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The serotonin transporter (5-HTT) plays a critical role in regulating serotonergic neurotransmission and is implicated in the pathophysiology of anxiety and affective disorders. Positron emission tomography scans using [(11)C]DASB [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile] to measure 5-HTT availability (an index of receptor density and binding) were performed in 34 rhesus monkeys in which the relationship between regional brain glucose metabolism and anxious temperament was previously established. 5-HTT availability in the amygdalohippocampal area and bed nucleus of the stria terminalis correlated positively with individual differences in a behavioral and neuroendocrine composite of anxious temperament. 5-HTT availability also correlated positively with stress-induced metabolic activity within these regions. Collectively, these findings suggest that serotonergic modulation of neuronal excitability in the neural circuitry associated with anxiety mediates the developmental risk for affect-related psychopathology.
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The length polymorphism of the serotonin (5-HT) transporter gene promoter region has been implicated in altered 5-HT function and, in turn, neuropsychiatric illnesses, such as anxiety and depression. The nonhuman primate has been used as a model to study anxiety-related mechanisms in humans based upon similarities in behavior and the presence of a similar 5-HT transporter gene polymorphism. Stressful and threatening contexts in the nonhuman primate model have revealed 5-HT transporter genotype dependent differences in regional glucose metabolism. Using the rhesus monkey, we examined the extent to which serotonin transporter genotype is associated with 5-HT transporter binding in brain regions implicated in emotion-related pathology. METHODS: Genotype data and high resolution PET scans were acquired in 29 rhesus (Macaca mulatta) monkeys. [C-11]DASB dynamic PET scans were acquired for 90 min in the anesthetized animals and images of distribution volume ratio (DVR) were created to serve as a metric of 5-HT transporter binding for group comparison based on a reference region method of analysis. Regional and voxelwise statistical analysis were performed with corrections for anatomical differences in gray matter probability, sex, age and radioligand mass. RESULTS: There were no significant differences when comparing l/l homozygotes with s-carriers in the regions of the brain implicated in anxiety and mood related illnesses (amygdala, striatum, thalamus, raphe nuclei, temporal and prefrontal cortex). There was a significant sex difference in 5-HT transporter binding in all regions with females having 18%-28% higher DVR than males. CONCLUSIONS: Because these findings are consistent with similar genotype findings in humans, this further strengthens the use of the rhesus model for studying anxiety-related neuropathologies.
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A variant allele in the promoter region of the serotonin transporter gene, SLC6A4, the s allele, is associated with increased vulnerability to develop anxiety-related traits and depression. Furthermore, functional magnetic resonance imaging (fMRI) studies reveal that s carriers have increased amygdala reactivity in response to aversive stimuli, which is thought to be an intermediate phenotype mediating the influences of the s allele on emotionality. We used high-resolution microPET [18F]fluoro-2-deoxy-D-glucose (FDG) scanning to assess regional brain metabolic activity in rhesus monkeys to further explore s allele-related intermediate phenotypes. Rhesus monkeys provide an excellent model to understand mechanisms underlying human anxiety, and FDG microPET allows for the assessment of brain activity associated with naturalistic environments outside the scanner. During FDG uptake, monkeys were exposed to different ethologically relevant stressful situations (relocation and threat) as well as to the less stressful familiar environment of their home cage. The s carriers displayed increased orbitofrontal cortex activity in response to both relocation and threat. However, during relocation they displayed increased amygdala reactivity and in response to threat they displayed increased reactivity of the bed nucleus of the stria terminalis. No increase in the activity of any of these regions occurred when the animals were administered FDG in their home cages. These findings demonstrate context-dependent intermediate phenotypes in s carriers that provide a framework for understanding the mechanisms underlying the vulnerabilities of s-allele carriers exposed to different types of stressors.
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This brief commentary highlights seven sins in the study of emotion that are explicitly treated in contemporary affective neuroscience. These sins are (1) Affect and cognition are subserved by separate and independent neural circuits; (2) Affect is subcortical; (3) Emotions are in the head; (4) Emotions can be studied from a purely psychological perspective; (5) Emotions are similar in structure across age and species; (6) Specific emotions are instantiated in discrete locations in the brain; and (7) Emotions are conscious feeling states. Each of these is briefly discussed and evidence from affective neuroscience that bears on these sins is noted. The articles in this Special Issue underscore the vitality of research in affective neuroscience and illustrate how some of these sins can be addressed and rectified using concepts and methods from affective neuroscience.
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Social class is shaped by an individual's material resources as well as perceptions of rank vis-à-vis others in society, and in this article, we examine how class influences behavior. Diminished resources and lower rank create contexts that constrain social outcomes for lower-class individuals and enhance contextualist tendencies--that is, a focus on external, uncontrollable social forces and other individuals who influence one's life outcomes. In contrast, abundant resources and elevated rank create contexts that enhance the personal freedoms of upper-class individuals and give rise to solipsistic social cognitive tendencies--that is, an individualistic focus on one's own internal states, goals, motivations, and emotions. Guided by this framework, we detail 9 hypotheses and relevant empirical evidence concerning how class-based contextualist and solipsistic tendencies shape the self, perceptions of the social environment, and relationships to other individuals. Novel predictions and implications for research in other socio-political contexts are considered.
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We present a new sparse shape modeling framework on the Laplace-Beltrami (LB) eigenfunctions. Traditionally, the LB-eigenfunctions are used as a basis for intrinsically representing surface shapes by forming a Fourier series expansion. To reduce high frequency noise, only the first few terms are used in the expansion and higher frequency terms are simply thrown away. However, some lower frequency terms may not necessarily contribute significantly in reconstructing the surfaces. Motivated by this idea, we propose to filter out only the significant eigenfunctions by imposing l1-penalty. The new sparse framework can further avoid additional surface-based smoothing often used in the field. The proposed approach is applied in investigating the influence of age (38-79 years) and gender on amygdala and hippocampus shapes in the normal population. In addition, we show how the emotional response is related to the anatomy of the subcortical structures.
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We used fMRI to examine amygdala activation in response to fearful facial expressions, measured over multiple scanning sessions. 15 human subjects underwent three scanning sessions, at 0, 2 and 8 weeks. During each session, functional brain images centered about the amygdala were acquired continuously while participants were shown alternating blocks of fearful, neutral and happy facial expressions. Intraclass correlation coefficients calculated across the sessions indicated stability of response in left amygdala to fearful faces (as a change from baseline), but considerably less left amygdala stability in responses to neutral expressions and for fear versus neutral contrasts. The results demonstrate that the measurement of fMRI BOLD responses in amygdala to fearful facial expressions might be usefully employed as an index of amygdala reactivity over extended periods. While signal change to fearful facial expressions appears robust, the experimental design employed here has yielded variable responsivity within baseline or comparison conditions. Future studies might manipulate the experimental design to either amplify or attenuate this variability, according to the goals of the research.
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Previous research has reported that individuals high in the need for Power, high in inhibition, and high in power stress (the HHH group) are more likely than other individuals to report more severe illnesses. The present study investigates the possibility that the mechanism underlying this relationship is greater sympathetic activation in the HHH group which has an immunosuppressive effect. College males with the HHH syndrome reported more frequent and more severe illnesses than other individuals, as in previous studies. More of the HHH than other subjects also showed above average epinephrine excretion rates in urine and below average concentrations of immunoglobulin A in saliva (S-IgA). Furthermore, higher rates of epinephrine excretion were significantly associated with lower S-IgA concentrations, and lower S-IgA concentrations were significantly associated with reports of more frequent illnesses. The findings are interpreted as consistent with the hypothesis that a strong need for Power, if it is inhibited and stressed, leads to chronic sympathetic overactivity which has an immunosuppressive effect making individuals characterized by this syndrome more susceptible to illness.
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The tensor-based morphometry (TBM) has been widely used in characterizing tissue volume difference between populations at voxel level. We present a novel computational framework for investigating the white matter connectivity using TBM. Unlike other diffusion tensor imaging (DTI) based white matter connectivity studies, we do not use DTI but only T1-weighted magnetic resonance imaging (MRI). To construct brain network graphs, we have developed a new data-driven approach called the e-neighbor method that does not need any predetermined parcellation. The proposed pipeline is applied in detecting the topological alteration of the white matter connectivity in maltreated children.
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BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) system activation is adaptive in response to stress, and HPA dysregulation occurs in stress-related psychopathology. It is important to understand the mechanisms that modulate HPA output, yet few studies have addressed the neural circuitry associated with HPA regulation in primates and humans. Using high-resolution F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in rhesus monkeys, we assessed the relation between individual differences in brain activity and HPA function across multiple contexts that varied in stressfulness. METHODS: Using a logical AND conjunctions analysis, we assessed cortisol and brain metabolic activity with FDG-PET in 35 adolescent rhesus monkeys exposed to two threat and two home-cage conditions. To test the robustness of our findings, we used similar methods in an archival data set. In this data set, brain metabolic activity and cortisol were assessed in 17 adolescent male rhesus monkeys that were exposed to three stress-related contexts. RESULTS: Results from the two studies revealed that subgenual prefrontal cortex (PFC) metabolism (Brodmann's area 25/24) consistently predicted individual differences in plasma cortisol concentrations regardless of the context in which brain activity and cortisol were assessed. CONCLUSIONS: These findings suggest that activation in subgenual PFC may be related to HPA output across a variety of contexts (including familiar settings and novel or threatening situations). Individuals prone to elevated subgenual PFC activity across multiple contexts may be individuals who consistently show heightened cortisol and may be at risk for stress-related HPA dysregulation.
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This article completes the analysis of parental narratives of tantrums had by 335 children aged 18 to 60 months. Modal tantrum durations were 0.5 to 1 minute; 75% of the tantrums lasted 5 minutes or less. If the child stamped or dropped to the floor in the first 30 seconds, the tantrum was likely to be shorter and the likelihood of parental intervention less. A novel analysis of behavior probabilities that permitted grouping of tantrums of different durations converged with our previous statistically independent results to yield a model of tantrums as the expression of two independent but partially overlapping emotional and behavioral processes: Anger and Distress. Anger rises quickly, has its peak at or near the beginning of the tantrum, and declines thereafter. Crying and comfort-seeking, components of Distress, slowly increase in probability across the tantrum. This model indicates that tantrums can provide a window on the intense emotional processes of childhood.
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Rats were implanted bilaterally with cannulae into the dorsal hippocampus and trained in a Pavlovian fear-conditioning paradigm. Four groups of rats were infused intra-cranially with 1-(5'-isoquinolinesulfonyl)-2-methylpiperazine (H7-dihydrochloride), a potent inhibitor of both protein kinase C (PKC) and cAMP-dependent protein kinase (PKA), at different time intervals in order to examine their involvement in the acquisition and consolidation of contextual fear memory. We demonstrate a significant consolidation deficit of long-term contextual fear-conditioning memory that is maximal when PKA and PKC are inhibited at 90 min post-training. These results suggest the existence of a critical time window, during which these enzymes must be activated for the consolidation of long-term memories.
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Several randomised controlled trials suggest that mindfulness-based approaches are helpful in preventing depressive relapse and recurrence, and the UK Government’s National Institute for Health and Clinical Excellence has recommended these interventions for use in the National Health Service. There are good grounds to suggest that mindfulness-based approaches are also helpful with anxiety disorders and a range of chronic physical health problems, and there is much clinical and research interest in applying mindfulness approaches to other populations and problems such as people with personality disorders, substance abuse, and eating disorders. We review the UK context for developments in mindfulness-based approaches and set out criteria for mindfulness teacher competence and training steps, as well as some of the challenges and future directions that can be anticipated in ensuring that evidence-based mindfulness approaches are available in health care and other settings.
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BACKGROUND: Many anecdotes and several uncontrolled case series have suggested that emotionally stressful events, and more specifically, anger, immediately precede and appear to trigger the onset of acute myocardial infarction. However, controlled studies to determine the relative risk of myocardial infarction after episodes of anger have not been reported. METHODS AND RESULTS: We interviewed 1623 patients (501 women) an average of 4 days after myocardial infarction. The interview identified the time, place, and quality of myocardial infarction pain and other symptoms, the estimated usual frequency of anger during the previous year, and the intensity and timing of anger and other potentially triggering factors during the 26 hours before the onset of myocardial infarction. Anger was assessed by the onset anger scale, a single-item, seven-level, self-report scale, and the state anger subscale of the State-Trait Personality Inventory. Occurrence of anger in the 2 hours preceding the onset of myocardial infarction was compared with its expected frequency using two types of self-matched control data based on the case-crossover study design. The onset anger scale identified 39 patients with episodes of anger in the 2 hours before the onset of myocardial infarction. The relative risk of myocardial infarction in the 2 hours after an episode of anger was 2.3 (95% confidence interval, 1.7 to 3.2). The state anger subscale corroborated these findings with a relative risk of 1.9 (95% confidence interval, 1.3 to 2.7). Regular users of aspirin had a significantly lower relative risk (1.4; 95% confidence interval, 0.8 to 2.6) than nonusers (2.9; 95% confidence interval, 2.0 to 4.1) (P<.05). CONCLUSIONS: Episodes of anger are capable of triggering the onset of acute myocardial infarction, but aspirin may reduce this risk. A better understanding of the manner in which external events trigger the onset of acute cardiovascular events may lead to innovative preventive strategies aimed at severing the link between these external stressors and their pathological consequences.
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Reputation systems promote cooperation and deter antisocial behavior in groups. Little is known, however, about how and why people share reputational information. Here, we seek to establish the existence and dynamics of prosocial gossip, the sharing of negative evaluative information about a target in a way that protects others from antisocial or exploitative behavior. We present a model of prosocial gossip and the results of 4 studies testing the model's claims. Results of Studies 1 through 3 demonstrate that (a) individuals who observe an antisocial act experience negative affect and are compelled to share information about the antisocial actor with a potentially vulnerable person, (b) sharing such information reduces negative affect created by observing the antisocial behavior, and (c) individuals possessing more prosocial orientations are the most motivated to engage in such gossip, even at a personal cost, and exhibit the greatest reduction in negative affect as a result. Study 4 demonstrates that prosocial gossip can effectively deter selfishness and promote cooperation. Taken together these results highlight the roles of prosocial motivations and negative affective reactions to injustice in maintaining reputational information sharing in groups. We conclude by discussing implications for reputational theories of the maintenance of cooperation in human groups.
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[F-18]Mefway was developed to provide an F-18 labeled positron emission tomography (PET) neuroligand with high affinity for the serotonin 5-HT(1A) receptor to improve the in vivo assessment of the 5-HT(1A) system. The goal of this work was to compare the in vivo kinetics of [F-18]mefway, [F-18]MPPF, and [C-11]WAY100635 in the rhesus monkey. METHODS: Each of four monkeys were given bolus injections of [F-18]mefway, [C-11]WAY100635, and [F-18]MPPF and scans were acquired with a microPET P4 scanner. Arterial blood was sampled to assay parent compound throughout the time course of the PET experiment. Time activity curves were extracted in the high 5-HT(1A) binding areas of the anterior cingulate cortex (ACG), mesial temporal cortex, raphe nuclei, and insula cortex. Time activity curves were also extracted in the cerebellum, which was used as a reference region. The in vivo kinetics of the radiotracers were compared based on the nondisplaceable distribution volume (V(ND) ) and binding potential (BP(ND) ). RESULTS: At 30 min, the fraction of radioactivity in the plasma due to parent compound was 19%, 28%, and 29% and cleared from the arterial plasma at rates of 0.0031, 0.0078, and 0.0069 (min⁻¹) ([F-18]mefway, [F-18]MPPF, [C-11]WAY100635). The BP(ND) in the brain regions were mesial temporal cortex: 7.4 ± 0.6, 3.1 ± 0.4, 7.0 ± 1.2, ACG: 7.2 ± 1.2, 2.1 ± 0.2, 7.9 ± 1.2; raphe nuclei: 3.7 ± 0.6, 1.3 ± 0.3, 3.3 ± 0.7; and insula cortex: 4.2 ± 0.6, 1.2 ± 0.1, 4.7 ± 1.0 for [F-18]mefway, [F-18]MPPF, and [C-11]WAY100635 respectively. CONCLUSIONS: In the rhesus monkey, [F-18]mefway has similar in vivo kinetics to [C-11]WAY100635 and yields greater than 2-fold higher BP(ND) than [F-18]MPPF. These properties make [F-18]mefway a promising radiotracer for 5-HT(1A) assay, providing higher counting statistics and a greater dynamic range in BP(ND).
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BACKGROUND: Patterns of temporal variation of cardiac arrests may be important for understanding mechanisms leading to the onset of acute cardiovascular disorders. Previous studies have reported diurnal variation of the onset of cardiac arrests, with high incidence in the morning and in the evening, lack of daily variation during the week, and some seasonal variation. METHODS AND RESULTS: We explored weekly and yearly (seasonal) temporal variation in 6603 out-of-hospital cardiac arrests attended by the Seattle Fire Department. We observed daily variation that peaks on Monday and seasonal variation that peaks in the winter. CONCLUSIONS: Cardiac arrests do not occur randomly during the week or year but follow certain periodic patterns. These patterns are probably associated with patterns of activities.
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BACKGROUND Seasonal and circadian variations in the occurrence of myocardial infarction and sudden cardiac death have been documented, suggesting that triggering factors may play a role in the causation of cardiac events. However, there are only sparse and conflicting data on the weekly distribution of the disorders. METHODS AND RESULTS To determine the weekly variation of acute myocardial infarction and sudden cardiac death, 5596 consecutive patients (71% men; age, 63 +/- 1 years) were analyzed in a regionally defined population (n = 330,000; age, 25 to 74 years) monitored from 1985 to 1990. The exact time of onset of symptoms was used to determine the day of the event. Patients with myocardial infarction (n = 2636) demonstrated a significant weekly variation (P < .01) with a peak on Monday, whereas patients with sudden cardiac death (n = 2960) were evenly distributed throughout the week. A similar weekly pattern was observed in subgroups of patients with myocardial infarction defined with respect to age, sex, cardiac risk factors, prior cardiac medication, and infarct characteristics. The working population demonstrated a weekly variation of myocardial infarction as opposed to the nonworking population, with a 33% increase in relative risk of disease onset on Monday (P < .05) and a trough on Sunday compared with the expected number of cases, if homogeneity was assumed. CONCLUSIONS The onset of acute myocardial infarction demonstrates a peak on Monday primarily in the working population. If this finding is confirmed in other communities, it may aid in identifying acute triggering events of myocardial infarction and perhaps in improving prevention of the disease. (Copyright © 1994 by American Heart Association)
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Who benefits most from making sacrifices for others? The current study provides one answer to this question by demonstrating the intrinsic benefits of sacrifice for people who are highly motivated to respond to a specific romantic partner's needs noncontingently, a phenomenon termed communal strength. In a 14-day daily-experience study of 69 romantic couples, communal strength was positively associated with positive emotions during the sacrifice itself, with feeling appreciated by the partner for the sacrifice, and with feelings of relationship satisfaction on the day of the sacrifice. Furthermore, feelings of authenticity for the sacrifice mediated these associations. Several alternative hypotheses were ruled out: The effects were not due to individuals higher in communal strength making qualitatively different kinds of sacrifices, being more positive in general, or being involved in happier relationships. Implications for research and theory on communal relationships and positive emotions are discussed.
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