Temperamentally anxious individuals can be identified in childhood and are at risk to develop anxiety and depressive disorders. In addition, these individuals tend to have extreme asymmetric right prefrontal brain activity. Although common and clinically important, little is known about the pathophysiology of anxious temperament. Regardless, indirect evidence from rodent studies and difficult to interpret primate studies is used to support the hypothesis that the amygdala plays a central role. In previous studies using rhesus monkeys, we characterized an anxious temperament endophenotype that is associated with excessive anxiety and fear-related responses and increased electrical activity in right frontal brain regions. To examine the role of the amygdala in mediating this endophenotype and other fearful responses, we prepared monkeys with selective fiber sparing ibotenic acid lesions of the amygdala. Unconditioned trait-like anxiety-fear responses remained intact in monkeys with >95% bilateral amygdala destruction. In addition, the lesions did not affect EEG frontal asymmetry. However, acute unconditioned fear responses, such as those elicited by exposure to a snake and to an unfamiliar threatening conspecific were blunted in monkeys with >70% lesions. These findings demonstrate that the primate amygdala is involved in mediating some acute unconditioned fear responses but challenge the notion that the amygdala is the key structure underlying the dispositional behavioral and physiological characteristics of anxious temperament.
<p>Virtually all developmental neuropsychiatric disorders involve some dysfunction or dysregulation of emotion. Moreover, many psychiatric disorders with adult onset have early subclinical manifestations in children. This essay selectively reviews the literature on the neuroimaging of affect and disorders of affect in children. Some critical definitional and conceptual issues are first addressed, including the distinctions between the perception and production of emotion and between emotional states and traits. Developmental changes in morphometric measures of brain structure are then discussed and the implications of such findings for studies of functional brain activity are considered. Data on functional neuroimaging and childhood depression are then reviewed. While the extant data in this area are meager, they are consistent with studies in adults that have observed decreased left-sided anterolateral prefrontal cortex activation in depression. Studies in children on the recognition of emotion and affective intent in faces using functional magnetic resonance imaging are then reviewed. These findings indicate that the amygdala plays an important role in such affective face processing in children, similar to the patterns of activation observed in adults. Moreover, one study has reported abnormalities in amygdala activation during a task requiring the judgment of affective intent from the eye region of the face in subjects with autism. Some of the methodological complexities of developmental research in this area are discussed, and directions for future research are suggested.</p>
Mindfulness-based cognitive therapy for children (MBCT-C) is a manualized group psychotherapy for children ages 9–13 years old, which was developed specifically to increase social-emotional resiliency through the enhancement of mindful attention. Program development is described along with results of the initial randomized controlled trial. We tested the hypotheses that children randomized to participate in MBCT-C would show greater reductions in (a) attention problems, (b) anxiety symptoms, and (c) behavior problems than wait-listed age and gender-matched controls. Participants were boys and girls aged 9–13 (N = 25), mostly from low-income, inner-city households. Twenty-one of 25 children were ethnic minorities. A randomized cross-lagged design provided a wait-listed control group, a second trial of MBCT-C, and a 3-month follow-up of children who completed the first trial. Measures included the Child Behavior Checklist, State-Trait Anxiety Inventory for Children, and Multidimensional Anxiety Scale for Children. Participants who completed the program showed fewer attention problems than wait-listed controls and those improvements were maintained at three months following the intervention [F (1, 1, 18) = 5.965, p = .025, Cohen’s d = .42]. A strong relationship was found between attention problems and behavior problems (r = .678, p < .01). Reductions in attention problems accounted for 46% of the variance of changes in behavior problems, although attention changes proved to be a non-significant mediator of behavior problems (p = .053). Significant reductions in anxiety symptoms and behavior problems were found for those children who reported clinically elevated levels of anxiety at pretest (n = 6). Results show that MBCT-C is a promising intervention for attention and behavior problems, and may reduce childhood anxiety symptoms.
BACKGROUND: Anhedonia, a reduced ability to experience pleasure, is a chief symptom of major depressive disorder and is related to reduced frontostriatal connectivity when attempting to upregulate positive emotion. The present study examined another facet of positive emotion regulation associated with anhedonia-namely, the downregulation of positive affect-and its relation to prefrontal cortex (PFC) activity. METHODS: Neuroimaging data were collected from 27 individuals meeting criteria for major depressive disorder as they attempted to suppress positive emotion during a positive emotion regulation task. Their PFC activation pattern was compared with the PFC activation pattern exhibited by 19 healthy control subjects during the same task. Anhedonia scores were collected at three time points: at baseline (time 1), 8 weeks after time 1 (i.e., time 2), and 6 months after time 1 (i.e., time 3). Prefrontal cortex activity at time 1 was used to predict change in anhedonia over time. Analyses were conducted utilizing hierarchical linear modeling software. RESULTS: Depressed individuals who could not inhibit positive emotion-evinced by reduced right ventrolateral prefrontal cortex activity during attempts to dampen their experience of positive emotion in response to positive visual stimuli-exhibited a steeper anhedonia reduction slope between baseline and 8 weeks of treatment with antidepressant medication (p < .05). Control subjects showed a similar trend between baseline and time 3. CONCLUSIONS: To reduce anhedonia, it may be necessary to teach individuals how to counteract the functioning of an overactive pleasure-dampening prefrontal inhibitory system.
Baseline resting electroencephalogram (EEG) activity was recorded from 6 normothymic depressives and 8 controls using three different reference montages. Power in all frequency bands was extracted by Fourier transformation. Significant Group X Region X Hemisphere interactions were found consistently for alpha band power only. Previously depressed subjects had less left-sided anterior and less right-sided posterior activation (i.e., more alpha activity) than did never depressed subjects. Previously depressed subjects had no history of pharmacological treatment and did not differ from controls in emotional state at the time of testing. The pattern of anterior and posterior asymmetry in the previously depressed subjects is similar to that found in acutely depressed subjects and suggests that this may be a state-independent marker for depression.
Electroencephalogram (EEG) alpha power has been demonstrated to be inversely related to mental activity and has subsequently been used as an indirect measure of brain activation. The thalamus has been proposed as an important site for modulation of rhythmic alpha activity. Studies in animals have suggested that cortical alpha rhythms are correlated with alpha rhythms in the thalamus. However, little empirical evidence exists for this relation in humans. In the current study, resting EEG and a fluorodeoxyglucose positron emission tomography scan were measured during the same experimental session. Over a 30-min period, average EEG alpha power across 28 electrodes from 27 participants was robustly inversely correlated with glucose metabolic activity in the thalamus. These data provide the first evidence for a relation between alpha EEG power and thalamic activity in humans.
OBJECTIVE Deficits in positive affect and their neural bases have been associated with major depression. However, whether reductions in positive affect result solely from an overall reduction in nucleus accumbens activity and fronto-striatal connectivity or the additional inability to sustain engagement of this network over time is unknown. The authors sought to determine whether treatment-induced changes in the ability to sustain nucleus accumbens activity and fronto-striatal connectivity during the regulation of positive affect are associated with gains in positive affect. METHOD Using fMRI, the authors assessed the ability to sustain activity in reward-related networks when attempting to increase positive emotion during performance of an emotion regulation paradigm in 21 depressed patients before and after 2 months of antidepressant treatment. Over the same interval, 14 healthy comparison subjects underwent scanning as well. RESULTS After 2 months of treatment, self-reported positive affect increased. The patients who demonstrated the largest increases in sustained nucleus accumbens activity over the 2 months were those who demonstrated the largest increases in positive affect. In addition, the patients who demonstrated the largest increases in sustained fronto-striatal connectivity were also those who demonstrated the largest increases in positive affect when controlling for negative affect. None of these associations were observed in healthy comparison subjects. CONCLUSIONS Treatment-induced change in the sustained engagement of fronto-striatal circuitry tracks the experience of positive emotion in daily life. Studies examining reduced positive affect in a variety of psychiatric disorders might benefit from examining the temporal dynamics of brain activity when attempting to understand changes in daily positive affect.
<p>OBJECTIVES: The study objectives were to develop and objectively assess the therapeutic effect of a novel movement-based complementary and alternative medicine approach for children with an autism-spectrum disorder (ASD). DESIGN: A within-subject analysis comparing pre- to post-treatment scores on two standard measures of childhood behavioral problems was used. SETTINGS AND LOCATION: The intervention and data analysis occurred at a tertiary care, medical school teaching hospital. SUBJECTS: Twenty-four (24) children aged 3-16 years with a diagnosis of an ASD comprised the study group. INTERVENTION: The efficacy of an 8-week multimodal yoga, dance, and music therapy program based on the relaxation response (RR) was developed and examined. OUTCOME MEASURES: The study outcome was measured using The Behavioral Assessment System for Children, Second Edition (BASC-2) and the Aberrant Behavioral Checklist (ABC). RESULTS: Robust changes were found on the BASC-2, primarily for 5-12-year-old children. Unexpectedly, the post-treatment scores on the Atypicality scale of the BASC-2, which measures some of the core features of autism, changed significantly (p=0.003). CONCLUSIONS: A movement-based, modified RR program, involving yoga and dance, showed efficacy in treating behavioral and some core features of autism, particularly for latency-age children.</p>
Depression has been associated with dysfunctional executive functions and abnormal activity within the anterior cingulate cortex (ACC), a region critically involved in action regulation. Prior research invites the possibility that executive deficits in depression may arise from abnormal responses to negative feedback or errors, but the underlying neural substrates remain unknown. We hypothesized that abnormal reactions to error would be associated with dysfunctional rostral ACC activity, a region previously implicated in error detection and evaluation of the emotional significance of events. To test this hypothesis, subjects with low and high Beck Depression Inventory (BDI) scores performed an Eriksen Flanker task. To assess whether tonic activity within the rostral ACC predicted post-error adjustments, 128-channel resting EEG data were collected before the task and analyzed with low-resolution electromagnetic tomography (LORETA) using a region-of-interest approach. High BDI subjects were uniquely characterized by significantly lower accuracy after incorrect than correct trials. Mirroring the behavioral findings, high BDI subjects had significantly reduced pretask gamma (36.5-44 Hz) current density within the affective (rostral; BA24, BA25, BA32) but not cognitive (dorsal; BA24', BA32') ACC subdivision. For low, but not high, BDI subjects pretask gamma within the affective ACC subdivision predicted post-error adjustments even after controlling for activity within the cognitive ACC subdivision. Abnormal responses to errors may thus arise due to lower activity within regions subserving affective and/or motivational responses to salient cues. Because rostral ACC regions have been implicated in treatment response in depression, our findings provide initial insight into putative mechanisms fostering treatment response.
Several different models postulate that depression is associated with decreased approach-related behavior. Relatively little has been done to date to specifically investigate this issue. In the present study, a signal-detection analysis was used to examine the response biases of dysphoric and nondysphoric female undergraduates during 3 payoff conditions: neutral, reward, and punishment. As predicted, the dysphoric subjects had a smaller change in bias from the neutral to the reward condition compared with the nondysphoric group. The 2 groups did not differ during the neutral and punishment conditions. These findings are consistent with the hypothesis that the left frontal hypoactivation observed in depression reflects a deficit in approach-related behavior.
Numerous studies demonstrate that the rhesus monkey is an excellent species with which to investigate mechanisms underlying human emotion and psychopathology. To examine the role of the central nucleus of the amygdala (CeA) in mediating the behavioral and physiological responses associated with fear and anxiety, we used rhesus monkeys to assess the effects of excitotoxic lesions of the CeA. Behavioral and physiological responses of nine monkeys with bilateral CeA destruction (ranging from 46 to 98%) were compared with five animals with asymmetric lesions (42-86.5% destruction on the most affected side) and with 16 unoperated controls. Results suggest that similar to rodent species, the primate CeA plays a role in mediating fear- and anxiety-related behavioral and endocrine responses. Compared with controls and the asymmetric-lesion group, bilaterally lesioned monkeys displayed significantly less fear-related behavior when exposed to a snake and less freezing behavior when confronted by a human intruder. In addition, bilaterally lesioned monkeys had decreased levels of CSF corticotrophin-releasing factor (CRF), and both lesioned groups had decreased plasma ACTH concentrations. In contrast to these findings, patterns of asymmetric frontal brain electrical activity, as assessed by regional scalp EEG, did not significantly differ between control and lesioned monkeys. These findings suggest that in primates, the CeA is involved in mediating fear- and anxiety-related behavioral and pituitary-adrenal responses as well as in modulating brain CRF activity.
BACKGROUND: Excessive behavioral inhibition during childhood marks anxious temperament and is a risk factor for the development of anxiety and affective disorders. Studies in nonhuman primates can provide important information related to the expression of this risk factor, since threat-induced freezing in rhesus monkeys is a trait-like characteristic analogous to human behavioral inhibition. The orbitofrontal cortex (OFC) and amygdala are part of a circuit involved in the processing of emotions and associated physiological responses. Earlier work demonstrated involvement of the primate central nucleus of the amygdala (CeA) in mediating anxious temperament. This study assessed the role of the primate OFC in mediating anxious temperament and its involvement in fear responses. METHODS: Twelve adolescent rhesus monkeys were studied (six lesion and six control monkeys). Lesions were targeted at regions of the OFC that are most interconnected with the amygdala. Behavior and physiological parameters were assessed before and after the lesions. RESULTS: The OFC lesions significantly decreased threat-induced freezing and marginally decreased fearful responses to a snake. The lesions also resulted in a leftward shift in frontal brain electrical activity consistent with a reduction in anxiety. The lesions did not significantly decrease hypothalamic-pituitary-adrenal (HPA) activity or cerebrospinal fluid (CSF) concentrations of corticotrophin-releasing factor (CRF). CONCLUSIONS: These findings demonstrate a role for the OFC in mediating anxious temperament and fear-related responses in adolescent primates. Because of the similarities between rhesus monkey threat-induced freezing and childhood behavioral inhibition, these findings are relevant to understanding mechanisms underlying anxious temperament in humans.
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.
OBJECTIVE: To test the hypothesis that socioeconomic status (SES) would be associated with sleep quality measured objectively, even after controlling for related covariates (health status, psychosocial characteristics). Epidemiological studies linking SES and sleep quality have traditionally relied on self-reported assessments of sleep. METHODS: Ninety-four women, 61 to 90 years of age, participated in this study. SES was determined by pretax household income and years of education. Objective and subjective assessments of sleep quality were obtained using the NightCap sleep system and the Pittsburgh Sleep Quality Index (PSQI), respectively. Health status was determined by subjective health ratings and objective measures of recent and chronic illnesses. Depressive symptoms and neuroticism were quantified using the Center for Epidemiological Studies Depression Scale and the Neuroticism subscale of the NEO Personality Inventory, respectively. RESULTS: Household income significantly predicted sleep latency and sleep efficiency even after adjusting for demographic factors, health status, and psychosocial characteristics. Income also predicted PSQI scores, although this association was significantly attenuated by inclusion of neuroticism in multivariate analyses. Education predicted both sleep latency and sleep efficiency, but the latter association was partially reduced after health status and psychosocial measures were included in analyses. Education predicted PSQI sleep efficiency component scores, but not global scores. CONCLUSIONS: These results suggest that SES is robustly linked to both subjective and objective sleep quality, and that health status and psychosocial characteristics partially explain these associations.
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.
The present study was undertaken to determine whether aversiveness contributes to startle potentiation in anticipation of affective pictures above and beyond the effects of emotional arousal. Further, participants high in trait anxious apprehension, which is characterized by worry about the future, were expected to show especially pronounced anticipatory startle responses. Startle blink reflex was measured during warning stimuli that predicted the valence of ensuing aversive/unpleasant, pleasant, or neutral pictures. Startle magnitude was larger in anticipation of aversive than of pleasant pictures and smallest in anticipation of neutral pictures. Enhanced startle potentiation was not found in anxious apprehension subjects. These data suggest that the aversive nature of stimuli contribute to the potentiation of startle above and beyond the effects of emotional arousal, which may be a universal phenomenon not modulated by individual differences.
Purpose: To systematically review articles reporting on depression, anxiety, and burnout among U.S. and Canadian medical students. Method: Medline and PubMed were searched to identify peer-reviewed English-language studies published between January 1980 and May 2005 reporting on depression, anxiety, and burnout among U.S. and Canadian medical students. Searches used combinations of the Medical Subject Heading terms medical student and depression, depressive disorder major, depressive disorder, professional burnout, mental health, depersonalization, distress, anxiety, or emotional exhaustion. Reference lists of retrieved articles were inspected to identify relevant additional articles. Demographic information, instruments used, prevalence data on student distress, and statistically significant associations were abstracted. Results: The search identified 40 articles on medical student psychological distress (i.e., depression, anxiety, burnout, and related mental health problems) that met the authors' criteria. No studies of burnout among medical students were identified. The studies suggest a high prevalence of depression and anxiety among medical students, with levels of overall psychological distress consistently higher than in the general population and age-matched peers by the later years of training. Overall, the studies suggest psychological distress may be higher among female students. Limited data were available regarding the causes of student distress and its impact on academic performance, dropout rates, and professional development. Conclusions: Medical school is a time of significant psychological distress for physicians-in-training. Currently available information is insufficient to draw firm conclusions on the causes and consequences of student distress. Large, prospective, multicenter studies are needed to identify personal and training-related features that influence depression, anxiety, and burnout among students and explore relationships between distress and competency.
Although tantrums are among the most common behavioral problems of young children and may predict future antisocial behavior, little is known about them. To develop a model of this important phenomenon of early childhood, behaviors reported in parental narratives of the tantrums of 335 children aged 18 to 60 months were encoded as present or absent in consecutive 30-second periods. Principal Component (PC) analysis identified Anger and Distress as major, independent emotional and behavioral tantrum constituents. Anger-related behaviors formed PCs at three levels of intensity. High-intensity anger decreased with age, and low-intensity anger increased. Distress, the fourth PC, consisted of whining, crying, and comfort-seeking. Coping Style, the fifth PC, had high but opposite loadings on dropping down and running away, possibly reflecting the tendency to either "submit" or "escape." Model validity was indicated by significant correlations of the PCs with tantrum variables that were, by design, not included in the PC analysis.
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.
BACKGROUND: EEG alpha power has been demonstrated to be inversely related to mental activity and has subsequently been used as an indirect measure of brain activation. The hypothesis that the thalamus serves as a neuronal oscillator of alpha rhythms has been supported by studies in animals, but only minimally by studies in humans. METHODS: In the current study, PET-derived measures of regional glucose metabolism, EEG, and structural MRI were obtained from each participant to assess the relation between thalamic metabolic activity and alpha power in depressed patients and healthy controls. The thalamus was identified and drawn on each subject's MRI. The MRI was then co-registered to the corresponding PET scan and metabolic activity from the thalamus extracted. Thalamic activity was then correlated with a 30-min aggregated average of alpha EEG power. RESULTS: Robust inverse correlations were observed in the control data, indicating that greater thalamic metabolism is correlated with decreased alpha power. No relation was found in the depressed patient data. CONCLUSIONS: The results are discussed in the context of a possible abnormality in thalamocortical circuitry associated with depression.
<p>This study is an open clinical trial that examined the feasibility and acceptability of a mindfulness training program for anxious children. We based this pilot initiative on a cognitively oriented model, which suggests that, since impaired attention is a core symptom of anxiety, enhancing self-management of attention should effect reductions in anxiety. Mindfulness practices are essentially attention enhancing techniques that have shown promise as clinical treatments for adult anxiety and depression (Baer, 2003). However, little research explores the potential benefits of mindfulness to treat anxious children. The present study provided preliminary support for our model of treating childhood anxiety with mindfulness. A 6-week trial was conducted with five anxious children aged 7 to 8 years old. The results of this study suggest that mindfulness can be taught to children and holds promise as an intervention for anxiety symptoms. Results suggest that clinical improvements may be related to initial levels of attention.</p>
OBJECTIVES: Affective neuroscience research that investigates core symptoms of pediatric bipolar disorder (PBD) may be effective in differentiating PBD phenotypes. The current study used affect-modulated startle to examine potential differences in reactivity to emotional stimuli (reward and punishment) in narrow and broad phenotype PBD and controls. METHODS: Thirty children meeting DSM-IV bipolar disorder criteria (i.e. narrow phenotype PBD with defined manic episodes with elevated/expansive mood), 19 children meeting criteria for severe mood dysregulation (i.e. broad phenotype with chronic irritability, hyper-reactivity, and hyperarousal), and 19 controls completed a lottery startle paradigm involving reward (money) and punishment (loud noise). Startle probes were presented during anticipation of the emotional stimulus, immediately following the presentation of the stimulus, or during return to baseline following the stimulus. RESULTS: By self-report, patients and controls found the putative punishment to be preferable to the neutral condition. In the reward condition, patient samples reported greater arousal than did controls, but no between-group differences were found on the magnitude of startle response during the reward, punishment, or neutral conditions. CONCLUSIONS: The failure to find differences in affect-modulated startle between control children and those with narrow or broad PBD phenotypes speaks to the methodological challenges associated with studying reward mechanisms in PBD. Alternative paradigms that focus on different aspects of reward mechanisms are discussed.
We present a novel weighted Fourier series (WFS) representation for cortical surfaces. The WFS representation is a data smoothing technique that provides the explicit smooth functional estimation of unknown cortical boundary as a linear combination of basis functions. The basic properties of the representation are investigated in connection with a self-adjoint partial differential equation and the traditional spherical harmonic (SPHARM) representation. To reduce steep computational requirements, a new iterative residual fitting (IRF) algorithm is developed. Its computational and numerical implementation issues are discussed in detail. The computer codes are also available at http://www.stat.wisc.edu/-mchung/softwares/weighted.SPHARM/weighted-SPHARM.html. As an illustration, the WFS is applied i n quantifying the amount ofgray matter in a group of high functioning autistic subjects. Within the WFS framework, cortical thickness and gray matter density are computed and compared.