the development of new pharmacological compounds in order to improve cognition has not progressed as quickly. This issue will review and discuss the main areas of clinical and basic research in this domain.\u2029","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":"21 1","pages":"223 - 224"},"PeriodicalIF":8.3,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41730718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-01DOI: 10.31887/DCNS.2019.21.3/mrossner
M. Stephan, Paul Volkmann, M. Rossner
New psychopharmacological treatments are needed for affective and nonaffective psychoses, especially for the associated negative and cognitive symptoms. Earlier developments mostly failed, probably partly because of limitations in behavioral models used for validation. Now, deeper understanding of the genetics underlying disease pathogenesis and progress in genetic engineering will generate many rodent models with increased construct validity. To improve these models’ translational value, we need complementary data from nonhuman primates. We also have to improve and streamline behavioral test systems to cope with increased demand. Here, we propose a comprehensive neurocognitive test battery that should overcome the disadvantages of single tests and yield cognitive/behavioral profiles for modeling subsets of patient symptoms. Further, we delineate a concept for classifying disease-relevant cognitive endophenotypes to balance between face and construct validity and clinical diagnostics. In summary, this review discusses new concepts and the limitations and future potential of translational research on cognition in psychiatry.
{"title":"Assessing behavior and cognition in rodents, nonhuman primates, and humans: where are the limits of translation?\u2029","authors":"M. Stephan, Paul Volkmann, M. Rossner","doi":"10.31887/DCNS.2019.21.3/mrossner","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.3/mrossner","url":null,"abstract":"New psychopharmacological treatments are needed for affective and nonaffective psychoses, especially for the associated negative and cognitive symptoms. Earlier developments mostly failed, probably partly because of limitations in behavioral models used for validation. Now, deeper understanding of the genetics underlying disease pathogenesis and progress in genetic engineering will generate many rodent models with increased construct validity. To improve these models’ translational value, we need complementary data from nonhuman primates. We also have to improve and streamline behavioral test systems to cope with increased demand. Here, we propose a comprehensive neurocognitive test battery that should overcome the disadvantages of single tests and yield cognitive/behavioral profiles for modeling subsets of patient symptoms. Further, we delineate a concept for classifying disease-relevant cognitive endophenotypes to balance between face and construct validity and clinical diagnostics. In summary, this review discusses new concepts and the limitations and future potential of translational research on cognition in psychiatry.\u2029","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":"21 1","pages":"249 - 259"},"PeriodicalIF":8.3,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45631593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-01DOI: 10.31887/DCNS.2019.21.3/skuehn
S. Kühn, J. Gallinat, Anna Mascherek
Video gaming as a popular form of leisure activity and its effect on cognition, brain function, and structure has come into focus in the field of neuroscience. Visuospatial cognition and attention seem to benefit the most, whereas for executive functions, memory, and general cognition, the results are contradictory. The particular characteristics of video games driving these effects remain poorly understood. We critically discuss major challenges for the existing research, namely, the lack of precise definitions of video gaming, the lack of distinct choice of cognitive ability under study, and the lack of standardized study protocols. Less research exists on neural changes in addition to cognitive changes due to video gaming. Existing studies reveal evidence for the involvement of similar brain regions in functional and structural changes. There seems to be a predominance in the hippocampal, prefrontal, and parietal brain regions; however, studies differ immensely, which makes a meta-analytic interpretation vulnerable. We conclude that theoretical work is urgently needed.
{"title":"Effects of computer gaming on cognition, brain structure, and function: a critical reflection on existing literature\u2029","authors":"S. Kühn, J. Gallinat, Anna Mascherek","doi":"10.31887/DCNS.2019.21.3/skuehn","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.3/skuehn","url":null,"abstract":"Video gaming as a popular form of leisure activity and its effect on cognition, brain function, and structure has come into focus in the field of neuroscience. Visuospatial cognition and attention seem to benefit the most, whereas for executive functions, memory, and general cognition, the results are contradictory. The particular characteristics of video games driving these effects remain poorly understood. We critically discuss major challenges for the existing research, namely, the lack of precise definitions of video gaming, the lack of distinct choice of cognitive ability under study, and the lack of standardized study protocols. Less research exists on neural changes in addition to cognitive changes due to video gaming. Existing studies reveal evidence for the involvement of similar brain regions in functional and structural changes. There seems to be a predominance in the hippocampal, prefrontal, and parietal brain regions; however, studies differ immensely, which makes a meta-analytic interpretation vulnerable. We conclude that theoretical work is urgently needed.\u2029","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":"21 1","pages":"319 - 330"},"PeriodicalIF":8.3,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48079379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-01DOI: 10.31887/DCNS.2019.21.2/rnesse
R. Nesse, Dan J Stein
The prevailing paradigm for psychopharmacology focuses on understanding brain mechanisms as the key to finding new medications and improving clinical outcomes, but frustration with slow progress has inspired many pleas for new approaches. Evolutionary psychiatry brings in an additional basic science that poses new questions about why natural selection left us vulnerable to so many mental disorders, and new insights about how drugs work. The integration of neuroscience with evolutionary psychiatry is synergistic, going beyond reductionism to provide a model like the one used by the rest of medicine. It recognizes negative emotions as symptoms, that are, like pain and cough, useful defenses whose presence should initiate a search for causes. An integrative evolutionary approach explains why agents that block useful aversive responses are usually safe, and how to anticipate when they may cause harm. More generally, an evolutionary framework suggests novel practical strategies for finding and testing new drugs.
{"title":"How evolutionary psychiatry can advance psychopharmacology\u2029","authors":"R. Nesse, Dan J Stein","doi":"10.31887/DCNS.2019.21.2/rnesse","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.2/rnesse","url":null,"abstract":"The prevailing paradigm for psychopharmacology focuses on understanding brain mechanisms as the key to finding new medications and improving clinical outcomes, but frustration with slow progress has inspired many pleas for new approaches. Evolutionary psychiatry brings in an additional basic science that poses new questions about why natural selection left us vulnerable to so many mental disorders, and new insights about how drugs work. The integration of neuroscience with evolutionary psychiatry is synergistic, going beyond reductionism to provide a model like the one used by the rest of medicine. It recognizes negative emotions as symptoms, that are, like pain and cough, useful defenses whose presence should initiate a search for causes. An integrative evolutionary approach explains why agents that block useful aversive responses are usually safe, and how to anticipate when they may cause harm. More generally, an evolutionary framework suggests novel practical strategies for finding and testing new drugs.\u2029","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":"21 1","pages":"167 - 175"},"PeriodicalIF":8.3,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45535487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-01DOI: 10.31887/DCNS.2019.21.2/vhede
V. Hede, C. Devillé
A few drugs prescribed in internal medicine, ie, non-psychotropic drugs, can be used to treat certain neuropsychiatric disorders. For most of these situations, the level of evidence remains low. But when sufficient data becomes available, these molecules are then included in official guidelines for the treatment of neuropsychiatric disorders. In this article we review interesting drugs which may be relevant from an evidence-based medicine point of view, and could become part of psychiatric practice in the future.
{"title":"Treating psychiatric symptoms and disorders with non-psychotropic medications\u2029","authors":"V. Hede, C. Devillé","doi":"10.31887/DCNS.2019.21.2/vhede","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.2/vhede","url":null,"abstract":"A few drugs prescribed in internal medicine, ie, non-psychotropic drugs, can be used to treat certain neuropsychiatric disorders. For most of these situations, the level of evidence remains low. But when sufficient data becomes available, these molecules are then included in official guidelines for the treatment of neuropsychiatric disorders. In this article we review interesting drugs which may be relevant from an evidence-based medicine point of view, and could become part of psychiatric practice in the future.\u2029","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":"21 1","pages":"193 - 201"},"PeriodicalIF":8.3,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41588250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-01DOI: 10.31887/DCNS.2019.21.2/fthibaut
F. Thibaut
Drug development in psychiatry is gradually moving from serendipity to personalized medicine. Some promising paths will be reviewed in this issue.
精神病学中的药物开发正逐渐从偶然发现转向个性化药物。本期将回顾一些有希望的途径。
{"title":"Future paths in psychopharmacology\u2029","authors":"F. Thibaut","doi":"10.31887/DCNS.2019.21.2/fthibaut","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.2/fthibaut","url":null,"abstract":"Drug development in psychiatry is gradually moving from serendipity to personalized medicine. Some promising paths will be reviewed in this issue.\u2029","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":"21 1","pages":"115 - 116"},"PeriodicalIF":8.3,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44983071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-01DOI: 10.31887/DCNS.2019.21.2/lloiacono
S. Bussone, L. Lo Iacono
The significance of early life for the long-term programming of mental health is increasingly being recognized. However, most psychotropic medications are currently intended for adult patients, and early psychopharmacological approaches aimed at reverting aberrant neurodevelopmental trajectories are missing. Psychopharmacologic intervention at an early age faces the challenge of operating in a highly plastic system and requires a comprehensive knowledge of neurodevelopmental mechanisms. Recently the systems biology approach has contributed to the understanding of neuroplasticity mechanisms from a new perspective that interprets them as the result of complex and dynamic networks of signals from different systems. This approach is creating opportunities for developmental psychopharmacology, suggesting novel targets that can modulate the course of development by interfering with neuroplasticity at an early age. We will discuss two interconnected systems—the immune and gut microbiota—that regulate neurodevelopment and that have been implicated in preclinical research as new targets in the prevention of aberrant brain development.
{"title":"The “systems approach” to treating the brain: opportunities in developmental psychopharmacology\u2029","authors":"S. Bussone, L. Lo Iacono","doi":"10.31887/DCNS.2019.21.2/lloiacono","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.2/lloiacono","url":null,"abstract":"The significance of early life for the long-term programming of mental health is increasingly being recognized. However, most psychotropic medications are currently intended for adult patients, and early psychopharmacological approaches aimed at reverting aberrant neurodevelopmental trajectories are missing. Psychopharmacologic intervention at an early age faces the challenge of operating in a highly plastic system and requires a comprehensive knowledge of neurodevelopmental mechanisms. Recently the systems biology approach has contributed to the understanding of neuroplasticity mechanisms from a new perspective that interprets them as the result of complex and dynamic networks of signals from different systems. This approach is creating opportunities for developmental psychopharmacology, suggesting novel targets that can modulate the course of development by interfering with neuroplasticity at an early age. We will discuss two interconnected systems—the immune and gut microbiota—that regulate neurodevelopment and that have been implicated in preclinical research as new targets in the prevention of aberrant brain development.\u2029","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":"21 1","pages":"211 - 215"},"PeriodicalIF":8.3,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43423856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-01DOI: 10.31887/DCNS.2019.21.2/nsurana
N. Surana
Studies over the last decade have transformed our previously simplistic view of microbes, having only a pathogenic role in disease to a more robust understanding that they are critical for maintaining human health. Indeed, our microbiota—the collection of commensal organisms that live in and on each of us—contributes to nearly every facet of host physiology, from ontogeny of the immune system to neurological function to metabolism. Although the specific details of these host–microbe interactions are still being elucidated for most diseases, the coupling of clinical samples with animal models of disease have provided key insights. This review provides some general background on the microbiota, highlights a few examples of how the microbiota influences diseases of the central nervous system, and provides a perspective for how these findings may be clinically translatable.
{"title":"Harnessing the microbiota to treat neurological diseases\u2029","authors":"N. Surana","doi":"10.31887/DCNS.2019.21.2/nsurana","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.2/nsurana","url":null,"abstract":"Studies over the last decade have transformed our previously simplistic view of microbes, having only a pathogenic role in disease to a more robust understanding that they are critical for maintaining human health. Indeed, our microbiota—the collection of commensal organisms that live in and on each of us—contributes to nearly every facet of host physiology, from ontogeny of the immune system to neurological function to metabolism. Although the specific details of these host–microbe interactions are still being elucidated for most diseases, the coupling of clinical samples with animal models of disease have provided key insights. This review provides some general background on the microbiota, highlights a few examples of how the microbiota influences diseases of the central nervous system, and provides a perspective for how these findings may be clinically translatable.\u2029","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":"21 1","pages":"159 - 165"},"PeriodicalIF":8.3,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49353503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-01DOI: 10.31887/DCNS.2019.21.2/dbertrand
S. Neale, K. Kambara, T. Salt, D. Bertrand
The progressive changes in research paradigms observed in the largest pharmaceutical companies and the burgeoning of biotechnology startups over the last 10 years have generated a need for outsourcing research facilities. In parallel, progress made in the fields of genomics, protein expression in recombinant systems, and electrophysiological recording methods have offered new possibilities for the development of contract research organizations (CROs). Successful partnering between pharmaceutical companies and CROs largely depends upon the competences and scientific quality on offer for the discovery of novel active molecules and targets. Thus, it is critical to review the knowledge in the field of neuroscience research, how genetic approaches are augmenting our knowledge, and how they can be applied in the translation from the identification of potential molecules up to the first clinical trials. Taking these together, it is apparent that CROs have an important role to play in the neuroscience of drug discovery.
{"title":"Receptor variants and the development of centrally acting medications\u2029","authors":"S. Neale, K. Kambara, T. Salt, D. Bertrand","doi":"10.31887/DCNS.2019.21.2/dbertrand","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.2/dbertrand","url":null,"abstract":"The progressive changes in research paradigms observed in the largest pharmaceutical companies and the burgeoning of biotechnology startups over the last 10 years have generated a need for outsourcing research facilities. In parallel, progress made in the fields of genomics, protein expression in recombinant systems, and electrophysiological recording methods have offered new possibilities for the development of contract research organizations (CROs). Successful partnering between pharmaceutical companies and CROs largely depends upon the competences and scientific quality on offer for the discovery of novel active molecules and targets. Thus, it is critical to review the knowledge in the field of neuroscience research, how genetic approaches are augmenting our knowledge, and how they can be applied in the translation from the identification of potential molecules up to the first clinical trials. Taking these together, it is apparent that CROs have an important role to play in the neuroscience of drug discovery.\u2029","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":"21 1","pages":"149 - 157"},"PeriodicalIF":8.3,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42130621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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