RESUMO
Psychopathy is characterized by antisocial behavior, poor behavioral control and lacking empathy, and structural alterations in the corresponding neural circuits. Molecular brain basis of psychopathy remains poorly characterized. Here we studied type 2 dopamine receptor (D2R) and mu-opioid receptor (MOR) availability in convicted violent offenders with high psychopathic traits (n = 11) and healthy matched controls (n = 17) using positron emission tomography (PET). D2R were measured with radioligand [11C]raclopride and MORs with radioligand [11C]carfentanil. Psychopathic subjects had lowered D2R availability in caudate and putamen, and striatal D2R availability was also associated with degree of psychopathic traits in this prisoner sample. No group differences were found in MOR availability, although in the prisoner sample, psychopathic traits were negatively correlated with MOR availability in the amygdala and nucleus accumbens. We conclude that D2R signaling could be the putative neuromolecular pathway for psychopathy, whereas evidence for alterations in the MOR system is more limited.
Assuntos
Transtorno da Personalidade Antissocial , Criminosos , Tomografia por Emissão de Pósitrons , Receptores de Dopamina D2 , Violência , Humanos , Receptores de Dopamina D2/metabolismo , Masculino , Transtorno da Personalidade Antissocial/diagnóstico por imagem , Transtorno da Personalidade Antissocial/metabolismo , Adulto , Tomografia por Emissão de Pósitrons/métodos , Receptores Opioides mu/metabolismo , Racloprida/farmacocinética , Adulto Jovem , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Fentanila/análogos & derivadosRESUMO
Humans rapidly extract diverse and complex information from ongoing social interactions, but the perceptual and neural organization of the different aspects of social perception remains unresolved. We showed short movie clips with rich social content to 97 healthy participants while their haemodynamic brain activity was measured with fMRI. The clips were annotated moment-to-moment for a large set of social features and 45 of the features were evaluated reliably between annotators. Cluster analysis of the social features revealed that 13 dimensions were sufficient for describing the social perceptual space. Three different analysis methods were used to map the social perceptual processes in the human brain. Regression analysis mapped regional neural response profiles for different social dimensions. Multivariate pattern analysis then established the spatial specificity of the responses and intersubject correlation analysis connected social perceptual processing with neural synchronization. The results revealed a gradient in the processing of social information in the brain. Posterior temporal and occipital regions were broadly tuned to most social dimensions and the classifier revealed that these responses showed spatial specificity for social dimensions; in contrast Heschl gyri and parietal areas were also broadly associated with different social signals, yet the spatial patterns of responses did not differentiate social dimensions. Frontal and subcortical regions responded only to a limited number of social dimensions and the spatial response patterns did not differentiate social dimension. Altogether these results highlight the distributed nature of social processing in the brain.
Assuntos
Mapeamento Encefálico , Encéfalo , Humanos , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Lobo Occipital/fisiologia , Imageamento por Ressonância Magnética , Percepção SocialRESUMO
Laughter and crying are universal signals of prosociality and distress, respectively. Here we investigated the functional brain basis of perceiving laughter and crying using naturalistic functional magnetic resonance imaging (fMRI) approach. We measured haemodynamic brain activity evoked by laughter and crying in three experiments with 100 subjects in each. The subjects i) viewed a 20-minute medley of short video clips, and ii) 30 min of a full-length feature film, and iii) listened to 13.5 min of a radio play that all contained bursts of laughter and crying. Intensity of laughing and crying in the videos and radio play was annotated by independent observes, and the resulting time series were used to predict hemodynamic activity to laughter and crying episodes. Multivariate pattern analysis (MVPA) was used to test for regional selectivity in laughter and crying evoked activations. Laughter induced widespread activity in ventral visual cortex and superior and middle temporal and motor cortices. Crying activated thalamus, cingulate cortex along the anterior-posterior axis, insula and orbitofrontal cortex. Both laughter and crying could be decoded accurately (66-77% depending on the experiment) from the BOLD signal, and the voxels contributing most significantly to classification were in superior temporal cortex. These results suggest that perceiving laughter and crying engage distinct neural networks, whose activity suppresses each other to manage appropriate behavioral responses to others' bonding and distress signals.
Assuntos
Choro , Riso , Humanos , Choro/fisiologia , Encéfalo/fisiologia , Mapeamento Encefálico , Giro do Cíngulo/fisiologiaRESUMO
Sex differences in brain activity evoked by sexual stimuli remain elusive despite robust evidence for stronger enjoyment of and interest toward sexual stimuli in men than in women. To test whether visual sexual stimuli evoke different brain activity patterns in men and women, we measured hemodynamic brain activity induced by visual sexual stimuli in two experiments with 91 subjects (46 males). In one experiment, the subjects viewed sexual and nonsexual film clips, and dynamic annotations for nudity in the clips were used to predict hemodynamic activity. In the second experiment, the subjects viewed sexual and nonsexual pictures in an event-related design. Men showed stronger activation than women in the visual and prefrontal cortices and dorsal attention network in both experiments. Furthermore, using multivariate pattern classification we could accurately predict the sex of the subject on the basis of the brain activity elicited by the sexual stimuli. The classification generalized across the experiments indicating that the sex differences were task-independent. Eye tracking data obtained from an independent sample of subjects (N = 110) showed that men looked longer than women at the chest area of the nude female actors in the film clips. These results indicate that visual sexual stimuli evoke discernible brain activity patterns in men and women which may reflect stronger attentional engagement with sexual stimuli in men.
Assuntos
Nível de Alerta , Comportamento Sexual , Humanos , Feminino , Masculino , Nível de Alerta/fisiologia , Comportamento Sexual/fisiologia , Caracteres Sexuais , Prazer , PercepçãoRESUMO
Psychopathy and autism are both associated with aberrant social skills and empathy, yet only psychopaths are markedly antisocial and violent. Here, we compared the functional neural alterations underlying these two groups that both have aberrant empathetic abilities but distinct behavioral phenotypes. We studied 19 incarcerated male offenders with high psychopathic traits, 20 males with high-functioning autism, and 19 age-matched healthy controls. All groups underwent functional magnetic resonance imaging while they viewed dynamic happy, angry, and disgusted faces or listened to laughter and crying sounds. Psychopathy was associated with reduced somatomotor responses to almost all expressions, while participants with autism demonstrated less marked and emotion-specific alterations in the somatomotor area. These data suggest that psychopathy and autism involve both common and distinct functional alterations in the brain networks involved in the socioemotional processing. The alterations are more profound in psychopathy, possibly reflecting the more severely disturbed socioemotional brain networks in this population.
Assuntos
Transtorno Autístico , Humanos , Masculino , Transtorno Autístico/diagnóstico por imagem , Emoções/fisiologia , Encéfalo/diagnóstico por imagem , Empatia , Mapeamento Encefálico , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia. METHODS: Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects. RESULTS: There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness. DISCUSSION: Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.
Assuntos
Esquizofrenia , Humanos , Feminino , Masculino , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiologia , Idade de Início , Manual Diagnóstico e Estatístico de Transtornos MentaisRESUMO
Music can induce strong subjective experience of emotions, but it is debated whether these responses engage the same neural circuits as emotions elicited by biologically significant events. We examined the functional neural basis of music-induced emotions in a large sample (n = 102) of subjects who listened to emotionally engaging (happy, sad, fearful, and tender) pieces of instrumental music while their hemodynamic brain activity was measured with functional magnetic resonance imaging (fMRI). Ratings of the four categorical emotions and liking were used to predict hemodynamic responses in general linear model (GLM) analysis of the fMRI data. Multivariate pattern analysis (MVPA) was used to reveal discrete neural signatures of the four categories of music-induced emotions. To map neural circuits governing non-musical emotions, the subjects were scanned while viewing short emotionally evocative film clips. The GLM revealed that most emotions were associated with activity in the auditory, somatosensory, and motor cortices, cingulate gyrus, insula, and precuneus. Fear and liking also engaged the amygdala. In contrast, the film clips strongly activated limbic and cortical regions implicated in emotional processing. MVPA revealed that activity in the auditory cortex and primary motor cortices reliably discriminated the emotion categories. Our results indicate that different music-induced basic emotions have distinct representations in regions supporting auditory processing, motor control, and interoception but do not strongly rely on limbic and medial prefrontal regions critical for emotions with survival value.
Assuntos
Córtex Auditivo/diagnóstico por imagem , Emoções/fisiologia , Córtex Motor/diagnóstico por imagem , Música/psicologia , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiologia , Córtex Auditivo/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Feminino , Neuroimagem Funcional , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiologia , Humanos , Córtex Insular/diagnóstico por imagem , Córtex Insular/fisiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiologia , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiologia , Córtex Somatossensorial/diagnóstico por imagem , Córtex Somatossensorial/fisiologia , Adulto JovemRESUMO
Psychopathy is characterized by persistent antisocial behavior, impaired empathy, and egotistical traits. These traits vary also in normally functioning individuals. Here, we tested whether such antisocial personalities are associated with similar structural and neural alterations as those observed in criminal psychopathy. Subjects were 100 non-convicted well-functioning individuals, 19 violent male offenders, and 19 matched controls. Subjects underwent T1-weighted magnetic resonance imaging and viewed movie clips with varying violent content during functional magnetic resonance imaging. Psychopathic traits were evaluated with Levenson Self-Report Psychopathy Scale (controls) and Psychopathy Checklist-Revised (offenders). Psychopathic offenders had lower gray matter density (GMD) in orbitofrontal cortex and anterior insula. In the community sample, affective psychopathy traits were associated with lower GMD in the same areas. Viewing violence increased brain activity in periaqueductal grey matter, thalamus, somatosensory, premotor, and temporal cortices. Psychopathic offenders had increased responses to violence in thalamus and orbitofrontal, insular, and cingulate cortices. In the community sample, impulsivity-related psychopathy traits were positively associated with violence-elicited responses in similar areas. We conclude that brain characteristics underlying psychopathic spectrum in violent psychopathy are related to those observed in well-functioning individuals with asocial personality features.
Assuntos
Transtorno da Personalidade Antissocial/diagnóstico por imagem , Transtorno da Personalidade Antissocial/psicologia , Encéfalo/diagnóstico por imagem , Criminosos/psicologia , Adulto , Afeto , Mapeamento Encefálico , Feminino , Substância Cinzenta/diagnóstico por imagem , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estimulação Luminosa , Autorrelato , Violência , Adulto JovemRESUMO
BACKGROUND: The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model. METHODS: Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed. RESULTS: The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage. CONCLUSIONS: The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct "cores" of schizophrenia, the "Positive" and the "Negative," while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.
Assuntos
Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Fear protects organisms by increasing vigilance and preparedness, and by coordinating survival responses during life-threatening encounters. The fear circuit must thus operate on multiple timescales ranging from preparatory sustained alertness to acute fight-or-flight responses. Here we studied the brain basis of sustained and acute fear using naturalistic functional magnetic resonance imaging (fMRI) enabling analysis of different time-scales of fear responses. Subjects (N â= â37) watched feature-length horror movies while their hemodynamic brain activity was measured with fMRI. Time-variable intersubject correlation (ISC) was used to quantify the reliability of brain activity across participants, and seed-based phase synchronization was used for characterizing dynamic connectivity. Subjective ratings of fear were used to assess how synchronization and functional connectivity varied with emotional intensity. These data suggest that acute and sustained fear are supported by distinct neural pathways, with sustained fear amplifying mainly sensory responses, and acute fear increasing activity in brainstem, thalamus, amygdala and cingulate cortices. Sustained fear increased ISC in regions associated with acute fear, and also amplified functional connectivity within this network. The results were replicated in an independent experiment with a different subject sample and stimulus movie. The functional interplay between cortical networks involved in sustained anticipation of, and acute response to, threat involves a complex and dynamic interaction that depends on the proximity of threat, and the need to employ threat appraisals and vigilance for decision making and response selection.
Assuntos
Antecipação Psicológica/fisiologia , Encéfalo/fisiologia , Medo/fisiologia , Medo/psicologia , Filmes Cinematográficos , Rede Nervosa/fisiologia , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Rede Nervosa/diagnóstico por imagem , Estimulação Luminosa/métodos , Adulto JovemRESUMO
Emotions can be characterized by dimensions of arousal and valence (pleasantness). While the functional brain bases of emotional arousal and valence have been actively investigated, the neuromolecular underpinnings remain poorly understood. We tested whether the opioid and dopamine systems involved in reward and motivational processes would be associated with emotional arousal and valence. We used in vivo positron emission tomography to quantify µ-opioid receptor and type 2 dopamine receptor (MOR and D2R, respectively) availability in brains of 35 healthy adult females. During subsequent functional magnetic resonance imaging carried out to monitor hemodynamic activity, the subjects viewed movie scenes of varying emotional content. Arousal and valence were associated with hemodynamic activity in brain regions involved in emotional processing, including amygdala, thalamus, and superior temporal sulcus. Cerebral MOR availability correlated negatively with the hemodynamic responses to arousing scenes in amygdala, hippocampus, thalamus, and hypothalamus, whereas no positive correlations were observed in any brain region. D2R availability-here reliably quantified only in striatum-was not associated with either arousal or valence. These results suggest that emotional arousal is regulated by the MOR system, and that cerebral MOR availability influences brain activity elicited by arousing stimuli.
Assuntos
Nível de Alerta , Encéfalo/fisiologia , Emoções/fisiologia , Receptores de Dopamina D2/metabolismo , Receptores Opioides mu/metabolismo , Adulto , Encéfalo/metabolismo , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Adulto JovemRESUMO
STUDY AIM: Retinal microvasculature changes reflect systemic small vessel damage from obesity. The impact of bariatric surgery induced weight loss on the microvasculature is relatively unknown. We hypothesized that weight loss following bariatric surgery would be associated with improved structural changes in the retinal microvasculature, reflecting an overall improvement in microvascular health. METHODS: The study included 22 obese subjects scheduled for bariatric surgery (laparoscopic Roux-en-Y gastric bypass or a sleeve gastrectomy) and 15 lean, age-matched controls. Ophthalmic examination, including fundus photography, was performed at baseline and 6-months. Retinal microvasculature caliber was analysed quantitatively using a semi-automated computer program and summarized as central retinal artery equivalent (CRAE) and venular equivalent (CRVE). RESULTS: Mean weight loss at 6 months was 26.1 kg ± 8 kg in the bariatric surgery group. Retinal artery caliber increased (136.0 ± 1.4 to 141.4 ± 1.4 µm, p = 0.013) and venular caliber decreased (202.9 ± 1.9 to 197.3 ± 1.9 µm, p = 0.046) in the bariatric surgery group by 6 months, with no change in arteriolar (136.6 ± 1.1 to 134.5 ± 1.2, p = 0.222) or venular (195.1 ± 2.1 to 193.3 ± 2.2, p = 0.550) caliber in the control group. The arteriolar to venular ratio increased in the bariatric surgery group, with no change in the control group at 6 months. CONCLUSIONS: The findings suggest obesity-related microvascular changes are reversible after bariatric surgery-induced weight loss. The capacity for the retinal microvasculature to improve following bariatric surgery suggests plasticity of the human microvasculature early in the disease course.
Assuntos
Cirurgia Bariátrica/estatística & dados numéricos , Microvasos/patologia , Obesidade Mórbida , Vasos Retinianos/patologia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/patologia , Obesidade Mórbida/cirurgia , Estudos Prospectivos , Resultado do Tratamento , Redução de Peso/fisiologiaRESUMO
INTRODUCTION: A specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method. METHODS: Twenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed. RESULTS: Exploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients. DISCUSSION: This study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time.
Assuntos
Progressão da Doença , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Esquizofrenia/diagnóstico , Adulto , Europa (Continente) , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria , Esquizofrenia/classificação , Esquizofrenia/fisiopatologia , Síndrome de Sotos , Adulto JovemRESUMO
AIMS: Bariatric surgery is the most effective treatment to tackle morbid obesity and type 2 diabetes, but the mechanisms of action are still unclear. The objective of this study was to investigate the effects of bariatric surgery on intestinal fatty acid (FA) uptake and blood flow. MATERIALS AND METHODS: We recruited 27 morbidly obese subjects, of whom 10 had type 2 diabetes and 15 were healthy age-matched controls. Intestinal blood flow and fatty acid uptake from circulation were measured during fasting state using positron emission tomography (PET). Obese subjects were re-studied 6 months after bariatric surgery. The mucosal location of intestinal FA retention was verified in insulin resistant mice with autoradiography. RESULTS: Compared to lean subjects, morbidly obese subjects had higher duodenal and jejunal FA uptake (P < .001) but similar intestinal blood flow (NS). Within 6 months after bariatric surgery, obese subjects had lost 24% of their weight and 7/10 diabetic subjects were in remission. Jejunal FA uptake was further increased (P < .03). Conversely, bariatric surgery provoked a decrease in jejunal blood flow (P < .05) while duodenal blood flow was preserved. Animal studies showed that FAs were taken up into enterocytes, for the most part, but were also transferred, in part, into the lumen. CONCLUSIONS: In the obese, the small intestine actively takes up FAs from circulation and FA uptake remains higher than in controls post-operatively. Intestinal blood flow was not enhanced before or after bariatric surgery, suggesting that enhanced intestinal FA metabolism is not driven by intestinal perfusion.
Assuntos
Absorção Fisiológica , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Absorção Intestinal , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Obesidade Mórbida/metabolismo , Adulto , Animais , Cirurgia Bariátrica , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Gorduras na Dieta/metabolismo , Ácidos Graxos não Esterificados/sangue , Feminino , Radioisótopos de Flúor , Intolerância à Glucose/sangue , Intolerância à Glucose/complicações , Intolerância à Glucose/metabolismo , Intolerância à Glucose/terapia , Humanos , Resistência à Insulina , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/diagnóstico por imagem , Intestino Delgado/irrigação sanguínea , Intestino Delgado/diagnóstico por imagem , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Obesidade Mórbida/terapia , Tomografia por Emissão de Pósitrons , Fluxo Sanguíneo Regional , Redução de Peso , Programas de Redução de PesoRESUMO
OBJECTIVE: We aimed to investigate the effect of bariatric surgery on lipid metabolism in supraclavicular brown adipose tissue in morbidly obese women. We hypothesized that lipid metabolism improves after surgery-induced weight loss. MATERIALS AND METHODS: A total of 23 morbidly obese women (BMI, 42.1 ± 4.2 kg/m2 ; age, 43.8 ± 9.8 years) were assessed before and 6 months after bariatric surgery and 15 age- and sex-matched controls (22.6 ± 2.8 kg/m2 ) were assessed once. In the supraclavicular fat depot, fractional (FUR) and NEFA uptake rates were measured with 18 F-FTHA-PET. We assessed tissue morphology (triglyceride content) using computed tomography (CT)-radiodensity (in Hounsfield Units[HU]) and the proportion of fat with high density (sBAT [%]) in the entire supraclavicular fat depot. RESULTS: The supraclavicular fractional uptake rate was lower in obese women compared to controls (0.0055 ± 0.0035 vs 0.0161 ± 0.0177 1/min, P = .001). Both FUR (to 0.0074 ± 0.0035 1/min, P = .01) and NEFA uptake rates (to 0.50 ± 0.50 µmol/100 g/min, P = .001) increased after surgery. Compared to controls, obese women had lower CT-radiodensity (-101.2 ± 10.1 vs -82.5 ± 5.8 HU, P < .001) and sBAT (43.4 ± 8.4% vs 64.5 ± 12.4%, P < .001). After surgery, CT-radiodensity increased (to -82.5 ± 9.6 HU, P < .001), signifying decreased triglyceride content and sBAT improved (to 58.0 ± 10.7%, P < .001), indicating an increased proportion of brown fat. The change in tissue morphology, reflected as increase in CT-radiodensity and sBAT (%), was associated with a decrease in adiposity indices and an increase in whole-body insulin sensitivity. CONCLUSIONS: A decrease in triglyceride content, coupled with the increased proportion of brown adipose tissue in the supraclavicular fat depot, may play a role in the improvement of whole-body insulin sensitivity observed in morbidly obese women after surgery-induced weight loss.
Assuntos
Tecido Adiposo Marrom/metabolismo , Cirurgia Bariátrica , Metabolismo Energético , Resistência à Insulina , Metabolismo dos Lipídeos , Obesidade Mórbida/metabolismo , Obesidade Mórbida/cirurgia , Absorção Fisiológica , Tecido Adiposo Marrom/diagnóstico por imagem , Adiposidade , Adulto , Índice de Massa Corporal , Clavícula , Ácidos Graxos não Esterificados/metabolismo , Feminino , Radioisótopos de Flúor , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Obesidade Mórbida/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Triglicerídeos/metabolismo , Redução de Peso , Imagem Corporal TotalRESUMO
Neuroimaging studies have shown that seeing others in pain activates brain regions that are involved in first-hand pain, suggesting that shared neuromolecular pathways support processing of first-hand and vicarious pain. We tested whether the dopamine and opioid neurotransmitter systems involved in nociceptive processing also contribute to vicarious pain experience. We used in vivo positron emission tomography to quantify type 2 dopamine and µ-opioid receptor (D2R and MOR, respectively) availabilities in brains of 35 subjects. During functional magnetic resonance imaging, the subjects watched short movie clips depicting persons in painful and painless situations. Painful scenes activated pain-responsive brain regions including anterior insulae, thalamus and secondary somatosensory cortices, as well as posterior superior temporal sulci. MOR availability correlated negatively with the haemodynamic responses during painful scenes in anterior and posterior insulae, thalamus, secondary and primary somatosensory cortices, primary motor cortex, and superior temporal sulci. MOR availability correlated positively with orbitofrontal haemodynamic responses during painful scenes. D2R availability was not correlated with the haemodynamic responses in any brain region. These results suggest that the opioid system contributes to neural processing of vicarious pain, and that interindividual differences in opioidergic system could explain why some individuals react more strongly than others to seeing pain.
Assuntos
Encéfalo/metabolismo , Empatia/fisiologia , Percepção da Dor/fisiologia , Receptores de Dopamina D2/metabolismo , Receptores Opioides mu/metabolismo , Percepção Visual/fisiologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Mapeamento Encefálico , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Empatia/efeitos dos fármacos , Feminino , Fentanila/análogos & derivados , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Imagem Multimodal , Oxigênio/sangue , Percepção da Dor/efeitos dos fármacos , Tomografia por Emissão de Pósitrons , Racloprida , Compostos Radiofarmacêuticos , Receptores Opioides mu/antagonistas & inibidores , Percepção Social , Percepção Visual/efeitos dos fármacos , Adulto JovemRESUMO
Body fat accumulation, distribution, and metabolic activity are factors in the pathophysiology of obesity and type 2 diabetes (T2D). We investigated adipose blood flow, fatty acid uptake (FAU), and subcutaneous and visceral fat cellularity in obese patients with or without T2D. A total of 23 morbidly obese (mean body mass index = 42 kg/m2) patients were studied before and 6 mo after bariatric surgery; 15 nonobese subjects served as controls. Positron emission tomography was used to measure tissue FAU (with 18F-FTHA) and blood flow (with H215O); MRI was used for fat distribution and fat biopsy for adipocyte size. Obese subjects had subcutaneous hyperplasia and hypertrophy and lower blood flow; when expressed per cell, flow was similar to controls. FAU into subcutaneous and visceral depots was increased in the obese; per unit tissue mass, however, FAU was similar to controls but reduced in skeletal muscle. Fatty acid fractional extraction in subcutaneous fat and muscle was only increased in obese patients with T2D. We conclude that surgery reduces subcutaneous fat hyperplasia and hypertrophy; subcutaneous blood flow and FAU decrease in absolute terms and per cell while fractional FAU remains unchanged in T2D. In the obese, subcutaneous blood flow is a determinant of FAU and is coupled with cellularity; efficiency of FAU is enhanced in subcutaneous fat and muscle in T2D.
Assuntos
Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/metabolismo , Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Ácidos Graxos/metabolismo , Obesidade Mórbida , Fluxo Sanguíneo Regional , Adipócitos/metabolismo , Adipócitos/patologia , Tecido Adiposo/patologia , Adiposidade , Adulto , Distribuição da Gordura Corporal , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Gordura Intra-Abdominal/irrigação sanguínea , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Metabolismo dos Lipídeos , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/cirurgia , Gordura Subcutânea/irrigação sanguínea , Gordura Subcutânea/metabolismo , Gordura Subcutânea/patologiaRESUMO
Neurochemical pathways involved in pathological overeating and obesity are poorly understood. Although previous studies have shown increased µ-opioid receptor (MOR) and decreased dopamine D2 receptor (D2R) availability in addictive disorders, the role that these systems play in human obesity still remains unclear. We studied 13 morbidly obese women [mean body mass index (BMI), 42 kg/m(2)] and 14 nonobese age-matched women, and measured brain MOR and D2R availability using PET with selective radioligands [(11)C]carfentanil and [(11)C]raclopride, respectively. We also used quantitative meta-analytic techniques to pool previous evidence on the effects of obesity on altered D2R availability. Morbidly obese subjects had significantly lower MOR availability than control subjects in brain regions relevant for reward processing, including ventral striatum, insula, and thalamus. Moreover, in these areas, BMI correlated negatively with MOR availability. Striatal MOR availability was also negatively associated with self-reported food addiction and restrained eating patterns. There were no significant differences in D2R availability between obese and nonobese subjects in any brain region. Meta-analysis confirmed that current evidence for altered D2R availability in obesity is only modest. Obesity appears to have unique neurobiological underpinnings in the reward circuit, whereby it is more similar to opioid addiction than to other addictive disorders. The opioid system modulates motivation and reward processing, and low µ-opioid availability may promote overeating to compensate decreased hedonic responses in this system. Behavioral and pharmacological strategies for recovering opioidergic function might thus be critical to curb the obesity epidemic.
Assuntos
Química Encefálica/fisiologia , Obesidade Mórbida/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores Opioides mu/metabolismo , Adulto , Anatomia Transversal , Ingestão de Alimentos/psicologia , Humanos , Processamento de Imagem Assistida por Computador , Obesidade Mórbida/diagnóstico por imagem , Obesidade Mórbida/psicologia , Tomografia por Emissão de Pósitrons , Inquéritos e QuestionáriosRESUMO
Obesity is associated with lowered brain's grey (GM) and white matter (WM) density as measured by voxel-based morphometry (VBM). Nevertheless, it remains unknown whether obesity has a causal influence on cerebral atrophy. We recruited 47 morbidly obese subjects (mean BMI = 42.2, SD = 4.0, 42 females and five males) eligible for bariatric surgery and 29 non-obese subjects (mean BMI = 23.2, SD = 2.8, 23 females and six males) served as controls. Baseline scans were acquired with T1-weighted magnetic resonance imaging (MRI) at 1.5 Tesla; obese participants were scanned again six months after the surgery. Local GM and WM densities were quantified using VBM. Full-volume analyses were used for comparing baseline between-group differences as well as the effects of surgery-induced weight loss in the morbidly obese. Metabolic variables were used in linear models to predict WM and GM densities. Obese subjects had initially lower GM densities in widespread cortical areas including frontal, parietal, and temporal regions as well as insulae. Lower WM densities were observed throughout the WM. Bariatric surgery and concomitant weight loss resulted in global increase in WM density. Grey matter increase was limited to occipital and inferior temporal regions. Metabolic variables were associated with brain densities. We conclude that weight loss results in global recovery of WM as well as local recovery of grey matter densities. These changes likely reflect improved brain tissue integrity. Hum Brain Mapp 37:3745-3756, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Cirurgia Bariátrica , Substância Cinzenta/diagnóstico por imagem , Obesidade Mórbida/diagnóstico por imagem , Obesidade Mórbida/cirurgia , Substância Branca/diagnóstico por imagem , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Colesterol/sangue , Feminino , Substância Cinzenta/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/metabolismo , Tamanho do Órgão , Resultado do Tratamento , Redução de Peso , Substância Branca/metabolismo , Adulto JovemRESUMO
Dopamine and opioid neurotransmitter systems share many functions such as regulation of reward and pleasure. µ-Opioid receptors (MOR) modulate the mesolimbic dopamine system in ventral tegmental area and striatum, key areas implicated in reward. We hypothesized that dopamine and opioid receptor availabilities correlate in vivo and that this correlation is altered in obesity, a disease with altered reward processing. Twenty lean females (mean BMI 22) and 25 non-binge eating morbidly obese females (mean BMI 41) underwent two positron emission tomography scans with [(11)C]carfentanil and [(11)C]raclopride to measure the MOR and dopamine D2 receptor (DRD2) availability, respectively. In lean subjects, the MOR and DRD2 availabilities were positively associated in the ventral striatum (r=0.62, p=0.003) and dorsal caudate nucleus (r=0.62, p=0.004). Moreover, DRD2 availability in the ventral striatum was associated with MOR availability in other regions of the reward circuitry, particularly in the ventral tegmental area. In morbidly obese subjects, this receptor interaction was significantly weaker in ventral striatum but unaltered in the caudate nucleus. Finally, the association between DRD2 availability in the ventral striatum and MOR availability in the ventral tegmental area was abolished in the morbidly obese. The study demonstrates a link between DRD2 and MOR availabilities in living human brain. This interaction is selectively disrupted in mesolimbic dopamine system in morbid obesity. We propose that interaction between the dopamine and opioid systems is a prerequisite for normal reward processing and that disrupted cross-talk may underlie altered reward processing in obesity.