RESUMO
Adverse childhood experiences (ACEs) have lifelong effects on emotional behavior and are frequent in Borderline Personality Disorder (BPD) and Major Depressive Disorder (MDD). The Central Autonomic Network (CAN), which modulates heart rate variability (HRV), comprises brain regions that mediate emotion regulation processes. However, it remains unclear the effect of ACEs on CAN dynamics and its relationship with HRV in these disorders. We studied the effects of ACEs on the brain and HRV simultaneously, during regulation of psychological stress in 19 BPD, 20 MDD and 20 healthy controls (HC). Participants underwent a cognitive reappraisal task during fMRI with simultaneous ECG acquisition. ACEs exposure was associated with increased activity of CAN and salience network components in patients with MDD compared to BPD during cognitive reappraisal. A brain-autonomic coupling was found in BPD relative to HC during emotion regulation, whereby greater activity of left anterior cingulate and medial superior frontal gyrus areas was coupled with increased HRV. Results suggest that ACEs exposure is associated with a distinct activation of the CAN and salience network regions governing responses to psychological stress in MDD compared to BPD. These alterations may constitute a distinctive neurobiological mechanism for abnormal emotion processing and regulation related to ACEs in MDD.
Assuntos
Experiências Adversas da Infância , Transtorno da Personalidade Borderline , Transtorno Depressivo Maior , Transtorno da Personalidade Borderline/psicologia , Cognição , Transtorno Depressivo Maior/diagnóstico por imagem , Emoções/fisiologia , HumanosRESUMO
A traditional hallmark of cognitive impairment associated with late-onset Alzheimer´s disease (LOAD) is episodic memory impairment. However, early alterations have been identified in brain regions associated with executive function in asymptomatic, middle-age offspring of patients with LOAD (O-LOAD) compared to those with no family history. We hypothesized that executive function among O-LOAD would correlate with structural and amyloid brain imaging differently from those without a family history of LOAD (control subjects, CS). Executive function, cortical thickness, and in-vivo Aß deposits were quantified in 30 O-LOAD and 25 CS. Associations were observed among O-LOAD only. Cortical thickness in the left lateral orbitofrontal cortex was positively associated with Design Fluency. The Stroop Color and Word Test, correlated positively with right rostral mid-frontal cortex thickness. Trails Making Test-B was inversely related to left medial orbitofrontal thickness. Tower of London total time was positively associated with ß-amyloid deposition in the right precuneus. These results support previous evidence that early executive dysfunction might reflect subtle, early changes in persons at risk of LOAD and suggests that executive function alterations deserve further exploration in the LOAD literature.
Assuntos
Doença de Alzheimer , Memória Episódica , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Função Executiva , Humanos , Tomografia por Emissão de PósitronsRESUMO
The natural history of preclinical late-onset Alzheimer's disease (LOAD) remains obscure and has received less attention than that of early-onset AD (EOAD), in spite of accounting for more than 99% of cases of AD. With the purpose of detecting early structural and functional traits associated with the disorder, we sought to characterize cortical thickness and subcortical grey matter volume, cerebral metabolism, and amyloid deposition in persons at risk for LOAD in comparison with a similar group without family history of AD. We obtained 3T T1 images for gray matter volume, FDG-PET to evaluate regional cerebral metabolism, and PET-PiB to detect fibrillar amyloid deposition in 30 middle-aged, asymptomatic, cognitively normal individuals with one parent diagnosed with LOAD (O-LOAD), and 25 comparable controls (CS) without family history of neurodegenerative disorders (CS). We observed isocortical thinning in AD-relevant areas including posterior cingulate, precuneus, and areas of the prefrontal and temporoparietal cortex in O-LOAD. Unexpectedly, this group displayed increased cerebral metabolism, in some cases overlapping with the areas of cortical thinning, and no differences in bilateral hippocampal volume and hippocampal metabolism. Given the importance of age in this sample of individuals potentially developing early AD-related changes, we controlled results for age and observed that most differences in cortical thickness and metabolism became nonsignificant; however, greater deposition of ß-amyloid was observed in the right hemisphere including temporoparietal cortex, postcentral gyrus, fusiform inferior and middle temporal and lingual gyri. If replicated, the present observations of morphological, metabolic, and amyloid changes in cognitively normal persons with family history of LOAD may bear important implications for the definition of very early phenotypes of this disorder.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides/metabolismo , Córtex Cerebral , Substância Cinzenta , Adulto , Filhos Adultos , Idade de Início , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/metabolismo , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de PósitronsRESUMO
BACKGROUND: We have obtained previous evidence of limbic dysfunction in middle-aged, asymptomatic offspring of late-onset Alzheimer's disease (LOAD) patients, and failure to recover from proactive semantic interference has been shown to be a sensitive cognitive test in other groups at risk for LOAD. OBJECTIVE: To assess the effects of specific proactive semantic interference deficits as they relate to functional magnetic resonance imaging (fMRI) neocortical and limbic functional connectivity in middle aged offspring of individuals with LOAD (O-LOAD) and age-equivalent controls. METHODS: We examined 21 O-LOAD and 20 controls without family history of neurodegenerative disorders (CS) on traditional measures of cognitive functioning and the LASSI-L, a novel semantic interference test uniquely sensitive to the failure to recover from proactive interference (frPSI). Cognitive tests then were correlated to fMRI connectivity of seeds located in entorhinal cortex and anterodorsal thalamic nuclei among O-LOAD and CS participants. RESULTS: Relative to CS, O-LOAD participants evidenced lower connectivity between entorhinal cortex and orbitofrontal, anterior cingulate, and anterior temporal cortex. In the offspring of LOAD patients, LASSI-L measures of frPSI were inversely associated with connectivity between anterodorsal thalamus and contralateral posterior cingulate. Intrusions on the task related to frPSI were inversely correlated with a widespread connectivity network involving hippocampal, insular, posterior cingulate, and dorsolateral prefrontal cortices, along with precunei and anterior thalamus in this group. Different patterns of connectivity associated with frPSI were observed among controls. CONCLUSION: The present results suggest that both semantic interference deficits and connectivity abnormalities might reflect limbic circuit dysfunction as a very early clinical signature of LOAD pathology, as previously demonstrated for other limbic phenotypes, such as sleep and circadian alterations.
Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Cognição , Predisposição Genética para Doença , Sistema Límbico/fisiopatologia , Filhos Adultos , Idade de Início , Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Mapeamento Encefálico , Estudos Transversais , Feminino , Humanos , Sistema Límbico/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Sintomas Prodrômicos , SemânticaRESUMO
Moral decision-making involves complex social cognitive processes which are known to be altered in patients with schizophrenia and first-degree relatives. Traditional philosophical views on human moral behavior have distinguished between utilitarian views (which emphasize outcomes) and deontological approaches (defining what is right to do according to certain norms). Since emotions have been suggested to play a determining role in moral behavior, we hypothesized patients with schizophrenia and unaffected siblings would make more utilitarian choices and show faulty activation of brain areas concerned with emotion regulation during such tasks. Unexpectedly, all participants (n = 13 per group) made the same proportion of utilitarian and deontological decisions. Brain activation common to all groups induced by moral decisions included two circumscribed portions of right ventromedial and dorsolateral prefrontal cortex, adding to previous evidence on a right prosencephalic cognitive network involved in ethical decisions. However, brain activation induced by moral decisions was different in healthy persons, schizophrenia patients, and nonpsychotic siblings in regards to areas directly concerned with emotion processing. These results seem to underscore the role of acquired norms in moral decisions, a frequently overlooked concept in the neurobiological characterization of human ethical behavior, and add to previous evidence of abnormal social cognitive processing in schizophrenia.
Assuntos
Princípios Morais , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/fisiopatologia , Percepção Social , Adulto , Tomada de Decisões/fisiologia , Emoções/fisiologia , Feminino , Lateralidade Funcional/fisiologia , Neuroimagem Funcional , Humanos , Masculino , Testes Neuropsicológicos , Psicologia do Esquizofrênico , IrmãosRESUMO
BACKGROUND: Social cognitive deficits contribute to functional disability in schizophrenia. Social cognitive tasks in healthy persons consistently evoke activation of medial prefrontal cortex, inferior frontal gyrus, temporoparietal gyrus, and posterior cingulate cortex/precuneus. We tested the hypothesis that patients with schizophrenia and their unaffected siblings share dysfunction of the same neural networks. METHODS: Neural activation during emotion processing (EP), theory of mind (ToM), and control tasks was measured using functional magnetic resonance imaging (fMRI) in 14 patients with schizophrenia, 14 nonpsychotic siblings of patients with schizophrenia, and 14 matched healthy subjects. RESULTS: Compared with healthy controls, patients with schizophrenia showed reduced activation of right hemisphere structures involved in EP and ToM including inferior frontal gyrus, middle frontal gyrus, and right temporoparietal junction. These deficits were shared, in part, by unaffected siblings. The latter group demonstrated deficits in bilateral precuneus activation during ToM, not present in patients. CONCLUSIONS: Schizophrenia appears to be associated with a deficit in activation of right hemisphere components of a ToM network. Such deficits are shared in part by those at high genetic risk but unaffected by schizophrenia.
Assuntos
Encéfalo/patologia , Transtornos Cognitivos/etiologia , Lateralidade Funcional/fisiologia , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Irmãos , Comportamento Social , Adulto , Análise de Variância , Encéfalo/irrigação sanguínea , Emoções , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Oxigênio/sangue , Reconhecimento Visual de Modelos , Escalas de Graduação Psiquiátrica , Tempo de Reação , Esquizofrenia/patologia , Teoria da Mente , Adulto JovemRESUMO
OBJECTIVE: The objective of the study was to determine whether patients with schizophrenia and their unaffected first-degree relatives have abnormal autonomic nervous system (ANS) responses to social cognition tasks. BACKGROUND: Social cognition impairments are significant in schizophrenia. ANS activity has been shown to be abnormal in schizophrenia patients, and some of the abnormalities seem to be shared by patients' unaffected relatives. METHOD: Heart rate variability (HRV) was measured at rest and during social cognition tasks, in patients with schizophrenia, their nonpsychotic first-degree relatives, and matched healthy controls (n=19 in each group). RESULTS: Social cognition tasks induced a shortening of the RR interval in unaffected relatives, but not in patients. Social cognition tasks generated decreases in high-frequency (indicating cardiac vagal activity) and low-frequency (reflecting predominantly sympathetic activity) HRV in patients. In relatives, the decrease occurred in the high-frequency component only. Low-frequency HRV was higher in patients during a theory of mind task than a control task. These changes were not observed in the controls. CONCLUSIONS: Social cognitive tasks induce a pattern of peripheral autonomic activity different from that seen in generic arousal responses, and this pattern is abnormal in schizophrenia patients. Autonomic abnormalities in unaffected first-degree relatives seem restricted to the parasympathetic division of the ANS.
Assuntos
Transtornos Cognitivos/psicologia , Família/psicologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Adulto , Idoso , Sistema Nervoso Autônomo/fisiopatologia , Estudos de Casos e Controles , Transtornos Cognitivos/complicações , Transtornos Cognitivos/fisiopatologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Psicológicos/estatística & dados numéricos , Desempenho Psicomotor/fisiologiaRESUMO
Previous studies have suggested that social cognition is affected in individuals with schizophrenia. The purpose of this study was to explore to what extent social cognition deficits are shared by unaffected first-degree relatives, and the nature of the relationship between performance in different paradigms of social cognition. 20 Schizophrenia patients (7 females, 31+/-10 years), 20 healthy age- and gender-matched individuals, 20 unaffected first-degree relatives of the schizophrenia patients (11 females, 50+/-20 years), and 20 healthy individuals matched for age and gender were recruited. Patients showed deficits in the detection of social Faux Pas (0.80+/-0.17 vs. controls: 0.94+/-0.09, p=0.025) and the correct identification of Theory of Mind stories (0.71+/-0.13 vs. controls: 0.82+/-0.12, p=0.038). Relatives performed poorly in the Faces Test (0.83+/-0.14 vs. controls: 0.9+/-0.08, p=0.048), the Reading the Mind in the Eyes Test (0.59+/-0.17 vs. controls: 0.71+/-0.14, p=0.046) and the detection of social Faux Pas (0.8+/-0.2 vs. controls: 0.93+/-0.09, p=0.024). Abnormalities were independent of age, years of education, and general cognitive performance in patients and their relatives. Performance in an Emotion Processing task (Faces Test) was correlated with performance in theory of mind tests in healthy individuals and relatives of patients with schizophrenia only. These results suggest that schizophrenia patients and their unaffected first-degree relatives display similar but nonidentical patterns of social cognition processing.
Assuntos
Afeto , Transtornos Cognitivos/epidemiologia , Família/psicologia , Esquizofrenia/epidemiologia , Percepção Social , Teoria da Mente , Transtornos Cognitivos/diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Esquizofrenia/diagnóstico , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Schizophrenia patients exhibit an abnormal autonomic response to mental stress. We sought to determine the cardiac autonomic response to mental arithmetic stress in their unaffected first-degree relatives. METHODS: Heart rate variability (HRV) analysis was performed on recordings obtained before, during, and after a standard mental arithmetic task to induce mental stress. 22 unaffected first-degree relatives of patients meeting DSM-IV criteria for schizophrenia (R) and 22 healthy individuals (C) were included in this study. RESULTS: Patients' relatives (R) had a normal response to the mental arithmetic stress test, showing an increased heart rate compared with controls. They also displayed the characteristic pattern of relative contributions of HRV components that consists of increased low-frequency (LF) HRV and decreased high-frequency (HF) HRV. Recovery of the resting pattern of HRV immediately after stress termination was observed in healthy subjects (LF 62+/-16% vs. 74+/-10% , HF 37+/-16% vs. 25+/-10%, F=9.616, p=0.004), but not in patients' relatives (LF 60+/-19% vs. 70+/-13%, HF 40+/-19% vs. 29+/-13%, F=8.4, p=0.056). CONCLUSIONS: First-degree relatives of schizophrenia patients exhibit an abnormal pattern of protracted response to mental arithmetic stress, though less intense than that observed in patients in a previous study. This suggests that a pattern of autonomic response to stress may therefore be familial and heritable.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Família , Frequência Cardíaca/fisiologia , Resolução de Problemas/fisiologia , Esquizofrenia/fisiopatologia , Estresse Psicológico/fisiopatologia , Adolescente , Adulto , Idoso , Feminino , Coração/inervação , Humanos , Masculino , Matemática , Pessoa de Meia-Idade , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Psicologia do Esquizofrênico , Estresse Psicológico/diagnóstico , Estresse Psicológico/genéticaRESUMO
In order to assess the relationships among mood, peripheral autonomic output and circulating immunoinflammatory mediators in older individuals with decompensated heart failure (CHF), 20 consecutive patients (78+/-7 years, 35% women) admitted to the coronary care unit with a clinical diagnosis of acute/decompensated CHF of coronary origin were examined. Mood was evaluated by the 21-item Hamilton Depression Scale (HAM-D). Four patients met the criteria for major depression. Heart rate variability (HRV) analysis and the levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL-4, IL-6 and IL-10 were measured within 24-72 h of admission. A significant positive relationship between score in HAM-D and serum IL-6 levels was detected with a similar trend as far as IL-2 levels. Circulating IL-2 levels were strongly associated with the HRV L/H quotient, an index of increased sympathetic and/or decreased parasympathetic thoracic activity. A negative correlation between vagal activity (as assessed by HRV) and IL-4 occurred. Neither TNF-alpha nor IL-10 were detectable in this group of elderly patients. The results add to the concept that mood and autonomic unbalance are associated with increased systemic inflammation in old patients with decompensated CHF, a potential mechanism for mood-related worsened prognosis of heart failure at an advanced age.
Assuntos
Doenças do Sistema Nervoso Autônomo/imunologia , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Insuficiência Cardíaca , Interferon gama/imunologia , Interleucina-10/imunologia , Interleucina-2/imunologia , Interleucina-4/imunologia , Interleucina-6/imunologia , Transtornos do Humor/epidemiologia , Transtornos do Humor/psicologia , Fragmentos de Peptídeos/imunologia , Células Th1/imunologia , Células Th2/imunologia , Fator de Necrose Tumoral alfa/imunologia , Nervo Vago/imunologia , Nervo Vago/fisiopatologia , Doença Aguda , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Dispneia/diagnóstico , Dispneia/epidemiologia , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/imunologia , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/fisiologia , Humanos , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-2/sangue , Interleucina-4/sangue , Interleucina-6/sangue , Masculino , Fragmentos de Peptídeos/sangue , Prevalência , Sons Respiratórios , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: The vulnerability-stress hypothesis is an established model of schizophrenia symptom formation. We sought to characterise the pattern of the cardiac autonomic response to mental arithmetic stress in patients with stable schizophrenia. METHODS: We performed heart rate variability (HRV) analysis on recordings obtained before, during, and after a standard test of autonomic function involving mental stress in 25 patients with DSM-IV schizophrenia (S) and 25 healthy individuals (C). RESULTS: Patients with schizophrenia had a normal response to the mental arithmetic stress test. Relative contributions of low-frequency (LF) HRV and high-frequency (HF) HRV influences on heart rate in patients were similar to controls both at rest (LF 64+/-19% (S) vs. 56+/-16% (C); HF 36+/-19% (S) vs. 44+/-16% (C), t=1.52, p=0.136) and during mental stress, with increased LF (S: 76+/-12%, C: 74+/-11%) and decreased HF (S: 24+/-12%, C: 26+/-11%) in the latter study condition. Whilst healthy persons recovered the resting pattern of HRV immediately after stress termination (LF 60+/-15%, HF 40+/-15%, F=18.5, p<0.001), in patients HRV remained unchanged throughout the observed recovery period, with larger LF (71+/-17%) and lower HF (29+/-17%) compared with baseline (F=7.3, p=0.013). CONCLUSIONS: Patients with schizophrenia exhibit a normal response to the mental arithmetic stress test as a standard test of autonomic function but in contrast with healthy individuals, they maintain stress-related changes of cardiac autonomic function beyond stimulus cessation.
Assuntos
Nível de Alerta/fisiologia , Sistema Nervoso Autônomo/fisiopatologia , Frequência Cardíaca/fisiologia , Resolução de Problemas/fisiologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Estresse Psicológico/complicações , Adulto , Eletrocardiografia , Feminino , Análise de Fourier , Habituação Psicofisiológica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Valores de Referência , Esquizofrenia/diagnóstico , Processamento de Sinais Assistido por ComputadorRESUMO
Patients with anorexia nervosa or bulimia nervosa often have signs of autonomic dysfunction potentially deleterious to the heart. The aim of this study was to ascertain the nonlinear properties of heart rate variability in patients with eating disorders. A group of 33 women with eating disorders (14 anorexia, 19 bulimia) and 19 healthy controls were included in the study. Conventional time- and frequency-domain heart rate variability measurements, along with nonlinear heart rate variability measurements including the short-term fractal scaling exponent alpha and approximate entropy (ApEn) were calculated. Anorexia nervosa patients exhibited decreased values of alpha, while bulimia nervosa patients had decreased values of ApEn. Low-frequency heart rate variability was decreased in patients with anorexia. In conclusion, these results are compatible with the view that a more severe alteration of cardiac autonomic function is present in anorexia than in bulimia.
Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Frequência Cardíaca/fisiologia , Adulto , Índice de Massa Corporal , Feminino , Humanos , Masculino , Dinâmica não LinearRESUMO
BACKGROUND/AIMS: Depression has been associated with increased mortality among individuals with heart failure, but the mechanism for this association is unsettled. Depression is often found to result in autonomic dysfunction which, if present in heart failure, might help explain worsened outcomes. METHODS: This study was a cross-sectional evaluation of the relationship between depressive symptoms and cardiac autonomic function, as assessed by short-term heart rate variability (HRV) analysis in aged patients with acute/decompensated heart failure of coronary origin (CHF). A 21-item Hamilton Depression score and measures of short-term HRV were obtained in 31 inpatients >or=65 years of age, 24-72 h after admission to the coronary care unit with a diagnosis of CHF. RESULTS: Clinical depression was present in 22.6% of participants. In the sample as a whole, increasing depressive symptoms were associated with decreased low-frequency HRV. CONCLUSION: These results may be important in light of recent indications that decreased low-frequency HRV is a predictor of mortality in patients with heart failure.