Pub Date : 2022-06-01Epub Date: 2022-03-03DOI: 10.1017/neu.2022.6
Siu Wa Tang, Brian E Leonard, Daiga Maret Helmeste
Long COVID refers to the lingering symptoms which persist or appear after the acute illness. The dominant long COVID symptoms in the two years since the pandemic began (2020-2021) have been depression, anxiety, fatigue, concentration and cognitive impairments with few reports of psychosis. Whether other symptoms will appear later on is not yet known. For example, dopamine-dependent movement disorders generally take many years before first symptoms are seen. Post-stroke depression and anxiety may explain many of the early long COVID cases. Hemorrhagic, hypoxic and inflammatory damages of the central nervous system, unresolved systematic inflammation, metabolic impairment, cerebral vascular accidents such as stroke, hypoxia from pulmonary damages and fibrotic changes are among the major causes of long COVID. Glucose metabolic and hypoxic brain issues likely predispose subjects with pre-existing diabetes, cardiovascular or lung problems to long COVID as well. Preliminary data suggest that psychotropic medications may not be a danger but could instead be beneficial in combating COVID-19 infection. The same is true for diabetes medications such as metformin. Thus, a focus on sigma-1 receptor ligands and glucose metabolism is expected to be useful for new drug development as well as the repurposing of current drugs. The reported protective effects of psychotropics and antihistamines against COVID-19, the earlier reports of reduced number of sigma-1 receptors in post-mortem schizophrenic brains, with many antidepressant and antipsychotic drugs being antihistamines with significant affinity for the sigma-1 receptor, support the role of sigma and histamine receptors in neuroinflammation and viral infections. Literature and data in all these areas are accumulating at a fast rate. We reviewed and discussed the relevant and important literature.
{"title":"Long COVID, neuropsychiatric disorders, psychotropics, present and future.","authors":"Siu Wa Tang, Brian E Leonard, Daiga Maret Helmeste","doi":"10.1017/neu.2022.6","DOIUrl":"https://doi.org/10.1017/neu.2022.6","url":null,"abstract":"<p><p>Long COVID refers to the lingering symptoms which persist or appear after the acute illness. The dominant long COVID symptoms in the two years since the pandemic began (2020-2021) have been depression, anxiety, fatigue, concentration and cognitive impairments with few reports of psychosis. Whether other symptoms will appear later on is not yet known. For example, dopamine-dependent movement disorders generally take many years before first symptoms are seen. Post-stroke depression and anxiety may explain many of the early long COVID cases. Hemorrhagic, hypoxic and inflammatory damages of the central nervous system, unresolved systematic inflammation, metabolic impairment, cerebral vascular accidents such as stroke, hypoxia from pulmonary damages and fibrotic changes are among the major causes of long COVID. Glucose metabolic and hypoxic brain issues likely predispose subjects with pre-existing diabetes, cardiovascular or lung problems to long COVID as well. Preliminary data suggest that psychotropic medications may not be a danger but could instead be beneficial in combating COVID-19 infection. The same is true for diabetes medications such as metformin. Thus, a focus on sigma-1 receptor ligands and glucose metabolism is expected to be useful for new drug development as well as the repurposing of current drugs. The reported protective effects of psychotropics and antihistamines against COVID-19, the earlier reports of reduced number of sigma-1 receptors in post-mortem schizophrenic brains, with many antidepressant and antipsychotic drugs being antihistamines with significant affinity for the sigma-1 receptor, support the role of sigma and histamine receptors in neuroinflammation and viral infections. Literature and data in all these areas are accumulating at a fast rate. We reviewed and discussed the relevant and important literature.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39907048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-01Epub Date: 2022-01-19DOI: 10.1017/neu.2022.2
Kenneth C Enevoldsen, Andreas A Danielsen, Christopher Rohde, Oskar H Jefsen, Kristoffer L Nielbo, Søren D Østergaard
The COVID-19 pandemic is believed to have a major negative impact on global mental health due to the viral disease itself as well as the associated lockdowns, social distancing, isolation, fear, and increased uncertainty. Individuals with preexisting mental illness are likely to be particularly vulnerable to these conditions and may develop outright 'COVID-19-related psychopathology'. Here, we trained a machine learning model on structured and natural text data from electronic health records to identify COVID-19 pandemic-related psychopathology among patients receiving care in the Psychiatric Services of the Central Denmark Region. Subsequently, applying this model, we found that pandemic-related psychopathology covaries with the pandemic pressure over time. These findings may aid psychiatric services in their planning during the ongoing and future pandemics. Furthermore, the results are a testament to the potential of applying machine learning to data from electronic health records.
{"title":"Monitoring of COVID-19 pandemic-related psychopathology using machine learning.","authors":"Kenneth C Enevoldsen, Andreas A Danielsen, Christopher Rohde, Oskar H Jefsen, Kristoffer L Nielbo, Søren D Østergaard","doi":"10.1017/neu.2022.2","DOIUrl":"https://doi.org/10.1017/neu.2022.2","url":null,"abstract":"<p><p>The COVID-19 pandemic is believed to have a major negative impact on global mental health due to the viral disease itself as well as the associated lockdowns, social distancing, isolation, fear, and increased uncertainty. Individuals with preexisting mental illness are likely to be particularly vulnerable to these conditions and may develop outright 'COVID-19-related psychopathology'. Here, we trained a machine learning model on structured and natural text data from electronic health records to identify COVID-19 pandemic-related psychopathology among patients receiving care in the Psychiatric Services of the Central Denmark Region. Subsequently, applying this model, we found that pandemic-related psychopathology covaries with the pandemic pressure over time. These findings may aid psychiatric services in their planning during the ongoing and future pandemics. Furthermore, the results are a testament to the potential of applying machine learning to data from electronic health records.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39920399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
INTRODUCTION The multiplicity and complexity of the neuronal connections in the central nervous system make it difficult to disentangle circuits that play an essential role in the development or treatment of (neuro)psychiatric disorders. By choosing the evolutionary development of the forebrain as a starting point, a certain order in the connections can be created. The dorsal diencephalic connection (DDC) system can be applied for the development of biomarkers that can predict treatment response. MATERIALS AND METHODS After providing a brief introduction to the theory, we examined neuroanatomical publications on the connectivity of the DDC system. We then searched for neurochemical components that are specific for the habenula. RESULTS AND DISCUSSION The best strategy to find biomarkers which reflect the function of the habenular connection is to use genetic variants of receptors, transporters or enzymes specific to this complex. By activating these with probes and measuring the response in people with different functional genotypes, the usefulness of biomarkers can be assessed. CONCLUSION The most promising biomarkers in this respect are those linked to activation or inhibition of the nicotine receptor, dopamine D4 receptor, μ-opioid receptor and also those of the functioning of habenular glia cells (astrocytes and microglia).
{"title":"Circuits Regulating Pleasure and Happiness - Focus on Potential Biomarkers for Circuitry including the Habenuloid Complex.","authors":"A. Loonen, S. Ivanova","doi":"10.1017/neu.2022.15","DOIUrl":"https://doi.org/10.1017/neu.2022.15","url":null,"abstract":"INTRODUCTION\u0000The multiplicity and complexity of the neuronal connections in the central nervous system make it difficult to disentangle circuits that play an essential role in the development or treatment of (neuro)psychiatric disorders. By choosing the evolutionary development of the forebrain as a starting point, a certain order in the connections can be created. The dorsal diencephalic connection (DDC) system can be applied for the development of biomarkers that can predict treatment response.\u0000\u0000\u0000MATERIALS AND METHODS\u0000After providing a brief introduction to the theory, we examined neuroanatomical publications on the connectivity of the DDC system. We then searched for neurochemical components that are specific for the habenula.\u0000\u0000\u0000RESULTS AND DISCUSSION\u0000The best strategy to find biomarkers which reflect the function of the habenular connection is to use genetic variants of receptors, transporters or enzymes specific to this complex. By activating these with probes and measuring the response in people with different functional genotypes, the usefulness of biomarkers can be assessed.\u0000\u0000\u0000CONCLUSION\u0000The most promising biomarkers in this respect are those linked to activation or inhibition of the nicotine receptor, dopamine D4 receptor, μ-opioid receptor and also those of the functioning of habenular glia cells (astrocytes and microglia).","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44747228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hussam Y. Alghamdi, Abdulaziz M. Alrashed, Amjad M. Jawhari, A. S. Abdel-Moneim
BACKGROUND Long haulers have been recently reported after contracting coronavirus disease (COVID-19). In the present study, we aimed to screen for the neuropsychiatric signs detected <1 to >6 months after infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to determine whether vaccination has an effect on them. METHODS An online survey was conducted among participants who had been diagnosed with laboratory-confirmed SARS-CoV-2 infection. The clinical signs and durations of neuropsychiatric complaints and their correlations to sex, age, severity of COVID-19 signs, and vaccination status were screened. RESULTS A total of 2218 individuals, including 1358 females and 860 males, with an age range of 12-70 years, submitted their responses. The respondents experienced cognitive dysfunction, mood alteration, depression, tinnitus, sleep disorders, and loss of taste and smell, with prevalence rates ranging from 18.9% (tinnitus) to 63.9% (loss of taste and smell). Of the respondents, 2.2-7.7% of confirmed the persistence of symptoms for >6 months. Tinnitus was the least common complaint, and only 2.2% of the study participants had tinnitus for >6 months. Meanwhile, mood alteration persisted for >6 months in 7.6% of the study participants. More respondents who received two doses of BNT162b2 vaccine showed persistent symptoms than those in the other groups. Disease severity and female sex were identified as potential determinants of the development and persistency of such symptoms. CONCLUSION Post-COVID neuropsychiatric symptoms were present in considerable percentages of the study participants with SARS-CoV-2 infection, persisting for >6 months in up to 7.6% of the participants.
{"title":"Neuropsychiatric symptoms in post COVID-19 long haulers.","authors":"Hussam Y. Alghamdi, Abdulaziz M. Alrashed, Amjad M. Jawhari, A. S. Abdel-Moneim","doi":"10.1017/neu.2022.13","DOIUrl":"https://doi.org/10.1017/neu.2022.13","url":null,"abstract":"BACKGROUND\u0000Long haulers have been recently reported after contracting coronavirus disease (COVID-19). In the present study, we aimed to screen for the neuropsychiatric signs detected <1 to >6 months after infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to determine whether vaccination has an effect on them.\u0000\u0000\u0000METHODS\u0000An online survey was conducted among participants who had been diagnosed with laboratory-confirmed SARS-CoV-2 infection. The clinical signs and durations of neuropsychiatric complaints and their correlations to sex, age, severity of COVID-19 signs, and vaccination status were screened.\u0000\u0000\u0000RESULTS\u0000A total of 2218 individuals, including 1358 females and 860 males, with an age range of 12-70 years, submitted their responses. The respondents experienced cognitive dysfunction, mood alteration, depression, tinnitus, sleep disorders, and loss of taste and smell, with prevalence rates ranging from 18.9% (tinnitus) to 63.9% (loss of taste and smell). Of the respondents, 2.2-7.7% of confirmed the persistence of symptoms for >6 months. Tinnitus was the least common complaint, and only 2.2% of the study participants had tinnitus for >6 months. Meanwhile, mood alteration persisted for >6 months in 7.6% of the study participants. More respondents who received two doses of BNT162b2 vaccine showed persistent symptoms than those in the other groups. Disease severity and female sex were identified as potential determinants of the development and persistency of such symptoms.\u0000\u0000\u0000CONCLUSION\u0000Post-COVID neuropsychiatric symptoms were present in considerable percentages of the study participants with SARS-CoV-2 infection, persisting for >6 months in up to 7.6% of the participants.","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45084662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-12DOI: 10.1101/2022.04.10.22273660
Dhurgham Shihab Al-Hadrawi, Haneen Tahseen Al-Rubaye, A. Almulla, H. Al-Hakeim, Michael Maes
Background: Long coronavirus disease 2019 (LC) is a chronic sequel of acute COVID-19. The exact pathophysiology of the affective, chronic fatigue and physiosomatic symptoms labeled as physio-affective phenome of LC has remained elusive. Objective: The current study aims to delineate the effects of oxygen saturation (SpO2) and body temperature during the acute phase on the physio-affective phenome of LC. Method: We recruited 120 LC patients and 36 controls. For all participants, we assessed the lowest SpO2 and peak body temperature during acute COVID-19, and the Hamilton Depression and Anxiety Rating Scale (HAMD/HAMA) and Fibro Fatigue (FF) scales 3 to 4 months later. Results: Lowered SpO2 and increased body temperature during the acute phase and female sex predict 60.7% of the variance in the physio-affective phenome of LC. Using unsupervised learning techniques we were able to delineate a new endophenotype class, which comprises around 26.7% of the LC patients and is characterized by very low SpO2 and very high body temperature, and depression, anxiety, chronic fatigue, and autonomic and gastro-intestinal symptoms scores. Single latent vectors could be extracted from both biomarkers, depression, anxiety and FF symptoms or from both biomarkers, insomnia, chronic fatigue, gastro-intestinal and autonomic symptoms. Conclusion: The newly constructed endophenotype class and pathway phenotypes indicate that the physio-affective phenome of LC is at least in part the consequence of the pathophysiology of acute COVID-19, namely the combined effects of lowered SpO2, increased body temperature and the associated immune-inflammatory processes and lung lesions.
{"title":"Lowered oxygen saturation and increased body temperature in acute COVID-19 largely predict chronic fatigue syndrome and affective symptoms due to LONG COVID: a precision nomothetic approach","authors":"Dhurgham Shihab Al-Hadrawi, Haneen Tahseen Al-Rubaye, A. Almulla, H. Al-Hakeim, Michael Maes","doi":"10.1101/2022.04.10.22273660","DOIUrl":"https://doi.org/10.1101/2022.04.10.22273660","url":null,"abstract":"Background: Long coronavirus disease 2019 (LC) is a chronic sequel of acute COVID-19. The exact pathophysiology of the affective, chronic fatigue and physiosomatic symptoms labeled as physio-affective phenome of LC has remained elusive. Objective: The current study aims to delineate the effects of oxygen saturation (SpO2) and body temperature during the acute phase on the physio-affective phenome of LC. Method: We recruited 120 LC patients and 36 controls. For all participants, we assessed the lowest SpO2 and peak body temperature during acute COVID-19, and the Hamilton Depression and Anxiety Rating Scale (HAMD/HAMA) and Fibro Fatigue (FF) scales 3 to 4 months later. Results: Lowered SpO2 and increased body temperature during the acute phase and female sex predict 60.7% of the variance in the physio-affective phenome of LC. Using unsupervised learning techniques we were able to delineate a new endophenotype class, which comprises around 26.7% of the LC patients and is characterized by very low SpO2 and very high body temperature, and depression, anxiety, chronic fatigue, and autonomic and gastro-intestinal symptoms scores. Single latent vectors could be extracted from both biomarkers, depression, anxiety and FF symptoms or from both biomarkers, insomnia, chronic fatigue, gastro-intestinal and autonomic symptoms. Conclusion: The newly constructed endophenotype class and pathway phenotypes indicate that the physio-affective phenome of LC is at least in part the consequence of the pathophysiology of acute COVID-19, namely the combined effects of lowered SpO2, increased body temperature and the associated immune-inflammatory processes and lung lesions.","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45049384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Riccardo Manca, Matteo De Marco, Amanda Colston, V. Raymont, J. Amin, R. Davies, Pramod Kumar, G. Russell, D. Blackburn, A. Venneri
OBJECTIVE Social distancing to limit COVID-19 transmission has led to extensive lifestyle changes, including for people with dementia (PWD). The aim of this study, therefore, was to assess the impact of lockdown on the mental health of PWD and their carers. METHODS Forty-five carers of PWD completed a telephone interview during the baseline assessment of the SOLITUDE study to gather information on life conditions and changes in symptoms of PWD during lockdown. Associations between changes in symptoms of PWD and carers' concerns and mental health were investigated. RESULTS About 44% of carers experienced anxiety and irritability and reported changes in behavioural and cognitive symptoms in PWD. These changes were associated with worse carers' mental health and concerns about faster disease progression (χ2 = 13.542, p < 0.001). CONCLUSION COVID-19-related social isolation has had a negative impact on patients' and carers' mental health. Potential long-term neurocognitive consequences require further investigation.
保持社交距离以限制COVID-19的传播已导致广泛的生活方式改变,包括痴呆症患者。因此,本研究的目的是评估封锁对残疾人士及其照顾者心理健康的影响。方法在孤独研究的基线评估期间,45名PWD护理人员完成了电话访谈,以收集有关禁闭期间PWD生活状况和症状变化的信息。调查了PWD症状变化与护理人员关注和心理健康之间的关系。结果约44%的护理人员经历焦虑和易怒,并报告在PWD中行为和认知症状发生变化。这些变化与护理人员的心理健康状况较差以及对疾病更快进展的担忧相关(χ2 = 13.542, p < 0.001)。结论新型冠状病毒肺炎相关社会隔离对患者和护理人员的心理健康产生了负面影响。潜在的长期神经认知后果需要进一步调查。
{"title":"The impact of social isolation due to the COVID-19 pandemic on patients with dementia and caregivers.","authors":"Riccardo Manca, Matteo De Marco, Amanda Colston, V. Raymont, J. Amin, R. Davies, Pramod Kumar, G. Russell, D. Blackburn, A. Venneri","doi":"10.1017/neu.2022.12","DOIUrl":"https://doi.org/10.1017/neu.2022.12","url":null,"abstract":"OBJECTIVE\u0000Social distancing to limit COVID-19 transmission has led to extensive lifestyle changes, including for people with dementia (PWD). The aim of this study, therefore, was to assess the impact of lockdown on the mental health of PWD and their carers.\u0000\u0000\u0000METHODS\u0000Forty-five carers of PWD completed a telephone interview during the baseline assessment of the SOLITUDE study to gather information on life conditions and changes in symptoms of PWD during lockdown. Associations between changes in symptoms of PWD and carers' concerns and mental health were investigated.\u0000\u0000\u0000RESULTS\u0000About 44% of carers experienced anxiety and irritability and reported changes in behavioural and cognitive symptoms in PWD. These changes were associated with worse carers' mental health and concerns about faster disease progression (χ2 = 13.542, p < 0.001).\u0000\u0000\u0000CONCLUSION\u0000COVID-19-related social isolation has had a negative impact on patients' and carers' mental health. Potential long-term neurocognitive consequences require further investigation.","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43109410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01Epub Date: 2021-10-20DOI: 10.1017/neu.2021.34
Erik Roj Larsen, Anette Juel, Erik Jensen, Tristan R Hollyer, Gregers Wegener
Background: The treatment of mania in bipolar disorders needs to be more efficient, as the manic condition creates severe problems for the patient when it comes to work, finances, relationships and health. This proof-of-concept study examines to what extent casein glycomacropeptide (CGMP) may reduce the precursors of dopamine, phenylalanine and tyrosine, in plasma, and therefore be a potential new intervention to treat acute manic episodes.
Method: The study was designed as a double-blind randomised dose-response study of CGMP (with added leucine and tryptophan) in 15 healthy men, receiving 3 different doses of CGMP with an interval of at least 14 days.
Results: Administration of CGMP produced a dose-dependent depletion of plasma aromatic amino acids. The total area under the curve of plasma ratios of phenylalanine-tyrosine compared to the level of leucine-isoleucine-valine--tryptophan was CGMP (20 g): 3.648 [SE:0.3281]; CGMP (40 g): 2.368 [SE:0.1858]; and CGMP (60 g)1.887 [SE:0.2591]. A comparison of the groups showed a dose-dependent statistical difference, with a one-way ANOVA summary (Dunnett) F = 11.87, p = 0.0003, CGMP 20 g versus CGMP 40 g, p = 0.0042, CGMP 20 g versus CGMP 60 g, p = 0.0002. No significant side effects were observed.
Conclusions: This study demonstrate CGMP is a well-tolerated and effective mixture, and that 60 g of CGMP produced the highest depletion of plasma aromatic amino acids (phenylalanine and tyrosine). The effect seems to be highest after 3-4 h. We therefore conclude that this dose should be the one considered for future studies involving CGMP in humans.
背景:双相情感障碍患者的躁狂症治疗需要更有效,因为躁狂症在工作、财务、人际关系和健康方面给患者带来了严重的问题。这项概念验证性研究考察了酪蛋白糖宏肽(CGMP)在多大程度上可能减少血浆中多巴胺、苯丙氨酸和酪氨酸的前体,因此可能成为治疗急性躁狂发作的新干预措施。方法:本研究设计为CGMP(添加亮氨酸和色氨酸)的双盲随机剂量-反应研究,在15名健康男性中,接受3种不同剂量的CGMP,间隔至少14天。结果:CGMP使血浆芳香氨基酸呈剂量依赖性耗竭。血浆苯丙氨酸-酪氨酸与亮氨酸-异亮氨酸-缬氨酸-色氨酸比值曲线下总面积为CGMP (20 g): 3.648 [SE:0.3281];CGMP (40 g): 2.368 [SE:0.1858];CGMP (60 g)1.887 [SE:0.2591]。组间比较显示剂量相关的统计学差异,单因素方差分析总结(Dunnett) F = 11.87, p = 0.0003, CGMP 20 g对CGMP 40 g, p = 0.0042, CGMP 20 g对CGMP 60 g, p = 0.0002。未观察到明显的副作用。结论:本研究证明CGMP是一种耐受性良好且有效的混合物,60 g CGMP可产生最高的血浆芳香族氨基酸(苯丙氨酸和酪氨酸)消耗。效果似乎在3-4小时后达到最高。因此,我们得出结论,该剂量应考虑用于未来涉及人体CGMP的研究。
{"title":"Dietary supplementation with casein glycomacropeptide, leucine and tryptophan reduces plasma amino acid levels in men.","authors":"Erik Roj Larsen, Anette Juel, Erik Jensen, Tristan R Hollyer, Gregers Wegener","doi":"10.1017/neu.2021.34","DOIUrl":"https://doi.org/10.1017/neu.2021.34","url":null,"abstract":"<p><strong>Background: </strong>The treatment of mania in bipolar disorders needs to be more efficient, as the manic condition creates severe problems for the patient when it comes to work, finances, relationships and health. This proof-of-concept study examines to what extent casein glycomacropeptide (CGMP) may reduce the precursors of dopamine, phenylalanine and tyrosine, in plasma, and therefore be a potential new intervention to treat acute manic episodes.</p><p><strong>Method: </strong>The study was designed as a double-blind randomised dose-response study of CGMP (with added leucine and tryptophan) in 15 healthy men, receiving 3 different doses of CGMP with an interval of at least 14 days.</p><p><strong>Results: </strong>Administration of CGMP produced a dose-dependent depletion of plasma aromatic amino acids. The total area under the curve of plasma ratios of phenylalanine-tyrosine compared to the level of leucine-isoleucine-valine--tryptophan was CGMP (20 g): 3.648 [SE:0.3281]; CGMP (40 g): 2.368 [SE:0.1858]; and CGMP (60 g)1.887 [SE:0.2591]. A comparison of the groups showed a dose-dependent statistical difference, with a one-way ANOVA summary (Dunnett) F = 11.87, p = 0.0003, CGMP 20 g versus CGMP 40 g, p = 0.0042, CGMP 20 g versus CGMP 60 g, p = 0.0002. No significant side effects were observed.</p><p><strong>Conclusions: </strong>This study demonstrate CGMP is a well-tolerated and effective mixture, and that 60 g of CGMP produced the highest depletion of plasma aromatic amino acids (phenylalanine and tyrosine). The effect seems to be highest after 3-4 h. We therefore conclude that this dose should be the one considered for future studies involving CGMP in humans.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39534309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01Epub Date: 2021-12-27DOI: 10.1017/neu.2021.47
Siu Wa Tang, Wayne H Tang, Brian E Leonard
Many patients under treatment for mood disorders, in particular patients with bipolar mood disorders, experience episodes of mood switching from one state to another. Various hypotheses have been proposed to explain the mechanism of mood switching, spontaneously or induced by drug treatment. Animal models have also been used to test the role of psychotropic drugs in the switching of mood states. We examine the possible relationship between the pharmacology of psychotropic drugs and their reported incidents of induced mood switching, with reference to the various hypotheses of mechanisms of mood switching.
{"title":"Treatment-induced mood switching in affective disorders.","authors":"Siu Wa Tang, Wayne H Tang, Brian E Leonard","doi":"10.1017/neu.2021.47","DOIUrl":"https://doi.org/10.1017/neu.2021.47","url":null,"abstract":"<p><p>Many patients under treatment for mood disorders, in particular patients with bipolar mood disorders, experience episodes of mood switching from one state to another. Various hypotheses have been proposed to explain the mechanism of mood switching, spontaneously or induced by drug treatment. Animal models have also been used to test the role of psychotropic drugs in the switching of mood states. We examine the possible relationship between the pharmacology of psychotropic drugs and their reported incidents of induced mood switching, with reference to the various hypotheses of mechanisms of mood switching.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39875625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01Epub Date: 2021-10-20DOI: 10.1017/neu.2021.36
Miranda Stiernborg, Paschalis Efstathopoulos, Andreas Lennartsson, Catharina Lavebratt, Aleksander A Mathé
Since the NAD+-dependent histone deacetylases sirtuin-1 (SIRT1) and sirtuin-2 (SIRT2) are critically involved in epigenetics, endocrinology and immunology and affect the longevity in model organisms, we investigated their expression in brains of 3-month-old and 14-15 months old rat model of depression Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats. In view of the dysregulated NPY system in depression, we also studied NPY in young and old FSL to explore the temporal trajectory of depressive-like-ageing interaction. Sirt1, Sirt2 and Npy mRNA were determined using qRT-PCR in prefrontal cortex (PFC) from young and old FSL and FRL, and in hippocampi from young FSL and FRL. PFC: Sirt1 expression was decreased in FSL (p = 0.001). An interaction between age and genotype was found (p = 0.032); young FSL had lower Sirt1 with respect to both age (p = 0.026) and genotype (p = 0.001). Sirt2 was lower in FSL (p = 0.003). Npy mRNA was downregulated in FSL (p = 0.001) but did not differ between the young and old rat groups. Hippocampus: Sirt1 was reduced in young FSL compared to young FRL (p = 0.005). There was no difference in Sirt2 between FSL and FRL. Npy levels were decreased in hippocampus of young FSL compared to young FRL (p = 0.003). Effects of ageing could not be investigated due to loss of samples. To conclude, i this is the first demonstration that SIRT1 and SIRT2 are changed in brain of FSL, a rat model of depression; ii the changes are age-dependent; iii sirtuins are potential targets for treatment of age-related neurodegenerative diseases.
{"title":"<i>Sirtuins</i> and <i>neuropeptide y</i> downregulation in Flinders Sensitive Line rat model of depression.","authors":"Miranda Stiernborg, Paschalis Efstathopoulos, Andreas Lennartsson, Catharina Lavebratt, Aleksander A Mathé","doi":"10.1017/neu.2021.36","DOIUrl":"https://doi.org/10.1017/neu.2021.36","url":null,"abstract":"<p><p>Since the NAD+-dependent histone deacetylases sirtuin-1 (SIRT1) and sirtuin-2 (SIRT2) are critically involved in epigenetics, endocrinology and immunology and affect the longevity in model organisms, we investigated their expression in brains of 3-month-old and 14-15 months old rat model of depression Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats. In view of the dysregulated NPY system in depression, we also studied NPY in young and old FSL to explore the temporal trajectory of depressive-like-ageing interaction. Sirt1, Sirt2 and Npy mRNA were determined using qRT-PCR in prefrontal cortex (PFC) from young and old FSL and FRL, and in hippocampi from young FSL and FRL. PFC: Sirt1 expression was decreased in FSL (p = 0.001). An interaction between age and genotype was found (p = 0.032); young FSL had lower Sirt1 with respect to both age (p = 0.026) and genotype (p = 0.001). Sirt2 was lower in FSL (p = 0.003). Npy mRNA was downregulated in FSL (p = 0.001) but did not differ between the young and old rat groups. Hippocampus: Sirt1 was reduced in young FSL compared to young FRL (p = 0.005). There was no difference in Sirt2 between FSL and FRL. Npy levels were decreased in hippocampus of young FSL compared to young FRL (p = 0.003). Effects of ageing could not be investigated due to loss of samples. To conclude, i this is the first demonstration that SIRT1 and SIRT2 are changed in brain of FSL, a rat model of depression; ii the changes are age-dependent; iii sirtuins are potential targets for treatment of age-related neurodegenerative diseases.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39557714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01Epub Date: 2021-11-24DOI: 10.1017/neu.2021.37
Hanne Würtzen, Line Helene Clausen, Peter Birkelund Andersen, Ziggi Ivan Santini, Jakob Erkmen, Heidi Frølund Pedersen
Aim: The aim of this study was to investigate the possible impact of the Covid-19 pandemic on general health, mental well-being, and experiences of control compared to pre-pandemic populations. Our hypotheses were that we would observe a significantly lower level of psychological well-being and general health in the 2020 sample compared to the pre-pandemic samples, and that we would observe younger age groups to be the most affected.
Method: Two representative Danish populations (2016, n = 1656) and (2017, n = 3366) were compared to a representative Danish population (2020, n = 1538) sampled during the first lockdown in May 2020. Two-tailed tests of proportions were used to investigate possible differences between samples in proportions reporting poorer mental well-being measured by 5-item World Health Organization Well-Being Index, general health, and internal locus of control.
Results: Younger men (aged 18-24) and younger women (aged 18-44) as well as elderly women (aged 65-74) reported lower mental well-being during the early phase of the pandemic compared to the population from 2016. Both women and men in 2020 reported significantly lower levels of internal locus of control compared to the 2017 sample. This was especially true for younger men and women. There were no statistically significant differences in general health between populations.
Discussion: This study partly supports the hypothesis that the Covid-19 pandemic affected mental well-being negatively among younger persons. However, longitudinal studies are needed to investigate possible long-term effects of the pandemic on mental health and well-being. Further, qualitative studies are needed to investigate the in-depth consequences of Covid-19.
{"title":"Mental well-being, health, and locus of control in Danish adults before and during COVID-19.","authors":"Hanne Würtzen, Line Helene Clausen, Peter Birkelund Andersen, Ziggi Ivan Santini, Jakob Erkmen, Heidi Frølund Pedersen","doi":"10.1017/neu.2021.37","DOIUrl":"https://doi.org/10.1017/neu.2021.37","url":null,"abstract":"<p><strong>Aim: </strong>The aim of this study was to investigate the possible impact of the Covid-19 pandemic on general health, mental well-being, and experiences of control compared to pre-pandemic populations. Our hypotheses were that we would observe a significantly lower level of psychological well-being and general health in the 2020 sample compared to the pre-pandemic samples, and that we would observe younger age groups to be the most affected.</p><p><strong>Method: </strong>Two representative Danish populations (2016, n = 1656) and (2017, n = 3366) were compared to a representative Danish population (2020, n = 1538) sampled during the first lockdown in May 2020. Two-tailed tests of proportions were used to investigate possible differences between samples in proportions reporting poorer mental well-being measured by 5-item World Health Organization Well-Being Index, general health, and internal locus of control.</p><p><strong>Results: </strong>Younger men (aged 18-24) and younger women (aged 18-44) as well as elderly women (aged 65-74) reported lower mental well-being during the early phase of the pandemic compared to the population from 2016. Both women and men in 2020 reported significantly lower levels of internal locus of control compared to the 2017 sample. This was especially true for younger men and women. There were no statistically significant differences in general health between populations.</p><p><strong>Discussion: </strong>This study partly supports the hypothesis that the Covid-19 pandemic affected mental well-being negatively among younger persons. However, longitudinal studies are needed to investigate possible long-term effects of the pandemic on mental health and well-being. Further, qualitative studies are needed to investigate the in-depth consequences of Covid-19.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39905516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}