Pub Date : 2023-12-01Epub Date: 2023-03-10DOI: 10.1017/neu.2023.18
Zita Dósa, Jose Luis Nieto-Gonzalez, Betina Elfving, Karin Sørig Hougaard, Mai Marie Holm, Gregers Wegener, Kimmo Jensen
Prenatal stress is believed to increase the risk of developing neuropsychiatric disorders, including major depression. Adverse genetic and environmental impacts during early development, such as glucocorticoid hyper-exposure, can lead to changes in the foetal brain, linked to mental illnesses developed in later life. Dysfunction in the GABAergic inhibitory system is associated with depressive disorders. However, the pathophysiology of GABAergic signalling is poorly understood in mood disorders. Here, we investigated GABAergic neurotransmission in the low birth weight (LBW) rat model of depression. Pregnant rats, exposed to dexamethasone, a synthetic glucocorticoid, during the last week of gestation, yielded LBW offspring showing anxiety- and depressive-like behaviour in adulthood. Patch-clamp recordings from dentate gyrus granule cells in brain slices were used to examine phasic and tonic GABAA receptor-mediated currents. The transcriptional levels of selected genes associated with synaptic vesicle proteins and GABAergic neurotransmission were investigated. The frequency of spontaneous inhibitory postsynaptic currents (sIPSC) was similar in control and LBW rats. Using a paired-pulse protocol to stimulate GABAergic fibres impinging onto granule cells, we found indications of decreased probability of GABA release in LBW rats. However, tonic GABAergic currents and miniature IPSCs, reflecting quantal vesicle release, appeared normal. Additionally, we found elevated expression levels of two presynaptic proteins, Snap-25 and Scamp2, components of the vesicle release machinery. The results suggest that altered GABA release may be an essential feature in the depressive-like phenotype of LBW rats.
{"title":"Reduction in hippocampal GABAergic transmission in a low birth weight rat model of depression.","authors":"Zita Dósa, Jose Luis Nieto-Gonzalez, Betina Elfving, Karin Sørig Hougaard, Mai Marie Holm, Gregers Wegener, Kimmo Jensen","doi":"10.1017/neu.2023.18","DOIUrl":"10.1017/neu.2023.18","url":null,"abstract":"<p><p>Prenatal stress is believed to increase the risk of developing neuropsychiatric disorders, including major depression. Adverse genetic and environmental impacts during early development, such as glucocorticoid hyper-exposure, can lead to changes in the foetal brain, linked to mental illnesses developed in later life. Dysfunction in the GABAergic inhibitory system is associated with depressive disorders. However, the pathophysiology of GABAergic signalling is poorly understood in mood disorders. Here, we investigated GABAergic neurotransmission in the low birth weight (LBW) rat model of depression. Pregnant rats, exposed to dexamethasone, a synthetic glucocorticoid, during the last week of gestation, yielded LBW offspring showing anxiety- and depressive-like behaviour in adulthood. Patch-clamp recordings from dentate gyrus granule cells in brain slices were used to examine phasic and tonic GABA<sub>A</sub> receptor-mediated currents. The transcriptional levels of selected genes associated with synaptic vesicle proteins and GABAergic neurotransmission were investigated. The frequency of spontaneous inhibitory postsynaptic currents (sIPSC) was similar in control and LBW rats. Using a paired-pulse protocol to stimulate GABAergic fibres impinging onto granule cells, we found indications of decreased probability of GABA release in LBW rats. However, tonic GABAergic currents and miniature IPSCs, reflecting quantal vesicle release, appeared normal. Additionally, we found elevated expression levels of two presynaptic proteins, <i>Snap-25</i> and <i>Scamp2</i>, components of the vesicle release machinery. The results suggest that altered GABA release may be an essential feature in the depressive-like phenotype of LBW rats.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9706509","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 : 2023-12-01Epub Date: 2023-08-22DOI: 10.1017/neu.2023.38
Fabricio Ferreira de Oliveira, Sandro Soares de Almeida, Elizabeth Suchi Chen, Marilia Cardoso Smith, Paulo Henrique Ferreira Bertolucci
Objective: In Alzheimer's disease (AD), angiotensin II receptor blockers (ARBs) could reduce cerebrovascular dysfunction, while angiotensin-converting enzyme inhibitors (ACEis) might increase brain amyloid-β by suppressing effects of the angiotensin-converting enzyme 1, an amyloid-β-degrading enzyme. However, ACEis could benefit patients with AD by reducing the amyloidogenic processing of the amyloid precursor protein, by central cholinergic and anti-inflammatory mechanisms, and by peripheral modulation of glucose homeostasis. We aimed to investigate whether the ACE insertion/deletion polymorphism is associated with clinical changes in patients with AD, while considering apolipoprotein E (APOE)-ϵ4 carrier status and blood pressure response to angiotensin modulators.
Methods: Consecutive outpatients with late-onset AD were screened with cognitive tests and anthropometric measurements, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic associations were estimated for 1 year, taking APOE-ϵ4 carrier status and genotypes of the ACE insertion/deletion polymorphism into account, along with treatment with ACEis or ARBs.
Results: For 193 patients (67.4% women, 53.4% APOE-ϵ4 carriers), the ACE insertion/deletion polymorphism was in Hardy-Weinberg equilibrium (p = 0.281), while arterial hypertension was prevalent in 80.3% (n = 124 used an ACEi, n = 21 used an ARB). ARBs benefitted mostly APOE-ϵ4 carriers concerning caregiver burden variations, cognitive and functional decline. ACEis benefitted APOE-ϵ4 non-carriers concerning cognitive and functional decline due to improved blood pressure control in addition to possible central mechanisms. The ACE insertion/deletion polymorphism led to variable response to angiotensin modulators concerning neurological outcomes and blood pressure variations.
Conclusion: Angiotensin modulators may be disease-modifiers in AD, while genetic stratification of samples is recommended in clinical studies.
{"title":"Pharmacogenetics of angiotensin modulators according to <i>APOE</i>-ϵ4 alleles and the <i>ACE</i> insertion/deletion polymorphism in Alzheimer's disease.","authors":"Fabricio Ferreira de Oliveira, Sandro Soares de Almeida, Elizabeth Suchi Chen, Marilia Cardoso Smith, Paulo Henrique Ferreira Bertolucci","doi":"10.1017/neu.2023.38","DOIUrl":"10.1017/neu.2023.38","url":null,"abstract":"<p><strong>Objective: </strong>In Alzheimer's disease (AD), angiotensin II receptor blockers (ARBs) could reduce cerebrovascular dysfunction, while angiotensin-converting enzyme inhibitors (ACEis) might increase brain amyloid-β by suppressing effects of the angiotensin-converting enzyme 1, an amyloid-β-degrading enzyme. However, ACEis could benefit patients with AD by reducing the amyloidogenic processing of the amyloid precursor protein, by central cholinergic and anti-inflammatory mechanisms, and by peripheral modulation of glucose homeostasis. We aimed to investigate whether the <i>ACE</i> insertion/deletion polymorphism is associated with clinical changes in patients with AD, while considering apolipoprotein E (<i>APOE</i>)-ϵ4 carrier status and blood pressure response to angiotensin modulators.</p><p><strong>Methods: </strong>Consecutive outpatients with late-onset AD were screened with cognitive tests and anthropometric measurements, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic associations were estimated for 1 year, taking <i>APOE</i>-ϵ4 carrier status and genotypes of the <i>ACE</i> insertion/deletion polymorphism into account, along with treatment with ACEis or ARBs.</p><p><strong>Results: </strong>For 193 patients (67.4% women, 53.4% <i>APOE</i>-ϵ4 carriers), the <i>ACE</i> insertion/deletion polymorphism was in Hardy-Weinberg equilibrium (<i>p</i> = 0.281), while arterial hypertension was prevalent in 80.3% (<i>n</i> = 124 used an ACEi, <i>n</i> = 21 used an ARB). ARBs benefitted mostly <i>APOE</i>-ϵ4 carriers concerning caregiver burden variations, cognitive and functional decline. ACEis benefitted <i>APOE</i>-ϵ4 non-carriers concerning cognitive and functional decline due to improved blood pressure control in addition to possible central mechanisms. The <i>ACE</i> insertion/deletion polymorphism led to variable response to angiotensin modulators concerning neurological outcomes and blood pressure variations.</p><p><strong>Conclusion: </strong>Angiotensin modulators may be disease-modifiers in AD, while genetic stratification of samples is recommended in clinical studies.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10521391","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 : 2023-10-01Epub Date: 2023-03-02DOI: 10.1017/neu.2023.15
Erfan Jalalifar, Amirreza Arad, Mohsen Rastkar, Rasa Beheshti
Coronavirus disease, one of the most disastrous epidemics, has caused a worldwide crisis, and the containment measures applied to decelerate the progression of the pandemic can increase the risk of obsessive-compulsive disorder (OCD). Identifying vulnerable groups in this area can lead us to better resource expenditure, and therefore, this systematic review aims to make a comparison between males and females to determine which of the two groups was most affected by the COVID-19 pandemic regarding OCD. Also, a meta-analysis was designed to investigate the prevalence of OCD during the COVID-19 pandemic. A comprehensive search was conducted among three databases (Medline, Scopus, Web of Science) until August 2021 which resulted in 197 articles, and 24 articles met our inclusion criteria. Overall, more than half of the articles stated the role of gender in OCD during the COVID-19 pandemic. Several articles emphasized the role of the female gender, and some others the role of the male gender. The meta-analysis revealed a 41.2% overall prevalence of OCD during the COVID pandemic and 47.1% and 39.1% OCD prevalence for female and male genders respectively. However, the difference between the two genders was not statistically significant. Generally, it seems that females are at greater risk of OCD during the COVID-19 pandemic. In the following groups, the female gender may have acted as a risk factor: under-18 years students, hospital staff, and the studies in the Middle East. In none of the categories, male gender was clearly identified as a risk factor.
冠状病毒病是最具灾难性的流行病之一,已经引发了一场全球性危机,为减缓疫情发展而采取的遏制措施可能会增加患强迫症的风险。确定这一领域的弱势群体可以帮助我们更好地使用资源,因此,本系统综述旨在对男性和女性进行比较,以确定哪一个群体受COVID-19大流行的影响最大。此外,还设计了一项荟萃分析,以调查COVID-19大流行期间强迫症的患病率。综合检索三个数据库(Medline、Scopus、Web of Science)至2021年8月,共检索到197篇文章,其中24篇符合我们的纳入标准。总体而言,超过一半的文章阐述了在COVID-19大流行期间性别在强迫症中的作用。有几篇文章强调了女性的作用,还有一些则强调了男性的作用。meta分析显示,COVID大流行期间强迫症的总体患病率为41.2%,女性和男性的强迫症患病率分别为47.1%和39.1%。然而,两性之间的差异没有统计学意义。一般来说,在COVID-19大流行期间,女性患强迫症的风险似乎更大。在以下群体中,女性可能是一个风险因素:18岁以下的学生、医院工作人员和中东的研究人员。在所有类别中,男性性别都没有被明确认定为风险因素。
{"title":"The COVID-19 pandemic and obsessive-compulsive disorder: a systematic review of comparisons between males and females.","authors":"Erfan Jalalifar, Amirreza Arad, Mohsen Rastkar, Rasa Beheshti","doi":"10.1017/neu.2023.15","DOIUrl":"10.1017/neu.2023.15","url":null,"abstract":"<p><p>Coronavirus disease, one of the most disastrous epidemics, has caused a worldwide crisis, and the containment measures applied to decelerate the progression of the pandemic can increase the risk of obsessive-compulsive disorder (OCD). Identifying vulnerable groups in this area can lead us to better resource expenditure, and therefore, this systematic review aims to make a comparison between males and females to determine which of the two groups was most affected by the COVID-19 pandemic regarding OCD. Also, a meta-analysis was designed to investigate the prevalence of OCD during the COVID-19 pandemic. A comprehensive search was conducted among three databases (Medline, Scopus, Web of Science) until August 2021 which resulted in 197 articles, and 24 articles met our inclusion criteria. Overall, more than half of the articles stated the role of gender in OCD during the COVID-19 pandemic. Several articles emphasized the role of the female gender, and some others the role of the male gender. The meta-analysis revealed a 41.2% overall prevalence of OCD during the COVID pandemic and 47.1% and 39.1% OCD prevalence for female and male genders respectively. However, the difference between the two genders was not statistically significant. Generally, it seems that females are at greater risk of OCD during the COVID-19 pandemic. In the following groups, the female gender may have acted as a risk factor: under-18 years students, hospital staff, and the studies in the Middle East. In none of the categories, male gender was clearly identified as a risk factor.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9227550","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 : 2023-10-01Epub Date: 2023-03-02DOI: 10.1017/neu.2023.17
Siu Wa Tang, Daiga Maret Helmeste, Brian E Leonard
There appear to be huge variations and aberrations in the reported data in COVID-19 2 years now into the pandemic. Conflicting data exist at almost every level and also in the reported epidemiological statistics across different regions. It is becoming clear that COVID-19 is a polymorphic inflammatory spectrum of diseases, and there is a wide range of inflammation-related pathology and symptoms in those infected with the virus. The host's inflammatory response to COVID-19 appears to be determined by genetics, age, immune status, health status and stage of disease. The interplay of these factors may decide the magnitude, duration, types of pathology, symptoms and prognosis in the spectrum of COVID-19 disorders, and whether neuropsychiatric disorders continue to be significant. Early and successful management of inflammation reduces morbidity and mortality in all stages of COVID-19.
{"title":"COVID-19 as a polymorphic inflammatory spectrum of diseases: a review with focus on the brain.","authors":"Siu Wa Tang, Daiga Maret Helmeste, Brian E Leonard","doi":"10.1017/neu.2023.17","DOIUrl":"10.1017/neu.2023.17","url":null,"abstract":"<p><p>There appear to be huge variations and aberrations in the reported data in COVID-19 2 years now into the pandemic. Conflicting data exist at almost every level and also in the reported epidemiological statistics across different regions. It is becoming clear that COVID-19 is a polymorphic inflammatory spectrum of diseases, and there is a wide range of inflammation-related pathology and symptoms in those infected with the virus. The host's inflammatory response to COVID-19 appears to be determined by genetics, age, immune status, health status and stage of disease. The interplay of these factors may decide the magnitude, duration, types of pathology, symptoms and prognosis in the spectrum of COVID-19 disorders, and whether neuropsychiatric disorders continue to be significant. Early and successful management of inflammation reduces morbidity and mortality in all stages of COVID-19.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9524325","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 : 2023-10-01Epub Date: 2023-01-12DOI: 10.1017/neu.2023.4
Rizia Rocha Silva, Douglas Assis Teles Santos, Bagnólia Araújo Costa, Nelson Carvalho Farias Júnior, Allison Gustavo Braz, Gustavo De Conti Teixeira Costa, Marilia Santos Andrade, Rodrigo Luiz Vancini, Katja Weiss, Beat Knechtle, Claudio Andre Barbosa de Lira
Background: During the coronavirus disease 2019 (COVID-19) pandemic, undergraduate students were exposed to symptoms of psychological suffering during remote classes. Therefore, it is important to investigate the factors that may be generated and be related to such outcomes.
Objective: To investigate the association between fear of COVID-19, depression, anxiety, and related factors in undergraduate students during remote classes.
Methods: This cross-sectional study included 218 undergraduate students (60.6% women and 39.4% men). Students answered a self-administered online questionnaire designed to gather personal information, pandemic exposure, physical activity level, fear of COVID-19 using the 'Fear of COVID-19 Scale', symptoms of depression using the Patient Health Questionnaire-9, and anxiety using General Anxiety Disorder-7.
Results: Undergraduate students had a high prevalence of depression and anxiety (83.0% and 76.1%, respectively) but a low prevalence of fear of COVID-19 (28.9%) during remote classes. Multivariate analysis revealed that women who reported health status as neither good nor bad and who had lost a family member from COVID-19 had the highest levels of fear. For depression and anxiety, the main related factors found were female gender, bad health status, insufficiently active, and complete adherence to the restriction measures.
Conclusion: These findings may be used to develop actions to manage symptoms of anxiety and depression among students, with interventions through physical activity programmes to improve mental health.
{"title":"Prevalence of fear of COVID-19, depression, and anxiety among undergraduate students during remote classes.","authors":"Rizia Rocha Silva, Douglas Assis Teles Santos, Bagnólia Araújo Costa, Nelson Carvalho Farias Júnior, Allison Gustavo Braz, Gustavo De Conti Teixeira Costa, Marilia Santos Andrade, Rodrigo Luiz Vancini, Katja Weiss, Beat Knechtle, Claudio Andre Barbosa de Lira","doi":"10.1017/neu.2023.4","DOIUrl":"10.1017/neu.2023.4","url":null,"abstract":"<p><strong>Background: </strong>During the coronavirus disease 2019 (COVID-19) pandemic, undergraduate students were exposed to symptoms of psychological suffering during remote classes. Therefore, it is important to investigate the factors that may be generated and be related to such outcomes.</p><p><strong>Objective: </strong>To investigate the association between fear of COVID-19, depression, anxiety, and related factors in undergraduate students during remote classes.</p><p><strong>Methods: </strong>This cross-sectional study included 218 undergraduate students (60.6% women and 39.4% men). Students answered a self-administered online questionnaire designed to gather personal information, pandemic exposure, physical activity level, fear of COVID-19 using the 'Fear of COVID-19 Scale', symptoms of depression using the Patient Health Questionnaire-9, and anxiety using General Anxiety Disorder-7.</p><p><strong>Results: </strong>Undergraduate students had a high prevalence of depression and anxiety (83.0% and 76.1%, respectively) but a low prevalence of fear of COVID-19 (28.9%) during remote classes. Multivariate analysis revealed that women who reported health status as neither good nor bad and who had lost a family member from COVID-19 had the highest levels of fear. For depression and anxiety, the main related factors found were female gender, bad health status, insufficiently active, and complete adherence to the restriction measures.</p><p><strong>Conclusion: </strong>These findings may be used to develop actions to manage symptoms of anxiety and depression among students, with interventions through physical activity programmes to improve mental health.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9188484","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 : 2023-10-01Epub Date: 2023-01-06DOI: 10.1017/neu.2023.2
Lara L W Chiminazzo, Thiago Berti Kirsten
Objective: The pandemic caused by the coronavirus disease 2019 (COVID-19, SARS-CoV-2 virus) has infected more than 646 million people and caused more than 6.6 million deaths worldwide (December/2022). It is surprising that a virus that affects airways can trigger neurological manifestations. The aim of this study was to create and apply specific questionnaires/evaluations for post-COVID-19 patients to profile any neurofunctional sequelae.
Methods: Epidemiological and psychomotor aspects as well as the intensity of cognitive, memory, attention, and concentration impairment were assessed. A total of 184 subjects post-COVID-19 and a control group (n = 30) were evaluated.
Results: The most prevalent blood types in the COVID-19 group were the same as those from control group and in Brazilian population (no influence). Loss of smell/taste and headache were the most common reported symptoms. Talking about psychomotor and neurofunctional aspects, COVID-19 induced marked impairments in the tests: fine motor development (diadochokinesis, puppets, fan, and knead paper); balance (immobility, static balance, feet in line, and persistence); episodic memory after distractors; verbal fluency; and clock, compared to the control group data. There was also marked increase of synkinesis. Therefore, COVID-19 induced impairments in psychomotor assessments and in different cognitive aspects of the Mini-Mental State Examination. These results are more surprising considering that most participants did not report pre-existing disease and did not require hospitalisation.
Conclusion: COVID-19 induced psychomotor, neurofunctional, and memory impairments, including in young and healthy subjects. The present study revealed neurological impairments, which should be considered in the development of rehabilitation protocols for patients affected by COVID-19.
{"title":"Psychomotor and neurofunctional aspects after COVID-19.","authors":"Lara L W Chiminazzo, Thiago Berti Kirsten","doi":"10.1017/neu.2023.2","DOIUrl":"10.1017/neu.2023.2","url":null,"abstract":"<p><strong>Objective: </strong>The pandemic caused by the coronavirus disease 2019 (COVID-19, SARS-CoV-2 virus) has infected more than 646 million people and caused more than 6.6 million deaths worldwide (December/2022). It is surprising that a virus that affects airways can trigger neurological manifestations. The aim of this study was to create and apply specific questionnaires/evaluations for post-COVID-19 patients to profile any neurofunctional sequelae.</p><p><strong>Methods: </strong>Epidemiological and psychomotor aspects as well as the intensity of cognitive, memory, attention, and concentration impairment were assessed. A total of 184 subjects post-COVID-19 and a control group (<i>n</i> = 30) were evaluated.</p><p><strong>Results: </strong>The most prevalent blood types in the COVID-19 group were the same as those from control group and in Brazilian population (no influence). Loss of smell/taste and headache were the most common reported symptoms. Talking about psychomotor and neurofunctional aspects, COVID-19 induced marked impairments in the tests: fine motor development (diadochokinesis, puppets, fan, and knead paper); balance (immobility, static balance, feet in line, and persistence); episodic memory after distractors; verbal fluency; and clock, compared to the control group data. There was also marked increase of synkinesis. Therefore, COVID-19 induced impairments in psychomotor assessments and in different cognitive aspects of the Mini-Mental State Examination. These results are more surprising considering that most participants did not report pre-existing disease and did not require hospitalisation.</p><p><strong>Conclusion: </strong>COVID-19 induced psychomotor, neurofunctional, and memory impairments, including in young and healthy subjects. The present study revealed neurological impairments, which should be considered in the development of rehabilitation protocols for patients affected by COVID-19.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10564824","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}
Sung Woo Joo, Young Tak Jo, Soojin Ahn, Young Jae Choi, Woohyeok Choi, Sang Kyoung Kim, Soohyun Joe, Jungsun Lee
Objective: Although disconnectivity among brain regions has been one of the main hypotheses for schizophrenia, the superficial white matter (SWM) has received less attention in schizophrenia research than the deep white matter (DWM) owing to the challenge of consistent reconstruction across subjects.
Methods: We obtained the diffusion magnetic resonance imaging (dMRI) data of 223 healthy controls and 143 patients with schizophrenia. After harmonising the raw dMRIs from three different studies, we performed whole-brain two-tensor tractography and fibre clustering on the tractography data. We compared the fractional anisotropy (FA) of white matter tracts between healthy controls and patients with schizophrenia. Spearman's rho was adopted for the associations with clinical symptoms measured by the Positive and Negative Syndrome Scale (PANSS). The Bonferroni correction was used to adjust multiple testing.
Results: Among the 33 DWM and 8 SWM tracts, patients with schizophrenia had a lower FA in 14 DWM and 4 SWM tracts than healthy controls, with small effect sizes. In the patient group, the FA deviations of the corticospinal and superficial-occipital tracts were negatively correlated with the PANSS negative score; however, this correlation was not evident after adjusting for multiple testing.
Conclusion: We observed the structural impairments of both the DWM and SWM tracts in patients with schizophrenia. The SWM could be a potential target of interest in future research on neural biomarkers for schizophrenia.
{"title":"Structural impairment in superficial and deep white matter in schizophrenia.","authors":"Sung Woo Joo, Young Tak Jo, Soojin Ahn, Young Jae Choi, Woohyeok Choi, Sang Kyoung Kim, Soohyun Joe, Jungsun Lee","doi":"10.1017/neu.2023.44","DOIUrl":"https://doi.org/10.1017/neu.2023.44","url":null,"abstract":"<p><strong>Objective: </strong>Although disconnectivity among brain regions has been one of the main hypotheses for schizophrenia, the superficial white matter (SWM) has received less attention in schizophrenia research than the deep white matter (DWM) owing to the challenge of consistent reconstruction across subjects.</p><p><strong>Methods: </strong>We obtained the diffusion magnetic resonance imaging (dMRI) data of 223 healthy controls and 143 patients with schizophrenia. After harmonising the raw dMRIs from three different studies, we performed whole-brain two-tensor tractography and fibre clustering on the tractography data. We compared the fractional anisotropy (FA) of white matter tracts between healthy controls and patients with schizophrenia. Spearman's rho was adopted for the associations with clinical symptoms measured by the Positive and Negative Syndrome Scale (PANSS). The Bonferroni correction was used to adjust multiple testing.</p><p><strong>Results: </strong>Among the 33 DWM and 8 SWM tracts, patients with schizophrenia had a lower FA in 14 DWM and 4 SWM tracts than healthy controls, with small effect sizes. In the patient group, the FA deviations of the corticospinal and superficial-occipital tracts were negatively correlated with the PANSS negative score; however, this correlation was not evident after adjusting for multiple testing.</p><p><strong>Conclusion: </strong>We observed the structural impairments of both the DWM and SWM tracts in patients with schizophrenia. The SWM could be a potential target of interest in future research on neural biomarkers for schizophrenia.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10198730","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}
Lasse Hansen, Kenneth Enevoldsen, Martin Bernstorff, Erik Perfalk, Andreas A Danielsen, Kristoffer L Nielbo, Søren D Østergaard
Objective: Natural language processing (NLP) methods hold promise for improving clinical prediction by utilising information otherwise hidden in the clinical notes of electronic health records. However, clinical practice - as well as the systems and databases in which clinical notes are recorded and stored - change over time. As a consequence, the content of clinical notes may also change over time, which could degrade the performance of prediction models. Despite its importance, the stability of clinical notes over time has rarely been tested.
Methods: The lexical stability of clinical notes from the Psychiatric Services of the Central Denmark Region in the period from January 1, 2011, to November 22, 2021 (a total of 14,811,551 clinical notes describing 129,570 patients) was assessed by quantifying sentence length, readability, syntactic complexity and clinical content. Changepoint detection models were used to estimate potential changes in these metrics.
Results: We find lexical stability of the clinical notes over time, with minor deviations during the COVID-19 pandemic. Out of 2988 data points, 17 possible changepoints (corresponding to 0.6%) were detected. The majority of these were related to the discontinuation of a specific note type.
Conclusion: We find lexical and syntactic stability of clinical notes from psychiatric services over time, which bodes well for the use of NLP for predictive modelling in clinical psychiatry.
{"title":"Lexical stability of psychiatric clinical notes from electronic health records over a decade.","authors":"Lasse Hansen, Kenneth Enevoldsen, Martin Bernstorff, Erik Perfalk, Andreas A Danielsen, Kristoffer L Nielbo, Søren D Østergaard","doi":"10.1017/neu.2023.46","DOIUrl":"https://doi.org/10.1017/neu.2023.46","url":null,"abstract":"<p><strong>Objective: </strong>Natural language processing (NLP) methods hold promise for improving clinical prediction by utilising information otherwise hidden in the clinical notes of electronic health records. However, clinical practice - as well as the systems and databases in which clinical notes are recorded and stored - change over time. As a consequence, the content of clinical notes may also change over time, which could degrade the performance of prediction models. Despite its importance, the stability of clinical notes over time has rarely been tested.</p><p><strong>Methods: </strong>The lexical stability of clinical notes from the Psychiatric Services of the Central Denmark Region in the period from January 1, 2011, to November 22, 2021 (a total of 14,811,551 clinical notes describing 129,570 patients) was assessed by quantifying sentence length, readability, syntactic complexity and clinical content. Changepoint detection models were used to estimate potential changes in these metrics.</p><p><strong>Results: </strong>We find lexical stability of the clinical notes over time, with minor deviations during the COVID-19 pandemic. Out of 2988 data points, 17 possible changepoints (corresponding to 0.6%) were detected. The majority of these were related to the discontinuation of a specific note type.</p><p><strong>Conclusion: </strong>We find lexical and syntactic stability of clinical notes from psychiatric services over time, which bodes well for the use of NLP for predictive modelling in clinical psychiatry.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10576692","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}
Mark Walterfang, Tsutomu Takahashi, Maria A Di Biase, Vanessa L Cropley, Daiki Sasabayashi, Michio Suzuki, Dennis Velakoulis, Christos Pantelis
Objective: A range of neuropathological changes occur in the brains of individuals with adult Niemann-Pick type C disease (NPC), a recessive disorder of cholesterol trafficking that results in accumulation of cholesterol and gangliosides in lysosomes, particularly in neurons. One of the most significant regions of grey matter loss occurs in the thalami, which abut the midline. What is not known is whether these are neurodevelopmental in origin well prior to symptomatic onset. We aimed to examine other markers of midline developmental anomalies in adults with NPC.
Method: We examined the size of adhesio interthalamica (AI) and cavum septum pellucidum (CSP) (if present) in nine individuals diagnosed with NPC and nine healthy comparison subjects, matched for age and gender, using a 3T magnetic resonance volumetric sequence and measured the length of the AI and CSP in mm.
Results: We found that 5/9 NPC patients and 0/9 controls had a missing AI. AI length was significantly shorter in the patient group. No subject in other group had a large CSP, and CSP length did not differ. Duration of illness showed a trend to a negative correlation with AI length in patients.
Conclusions: Our findings suggest that adult NPC patients show some markers of early neurodevelopmental disturbance, matching findings seen in psychotic disorders. The differences in AI, but not CSP, suggest neurodevelopmental change may occur early in gestation rather than post-partum. The relationship with duration of illness suggests that there may be atrophy over time in these structures, consistent with prior analyses of grey matter regions in NPC.
{"title":"Midline brain structures in adult Niemann-Pick type C disease: a cross-sectional study.","authors":"Mark Walterfang, Tsutomu Takahashi, Maria A Di Biase, Vanessa L Cropley, Daiki Sasabayashi, Michio Suzuki, Dennis Velakoulis, Christos Pantelis","doi":"10.1017/neu.2023.43","DOIUrl":"10.1017/neu.2023.43","url":null,"abstract":"<p><strong>Objective: </strong>A range of neuropathological changes occur in the brains of individuals with adult Niemann-Pick type C disease (NPC), a recessive disorder of cholesterol trafficking that results in accumulation of cholesterol and gangliosides in lysosomes, particularly in neurons. One of the most significant regions of grey matter loss occurs in the thalami, which abut the midline. What is not known is whether these are neurodevelopmental in origin well prior to symptomatic onset. We aimed to examine other markers of midline developmental anomalies in adults with NPC.</p><p><strong>Method: </strong>We examined the size of adhesio interthalamica (AI) and cavum septum pellucidum (CSP) (if present) in nine individuals diagnosed with NPC and nine healthy comparison subjects, matched for age and gender, using a 3T magnetic resonance volumetric sequence and measured the length of the AI and CSP in mm.</p><p><strong>Results: </strong>We found that 5/9 NPC patients and 0/9 controls had a missing AI. AI length was significantly shorter in the patient group. No subject in other group had a large CSP, and CSP length did not differ. Duration of illness showed a trend to a negative correlation with AI length in patients.</p><p><strong>Conclusions: </strong>Our findings suggest that adult NPC patients show some markers of early neurodevelopmental disturbance, matching findings seen in psychotic disorders. The differences in AI, but not CSP, suggest neurodevelopmental change may occur early in gestation rather than post-partum. The relationship with duration of illness suggests that there may be atrophy over time in these structures, consistent with prior analyses of grey matter regions in NPC.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10059017","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}
Megan L Campbell, Shareefa Dalvie, Alexey Shadrin, Dennis van der Meer, Kevin O'Connell, Oleksander Frei, Ole A Andreassen, Dan J Stein, Jaroslav Rokicki
Background: The corpus callosum (CC) is a brain structure with a high heritability and potential role in psychiatric disorders. However, the genetic architecture of the CC and the genetic link with psychiatric disorders remain largely unclear. We investigated the genetic architectures of the volume of the CC and its subregions and the genetic overlap with psychiatric disorders.
Methods: We applied multivariate genome-wide association study (GWAS) to genetic and T1-weighted magnetic resonance imaging (MRI) data of 40,894 individuals from the UK Biobank, aiming to boost genetic discovery and to assess the pleiotropic effects across volumes of the five subregions of the CC (posterior, mid-posterior, central, mid-anterior and anterior) obtained by FreeSurfer 7.1. Multivariate GWAS was run combining all subregions, co-varying for relevant variables. Gene-set enrichment analyses were performed using MAGMA. Linkage disequilibrium score regression (LDSC) was used to determine Single nucleotide polymorphism (SNP)-based heritability of total CC volume and volumes of its subregions as well as their genetic correlations with relevant psychiatric traits.
Results: We identified 70 independent loci with distributed effects across the five subregions of the CC (p < 5 × 10-8). Additionally, we identified 33 significant loci in the anterior subregion, 23 in the mid-anterior, 29 in the central, 7 in the mid-posterior and 56 in the posterior subregion. Gene-set analysis revealed 156 significant genes contributing to volume of the CC subregions (p < 2.6 × 10-6). LDSC estimated the heritability of CC to (h2SNP = 0.38, SE = 0.03) and subregions ranging from 0.22 (SE = 0.02) to 0.37 (SE = 0.03). We found significant genetic correlations of total CC volume with bipolar disorder (BD, rg = -0.09, SE = 0.03; p = 5.9 × 10-3) and drinks consumed per week (rg = -0.09, SE = 0.02; p = 4.8 × 10-4), and volume of the mid-anterior subregion with BD (rg = -0.12, SE = 0.02; p = 2.5 × 10-4), major depressive disorder (MDD) (rg = -0.12, SE = 0.04; p = 3.6 × 10-3), drinks consumed per week (rg = -0.13, SE = 0.04; p = 1.8 × 10-3) and cannabis use (rg = -0.09, SE = 0.03; p = 8.4 × 10-3).
Conclusions: Our results demonstrate that the CC has a polygenic architecture implicating multiple genes and show that CC subregion volumes are heritable. We found that distinct genetic factors are involved in the development of anterior and posterior subregions, consistent with their divergent functional specialisation. Significant genetic correlation between volumes of the CC and BD, drinks per week, MDD and cannabis consumption subregion v
{"title":"Distributed genetic effects of the corpus callosum subregions suggest links to neuropsychiatric disorders and related traits.","authors":"Megan L Campbell, Shareefa Dalvie, Alexey Shadrin, Dennis van der Meer, Kevin O'Connell, Oleksander Frei, Ole A Andreassen, Dan J Stein, Jaroslav Rokicki","doi":"10.1017/neu.2023.32","DOIUrl":"10.1017/neu.2023.32","url":null,"abstract":"<p><strong>Background: </strong>The corpus callosum (CC) is a brain structure with a high heritability and potential role in psychiatric disorders. However, the genetic architecture of the CC and the genetic link with psychiatric disorders remain largely unclear. We investigated the genetic architectures of the volume of the CC and its subregions and the genetic overlap with psychiatric disorders.</p><p><strong>Methods: </strong>We applied multivariate genome-wide association study (GWAS) to genetic and T1-weighted magnetic resonance imaging (MRI) data of 40,894 individuals from the UK Biobank, aiming to boost genetic discovery and to assess the pleiotropic effects across volumes of the five subregions of the CC (posterior, mid-posterior, central, mid-anterior and anterior) obtained by FreeSurfer 7.1. Multivariate GWAS was run combining all subregions, co-varying for relevant variables. Gene-set enrichment analyses were performed using MAGMA. Linkage disequilibrium score regression (LDSC) was used to determine Single nucleotide polymorphism (SNP)-based heritability of total CC volume and volumes of its subregions as well as their genetic correlations with relevant psychiatric traits.</p><p><strong>Results: </strong>We identified 70 independent loci with distributed effects across the five subregions of the CC (<i>p</i> < 5 × 10<sup>-8</sup>). Additionally, we identified 33 significant loci in the anterior subregion, 23 in the mid-anterior, 29 in the central, 7 in the mid-posterior and 56 in the posterior subregion. Gene-set analysis revealed 156 significant genes contributing to volume of the CC subregions (<i>p</i> < 2.6 × 10<sup>-6</sup>). LDSC estimated the heritability of CC to (<i>h</i><sup>2</sup><sub>SNP</sub> = 0.38, SE = 0.03) and subregions ranging from 0.22 (SE = 0.02) to 0.37 (SE = 0.03). We found significant genetic correlations of total CC volume with bipolar disorder (BD, <i>r<sub>g</sub></i> = -0.09, SE = 0.03; <i>p</i> = 5.9 × 10<sup>-3</sup>) and drinks consumed per week (<i>r<sub>g</sub></i> = -0.09, SE = 0.02; <i>p</i> = 4.8 × 10<sup>-4</sup>), and volume of the mid-anterior subregion with BD (<i>r<sub>g</sub></i> = -0.12, SE = 0.02; <i>p</i> = 2.5 × 10<sup>-4</sup>), major depressive disorder (MDD) (<i>r<sub>g</sub></i> = -0.12, SE = 0.04; <i>p</i> = 3.6 × 10<sup>-3</sup>), drinks consumed per week (<i>r<sub>g</sub></i> = -0.13, SE = 0.04; <i>p</i> = 1.8 × 10<sup>-3</sup>) and cannabis use (<i>r<sub>g</sub></i> = -0.09, SE = 0.03; <i>p</i> = 8.4 × 10<sup>-3</sup>).</p><p><strong>Conclusions: </strong>Our results demonstrate that the CC has a polygenic architecture implicating multiple genes and show that CC subregion volumes are heritable. We found that distinct genetic factors are involved in the development of anterior and posterior subregions, consistent with their divergent functional specialisation. Significant genetic correlation between volumes of the CC and BD, drinks per week, MDD and cannabis consumption subregion v","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10891296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10433986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}