Based on promising results with adults, Acceptance and Commitment Therapy (ACT) presents as a treatment opportunity for depressed adolescents. We present a pilot study that compares ACT with treatment as usual (TAU), using random allocation of participants who were clinically referred to a psychiatric outpatient service. Participants were 30 adolescents, aged M = 14.9 (SD = 2.55), with 73.6% in the clinical range for depression. At posttreatment on measures of depression participants in the ACT condition showed significantly greater improvement statistically (d = 0.38), and 58% showed clinically reliable change with a response ratio of 1.59 in favor of ACT. Outcomes from 3-month follow-up data are tentative due to small numbers but suggest that improvement increased in magnitude. Measures of global functioning showed statistically significant improvement for both conditions, although clinical change measures favored only the ACT condition. The results support conducting a larger trial of ACT for the treatment of adolescent depression.
OBJECTIVE: To investigate the effect of a short-term yoga-based lifestyle intervention on risk factors for cardiovascular disease (CVD) and markers of inflammation and endothelial function in overweight and obese men. DESIGN: Nonrandomized prospective lifestyle intervention study with pre-post design. SETTING AND LOCATION: Integral Health Clinic, an outpatient facility providing yoga-based lifestyle intervention programs for prevention and management of chronic diseases. SUBJECTS: Overweight and obese men (n=51) were enrolled in the study. Subjects who were physically unable to participate and those participating in other interventions were excluded from the study. INTERVENTION: A pretested intervention program including asanas (physical postures), pranayama (breathing exercises), group discussions, lectures, and individualized advice. OUTCOME MEASURES: The primary outcome measure was weight loss, and the secondary outcome measures were clinical and laboratory correlates of CVD risk, levels of interleukin-6 (IL-6), adiponectin, and endothelin-1 (ET-1). RESULTS: Men (n=51, body mass index [BMI] 26.26±2.42 kg/m(2)) were enrolled and underwent a yoga-based lifestyle intervention for 10 days. Of 51 subjects, 30 completed the study. There was a significant reduction in weight from Baseline to Day 10 (74.60±7.98, 72.69±8.37 kg, p<0.001, respectively), BMI (26.26±2.42, 25.69±2.47 kg/m(2), p<0.001, respectively), and systolic BP (121.73±11.58, 116.73±9.00, p=0.042, respectively). There was a significant reduction in plasma IL-6 from Baseline to Day 10 (median 2.24 vs. 1.26 pg/mL, respectively, p=0.012). There was a significant increase in the plasma adiponectin from Baseline to Day 10 (median 4.95 vs. 6.26 μg/mL, respectively, p=0.014). Plasma ET-1 level remained unchanged. CONCLUSION: These findings suggest that even a short-term yoga-based lifestyle intervention may be an important modality to reduce the risk for CVD as indicated by weight loss, reduction in systolic blood pressure, an increase in adiponectin, and decrease in IL-6 in overweight and obese men.
This past year has seen significant advances in our understanding of the physiology of emotion. Attention continues to focus on the amygdala and its interconnections with prefrontal cortical regions. New evidence underscores the importance of lateralization for emotion. There are also new findings on the physiological predictors of individual differences in emotional behavior and experience, and on the role of autonomic arousal in emotional memory.
Anxious temperament (AT) in human and non-human primates is a trait-like phenotype evident early in life that is characterized by increased behavioural and physiological reactivity to mildly threatening stimuli. Studies in children demonstrate that AT is an important risk factor for the later development of anxiety disorders, depression and comorbid substance abuse. Despite its importance as an early predictor of psychopathology, little is known about the factors that predispose vulnerable children to develop AT and the brain systems that underlie its expression. To characterize the neural circuitry associated with AT and the extent to which the function of this circuit is heritable, we studied a large sample of rhesus monkeys phenotyped for AT. Using 238 young monkeys from a multigenerational single-family pedigree, we simultaneously assessed brain metabolic activity and AT while monkeys were exposed to the relevant ethological condition that elicits the phenotype. High-resolution (18)F-labelled deoxyglucose positron-emission tomography (FDG-PET) was selected as the imaging modality because it provides semi-quantitative indices of absolute glucose metabolic rate, allows for simultaneous measurement of behaviour and brain activity, and has a time course suited for assessing temperament-associated sustained brain responses. Here we demonstrate that the central nucleus region of the amygdala and the anterior hippocampus are key components of the neural circuit predictive of AT. We also show significant heritability of the AT phenotype by using quantitative genetic analysis. Additionally, using voxelwise analyses, we reveal significant heritability of metabolic activity in AT-associated hippocampal regions. However, activity in the amygdala region predictive of AT is not significantly heritable. Furthermore, the heritabilities of the hippocampal and amygdala regions significantly differ from each other. Even though these structures are closely linked, the results suggest differential influences of genes and environment on how these brain regions mediate AT and the ongoing risk of developing anxiety and depression.
This article presents an overview of the author's recent electrophysiological studies of anterior cerebral asymmetries related to emotion and affective style. A theoretical account is provided of the role of the two hemispheres in emotional processing. This account assigns a major role in approach- and withdrawal-related behavior to the left and right frontal and anterior temporal regions of two hemispheres, respectively. Individual differences in approach- and withdrawal-related emotional reactivity and temperament are associated with stable differences in baseline measures of activation asymmetry in these anterior regions. Phasic state changes in emotion result in shifts in anterior activation asymmetry which are superimposed upon these stable baseline differences. Future directions for research in this area are discussed.
On the basis of a review of the extant literature describing emotion-cognition interactions, the authors propose 4 methodological desiderata for studying how task-irrelevant affect modulates cognition and present data from an experiment satisfying them. Consistent with accounts of the hemispheric asymmetries characterizing withdrawal-related negative affect and visuospatial working memory (WM) in prefrontal and parietal cortices, threat-induced anxiety selectively disrupted accuracy of spatial but not verbal WM performance. Furthermore, individual differences in physiological measures of anxiety statistically mediated the degree of disruption. A second experiment revealed that individuals characterized by high levels of behavioral inhibition exhibited more intense anxiety and relatively worse spatial WM performance in the absence of threat, solidifying the authors' inference that anxiety causally mediates disruption. These observations suggest a revision of extant models of how anxiety sculpts cognition and underscore the utility of the desiderata.
Theories typically emphasize affordances or intentions as the primary determinant of an object's perceived function. The HIPE theory assumes that people integrate both into causal models that produce functional attributions. In these models, an object's physical structure and an agent's action specify an affordance jointly, constituting the immediate causes of a perceived function. The object's design history and an agent's goal in using it constitute distant causes. When specified fully, the immediate causes are sufficient for determining the perceived function--distant causes have no effect (the causal proximity principle). When the immediate causes are ambiguous or unknown, distant causes produce inferences about the immediate causes, thereby affecting functional attributions indirectly (the causal updating principle). Seven experiments supported HIPE's predictions.
Objective: The purpose of the study was to examine the association of temporal factors, in particular days of the week and seasons of the year and death from suicide in the United States. Method: Data were pooled from the Multiple Cause of Death Files. Hierarchical logistic regression models were fitted to all deaths occurring in 2000 through 2004 by suicide. Results: The incidence of suicide was significantly higher on Wednesdays, compared to Sunday. Specifically, individuals were 99% more likely to kill themselves on Wednesday than on Sunday. Suicides were more prevalent in the summer months, and they were less likely to occur in winter. The state suicide rate significantly elevated individual suicide risk. The results held even after controlling for the potentially confounding effects of socio-economic and demographic variables at both the individual and state levels. Conclusion: It was concluded that the observed association between seasonality and suicide cannot be discounted as a mere coincidence. Future research ought to focus on integrating individual level data and contextual variables when testing for seasonality effects.
The authors examined the hypothesis that rhesus monkeys with extreme right frontal electroencephalographic activity would have higher cortisol levels and would be more fearful compared with monkeys with extreme left frontal activity. The authors first showed that individual differences in asymmetric frontal electrical activity are a stable characteristic. Next, the authors demonstrated that relative right asymmetric frontal activity and cortisol levels are correlated in animals 1 year of age. Additionally, extreme right frontal animals had elevated cortisol concentrations and more intense defensive responses. At 3 years of age, extreme right frontal animals continued to have elevated cortisol concentrations. These findings demonstrate important relations among extreme asymmetric frontal electrical activity, cortisol levels, and trait-like fear-related behaviors in young rhesus monkeys.
Biological systems are particularly prone to variation, and the authors argue that such variation must be regarded as important data in its own right. The authors describe a method in which individual differences are studied within the framework of a general theory of the population as a whole and illustrate how this method can be used to address three types of issues: the nature of the mechanisms that give rise to a specific ability, such as mental imagery; the role of psychological or biological mediators of environmental challenges, such as the biological bases for differences in dispositional mood; and the existence of processes that have nonadditive effects with behavioral and physiological variables, such as factors that modulate the response to stress and its effects on the immune response.
Children with anxious temperament (AT) are particularly sensitive to new social experiences and have increased risk for developing anxiety and depression. The young rhesus monkey is optimal for studying the origin of human AT because it shares with humans the genetic, neural, and phenotypic underpinnings of complex social and emotional functioning. In vivo imaging in young monkeys demonstrated that central nucleus of the amygdala (Ce) metabolism is relatively stable across development and predicts AT. Transcriptome-wide gene expression, which reflects combined genetic and environmental influences, was assessed within the Ce. Results support a maladaptive neurodevelopmental hypothesis linking decreased amygdala neuroplasticity to early-life dispositional anxiety. For example, high AT individuals had decreased mRNA expression of neurotrophic tyrosine kinase, receptor, type 3 (NTRK3). Moreover, variation in Ce NTRK3 expression was inversely correlated with Ce metabolism and other AT-substrates. These data suggest that altered amygdala neuroplasticity may play a role the early dispositional risk to develop anxiety and depression.
BACKGROUND: Asymmetric patterns of frontal brain activity and brain corticotropin-releasing hormone (CRH) systems have both been separately implicated in the processing of normal and abnormal emotional responses. Previous studies in rhesus monkeys demonstrated that individuals with extreme right frontal asymmetric brain electrical activity have high levels of trait-like fearful behavior and increased plasma cortisol concentrations. METHODS: In this study we assessed cerebrospinal fluid (CSF) CRH concentrations in monkeys with extreme left and extreme right frontal brain electrical activity. CSF was repeatedly collected at 4, 8, 14, 40, and 52 months of age. RESULTS: Monkeys with extreme right frontal brain activity had increased CSF CRH concentrations at all ages measured. In addition, individual differences in CSF CRH concentrations were stable from 4 to 52 months of age. CONCLUSIONS: These findings suggest that, in primates, the fearful endophenotype is characterized by increased fearful behavior, a specific pattern of frontal electrical activity, increased pituitary-adrenal activity, and increased activity of brain CRH systems. Data from other preclinical studies suggests that the increased brain CRH activity may underlie the behavioral and physiological characteristics of fearful endophenotype.
Some children show emotion that is not consistent with normative appraisal of the context and can therefore be defined as context inappropriate (CI). The authors used individual growth curve modeling and hierarchical multiple regression analyses to examine whether CI anger predicts differences in hypothalamic-pituitary-adrenal axis activity, as manifest in salivary cortisol measures. About 23% of the 360 children (ages 6-10 years, primarily 7-8) showed at least 1 expression of CI anger in situations designed to elicit positive affect. Expression of anger across 2 positive assessments was less common (around 4%). CI anger predicted the hypothesized lower levels of cortisol beyond that attributed to context appropriate anger. Boys' CI anger predicted lower morning cortisol and flatter slopes. Results suggest that this novel approach to studying children's emotion across varying contexts can provide insight into affective style.
The cholinergic system has consistently been implicated in Pavlovian fear conditioning. Considerable work has been done to localize specific nicotinic receptor subtypes in the hippocampus and determine their functional importance; however, the specific function of many of these subtypes has yet to be determined. An alpha7 nicotinic antagonist methyllycaconitine (MLA) (35 microg), and a broad spectrum non-alpha7 nicotinic antagonist mecamylamine (35 microg) was injected directly into the dorsal hippocampus or overlying cortex either 15 min pre-, 1 min post-, or 6h post-fear conditioning. One week after conditioning, retention of contextual and cue (tone) conditioning were assessed. A significant impairment in retention of contextual fear was observed when mecamylamine was injected 15 min pre- and 1 min post-conditioning. No significant impairment was observed when mecamylamine was injected 6h post-conditioning. Likewise, a significant impairment in retention of contextual fear was observed when MLA was injected 1 min post-conditioning; however, in contrast, MLA did not show any significant impairments when injected 15 min pre-conditioning, but did show a significant impairment when injected 6h post-conditioning. There were no significant impairments observed when either drug was injected into overlying cortex. No significant impairments were observed in cue conditioning for either drug. In general, specific temporal dynamics involved in nicotinic receptor function were found relative to time of receptor dysfunction. The results indicate that the greatest deficits in long-term retention (1 week) of contextual fear are produced by central infusion of MLA minutes to hours post-conditioning or mecamylamine within minutes of conditioning.
First described for use in mapping the human visual cortex in 1991, functional magnetic resonance imaging (fMRI) is based on blood-oxygen level dependent (BOLD) changes in cortical regions that occur during specific tasks. Typically, an overabundance of oxygenated (arterial) blood is supplied during activation of brain areas. Consequently, the venous outflow from the activated areas contains a higher concentration of oxyhemoglobin, which changes the paramagnetic properties of the tissue that can be detected during a T2-star acquisition. fMRI data can be acquired in response to specific tasks or in the resting state. fMRI has been widely applied to studying physiologic and pathophysiologic diseases of the brain. This review will discuss the most common current clinical applications of fMRI as well as emerging directions.
Motion correction of fMRI data is a widely used step prior to data analysis. In this study, a comparison of the motion correction tools provided by several leading fMRI analysis software packages was performed, including AFNI, AIR, BrainVoyager, FSL, and SPM2. Comparisons were performed using data from typical human studies as well as phantom data. The identical reconstruction, preprocessing, and analysis steps were used on every data set, except that motion correction was performed using various configurations from each software package. Each package was studied using default parameters, as well as parameters optimized for speed and accuracy. Forty subjects performed a Go/No-go task (an event-related design that investigates inhibitory motor response) and an N-back task (a block-design paradigm investigating working memory). The human data were analyzed by extracting a set of general linear model (GLM)-derived activation results and comparing the effect of motion correction on thresholded activation cluster size and maximum t value. In addition, a series of simulated phantom data sets were created with known activation locations, magnitudes, and realistic motion. Results from the phantom data indicate that AFNI and SPM2 yield the most accurate motion estimation parameters, while AFNI's interpolation algorithm introduces the least smoothing. AFNI is also the fastest of the packages tested. However, these advantages did not produce noticeably better activation results in motion-corrected data from typical human fMRI experiments. Although differences in performance between packages were apparent in the human data, no single software package produced dramatically better results than the others. The "accurate" parameters showed virtually no improvement in cluster t values compared to the standard parameters. While the "fast" parameters did not result in a substantial increase in speed, they did not degrade the cluster results very much either. The phantom and human data indicate that motion correction can be a valuable step in the data processing chain, yielding improvements of up to 20% in the magnitude and up to 100% in the cluster size of detected activations, but the choice of software package does not substantially affect this improvement.
What is compassion? And how did it evolve? In this review, we integrate 3 evolutionary arguments that converge on the hypothesis that compassion evolved as a distinct affective experience whose primary function is to facilitate cooperation and protection of the weak and those who suffer. Our empirical review reveals compassion to have distinct appraisal processes attuned to undeserved suffering; distinct signaling behavior related to caregiving patterns of touch, posture, and vocalization; and a phenomenological experience and physiological response that orients the individual to social approach. This response profile of compassion differs from those of distress, sadness, and love, suggesting that compassion is indeed a distinct emotion. We conclude by considering how compassion shapes moral judgment and action, how it varies across different cultures, and how it may engage specific patterns of neural activation, as well as emerging directions of research.
Greater levels of conscientiousness have been associated with lower levels of negative affect. We focus on one mechanism through which conscientiousness may decrease negative affect: effective emotion regulation, as reflected by greater recovery from negative stimuli. In 273 adults who were 35-85 years old, we collected self-report measures of personality including conscientiousness and its self-control facet, followed on average 2 years later by psychophysiological measures of emotional reactivity and recovery. Among middle-aged adults (35-65 years old), the measures of conscientiousness and self-control predicted greater recovery from, but not reactivity to, negative emotional stimuli. The effect of conscientiousness and self-control on recovery was not driven by other personality variables or by greater task adherence on the part of high conscientiousness individuals. In addition, the effect was specific to negative emotional stimuli and did not hold for neutral or positive emotional stimuli.
In a recent neuroimaging study of macaque monkeys, Gil-da-Costa and colleagues reported that a distributed circuit of modality-specific properties represents macaques' conceptual knowledge of social situations. The circuit identified shows striking similarities to analogous circuits in humans that represent conceptual knowledge. This parallel suggests that a common architecture underlies the conceptual systems of different species, although with additional systems extending human conceptual abilities significantly.
The corticotrophin-releasing hormone (CRH) system integrates the stress response and is associated with stress-related psychopathology. Previous reports have identified interactions between childhood trauma and sequence variation in the CRH receptor 1 gene (CRHR1) that increase risk for affective disorders. However, the underlying mechanisms that connect variation in CRHR1 to psychopathology are unknown. To explore potential mechanisms, we used a validated rhesus macaque model to investigate association between genetic variation in CRHR1, anxious temperament (AT) and brain metabolic activity. In young rhesus monkeys, AT is analogous to the childhood risk phenotype that predicts the development of human anxiety and depressive disorders. Regional brain metabolism was assessed with (18)F-labeled fluoro-2-deoxyglucose (FDG) positron emission tomography in 236 young, normally reared macaques that were also characterized for AT. We show that single nucleotide polymorphisms (SNPs) affecting exon 6 of CRHR1 influence both AT and metabolic activity in the anterior hippocampus and amygdala, components of the neural circuit underlying AT. We also find evidence for association between SNPs in CRHR1 and metabolism in the intraparietal sulcus and precuneus. These translational data suggest that genetic variation in CRHR1 affects the risk for affective disorders by influencing the function of the neural circuit underlying AT and that differences in gene expression or the protein sequence involving exon 6 may be important. These results suggest that variation in CRHR1 may influence brain function before any childhood adversity and may be a diathesis for the interaction between CRHR1 genotypes and childhood trauma reported to affect human psychopathology.
Cyclic AMP (cAMP) is a second messenger involved in many processes including mnemonic processing and anxiety. Memory deficits and anxiety are noted in the phenotype of fragile X (FX), the most common heritable cause of mental retardation and autism. Here we review reported observations of altered cAMP cascade function in FX and autism. Cyclic AMP is a potentially useful biochemical marker to distinguish autism comorbid with FX from autism per se and the cAMP cascade may be a viable therapeutic target for both FX and autism.
PET imaging of the neuroreceptor systems in the brain has earned a prominent role in studying normal development, neuropsychiatric illness and developing targeted drugs. The dopaminergic system is of particular interest due to its role in the development of cognitive function and mood as well as its suspected involvement in neuropsychiatric illness. Nonhuman primate animal models provide a valuable resource for relating neurochemical changes to behavior. To facilitate comparison within and between primate models, we report in vivo D2/D3 binding in a large cohort of adolescent rhesus monkeys. METHODS: In this work, the in vivo D2/D3 dopamine receptor availability was measured in a cohort of 33 rhesus monkeys in the adolescent stage of development (3.2-5.3 years). Both striatal and extrastriatal D2/D3 binding were measured using [F-18]fallypride with a high resolution small animal PET scanner. The distribution volume ratio (DVR) was measured for all subjects and group comparisons of D2/D3 binding among the cohort were made based on age and sex. Because two sequential studies were acquired from a single [F-18]fallypride batch, the effect of competing (unlabeled) ligand mass was also investigated. RESULTS: Among this cohort, the rank order of regional D2/D3 receptor binding did not vary from previous studies with adult rhesus monkeys, with: putamen>caudate>ventral striatum>amygdala approximately substantia nigra>medial dorsal thalamus>lateral temporal cortex approximately frontal cortex. The DVR coefficient of variation ranged from 14%-26%, with the greatest variance seen in the head of the caudate. There were significant sex differences in [F-18]fallypride kinetics in the pituitary gland, but this was not observed for regions within the blood-brain barrier. Furthermore, no regions in the brain showed significant sex or age related differences in DVR within this small age range. Based on a wide range of injected fallypride mass across the cohort, significant competition effects could only be detected in the substantia nigra, thalamus, and frontal cortex, and were not evident above intersubject variability in all other regions. CONCLUSION: These data represent the first report of large cohort in vivo D2/D3 dopamine whole brain binding in the adolescent brain and will serve as a valuable comparison for understanding dopamine changes during this critical time of development and provide a framework for creating a dopaminergic biochemical atlas for the rhesus monkey.
Sensitivity, specificity, and reproducibility are vital to interpret neuroscientific results from functional magnetic resonance imaging (fMRI) experiments. Here we examine the scan-rescan reliability of the percent signal change (PSC) and parameters estimated using Dynamic Causal Modeling (DCM) in scans taken in the same scan session, less than 5 min apart. We find fair to good reliability of PSC in regions that are involved with the task, and fair to excellent reliability with DCM. Also, the DCM analysis uncovers group differences that were not present in the analysis of PSC, which implies that DCM may be more sensitive to the nuances of signal changes in fMRI data.
Asymmetry of waking electroencephalography (EEG) alpha power in frontal regions has been correlated with waking emotional reactivity and the emotional content of dream reports. Little is known regarding alpha asymmetry during sleep. The present study was performed to compare alpha power and alpha power asymmetry in various brain regions across states of sleep and wakefulness. Waking and sleep EEG were recorded in a group of patients undergoing polysomnographic evaluation for possible sleep disorders. Alpha EEG asymmetry in frontal and temporal regions was significantly correlated in waking versus sleep, particularly during rapid eye movement (REM) sleep. These results suggest that patterns of frontal alpha asymmetry are stable across sleep and waking and may be related to emotional reactivity during dreaming. During sleep, alpha power was highest during slow-wave sleep and lowest during REM sleep. Implications of these data for understanding the functional significance of alpha power during waking and sleeping are considered.