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1.
J Head Trauma Rehabil ; 38(1): E56-E64, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36594864

RESUMO

OBJECTIVE: To investigate the factor structure of the Agitated Behavior Scale (ABS) in patients with traumatic brain injury (TBI) in posttraumatic amnesia (PTA). SETTING: Inpatient TBI rehabilitation ward in Victoria, Australia. PARTICIPANTS: A total of 364 patients aged 16 to 92 years meeting diagnostic criteria for TBI and PTA admitted between September 2013 and October 2020. DESIGN: Retrospective cohort study utilizing electronic medical record data. MAIN MEASURES: The ABS and the Westmead Post-Traumatic Amnesia Scale (WPTAS). RESULTS: Exploratory factor analysis uncovered 2 moderately correlated underlying factors (0.52), labeled Restlessness and Aggression/Lability. Two items failed to demonstrate sufficiently large loadings on either factor. Both factors demonstrated adequate reliability (Cronbach α = 0.87 and 0.81 for Restlessness and Aggression/Lability, respectively). Linear regression indicated that higher WPTAS scores were associated with lower levels of Restlessness (ß = -.14, P < .001), supporting construct validity. Conversely, WPTAS scores were not significantly associated with Aggression/Lability (ß = -.12, P = .08). Subgroup analysis indicated that a history of mood disorder was associated with greater severity of Aggression/Lability (P = .02). Confirmatory factor analysis indicated superior fit of the identified 2-factor solution when compared with previously explored 1-, 2-, 3-, and 4-factor structures. CONCLUSION: This study suggests that the latent structure of the ABS is best explained by a single construct of agitation with 2 discrete facets reflecting Restlessness and Aggression/Lability. These subscales may be used in clinical practice to evaluate the severity of different aspects of agitated behavior, inform treatment decisions, and judge the efficacy of interventions over time. Further research is required to explain low factor loadings demonstrated by 2 items.


Assuntos
Lesões Encefálicas Traumáticas , Agitação Psicomotora , Humanos , Agitação Psicomotora/diagnóstico , Agitação Psicomotora/etiologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/reabilitação , Amnésia/diagnóstico , Amnésia/etiologia , Vitória
2.
Brain Behav Immun ; 108: 176-187, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36494046

RESUMO

Evidences suggest that inflammation is increased in a subgroup of patients with depression. Moreover, increased peripheral inflammatory markers (cells and proteins) are associated with some, but not all depressive symptoms. On the other hand, similar studies on bipolar disorders mainly focused on blood cytokines. Here, we analysed data from a large (N = 3440), well-characterized cohort of individuals with bipolar disorder using Kendall partial rank correlation, multivariate linear regression, and network analyses to determine whether peripheral blood cell counts are associated with depression severity, its symptoms, and dimensions. Based on the self-reported 16-Item Quick Inventory of Depressive Symptomatology questionnaire scores, we preselected symptom dimensions based on literature and data-driven principal component analysis. We found that the counts of all blood cell types were only marginally associated with depression severity. Conversely, white blood cell count was significantly associated with the sickness dimension and its four components (anhedonia, slowing down, fatigue, and appetite loss). Platelet count was associated with the insomnia/restlessness dimension and its components (initial, middle, late insomnia and restlessness). Principal component analyses corroborated these results. Platelet count was also associated with suicidal ideation. In analyses stratified by sex, the white blood cell count-sickness dimension association remained significant only in men, and the platelet count-insomnia/restlessness dimension association only in women. Without implying causation, these results suggest that peripheral blood cell counts might be associated with different depressive symptoms in individuals with bipolar disorder, and that white blood cells might be implicated in sickness symptoms and platelets in insomnia/agitation and suicidal ideation.


Assuntos
Transtorno Bipolar , Distúrbios do Início e da Manutenção do Sono , Masculino , Humanos , Feminino , Transtorno Bipolar/diagnóstico , Depressão , Contagem de Plaquetas , Agitação Psicomotora , Ideação Suicida , Leucócitos
3.
J Pharmacol Sci ; 151(1): 9-16, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36522124

RESUMO

Tardive akathisia is a movement disorder characterized by internal restlessness with an uncontrollable urge to move, leading to repetitive movements. It is a common side effect of long-term treatment with dopamine D2 receptor antagonists. In the present study, we analyzed the FDA Adverse Event Reporting System and IBM MarketScan Research Database to find a drug that can be used concomitantly with dopamine D2 receptor antagonists and still reduce the risk of akathisia. Acetaminophen was determined to be the most effective akathisia-suppressing drug. In an experimental validation of the hypothesis, chronic treatment of rats with haloperidol caused akathisia symptoms, including increased stereotyped behavior and locomotor activity, and decreased immobility time. Acute treatment with acetaminophen significantly attenuated haloperidol-induced akathisia. In the ventral striata of these rats, acetaminophen prevented haloperidol-induced decrease in the number of c-Fos+ preproenkephalin+ neurons. These results suggest that acetaminophen is effective in suppressing tardive akathisia by activating indirect-pathway medium spiny neurons.


Assuntos
Acatisia Induzida por Medicamentos , Antipsicóticos , Animais , Ratos , Acatisia Induzida por Medicamentos/tratamento farmacológico , Acatisia Induzida por Medicamentos/etiologia , Acatisia Induzida por Medicamentos/prevenção & controle , Haloperidol/efeitos adversos , Dopamina , Acetaminofen/efeitos adversos , Agitação Psicomotora/etiologia , Agitação Psicomotora/complicações , Antagonistas dos Receptores de Dopamina D2 , Antipsicóticos/efeitos adversos
4.
J Clin Pharm Ther ; 47(12): 2083-2090, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36543254

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Traumatic brain injury (TBI) is a major cause of disability, and it has been associated with agitation and aggression. In a previous study, we reviewed the literature to identify evidence-based pharmacological agents for treatment of agitation in TBI. Based on the results of our previous study that summarizes the findings of several systematic reviews, the use of haloperidol and benzodiazepines is not supported by the available evidence while the use of amantadine, beta blockers, antiepileptics and methylphenidate is supported by the limited available evidence. In this study, we describe the psycho-pharmacological agents that were administered to patients with agitation and/or aggression in the context of TBI in inpatient facilities of a private, non-profit health care system in southwest Virginia. We will also compare the psycho-pharmacological agents ordered before and after psychiatric consultation. METHODS: Adult patients who were admitted to Carilion Clinic's inpatient facilities from March 30, 2013, to March 30, 2018, had a diagnosis of TBI, and received psychiatric consultation for agitation and/or aggression were enrolled in this study. A retrospective review of electronic medical records was conducted by researchers and data were collected on the following measures: ordered psycho-pharmacological agents, frequency, dosing and duration of orders, whether each administered psycho-pharmacological agent was started before or after psychiatric consultation, and psycho-pharmacological agents prescribed upon discharge. RESULTS AND DISCUSSION: About 68% of patients were started on benzodiazepines and/or typical antipsychotics and 23% of patients were subsequently discharged on these medication categories. Only 23% of patients were ordered to receive medications supported by the evidence such as amantadine, beta blockers or antiepileptics. The percentage of patient-days with an order to receive typical antipsychotics significantly decreased following psychiatric consultation (p = 0.0056), but the percentage of patient-days with an order to receive benzodiazepines significantly increased following psychiatric consultation (p = 0.0001). This finding remained statistically significant after excluding patients with active or unclear alcohol/benzodiazepine withdrawal (p < 0.0001). WHAT IS NEW AND CONCLUSION: This study demonstrates the widespread use of typical antipsychotics and benzodiazepines in the management of agitation in TBI and the importance of multidisciplinary collaboration, research and education of providers to improve patient care.


Assuntos
Antipsicóticos , Lesões Encefálicas Traumáticas , Adulto , Humanos , Anticonvulsivantes/uso terapêutico , Pacientes Internados , Virginia , Agitação Psicomotora/tratamento farmacológico , Agitação Psicomotora/etiologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Agressão/psicologia , Amantadina/uso terapêutico , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico
5.
Artigo em Inglês | MEDLINE | ID: mdl-36498042

RESUMO

Psychomotor agitation is characterised by an increase in psychomotor activity, restlessness and irritability. People with psychomotor agitation respond by over-reacting to both intrinsic and extrinsic stimuli, experiencing stress and/or altered cognition. The objective of this study is to assess the clinical and sociodemographic profile of psychomotor agitation in patients with severe mental disorders. The study was carried out in Spain by means of multicentre cross-sectional convenience sampling involving 140 patients who had been admitted to psychiatric hospital units and had experienced an episode of psychomotor agitation between 2018 and 2021.Corrigan's Agitated Behaviour Scale was used to assess psychomotor agitation. The results show that the predominant characteristic in psychomotor agitation is aggressiveness, which is also the most reported factor in patients with severe mental disorder. Patients who also have anxiety develop psychomotor agitation symptoms of moderate/severe intensity. The clinical and sociodemographic profile found in our study is consistent with other studies on the prevalence of psychomotor agitation.


Assuntos
Saúde Mental , Agitação Psicomotora , Humanos , Estudos Transversais , Agitação Psicomotora/epidemiologia , Ansiedade/psicologia , Hospitalização
6.
Braz J Psychiatry ; 44(6): 576-583, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36580584

RESUMO

OBJECTIVE: To explore whether there is an association between distractibility, anxiety, irritability, and agitation (DAIA) symptoms and the severity of depressive and manic symptoms. METHODS: Patients with unipolar and bipolar disorder (I and II) and mixed depression were evaluated. DAIA symptoms were assessed using previously described definitions. RESULTS: The full analysis set comprised 100 patients. The severity of depressive symptoms in mixed depression, assessed by Montgomery-Åsberg Depression Rating Scale (MADRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample, influenced mainly by anxiety. The severity of manic symptoms in mixed depression, assessed by Young Mania Rating Scale (YMRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample and three or four DAIA symptoms in the unipolar sample. CONCLUSION: DAIA symptoms were associated with greater severity of manic symptoms in mixed depression. DAIA symptoms must be evaluated in all patients with mixed features and are associated with the severity of depressive and manic symptoms in mixed depression.


Assuntos
Transtorno Bipolar , Depressão , Humanos , Depressão/diagnóstico , Transtorno Bipolar/diagnóstico , Ansiedade/diagnóstico , Humor Irritável , Agitação Psicomotora
8.
Zh Nevrol Psikhiatr Im S S Korsakova ; 122(11. Vyp. 2): 67-72, 2022.
Artigo em Russo | MEDLINE | ID: mdl-36412159

RESUMO

Imperative movements have an intermediate position between voluntary and involuntary movements and are also referred to as semi-voluntary, or induced. Their common characteristic is the urge, forcing the patient to perform an action that can have a different duration and degree of complexity - from a short twitch (with tics) to prolonged episodes of general motor restlessness (for example, akathisia or stereotypes). The ability to slow down this movement for a short or longer period of time by volitional effort is associated with the urge to make a movement, which predetermines the patient's perception of the degree of its imperativeness and arbitrariness. All motor syndromes based on an imperative need to make movements (akathisia, tics, restless legs syndrome, some levodopa-induced dyskinesias, tardive dyskinesia, compulsive disorders, stereotypes), despite their differences, can be conditionally combined by the term «akathisia spectrum disorders¼. In some cases, violent imperative movements are paradoxically combined with hypokinetic disorders, primarily with parkinsonism, which makes the discomfort experienced by patients particularly severe.


Assuntos
Transtornos dos Movimentos , Transtornos de Tique , Tiques , Humanos , Agitação Psicomotora , Transtornos dos Movimentos/etiologia , Volição
10.
Biosensors (Basel) ; 12(11)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36354433

RESUMO

Treating opioid use disorder (OUD) is a significant healthcare challenge in the United States. Remaining abstinent from opioids is challenging for individuals with OUD due to withdrawal symptoms that include restlessness. However, to our knowledge, studies of acute withdrawal have not quantified restlessness using involuntary movements. We hypothesized that wearable accelerometry placed mid-sternum could be used to detect withdrawal-related restlessness in patients with OUD. To study this, 23 patients with OUD undergoing active withdrawal participated in a protocol involving wearable accelerometry, opioid cues to elicit craving, and non-invasive Vagal Nerve Stimulation (nVNS) to dampen withdrawal symptoms. Using accelerometry signals, we analyzed how movements correlated with changes in acute withdrawal severity, measured by the Clinical Opioid Withdrawal Scale (COWS). Our results revealed that patients demonstrating sinusoidal-i.e., predominantly single-frequency oscillation patterns in their motion almost exclusively demonstrated an increase in the COWS, and a strong relationship between the maximum power spectral density and increased withdrawal over time, measured by the COWS (R = 0.92, p = 0.029). Accelerometry may be used in an ambulatory setting to indicate the increased intensity of a patient's withdrawal symptoms, providing an objective, readily-measurable marker that may be captured ubiquitously.


Assuntos
Transtornos Relacionados ao Uso de Opioides , Síndrome de Abstinência a Substâncias , Humanos , Analgésicos Opioides/uso terapêutico , Prognóstico , Agitação Psicomotora , Síndrome de Abstinência a Substâncias/diagnóstico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Acelerometria
11.
Geriatr Psychol Neuropsychiatr Vieil ; 20(3): 329-337, 2022 09 01.
Artigo em Francês | MEDLINE | ID: mdl-36322800

RESUMO

Progressive neurocognitive pathologies frequently alter the architecture of sleep with: advanced sleep phase or phase delay, sleep fragmentation, decrease of slow-wave sleep, REM sleep, nocturnal agitation and wandering or even complete reversal of the nycthemeral rhythm. This has a clear impact on the health and quality of life of the patient. Hospitalization increases the risk of sleep disturbances due to inactivity, some sensory deprivation and daytime hypovigilance. The therapeutic gardens offer in an attractive, sensorially stimulating setting and exposed to natural light, the possibility of an adapted physical exercise. Their impact on the quality and quantity of sleep in cognitive-behavioral units has been evaluated in an exploratory manner. The hypnogram of two groups of 30 patients was compared depending on whether they used the garden (weather permitting, in summer) or not (in winter). The results show that the patients who use the garden are significantly more active during the day, have a longer nighttime sleep duration and are less restless at night. In addition, patients who use and walk longer in the garden benefit from an increase in their sleep time. In view of their multiple interests, therapeutic gardens, if they meet validated design criteria, should be integrated more widely into establishments welcoming people with neurocognitive diseases.


Les pathologies neurocognitives évolutives altèrent fréquemment l'architecture du sommeil avec : avance ou retard de phase, fragmentation du sommeil, diminution du sommeil lent profond et du sommeil paradoxal, agitation et déambulation nocturnes voire inversion complète du rythme nycthéméral. Cela retentit nettement sur la santé et la qualité de vie du patient. L'hospitalisation accroît le risque de perturbations du sommeil du fait de l'inactivité, d'une certaine privation sensorielle et de l'hypovigilance diurne. Les jardins thérapeutiques offrent, dans un cadre attractif, stimulant sensoriellement et exposé à la lumière naturelle, la possibilité d'un exercice physique adapté. Leur impact sur la qualité et la quantité de sommeil en Unité cognitivo-comportementale a été évalué de manière exploratoire. L'hypnogramme de deux groupes de 30 patients a été comparé selon qu'ils utilisaient le jardin (lorsque la météo le permettait, en été) ou non (en hiver). Les résultats montrent que les patients qui utilisent le jardin sont significativement plus actifs la journée, ont une durée supérieure de sommeil nocturne et sont moins agités la nuit. De plus, les patients utilisant et marchant plus longtemps dans le jardin bénéficient d'une augmentation de leur durée de sommeil. Au vu de leurs intérêts multiples, les jardins thérapeutiques, pour peu qu'ils répondent à des critères de conception validés, devraient être intégrés plus largement dans les établissements accueillants des personnes atteintes de maladies neurocognitives.


Assuntos
Qualidade de Vida , Transtornos do Sono-Vigília , Humanos , Sono , Transtornos do Sono-Vigília/terapia , Jardinagem , Agitação Psicomotora
12.
Mol Brain ; 15(1): 96, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36447257

RESUMO

Dopamine-deficient (DD) mice exhibit psychomotor hyperactivity that might be related to a decrease in muscarinic signaling. In the present study, muscarinic acetylcholine receptor M2 (CHRM2) density decreased in the cortex in DD mice. This is significant because cortical CHRM2 acts as an autoreceptor; therefore, changes in CHRM2 levels could alter acetylcholine in DD mice. We also found that the CHRM1/CHRM4 agonist xanomeline and CHRM2 agonist arecaidine propargyl ester tosylate inhibited hyperactivity in DD mice, suggesting that postsynaptic CHRM1 and CHRM2 and presynaptic CHRM2 may be involved in hyperactivity in DD mice.


Assuntos
Dopamina , Agitação Psicomotora , Camundongos , Animais , Acetilcolina/farmacologia , Ésteres , Transdução de Sinais
13.
Cell Rep ; 41(9): 111744, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36450260

RESUMO

Mitochondrial dysfunction, a hallmark of aging, has been associated with the onset of aging phenotypes and age-related diseases. Here, we report that impaired mitochondrial function is associated with increased glutamine catabolism in senescent human mesenchymal stem cells (MSCs) and myofibroblasts derived from patients suffering from Hutchinson-Gilford progeria syndrome. Increased glutaminase (GLS1) activity accompanied by loss of urea transporter SLC14A1 induces urea accumulation, mitochondrial dysfunction, and DNA damage. Conversely, blocking GLS1 activity restores mitochondrial function and leads to amelioration of aging hallmarks. Interestingly, GLS1 expression is regulated through the JNK pathway, as demonstrated by chemical and genetic inhibition. In agreement with our in vitro findings, tissues isolated from aged or progeria mice display increased urea accumulation and GLS1 activity, concomitant with declined mitochondrial function. Inhibition of glutaminolysis in progeria mice improves mitochondrial respiratory chain activity, suggesting that targeting glutaminolysis may be a promising strategy for restoring age-associated loss of mitochondrial function.


Assuntos
Progéria , Humanos , Camundongos , Animais , Idoso , Mitocôndrias , Células-Tronco , Membranas Mitocondriais , Envelhecimento , Agitação Psicomotora
14.
Nutrients ; 14(22)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36432444

RESUMO

BACKGROUND: Human milk does not meet the nutritional needs to support optimal growth of very preterm infants during the first weeks of life. Nutrient fortifiers are therefore added to human milk, though these products are suspected to increase gut dysmotility. The objective was to evaluate whether fortification with bovine colostrum (BC) improves bowel habits compared to a conventional fortifier (CF) in very preterm infants. METHODS: In an unblinded, randomized study, 242 preterm infants (26-31 weeks of gestation) were randomized to receive BC (BC, Biofiber Damino, Gesten, Denmark) or CF (FM85 PreNAN, Nestlé, Vevey, Switzerland) as a fortifier. Stools (Amsterdam Stool Scale), bowel gas restlessness, stomach appearance score, volume, and frequency of gastric residuals were recorded before each meal until 35 weeks post-menstrual age. RESULTS: As intake of fortifiers increased, stools became harder in both groups (p < 0.01) though less in BC infants (p < 0.05). The incidence of bowel gas restlessness increased with laxative treatments and days of fortification in both groups (p < 0.01), but laxatives were prescribed later in BC infants (p < 0.01). With advancing age, stomach appearance scores improved, but more so in BC infants (p < 0.01). CONCLUSIONS: Although there are limitations, a minimally processed, bioactive milk product such as BC induced similar or slightly improved bowel habits in preterm infants.


Assuntos
Doenças do Prematuro , Leite Humano , Lactente , Gravidez , Feminino , Humanos , Recém-Nascido , Bovinos , Animais , Recém-Nascido Prematuro , Colostro , Agitação Psicomotora , Alimentos Fortificados , Hábitos
16.
Expert Opin Drug Saf ; 21(10): 1289-1301, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36252087

RESUMO

INTRODUCTION: At present, no pharmacological interventions have been approved for the treatment of agitation in Alzheimer's disease (AD), an important neuropsychiatric symptom that has been linked to increased mortality and greater caregiver burden. Antipsychotics offer some benefit, but increase the risk of adverse events such as falls, extrapyramidal symptoms, stroke, and mortality. Over the past 10 years, several new and repurposed medications have shown promise for treating AD-associated agitation. AREAS COVERED: We review the risks and benefits of emerging therapies for agitation in AD, which include newer atypical antipsychotics, selective serotonin reuptake inhibitors, cannabinoids, and dextromethorphan combination products. Other drugs such as mirtazapine, prazosin, and lithium are also discussed. Clinicaltrials.gov, PubMed/MEDLINE, EMBASE and Cochrane Central databases were searched for relevant studies from 1 January 2012 to 1 May 2022. EXPERT OPINION: At the present time, there are no pharmacological interventions for the treatment of agitation in AD whose benefits clearly outweigh their potential safety concerns. Therefore, management of agitation in AD should primarily be based on non-pharmacological approaches. When medications are considered necessary, they should only be initiated with the caregiver's appreciation of their risks and benefits and with careful and ongoing assessment of their safety.


Assuntos
Doença de Alzheimer , Antipsicóticos , Humanos , Doença de Alzheimer/tratamento farmacológico , Agitação Psicomotora/tratamento farmacológico , Agitação Psicomotora/etiologia , Antipsicóticos/efeitos adversos , Medição de Risco
17.
Artigo em Inglês | MEDLINE | ID: mdl-36293815

RESUMO

The aim of this study is to examine the relationship between chronotype, classroom behaviour and school performance in 140 healthy school-age children attending various levels of education during the 1st cycle during 2021 in Portugal. In this cross-sectional and quantitative study, the Chronotype Questionnaire for Children (to assess the chronotype) and the Conners Scale-a reduced version was presented to the teachers (to assess behaviours such as excessive movement, inattention and oppositional behaviours)-were used. The methodology of this study followed a comparative method since the independent variables were not controlled, and therefore, it was still possible to compare the differences between the morning and evening groups. Statistical methods were used such as multivariate analyses, inter-item correlations and reliability tests, and descriptive tests were used for the percentile analysis. The sample was divided into three groups based on the identification of the chronotype-morning, intermediate and evening types-to further study the relationship between these chronotypes, their academic performance and classroom behaviour were studied. A multivariate analysis of variance revealed that there was a higher rate of oppositional behaviour in the morning type and no differences in the school performance during the two semesters (covering all of the school periods) regarding the chronotype effect, even with the analysis of regression parameters and covariates. On the other hand, the morning-type children showed a greater amount of motor agitation and impulsivity after controlling for the gender covariate. Age had an effect on the chronotype, after controlling for the covariate parental education. This study highlights the need for further research on the chronotype of the morning children in order to regulate their behaviour. The data that were obtained raise questions that have not been yet considered in the literature in the area of education and infant development.


Assuntos
Ritmo Circadiano , Sono , Criança , Humanos , Estudos Transversais , Ritmo Circadiano/fisiologia , Sono/fisiologia , Agitação Psicomotora , Reprodutibilidade dos Testes , Inquéritos e Questionários
18.
Neuroscience ; 505: 78-90, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36244636

RESUMO

Genetic analyses have linked BTBD9 to restless legs syndrome (RLS) and sleep regulation. Btbd9 knockout mice show RLS-like motor restlessness. Previously, we found hyperactivity of cerebellar Purkinje cells (PCs) in Btbd9 knockout mice, which may contribute to the motor restlessness observed. However, underlying mechanisms for PC hyperactivity in Btbd9 knockout mice are unknown. Here, we used dissociated PC recording, brain slice recording and western blot to address this question. Our dissociated recording shows that knockout PCs had increased TEA-sensitive, Ca2+-dependent K+ currents. Applying antagonist to large conductance Ca2+-activated K+ (BK) channels further isolated the increased current as BK current. Consistently, we found increased amplitude of afterhyperpolarization and elevated BK protein levels in the knockout mice. Dissociated recording also shows a decrease in TEA-insensitive, Ca2+-dependent K+ currents. The result is consistent with reduced amplitude of tail currents, mainly composed of small conductance Ca2+-activated K+ (SK) currents, in slice recording. Our results suggest that BK and SK channels may be responsible for the hyperactivity of knockout PCs. Recently, BTBD9 protein was shown to associate with SYNGAP1 protein. We found a decreased cerebellar level of SYNGAP1 in Btbd9 knockout mice. However, Syngap1 heterozygous knockout mice showed nocturnal, instead of diurnal, motor restlessness. Our results suggest that SYNGAP1 deficiency may not contribute directly to the RLS-like motor restlessness observed in Btbd9 knockout mice. Finally, we found that PC-specific Btbd9 knockout mice exhibited deficits in motor coordination and balance similar to Btbd9 knockout mice, suggesting that the motor effect of BTBD9 in PCs is cell-autonomous.


Assuntos
Síndrome das Pernas Inquietas , Camundongos , Animais , Síndrome das Pernas Inquietas/genética , Síndrome das Pernas Inquietas/metabolismo , Agitação Psicomotora , Proteínas do Tecido Nervoso/metabolismo , Camundongos Knockout , Cerebelo/metabolismo , Sono , Proteínas Ativadoras de ras GTPase/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-36168659

RESUMO

OBJECTIVES: The effects of masupirdine on the neuropsychiatric symptoms were explored. METHODS: Masupirdine (SUVN-502) was evaluated for its effects on cognition in patients with moderate AD. The prespecified primary outcome showed no drug-placebo difference. Post hoc analyses of domains of the 12-item neuropsychiatric inventory scale were carried out. RESULTS: In a subgroup of patients (placebo, n = 57; masupirdine 50 mg, n = 53; masupirdine 100 mg, n = 48) with baseline agitation/aggression symptoms ≥1, a statistically significant reduction in agitation/aggression scores was observed in masupirdine 50 mg (95% confidence interval (CI), -1.9 to -0.5, p < 0.001) and masupirdine 100 mg (95% CI, -1.7 to -0.3, p = 0.007) treated arms at Week 13 in comparison to placebo and the effect was sustained for trial duration of 26 weeks in the masupirdine 50 mg treatment arm (95% CI, -2.3 to -0.8, p < 0.001). Similar observations were noted in the subgroup of patients (placebo, n = 29; masupirdine 50 mg, n = 30; masupirdine 100 mg, n = 21) with baseline agitation/aggression symptoms ≥3. In the subgroup of patients (placebo, n = 28; masupirdine 50 mg, n = 28; masupirdine 100 mg, n = 28) who had baseline psychosis symptoms and/or symptom emergence, a significant reduction in psychosis scores was observed in the masupirdine 50 mg (Week 4: 95% CI, -2.8 to -1.4, p < 0.001; Week 13: 95% CI, -3.3 to -1.3, p < 0.001) and masupirdine 100 mg (Week 4: 95% CI, -1.4 to 0, p = 0.046; Week 13: 95% CI, -1.9 to 0.1, p = 0.073) treatment arms in comparison to placebo. CONCLUSION: Further research is warranted to explore the potential beneficial effects of masupirdine on NPS.


Assuntos
Doença de Alzheimer , Transtornos Psicóticos , Agressão , Doença de Alzheimer/psicologia , Método Duplo-Cego , Humanos , Indóis , Piperazinas , Agitação Psicomotora/tratamento farmacológico , Agitação Psicomotora/etiologia , Agitação Psicomotora/psicologia , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/psicologia , Resultado do Tratamento
20.
Rev Med Chil ; 150(3): 361-367, 2022 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-36156721

RESUMO

BACKGROUND: Neuropsychiatric symptoms can be part of the clinical spectrum of COVID-19 infections. AIM: To devise an evidence based clinical algorithm as a guide for clinicians, to identify and treat underlying clinical syndromes of psychomotor agitation, such as delirium, catatonia or substance withdrawal in patients who are hospitalized and infected with SARS-CoV-2. MATERIAL AND METHODS: A review of the literature about the pharmacological management of neuropsychiatric manifestations of COVID-19 at the general hospital, to develop a clinical protocol based on a consensus from an interdisciplinary expert panel at a Clinical Hospital. RESULTS: A consensual clinical algorithm for the management of delirium, catatonia, and substance withdrawal, manifested as psychomotor agitation in patients hospitalized with COVID-19, was developed as a clinical proposal for physicians at different levels of complexity in health services. CONCLUSIONS: Cooperation among different clinical units in the general hospital facilitated the implementation of a clinical algorithm for clinicians for the management of psychomotor agitation in COVID-19 patients.


Assuntos
COVID-19 , Catatonia , Delírio , Síndrome de Abstinência a Substâncias , COVID-19/complicações , Catatonia/tratamento farmacológico , Catatonia/etiologia , Delírio/tratamento farmacológico , Delírio/etiologia , Hospitais Gerais , Humanos , Agitação Psicomotora/tratamento farmacológico , Agitação Psicomotora/etiologia , SARS-CoV-2 , Síndrome de Abstinência a Substâncias/tratamento farmacológico
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