RESUMO
Prior research has identified differential protein expression levels of linker histone H1x within the ventral hippocampus (vHipp) of stress-susceptible versus stress-resilient mice. These mice are behaviorally classified based on their divergent responses to chronic social stress. Here, we sought to determine whether elevated vHipp H1x protein levels directly contribute to these diverging behavioral adaptations to stress. First, we demonstrated that stress-susceptible mice uniquely express elevated vHipp H1x protein levels following chronic stress. Given that linker histones coordinate heterochromatin compaction, we hypothesize that elevated levels of H1x in the vHipp may impede pro-resilience transcriptional adaptations and prevent development of the resilient phenotype following social stress. To test this, 8-10-week-old male C57BL/6 J mice were randomly assigned to groups undergoing 10 days of chronic social defeat stress (CSDS) or single housing, respectively. Following CSDS, mice were classified as susceptible versus resilient based on their social interaction behaviors. We synthesized a viral overexpression (OE) vector for H1x and transduced all stressed and single housed mice with either H1x or control GFP within vHipp. Following viral delivery, we conducted social, anxiety-like, and memory-reliant behavior tests on distinct cohorts of mice. We found no behavioral adaptations following H1x OE compared to GFP controls in susceptible, resilient, or single housed mice. In sum, although we confirm elevated vHipp protein levels of H1x associate with susceptibility to social stress, we observe no significant behavioral consequence of H1x OE. Thus, we conclude elevated levels of H1x are associated with, but are not singularly sufficient to drive development of behavioral adaptations to stress.
Assuntos
Comportamento Animal , Hipocampo , Histonas , Camundongos Endogâmicos C57BL , Estresse Psicológico , Animais , Masculino , Hipocampo/metabolismo , Camundongos , Estresse Psicológico/metabolismo , Histonas/metabolismo , Comportamento Animal/fisiologia , Adaptação Psicológica/fisiologia , Resiliência Psicológica , Derrota Social , Ansiedade/metabolismoRESUMO
The neurobiological origins of social behaviors are incompletely understood. Here we utilized synthetic biology approaches to reprogram the function of ZFP189, a transcription factor whose expression and function in rodent prefrontal cortex was previously demonstrated to be protective against stress-induced social deficits. We created novel synthetic ZFP189 transcription factors including ZFP189VPR, which activates the transcription of target genes and therefore exerts opposite functional control from the endogenous, transcriptionally repressive ZFP189WT. Following viral delivery of these synthetic ZFP189 transcription factors to mouse prefrontal cortex, we observe that ZFP189-mediated transcriptional control promotes mature dendritic spine morphology on transduced pyramidal neurons. Interestingly, inversion of ZFP189-mediated transcription in this brain area, achieved by viral delivery of synthetic ZFP189VPR, precipitates social behavioral deficits in terms of social interaction, motivation, and the cognition necessary for the maintenance of social hierarchy, without other observable behavioral deficits. RNA sequencing of virally manipulated prefrontal cortex tissues reveals that ZFP189 transcription factors of opposing regulatory function (ZFP189WT versus ZFP189VPR) have opposite influence on the expression of genetic transposable elements as well as genes that participate in adaptive immune functions. Collectively, this work reveals that ZFP189 function in the prefrontal cortex coordinates structural and transcriptional neuroadaptations necessary for complex social behaviors while regulating transposable element-rich regions of DNA and the expression of immune-related genes. Given the evidence for a co-evolution of social behavior and the brain immune response, we posit that ZFP189 may have evolved to augment brain transposon-associated immune function as a way of enhancing an animal's capacity for functioning in social groups.
Assuntos
Elementos de DNA Transponíveis , Fatores de Transcrição , Camundongos , Animais , Fatores de Transcrição/genética , Córtex Pré-Frontal/metabolismo , Comportamento Social , Dedos de Zinco/genética , Roedores/genética , Roedores/metabolismo , ImunidadeRESUMO
Prior research has identified differential protein expression levels of linker histone H1x within the ventral hippocampus (vHipp) of stress-susceptible versus stress-resilient mice. These mice are behaviorally classified based on their divergent responses to chronic social stress. Here, we sought to determine whether elevated vHipp H1x protein levels directly contribute to these diverging behavioral adaptations to stress. First, we demonstrate that stress-susceptible mice uniquely express elevated vHipp H1x protein levels following chronic stress. Given that linker histones coordinate heterochromatin compaction, we hypothesize that elevated levels of H1x in the vHipp may impede pro-resilience transcriptional adaptations and prevent development of the resilient phenotype following social stress. To test this, 8-10-week-old male C57BL/6J mice were randomly assigned to stressed and unstressed groups undergoing 10 days of chronic social defeat stress (CSDS) or single housing respectively. Following CSDS, mice were classified as susceptible versus resilient based on their social interaction behaviors. We synthesized a viral overexpression (OE) vector for H1x and transduced experimental mice with either H1x or control GFP within vHipp. Following viral delivery, we conducted social, anxiety-like, and memory-reliant behavior tests on distinct cohorts of mice. We found no behavioral adaptations following H1x OE compared to GFP controls in susceptible, resilient, or unstressed mice. In sum, although we confirm vHipp protein levels of H1x correlate with susceptibility to social stress, we observe no significant behavioral consequence of H1x OE. Thus, we conclude elevated levels of H1x are correlated with, but are not singularly sufficient to drive development of behavioral adaptations to stress.
RESUMO
The neurobiological origins of social behaviors are incompletely understood. Here we utilized synthetic biology approaches to reprogram the function of ZFP189, a transcription factor whose expression and function in the rodent prefrontal cortex was previously determined to be protective against stress-induced social deficits. We created novel synthetic ZFP189 transcription factors including ZFP189VPR, which activates the transcription of target genes and therefore exerts opposite functional control from the endogenous, transcriptionally repressive ZFP189WT. Upon viral delivery of these synthetic ZFP189 transcription factors to mouse prefrontal cortex, we observe that ZFP189-mediated transcriptional control promotes mature dendritic spine morphology on transduced pyramidal neurons. Interestingly, dysregulation of ZFP189-mediated transcription in this brain area, achieved by delivery of synthetic ZFP189VPR, precipitates social behavioral deficits in terms of social interaction, motivation, and the cognition necessary for the maintenance of social hierarchy, without other observable behavioral deficits. By performing RNA sequencing in virally manipulated prefrontal cortex tissues, we discover that ZFP189 transcription factors of opposing regulatory function have opposite influence on the expression of genetic transposable elements as well as genes that participate in immune functions. Collectively, this work reveals that ZFP189 function in the prefrontal cortex coordinates structural and transcriptional neuroadaptations necessary for social behaviors by binding transposable element-rich regions of DNA to regulate immune-related genes. Given the evidence for a co-evolution of social behavior and the brain immune response, we posit that ZFP189 may have evolved to augment brain transposon-associated immune function as a way of enhancing an animal's capacity for functioning in social groups.
RESUMO
BACKGROUND: Over the course of chronic drug use, brain transcriptional neuroadaptation is thought to contribute to a change in drug use behavior over time. The function of the transcription factor CREB (cAMP response element binding protein) within the nucleus accumbens (NAc) has been well documented in opposing the rewarding properties of many classes of drugs, yet the gene targets through which CREB causally manifests these lasting neuroadaptations remain unknown. Here, we identify zinc finger protein 189 (Zfp189) as a CREB target gene that is transcriptionally responsive to acute and chronic cocaine use within the NAc of mice. METHODS: To investigate the role of the CREB-Zfp189 interaction in cocaine use, we virally delivered modified clustered regularly interspaced short palindromic repeats (CRISPR)/dCas9 constructs capable of selectively localizing CREB to the Zfp189 gene promoter in the NAc of mice. RESULTS: We observed that CREB binding to the Zfp189 promoter increased Zfp189 expression and diminished the reinforcing responses to cocaine. Furthermore, we showed that NAc Zfp189 expression increased within D1 medium spiny neurons in response to acute cocaine but increased in both D1- and D2-expressing medium spiny neurons in response to chronic cocaine. CREB-mediated induction of Zfp189 potentiated electrophysiological activity of D1- and D2-expressing medium spiny neurons, recapitulating the known effect of CREB on these neurons. Finally, targeting CREB to the Zfp189 promoter within NAc Drd2-expressing neurons, but not Drd1-expressing neurons, was sufficient to diminish cocaine-conditioned behaviors. CONCLUSIONS: Together, these findings point to the CREB-Zfp189 interaction within the NAc Drd2+ neurons as a molecular signature of chronic cocaine use that is causal in counteracting the reinforcing effects of cocaine.
Assuntos
Adaptação Fisiológica , Transtornos Relacionados ao Uso de Cocaína , Cocaína , Neurônios Espinhosos Médios , Regiões Promotoras Genéticas , Fatores de Transcrição , Animais , Camundongos , Adaptação Fisiológica/genética , Cocaína/farmacologia , Cocaína/metabolismo , Transtornos Relacionados ao Uso de Cocaína/genética , Neurônios Espinhosos Médios/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Núcleo Accumbens , Receptores de Dopamina D1/genética , Receptores de Dopamina D1/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Objective: The process of detecting faces can be considered one of the initial steps in face recognition, which is essential for human interaction. We sought to investigate whether a face perception task reliably detects subtle perceptual disturbances between patients with bipolar disorder (BD) and healthy controls. Methods: In this multisite study, we examined differences between BD patients and matched healthy controls. Participants were instructed to detect the orientation (either left or right) of a face when it was presented as a face/non-face pair on a computer screen using Bayesian entropy estimation. Data analyses compared performance between the groups. Results: Overall, BD patients exhibited more perceptual disturbances compared with controls. BD patients who took olanzapine had better performance and faster reaction times (RTs) than patients who took lithium or were medication-naive. BD patients who took lithium had better performance and faster RTs than medication-naive patients. The medication-naive BD group exhibited greater disturbances than all other groups. Conclusion: These findings highlight the reliability of the face perception task used herein and may be important for public health initiatives and follow-up studies that seek to understand the diverse effects of other variables that can affect sensory processing in this population.
RESUMO
People with social anxiety disorder (SAD) are at increased risk for alcohol-related problems. Most research exploring social anxiety and alcohol use has examined negative drinking consequences, with less consideration of positive consequences-namely positive social experiences-that may reinforce alcohol use. In this daily diary study, we examined how adults diagnosed with SAD (Nâ¯=â¯26) and a psychologically healthy control group (Nâ¯=â¯28) experienced positive drinking consequences in naturally occurring drinking episodes during the study period. For 14 consecutive days, participants answered questions about alcohol use, motives for drinking, and positive consequences of drinking. On days when participants drank, those with SAD were more likely than healthy controls to perceive a reduction in anxiety, but the two groups did not differ in their likelihood of experiencing positive social drinking consequences. For both groups, on days when they were more motivated to drink to enhance social experiences (affiliation motives) or cope with distress (coping motives), they were more likely to obtain positive consequences from drinking. Compared to controls, participants with SAD endorsed stronger trait and daily coping motives (anxiety-coping, social anxiety-coping, and depression-coping). Results are discussed in the context of reinforcement mechanisms that may maintain social anxiety and alcohol use.
Assuntos
Fobia Social , Adaptação Psicológica , Adulto , Consumo de Bebidas Alcoólicas , Ansiedade , Humanos , MotivaçãoRESUMO
Bipolar (BPD) patients have deficits in cognition, but there are still controversies about the effects of some medications on their cognitive performance. Here, we investigated the relationship between cognition in terms of executive functions, memory, and attention in both first-episode medication-naive BPD patients and BPD patients taking olanzapine. Forty-one healthy controls, 40 unmedicated drug-naive BPD patients, and 34 BPD patients who took only olanzapine were recruited for the study. Cognitive performance was assessed using the Flanker test, Stroop test, and Corsi-block test. Bayesian multivariate regression analysis was run considering maximum robustness to avoid bias and to predict the outcomes. Our results revealed that unmedicated medication-naive BPD patients performed worse than healthy controls and the olanzapine group in some tasks. Additionally, BPD patients who took olanzapine had better cognitive performance than healthy controls and unmedicated BPD patients. The acute cognitive effects were predicted by olanzapine dosage and serum levels (i.e., large effects). The potential pro-cognitive effects of olanzapine in BPD patients should be carefully interpreted by considering various other clinical variables. We expect that our findings will contribute to further research in this area, with the goal of helping other researchers, patients, and the population.
Assuntos
Transtorno Bipolar , Teorema de Bayes , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Cognição , Função Executiva , Humanos , Testes Neuropsicológicos , Olanzapina/uso terapêuticoRESUMO
The use of noninvasive tools can help understand mental states and changes that are caused by medications, symptom severity, and other clinical variables. We investigated low-level visual processing using the contrast sensitivity function (CSF), a reliable, robust, and widely used approach. Our main purpose was (1) to evaluate visual impairments in schizophrenia (SCZ) and bipolar disorder (BPD) patients and (2) to investigate associations between clinical variables and visual function in both diseases. Fifty-six healthy controls (HCs; mean age = 31.04 years), 42 BPD patients (mean age = 32.84 years) who took only lithium, and 39 SCZ patients who took only olanzapine (mean age = 32.80 years) were recruited for this study. CSF differed between groups. Both groups of patients exhibited lower discrimination at low, mid-, and high spatial frequencies compared with HCs. No differences were observed between patients, with the exception of high spatial frequency. These impairments were also related to clinical variables, revealed by a strong effect in the mediation analyses. These findings may aid investigations of other clinical variables and the role of state- and trait-like effects on visual and cognitive processing in these patient populations. This study underscores the need for visual remediation interventions.
Assuntos
Transtorno Bipolar , Esquizofrenia , Adulto , Transtorno Bipolar/complicações , Cognição , Humanos , Percepção VisualRESUMO
Chronic tobacco consumption, identified as Tobacco Use Disorder (TUD), is a public health problem. We present a case report of a 37-year-old Brazilian male diagnosed with TUD at age 26, with no comorbidities, that presented visual improvements (i.e., lower thresholds and better discrimination) after nicotine gum administration. Here, we assessed contrast sensitivity and chromatic discrimination using the Metropsis and the Cambridge Colour Test, respectively. Results showed lower thresholds for both visual tasks after the use of nicotine gum. Even considering this is a single case report, our intent is to open new avenues for research involving smoking, addiction and the use of nicotine gum as a replacement tool or adjuvant tool for improvement of visual and/or cognitive processing. It is well known that nicotine gum has protective effects for some diseases, and improves some cognitive functions. However, unclear were its effects on visual processing of people with TUD.
Assuntos
Abandono do Hábito de Fumar , Tabagismo , Adulto , Humanos , Masculino , Nicotina/uso terapêutico , Fumar/psicologia , Abandono do Hábito de Fumar/métodos , Dispositivos para o Abandono do Uso de Tabaco , Tabagismo/tratamento farmacológicoRESUMO
Previous studies have reported visual impairments in patients with bipolar disorder (BPD), but unclear were whether clinical variables would be associated with those disturbances. Here, we investigate the relationship between visual functioning, in terms of color discrimination, and the impact of BPD duration, mood state, and the patients' medication. Forty-five participants (25-45 years old) were recruited for this study. Color discrimination was performed using the Cambridge Colour Test. Serial multiple mediations were run to investigate the assumption of association between color discrimination and the clinical variables. Our findings showed that, compared with healthy controls, BPD patients' performance was worse for the Protan, Deutan, and Tritan vectors, revealing deterioration of color discrimination. In addition, the mediation analyses revealed a strong direct (p < .001) and moderate-to-high indirect effects (p < .01) of medication and symptom severity on color discrimination. Overall, both longer the duration of the disease and greater the symptom severity of BPD patients resulted in worse performance. It highlights the importance of examining the wider clinical context of an affective disorder to understand how it affects visual processing in this population.
Assuntos
Transtorno Bipolar , Adulto , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Cognição , Percepção de Cores , Humanos , Pessoa de Meia-Idade , Percepção VisualRESUMO
Estudos mostram que o tabagismo é responsável por afetar algumas funções cognitivas. No entanto, a nicotina é apenas um dos componentes existentes no cigarro e existem evidências de que pode servir como agente neuroprotetivo e causar melhoras em algumas funções cognitivas. O objetivo desta pesquisa foi investigar como a nicotina interage com algumas funções cognitivas. Um ensaio clínico piloto com administração de gomas de nicotina contendo 2-mg ou 4-mg, ou gomas placebo contendo a mesma textura, sabor e aparência, foi realizado. Quarenta e dois participantes participaram da pesquisa e os resultados indicaram que a relação entre nicotina e o desempenho na tarefa Go/No-Go podem ser bidirecionais. Os resultados indicaram que participantes do grupo que utilizaram 4-mg de nicotina apresentaram menor desempenho, enquanto os participantes que fizeram uso de 2-mg de nicotina tiveram melhor desempenho do que os demais. Esta pesquisa tem aplicações biopsicossociais e podem ajudar na compreensão da relação entre tabagismo e nicotina, além de contribuir para estratégias que possam ajudar no abandono do cigarro ou na melhora de condições que afetem a cognição (AU).
Past findings in the literature indicated that smoking could affect given cognitive functions. However, nicotine is only one of the components in cigarettes and there is evidence that it may act as a neuroprotective agent and improve some cognitive functions. The purpose of this research was to investigate how nicotine interacts with certain cognitive functions. We conducted a pilot clinical trial using nicotine gum containing 2-mg or 4-mg, or placebo gum with the same texture, flavor, and appearance. Forty-two healthy nonsmokers were enrolled in this research. Our findings indicated that the relationship between nicotine and performance on the Go/No-Go task might be opposite. The results showed that participants in the 4-mg group performed worse, while participants who used 2-mg of nicotine performed better than the others. This research supports biopsychosocial applications and can help interpret the relationship between smoking and nicotine, and contribute to strategies that may support smoking cessation, or improve conditions that affect cognition (AU).
Estudios demuestran que el tabaquismo es responsable de afectar a algunas funciones cognitivas. Sin embargo, la nicotina es solo uno de los componentes de los cigarrillos, y existen evidencias de que la nicotina puede actuar como un agente neuroprotector y mejorar algunas funciones cognitivas. El objetivo de este estudio fue investigar cómo la nicotina interactúa con algunas funciones cognitivas. Se realizó un ensayo clínico piloto con la administración de chicles de nicotina de 2 mg o 4 mg, o chicles de placebo con la misma textura, sabor y apariencia. Cuarenta y dos participantes participaron en la investigación y los resultados indicaron que la relación entre la nicotina y el rendimiento en la tarea Go/No-go puede ser bidireccional. Los resultados indicaron que los participantes del grupo de 4 mg obtuvieron un menor rendimiento en las variables del Go/No-Go, mientras que los participantes que utilizaron 2 mg de nicotina obtuvieron un mejor rendimiento que los demás. Esta investigación respalda las aplicaciones biopsicosociales y puede ayudar a interpretar la relación entre el tabaquismo y la nicotina, además de contribuir a las estrategias que pueden ayudar a dejar de fumar o mejorar las condiciones que afectan la cognición (AU).
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Função Executiva , Goma de Mascar de Nicotina , Nicotina/administração & dosagem , Placebos/administração & dosagem , Tabagismo/psicologia , Distribuição de Qui-Quadrado , Projetos Piloto , Método Duplo-Cego , Análise de VariânciaRESUMO
Objectives: The effects of smoking on color vision have been scarcely studied. To bridge such gap, this study examined if there were differences in chromatic discrimination between heavy and light smokers. Methods: The psychophysical Trivector test was used to evaluate chromatic discrimination in healthy controls (n = 36), heavy smokers (n = 29), and light smokers (n = 32). The subject's task was to identify the orientation of the Landolt C ring gap - presented and randomized in one of the four positions (e.g., up, down, right, and left). Results: The thresholds for Protan (red), Deutan (green) and Tritan (blue) were higher in heavy smokers compared to nonsmokers but not to light smokers. Conclusions: The results confirm that heavy smoking and chronic exposure to its harmful compounds affect color discrimination when compared to light smoking; and this is more pronounced in heavy smokers than light smokers. This is particularly important to understand the differences among smokers on visual and multisensory processing.
Assuntos
Testes de Percepção de Cores , Percepção de Cores , Testes de Percepção de Cores/métodos , Humanos , Fumantes , Fumar/epidemiologiaRESUMO
OBJECTIVE: The process of detecting faces can be considered one of the initial steps in face recognition, which is essential for human interaction. We sought to investigate whether a face perception task reliably detects subtle perceptual disturbances between patients with bipolar disorder (BD) and healthy controls. METHODS: In this multisite study, we examined differences between BD patients and matched healthy controls. Participants were instructed to detect the orientation (either left or right) of a face when it was presented as a face/non-face pair on a computer screen using Bayesian entropy estimation. Data analyses compared performance between the groups. RESULTS: Overall, BD patients exhibited more perceptual disturbances compared with controls. BD patients who took olanzapine had better performance and faster reaction times (RTs) than patients who took lithium or were medication-naive. BD patients who took lithium had better performance and faster RTs than medication-naive patients. The medication-naive BD group exhibited greater disturbances than all other groups. CONCLUSION: These findings highlight the reliability of the face perception task used herein and may be important for public health initiatives and follow-up studies that seek to understand the diverse effects of other variables that can affect sensory processing in this population.
Assuntos
Transtorno Bipolar , Humanos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Emoções , Lítio/farmacologia , Teorema de Bayes , Reprodutibilidade dos Testes , Expressão Facial , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: The main purpose of this study was to investigate the isolated effects of nicotine on visual processing, namely contrast processing. METHODS: Thirteen participants, aged 18-40 years, were enrolled in this double blind, randomized and pilot controlled trial involving nicotine gum administration (placebo, 2-mg and 4-mg doses). The participants' instruction was to detect the location of vertical gratings (0.2; 1.0; 3.3; 5.7; 8.8; 13.2 and 15.9 cycles per degree) when it was presented either left or right on the monitor screen. A repeated multivariate analysis of variance was conducted to analyse the results for the visual processing tasks. Bayesian analyses were also carried out considering maximum robustness to avoid bias. RESULTS: The findings that nicotine gum administration resulted in better contrast discrimination when compared to placebo gum (p < .001). More specifically, the 4-mg resulted in better visual sensitivity when compared to the 2-mg (p < .01) and the placebo (p < .001) gum. Demographic data were not related to the outcomes. CONCLUSIONS: These data bring the need for support the findings. If proved, it is possible that nicotine, in small doses, can have a potential therapeutic use for those populations with low vision. TRIAL REGISTRATION NUMBER: RBR-46tjy3.
Assuntos
Nicotina , Abandono do Hábito de Fumar , Teorema de Bayes , Método Duplo-Cego , Humanos , Imageamento por Ressonância Magnética , não Fumantes , Percepção VisualRESUMO
Objective: The main purpose of this study was to investigate short-term effects of nicotine gum on facial detection. Methods: Fourteen participants (mean age = 26.8 years, SD = 2.5 years; eight males) were enrolled in this pilot randomized controlled trial of nicotine gum administration (placebo, 2-mg and 4-mg doses). The participants were instructed to detect the location of a face when it was presented in a face/nonface pair on the screen. A repeated multivariate analysis of variance was conducted to analyze the results for reaction time and discrimination index. Demographics were used to explore significant association on facial detection. Bayesian analyses were also carried out considering maximum robustness to avoid bias. Results: The results indicated that the 2-mg dose resulted in faster reaction time and better discrimination than the 4-mg dose (p < 0.001). The 4-mg dose resulted in slower reaction time and lower discrimination index compared to both placebo (p < 0.01) and 2-mg doses (p < 0.001). Demographic data were not related to the outcomes. Conclusions: The results indicate that nicotine improved facial detection, but only at low doses (i.e., 2-mg), following a U-shaped curve. We trust future studies will continue to advance this research field, and if further work supports these preliminary findings, nicotine can act as therapeutic target in populations such as those with low vision.
Assuntos
Reconhecimento Facial , Gengiva , Voluntários Saudáveis/estatística & dados numéricos , Nicotina/administração & dosagem , não Fumantes , Tempo de Reação , Adulto , Cotinina/sangue , Feminino , Humanos , Masculino , Projetos PilotoRESUMO
OBJECTIVE: Chronic tobacco consumption, classified as tobacco use disorder (TUD), has been associated with a variety of health problems. Investigations of face processing in TUD are hampered by lack of evidence. Here, we evaluated facial detection in TUD and assessed test-retest reliability for a facial detection task. METHODS: Participants were instructed to detect the orientation (either left or right) of a face when it was presented with a face/non-face pair on the monitor screen, using Bayesian entropy estimation. Bland-Altman analysis and intraclass correlation coefficients were used to test the reliability of the task. The general linear model and Bayesian statistics were then used to evaluate differences between TUD (n=48) and healthy controls (n=34). RESULTS: The reliability of the task was high for the 96 stimuli presentations. Slower reaction times (p < 0.001) and lower discrimination index (p < 0.001) were observed in the TUD group than for healthy controls. Mediation analysis indicated direct effects of smoking duration on reaction time (p < 0.001) and discrimination index (p < 0.001). CONCLUSIONS: Overall, we observed high reliability of this task and reduction of facial detection in tobacco use disorder. We conclude our findings are significant for public health initiatives and call for follow-up studies.
Assuntos
Tabagismo , Teorema de Bayes , Humanos , Reprodutibilidade dos Testes , Fumar , Uso de Tabaco , Tabagismo/diagnósticoRESUMO
The GH/IGF-I axis has essential roles in regulating bone and vascular status. The age-related decrease in GH secretion ("somatopause") may contribute to osteoporosis and atherosclerosis, commonly observed in the elderly. Adult-onset GH deficiency (GHD) has been reported to be associated with reduced bone mineral density (BMD), increased risk of fractures, and premature atherosclerosis. We have shown the young adult individuals with isolated GHD (IGHD) due to a homozygous for the c.57+1G>A GHRH receptor gene mutation have normal volumetric BMD (vBMD), and not develop premature atherosclerosis, despite adverse risk factor profile. However, the bone and vascular impact of lifetime GHD on the aging process remains unknown. We studied a group of ten older IGHD subjects (≥60 years) homozygous for the mutation, comparing them with 20 age- and gender-matched controls (CO). Areal BMD was measured, and vBMD was calculated at the lumbar spine and total hip. Vertebral fractures and abdominal aortic calcifications (expressed as calcium score) were also assessed. Areal BMD was lower in IGHD, but vBMD was similar in the two groups. The percent of fractured individuals was similar, but the mean number of fractures per individual was lower in IGHD than CO. Calcium score was similar in the two groups. A positive correlation was found between calcium score and number of fractures. Untreated lifetime IGHD has beneficial consequences on bone status and does not have a deleterious effect on abdominal aorta calcification.
Assuntos
Envelhecimento/fisiologia , Doenças da Aorta/epidemiologia , Densidade Óssea , Nanismo Hipofisário/epidemiologia , Calcificação Vascular/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal/patologia , Estudos de Casos e Controles , Nanismo Hipofisário/genética , Feminino , Nível de Saúde , Hormônio do Crescimento Humano/deficiência , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Receptores de Neuropeptídeos/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética , Fraturas da Coluna Vertebral/epidemiologia , Coluna VertebralRESUMO
CONTEXT: The GH/IGF-I axis is important for bone growth, but its effects on joint function are not completely understood. Adult-onset GH-deficient individuals have often reduced bone mineral density (BMD). However, there are limited data on BMD in adult patients with untreated congenital isolated GH-deficient (IGHD). We have shown that adult IGHD individuals from the Itabaianinha, homozygous for the c.57+1G>A GHRHR mutation, have reduced bone stiffness, but BMD and joint status in this cohort are unknown. OBJECTIVE: The goal is to study BMD, joint function, and osteoarthritis score in previously untreated IGHD adults harboring the c.57+1G>A GHRHR mutation. DESIGN: This is a cross-sectional study. METHODS: Areal BMD by dual-energy X-ray absorptiometry was measured in 25 IGHD and 23 controls (CO). Volumetric BMD (vBMD) was calculated at the lumbar spine and total hip. Joint function was assessed by goniometry of elbow, hips, and knees. X-rays were used to measure the anatomic axis of knee and the severity of osteoarthritis, using a classification for osteophytes (OP) and joint space narrowing (JSN). RESULTS: Genu valgum was more prevalent in IGHD than CO. The osteoarthritis knees OP score was similar in both groups, and knees JSN score showed a trend to be higher in IGHD. The hips OP score and JSN score were higher in IGHD. Areal BMD was lower in IGHD than CO, but vBMD was similar in the two groups. Range of motion was similar in elbow, knee, and hip in IGHD and CO. CONCLUSIONS: Untreated congenital IGHD due to a GHRHR mutation causes hip joint problems and genu valgum, without apparent clinical significance, reduces bone size, but does not reduce vBMD of the lumbar spine and hip.