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A polymorphism of the human Brain Derived Neurotrophic Factor (BDNF) gene that produces a valine-to-methionine substitution at codon 66 (Val66Met) is linked to adult anxiety and mood disorders, possibly through effects on brain circuitry function. Associations between BDNF gene variants and brain activity have not been explored in anxious and depressed adolescents. The current study investigated the association between BDNF genotype and amygdala-hippocampal responses to emotional stimuli in adolescents with anxiety disorders and/or major depressive disorder (MDD) and in healthy adolescents. Twenty-seven unmedicated patients with acutely-impairing current anxiety disorders and/or MDD and 31 healthy adolescents, matched on age, gender and IQ, rated their fear of fearful, angry, neutral and happy facial expressions during collection of fMRI data on the amygdala and hippocampus. Left and right amygdala and hippocampal responses were analyzed using repeated-measures analyses of variance models, with diagnosis (patients, healthy) and genotype (Met-carriers, Val/Val homozygotes) as between-group factors and facial expression (fearful, angry, neutral, happy) as a within-subject factor. Significant effects of diagnosis and diagnosis-by-genotype interactions (F's>4, p's

The ability of positive and negative facial signals to influence attention orienting is crucial to social functioning. Given the dramatic developmental change in neural architecture supporting social function, positive and negative facial cues may influence attention orienting differently in relatively young or old individuals. However, virtually no research examines such age-related differences in the neural circuitry supporting attention orienting to emotional faces. We examined age-related correlations in attention-orienting biases to positive and negative face emotions in a healthy sample (N = 37; 9–40 years old) using functional magnetic resonance imaging and a dot-probe task. The dot-probe task in an fMRI setting yields both behavioral and neural indices of attention biases towards or away from an emotional cue (happy or angry face). In the full sample, angry-face attention bias scores did not correlate with age, and age did not correlate with brain activation to angry faces. However, age did positively correlate with attention bias towards happy faces; age also negatively correlated with left cuneus and left caudate activation to a happy bias fMRI contrast. Secondary analyses suggested age-related changes in attention bias to happy faces. The tendency in younger children to direct attention away from happy faces (relative to neutral faces) was diminished in the older age groups, in tandem with increasing neural deactivation. Implications for future work on developmental changes in attention–emotion processing are discussed.

Functional imaging data were acquired during performance of a reward-contingency task in a unique cohort of adolescents (ages 14-18 years) who were characterized since infancy on measures of temperamental behavioral inhibition. Neural activation was examined in striatal structures (nucleus accumbens, putamen, caudate) with a known role in facilitating response to salient reward-related cues. Adolescents with a history of behavioral inhibition, relative to noninhibited adolescents, showed increased activation in the nucleus accumbens when they believed their selection of an action would affect reward outcome. Neural responses did not differ between the two groups when participants made a prespecified response that they knew would result in reward or when they produced random motor responses that they knew would not be rewarded. These results link inhibited temperament and perturbed neural responses to reward-contingency cues.

Rates of anxiety and depression markedly increase in adolescence.1,2 Comorbidity data3–10 suggest that these conditions may share brain-based diatheses.11–13 However, noncomorbid cases of anxiety and depression2,10,14 raise questions about neural differences. In adults, biased amygdala engagement occurs in major depressive disorder (MDD)15–18 and anxiety disorders.19–24 For both conditions, increased amygdala activation has been reliably seen, suggesting shared neural-circuitry dysfunction. However, strong conclusions cannot be drawn because few studies directly contrast patient groups with each other and with healthy individuals. Vital questions emerge on commonalities and distinctions between adolescent MDD and anxiety disorders. Work is important in this age group because most adult mood and anxiety disorders are preceded by adolescent disorders.5,6 Similar functional perturbations could present in adolescent and adult mood and anxiety disorders; alternatively, unique perturbations could present in adolescence that ultimately evolve into adult profiles. Studies of adolescents begin to consider these possibilities by charting early-emerging correlates of mood and anxiety disorders. Because anxiety disorders differ from MDD in several ways,1,2,10,25,26 specific neural correlates may be expected. Nevertheless, few neuroimaging studies compare adequately sized samples of patients with MDD and anxiety disorder at any age, and studies in adolescents appear to be especially rare. As in adults, initial findings in anxious adolescents27–30 and in individuals at risk for anxiety disorders31 show altered amygdala function relative to healthy subjects, with signs of enhanced activation to fearful faces.27,28,31 To our knowledge, only 2 studies have examined amygdala response to facial stimuli in adolescent MDD.28,29 Their results are inconsistent, with one study finding increased29 and the other decreased28 amygdala activity in MDD relative to healthy participants. Findings from 2 other studies32,33 suggest that biased amygdala function in individuals at risk for MDD occurs specifically when passively viewing emotional stimuli. Because neither study excluded subjects with anxiety disorders, the influence of anxiety on amygdala response remains unclear. The primary goal of the present study is to compare amygdala engagement while varying attentional context and face-emotion stimuli among 3 groups of adolescents: patients with MDD, patients with anxiety disorder, and healthy subjects. Comparative analyses require “pure” groups, but previous research in adolescent MDD28,29,33,34 has included anxious individuals. Thus, we studied patients with MDD who did and did not have comorbid anxiety. Existing data support competing hypotheses. On the one hand, data in adults,16–21,24 together with the strong cross-sectional, longitudinal, and familial relationships among adolescent and adult anxiety and MDD,3–10,14 raise the expectation of overlapping amygdala perturbations, consistent with a “shared diathesis” perspective.11,12 On the basis of these data, one might expect similarly biased amygdala engagement in anxious and depressed adolescents relative to healthy peers. On the other hand, preliminary data suggest that amygdala engagement in anxious and depressed adolescents might vary with changing emotional state and attention,27,31–33 consistent with evidence of disorder-specific cognitive biases.13,35,36

Social context strongly influences human motivated behavior. The triadic model implicates three major nodes in the regulation of motivated behavior, i.e. amygdala, medial prefrontal cortex (mPFC) and striatum. The present work examines how social context modulates this system. Nineteen healthy subjects completed an event-related functional magnetic resonance imaging study of a monetary betting task in the presence (social trials) and in the absence of a social peer (nonsocial trials). In the social trials, the scanned subject played along with another subject, although their performances were independent from one another. In the nonsocial trials the scanned subject played alone. Although behavioral performance did not differ between social and nonsocial trials, BOLD signal changes during betting were significantly greater in the amygdala bilaterally and the right dorsolateral prefrontal cortex (BA 9) in the social condition relative to the nonsocial condition. In contrast, activation was greater in ventral striatum in the nonsocial condition relative to the social condition. These findings suggest that social context modulates the triadic neural-systems ensemble to adjust motivated behavior to the unique demands associated with the presence of conspecifics.

Non-human primates have been used to model psychiatric disease for several decades. The success of this paradigm has issued from comparable cognitive skills, brain morphology, and social complexity in adult monkeys and humans. Recently, interest in biological psychiatry has focused on similar brain, social, and emotional developmental processes in monkeys. In part, this is related to evidence that early postnatal experiences in human development may have profound implications for subsequent mental health. Non-human primate studies of postnatal phenomenon have generally fallen into three basic categories: experiential manipulation (largely manipulations of rearing), pharmacological manipulation (eg drug-induced psychosis), and anatomical localization (defined by strategic surgical damage). Although these efforts have been very informative each of them has certain limitations. In this review we highlight general findings from the non-human primate postnatal developmental literature and their implications for primate models in psychiatry. We argue that primates are uniquely capable of uncovering interactions between genes, environmental challenges, and development resulting in altered risk for psychopathology.

Summary Monkeys separated from their mothers soon after birth and raised with peers display many disturbances in emotional behavior that are similar to human mood and anxiety disorders. In addition to emotional disturbances, both mood and anxiety disorders are often characterized by disruptions in normal sleep–wake cycles, a behavior that has not been well characterized in adversely reared non-human primates. Because polysomnographic measures are difficult to obtain in unrestrained monkeys we used 24-h actigraphy measures to assess probable sleep–wake patterns in juvenile nursery- and mother-reared rhesus macaques ( Macaca mulatta , N = 16) over several days in the home cage. In addition we assayed plasma cortisol in the morning, afternoon, and evening. Relative to mother-reared (MR) monkeys, actigraphic algorithms indicated that nursery-reared (NR) animals had shorter durations of nocturnal sleep, earlier morning waking, and longer periods of sleep during the active period, specifically in the mid morning. No shift in diurnal patterns of cortisol was observed, but NR animals displayed an overall elevation in cortisol. Finally a significant interaction was found between cortisol and actigraphic determination of sleep efficiency in the two groups. A strong positive relationship ( r 2 > 0.8) was found between mean cortisol levels and sleep efficiency for the MR monkeys, but a significant negative relationship was found between these same variables for the NR monkeys, indicating a fundamentally different relationship between waking cortisol and actigraphy patterns in these two groups.

Previous studies have indicated abnormalities in response flexibility in pediatric bipolar disorder (BD). Dysfunction in response flexibility may contribute to the pattern of behavioral and emotional dysregulation that is characteristic of BD, since depressed and manic patients respond inflexibly to emotional stimuli (i.e., anhedonia in the case of depression or inappropriate positive affect in the case of mania). The present study was undertaken to determine if neuronal responses differed between BD and control subjects on a simple motor response flexibility task.To elucidate the neural substrates mediating response flexibility in pediatric BD, we studied 25 youth with BD and 17 age-, gender- and IQ-matched controls (CON) as they performed the change task while undergoing event-related functional magnetic resonance imaging (fMRI). The change task is a new fMRI task that requires subjects to both inhibit and replace a prepotent motor response with another motor response after the initial response has been cued.On correctly performed change trials relative to correctly performed go trials, BD patients generated significantly more activity in the left dorsolateral prefrontal cortex (DLPFC) and in the primary motor cortex than did healthy controls, even though performance levels did not differ across groups.These results indicate that functional deficits within the left DLPFC may mediate deficits in response flexibility in pediatric BD. This deficit may extend beyond the realm of motor control and also affect emotion regulation.

Objective Clinicians and researchers debate whether children with chronic, nonepisodic irritability should receive the diagnosis of bipolar disorder (BD). To address this debate, we evaluated cognitive flexibility, or the ability to adapt to changing contingencies, in three groups of children: narrow-phenotype BD (NP-BD; full-duration manic episodes of elevated/expansive mood; N = 50; 13.1 ± 2.9 years), severe mood dysregulation (SMD; chronic, nonepisodic irritability; N = 44; 12.2 ± 2.1 years), and healthy controls (N = 43; 13.6 ± 2.4 years). Cognitive flexibility is relevant to symptoms of BD involving dysfunctional reward systems (e.g., excessive goal-directed activity and pleasure-seeking in mania; anhedonia in depression). Method We studied simple and compound reversal stages of the intra-/extradimensional shift task and change task that involves inhibiting a prepotent response and substituting a novel response. Results On the simple reversal, NP-BD youths were significantly more impaired than both the SMD group and controls. On the compound reversal, NP-BD and SMD youths performed worse than controls. On the change task, NP-BD youths were slower to adapt than SMD subjects. Conclusions Phenotypic differences in cognitive flexibility may reflect different brain/behavior mechanisms in these two patient populations.

In this study, we examined the impact of goal-directed processing on the response to emotional pictures and the impact of emotional pictures on goal-directed processing. Subjects (N=22) viewed neutral or emotional pictures in the presence or absence of a demanding cognitive task. Goal-directed processing disrupted the BOLD response to emotional pictures. In particular, the BOLD response within bilateral amygdala and inferior frontal gyrus decreased during concurrent task performance. Moreover, the presence of both positive and negative distractors disrupted task performance, with reaction times increasing for emotional relative to neutral distractors. Moreover, in line with the suggestion of the importance of lateral frontal regions in emotional regulation [Ochsner, K. N., Ray, R. D., Cooper, J. C., Robertson, E. R., Chopra, S., Gabrieli, J. D., et al. (2004). For better or for worse: neural systems supporting the cognitive down-and up-regulation of negative emotion. NeuroImage, 23(2), 483-499], connectivity analysis revealed positive connectivity between lateral superior frontal cortex and regions of middle frontal cortex previously implicated in emotional suppression [Beauregard, M., Levesque, J., and Bourgouin, P. (2001). Neural correlates of conscious self-regulation of emotion. J. Neurosci., 21 (18), RC165.; Levesque, J., Eugene, F., Joanette, Y., Paquette, V., Mensour, B., Beaudoin, G., et al. (2003). Neural circuitry underlying voluntary suppression of sadness. Biol. Psychiatry, 53 (6), 502-510.; Ohira, H., Nomura, M., Ichikawa, N., Isowa, T., Iidaka, T., Sato, A., et al. (2006). Association of neural and physiological responses during voluntary emotion suppression. NeuroImage, 29 (3), 721-733] and negative connectivity with bilateral amygdala. These data suggest that processes involved in emotional regulation are recruited during task performance in the context of emotional distractors.

Behavioral inhibition (BI) is a risk factor for anxiety disorders. While the two constructs bear behavioral similarities, previous work has not extended these parallels to the neural level. This study examined amygdala reactivity during a task previously used with clinically anxious adolescents. Adolescents were selected for enduring patterns of BI or non-inhibition (BN). We examined amygdala response to evocative emotion faces in BI (N=10, mean 12.8 years) and BN (N=17, mean 12.5 years) adolescents while systematically manipulating attention. Analyses focused on amygdala response during subjective ratings of internal fear (constrained attention) and passive viewing (unconstrained attention) during the presentation of emotion faces (Happy, Angry, Fearful, and Neutral). BI adolescents, relative to BN adolescents, showed exaggerated amygdala response during subjective fear ratings and deactivation during passive viewing, across all emotion faces. In addition, the BI group showed an abnormally high amygdala response to a task condition marked by novelty and uncertainty (i.e., rating fear state to a Happy face). Perturbations in amygdala function are evident in adolescents temperamentally at risk for anxiety. Attention state alters the underlying pattern of neural processing, potentially mediating the observed behavioral patterns across development. BI adolescents also show a heightened sensitivity to novelty and uncertainty, which has been linked to anxiety. These patterns of reactivity may help sustain early temperamental biases over time and contribute to the observed relation between BI and anxiety.

Early disruption of steroids affects the development of mammalian neural circuits underlying affective processes. In humans, patients with classic congenital adrenal hyperplasia (CAH) can serve as a natural model to study early hormonal alterations on functional brain development. CAH is characterized by congenital glucocorticoid insufficiency, leading to altered hypothalamic-pituitary-adrenal (HPA) function, and hyperandrogenism. Using fMRI, we compared fourteen adolescents with CAH to 14 healthy controls on amygdala response to a face viewing task. In response to negative facial emotions, CAH females activated the amygdala significantly more than healthy females, whereas CAH males did not differ from control males. Furthermore, females with CAH showed a similar pattern of amygdala activation to control males, suggesting virilized amygdala function in females with CAH. These findings suggest a prominent effect of early hyperandrogenism on the development and function of the amygdala in females with CAH, whereas no effects were detected in males with CAH. This study provides data that can be further tested in a model of the neurobiological mechanisms underlying early androgen organizational effects on amygdala function.

The temperamental style of behavioral inhibition has been characterized by exaggerated behavioral and neural responses to cues signaling threat. Virtually no work, however, has addressed whether behavioral inhibition may also confer heightened brain activation in response to positively valenced incentives. We used event-related functional MRI (fMRI) and a monetary incentive delay task to examine whether the neural response to incentives is also greater in adolescents characterized as behaviorally inhibited early in life compared with those characterized as non-inhibited. Whereas task performance did not differ between groups, fMRI revealed greater striatal activation to incentives in behaviorally inhibited adolescents than in non-inhibited adolescents. This was regardless of whether the incentive was an anticipated gain or loss. Alteration in neural systems underlying behavior modulated by both negative and positive contingencies may represent a correlate of behavioral inhibition that also underlies vulnerability to various forms of developmental psychopathology.

Introduction A growing number of studies have found evidence that anxiety and depressive disorders are associated with atypical amygdala hyperactivation, which decreases with effective treatment. Interest has emerged in this phenomenon as a possible biological marker for individuals who are likely to benefit from tailored treatment approaches. Objective The present study was designed to examine relationships between pretreatment amygdala activity and treatment response in a sample of anxious children and adolescents. Materials and methods Participants, who were diagnosed predominantly with generalized anxiety disorder (GAD), underwent functional magnetic resonance imaging (fMRI) scanning before treatment with fluoxetine or cognitive behavioral therapy (CBT). Results Results indicated significant negative associations between degree of left amygdala activation and measures of posttreatment symptom improvement in the group, as a whole. Discussion Taken together with research on associations between adult amygdala activation and treatment response, these findings suggest that patients whose pretreatment amygdala activity is the strongest may be particularly likely to respond well to such widely used treatments as selective serotonin reuptake inhibitor (SSRI) medications and CBT.

In addition to the role of oxytocin in affiliative behaviors of adult mammals, some evidence also indicates that oxytocin may modulate the affiliative behavior of mammalian infants. Pharmacological and comparative studies have indicated that central oxytocin may attenuate the production of ultrasonic vocalizations in isolated rodents.'.2 Recently it was reported that in infant rats, central oxytocin antagonism blocked the acquisition of a preference for a maternally associated odor.3 Understanding the behavioral significance of oxytocin in infant rats may provide insights into the developmental establishment of affiliative behaviors. We report here a behavioral phenomenon, paw sucking, that we have observed in infant rats following central oxytocin administration. Ten-day-old pups (n = 27, from 6 litters) were removed from the nest and injected intracranially with saline solution, oxytocin (50 ng), or the oxytocin antagonist OTA (500 ng). Injections in a volume of 5 pl were made directly through the uncalcified skull. Pups were then placed in a glass dish for 10 minutes. For the first 5 minutes, pups were not disturbed. For the second half of the test session, pups were intermittently stroked with a cotton swab directed at the side of the face and vibrissae. Pups were videotaped from a camera placed underneath the dish during the test period. These tapes were later analyzed for oral behaviors. A two-variable ANOVA for drug treatment and stimulation revealed a significant drug effect on paw sucking (F (2,24) = 5.5, p < 0.05) and a significant stimulation effect on mouthing (F (1,24) = 16.4, p c 0.001). A significant drug effect was also evident on grooming, but only during the stimulation phase (F (2,24) = 7.0, p c 0.01). In the adult rat, many affiliative behaviors such as licking, grooming, nesting, and retrieving young engage the perioral region, and many of these behaviors are thought to be mediated by central oxytocinergic projections. In the rat pup, affiliative behavior likewise involves a great deal of perioral activity. Suckling, probing, and even huddling contain strong perioral components. The central administration of oxytocin induced an array of oral behaviors in 10-day-old rats, and the central administration of an oxytocin antagonist reduced oral behaviors. These drug effects were most pronounced during somatosensory stimulation. These results indicate that the oxytocinergic substrates for oral behaviors and perhaps the oxytocinergic substrates for certain affiliative behaviors develop at an early age in rats. Furthermore

Background Although major depressive disorder (MDD) represents one of the most serious psychiatric problems afflicting adolescents, efforts to understand the neural circuitry of adolescent MDD have lagged behind those of adult MDD. This study tests the hypothesis that adolescent MDD is associated with abnormal amygdala activity during evocative-face viewing. Methods Using functional magnetic resonance imaging (fMRI), between-group differences among MDD ( n = 10), anxious ( n = 11), and non-psychiatric comparisons ( n = 23) were examined during successful vs. unsuccessful face encoding, with encoding success measured post-scan. Results Compared to healthy adolescents, MDD patients exhibited poorer memory for faces. fMRI analyses accounted for this performance difference through event-related methods. In an analysis comparing successful vs. unsuccessful face encoding, MDD patients exhibited greater left amygdala activation relative to healthy and anxious youth. Conclusions Given prior findings among adults, this study suggests that adolescent and adult MDD may involve similar underlying abnormalities in amygdala functioning.

Little is understood about the brain basis of anxiety, particularly among youth. However, threat paradigms with animals are delineating the relationship between anxietylike behaviors and brain function. We adapted a threat paradigm for adolescents using functional magnetic resonance imaging. The aim was to examine amygdala activation to fear. The threat was an aversive air blast directed to the larynx. Participants were explicitly informed that they might receive the air blast when viewing one stimulus (threat condition) and would not receive the blast when viewing the other stimulus (safe condition). Participants provided fear ratings immediately after each trial. Based on the relatively mild nature of the air blast, we expected participants to report varying degrees of fear. Those who reported increased fear showed right amygdala activation during the threat condition and left amygdala activation in the safe condition. These procedures offer a promising tool for studying youth with anxiety disorders.

Biased attention to threat represents a key feature of anxiety disorders. This bias is altered by therapeutic or stressful experiences, suggesting that the bias is plastic. Charting on-line behavioral and neurophysiological changes in attention bias may generate insights on the nature of such plasticity. We used an attention-orientation task with threat cues to examine how healthy individuals alter their response over time to such cues. In Experiments 1 through 3, we established that healthy individuals demonstrate an increased attention bias away from threat over time. For Experiment 3, we used functional magnetic resonance imaging to determine the neural bases for this phenomenon. Gradually increasing attention bias away from threat is associated with increased activation in the occipitotemporal cortex. Examination of plasticity of attention bias with individuals at risk for anxiety disorders may reveal how threatening stimuli come to be categorized differently in this population over time.

Prior studies document strong interactions between emotional and mnemonic processes. These interactions have been shown to vary across development and psychopathology, particularly mood and anxiety disorders.The present study used functional neuroimaging to assess the degree to which adolescents and adults differ in patterns of neuronal engagement during implicit encoding of affective stimuli. Subjects underwent rapid event-related fMRI while viewing faces with angry, fearful, happy, and neutral expressions. A surprise post-scan memory test was administered.Consistent with previous findings, both adolescents and adults displayed engagement of left ventrolateral prefrontal cortex when viewing subsequently recognized stimuli. Age differences emerged in patterns of neuronal activation associated with subsequent recognition of specific face-emotion types. Relative to adults, adolescents displayed more activity in the anterior cingulate when viewing subsequently remembered angry faces, and more activity in the right temporal pole when viewing subsequently remembered fear faces. Conversely, adults displayed more activity in the subgenual anterior cingulate when viewing subsequently remembered happy faces and more activity in the right posterior hippocampus when viewing subsequently remembered neutral faces. These age-related differences emerged in the absence of differences in behavioral performance.These findings document developmental differences in the degree to which engagement of affective circuitry contributes to memory formation.

The authors demonstrated individual differences in inhibited behavior and withdrawal responses of laboratory-born rhesus monkeys when initially exposed to a snake. Most monkeys displayed a small significant increase in their behavioral inhibition in the presence of a snake. A few monkeys had marked responses, and some actively withdrew. Although the responses of the most extreme laboratory-born monkeys were comparable to feral-born monkeys, the responses of the laboratory-born monkeys rapidly habituated. The individual differences in the responses of naive monkeys likely reflect a continuum from orienting to wariness to fear. A neurobiological model is presented that addresses potential mechanisms underlying these individual differences, their relation to fear, and how they may predispose to phobia development.

Background Females appear to be more sensitive and responsive to social cues, including threat signals, than are males. Recent theoretical models suggest that developmental changes in brain functioning play important roles in the emergence of such gender differences. Methods We used functional magnetic resonance imaging to examine developmental and gender differences in activation of neural structures thought to mediate attention to emotional faces depicting varying degrees of threat. Analyses focused on the orbitofrontal cortex, amygdala, and anterior cingulate cortex during the evaluation of threat conveyed by faces. Healthy adolescents (n = 17; 53% male) and adults (n = 17; 53% male) were scanned while they rated how threatening pictures of neutral and emotional (angry, fearful, or happy) faces appeared. Results Results indicate significant interactions among age, gender, and face type for activation during explicit threat monitoring. In particular, adult women activated orbitofrontal cortex and amygdala selectively to unambiguous threat (angry) cues, while adult men showed a less discriminating pattern of activation. No gender differences were evident for adolescents, who as a group resembled adult males. Conclusions These findings suggest that there are gender differences in patterns of neural responses to emotional faces that are not fully apparent until adulthood.

In adult rats, oxytocin (OT) has been shown to reduce the intake of both food and fluids, and oxytocinergic cells are activated by gastric distension and administration of the intestinal peptide cholecystokinin (CCK-8). These and other findings indicate that OT can play a role in inhibiting ingestion under some conditions. A previous study has shown, however, that oxytocinergic cells are unresponsive to CCK-8 in 2-day-old rats. We report here that OT is elevated in the plasma of 10-day-old rats after induction of gastric distension with both mother's milk and saline. These results indicate that the vagal-hypothalamic axis becomes mature between 2- and 10-days of age in infant rats.

The aim of this paper is to review recent work concerning the psychobiological substrates of social bonding, focusing on the literature attributed to opioids, oxytocin and norepinephrine in rats. Existing evidence and thinking about the biological foundations of attachment in young mammalian species and the neurobiology of several other affiliative behaviors including maternal behavior, sexual behavior and social memory is reviewed. We postulate the existence of social motivation circuitry which is common to all mammals and consistent across development. Oxytocin, vasopressin, endogenous opioids and catecholamines appear to participate in a wide variety of affiliative behaviors and are likely to be important components in this circuitry. It is proposed that these same neurochemical and neuroanatomical patterns will emerge as key substrates in the neurobiology of infant attachments to their caregivers.

Melatonin (0.1-1.0 mg/kg) reduced isolation-induced distress vocalizations (DVs) in young domestic chickens in a dose-dependent manner. This effect was unaffected by the administration of d-amphetamine (1.0 mg/kg) suggesting that melatonin's effects were not merely due to fatigue. The melatonin reduction in DVs was not naloxone reversible, indicating an action independent of the endogenous opioid system. However, chronic pretreatment with naltrexone facilitated the melatonin effect, suggesting a complex relationship between melatonin and the endogenous opioids in regulating distress vocalizations. Chickens exhibited a marked reduction in DVs when isolation chambers were darkened, suggesting endogenous, as well as exogenous, melatonin mediation of isolation distress; however; pinealectomy only partially reversed the darkness effect. Pinealectomized animals, like control animals, exhibited a reduction in DVs following melatonin treatment; however, the melatonin effect was shorter lasting. The implications that these results may have for socialization and emotional distress are discussed.

Social loss is considered to be one of the major precipitants of depression. Prior work with the Porsolt forced swimming test (FST) has failed to demonstrate increases in despair-like immobility as a result of prior social isolation in adult animals. In the present work, increased immobility was observed in young Swiss Webster mice that had been socially isolated for 24 h prior to a 15-minute FST. The effect was not apparent until after the first five minutes of testing. The increase in immobility as a result of social isolation was apparent in 17–21-day-old animals but not in 26–30-day-old ones. Control experiments indicated that the increase in immobility was not due to the slightly higher weight loss of the socially isolated animals. Administration of reserpine (0.25 mg/kg) induced a marginal increase in immobility in the youngest animals but decreased immobility at later ages. These data suggest that the mouse only exhibits a short period of time during early development where social isolation can promote despair-like immobility in the FST and suggest that analyses of depressive processes which result from social variables may be best studied during a limited age range in this species.

Social isolation is widely considered to be one of the major vectors which contributes to the onset of depression. Although an isolation-induced “despair” model of depression is available for primates, neuroscience work would be facilitated by a simplified model that could be used routinely. In the following work we analyzed the ability of social isolation to facilitate immobility in the mouse forced swimming test and to decrease separation induced distress vocalizations (DVs) in young chicks. Isolation increased immobility only in very young mice (17–21 days of age) but not in older juveniles or adults. Chronic isolation reduced DVs in chicks and made them more susceptible to the DV reducing effects of reserpine. The chronically isolated young chick appears to be an excellent and inexpensive model for the analysis of despair/depression processes in brain.

Context Amygdala and ventrolateral prefrontal cortex (vlPFC) dysfunction manifests in adolescents with anxiety disorders when they view negatively valenced stimuli in threatening contexts. Such fear-circuitry dysfunction may also manifest when anticipated social evaluation leads socially anxious adolescents to misperceive peers as threatening. Objective To determine whether photographs of negatively evaluated smiling peers viewed during anticipated social evaluation engage the amygdala and vlPFC differentially in adolescents with and without social anxiety. Design Case-control study. Setting Government clinical research institute. Participants Fourteen adolescents with anxiety disorders associated with marked concerns of social evaluation and 14 adolescents without a psychiatric diagnosis matched on sex, age, intelligence quotient, and socioeconomic status. Main Outcome Measures Blood oxygenation level–dependent signal measured with event-related functional magnetic resonance imaging. Before and during neuroimaging scans, participants anticipating social evaluation completed peer- and self-appraisals. Event-related analyses were tailored to participants' ratings of specific peers. Results Participants classified 40 pictures of same-age peers as ones with whom they did or did not want to engage in a social interaction. Anxious adolescents showed greater amygdala activation than healthy adolescents when anticipating evaluation from peers previously rated as undesired for an interaction. Psychophysiological interaction connectivity analyses also revealed a significant positive association between amygdala and vlPFC activation in anxious vs healthy adolescents in response to these stimuli. Conclusions Anticipating social evaluation from negatively perceived peers modulates amygdala and vlPFC engagement differentially in anxious and healthy adolescents. Amygdala and vlPFC dysfunction manifests in adolescent anxiety disorders in specific contexts of anticipated peer evaluation.

Objective: Deficits in motor inhibition may contribute to impulsivity and irritability in children with bipolar disorder. Studies of the neural circuitry engaged during failed motor inhibition in pediatric bipolar disorder may increase our understanding of the pathophysiology of the illness. The authors tested the hypothesis that children with bipolar disorder and comparison subjects would differ in ventral prefrontal cortex, striatal, and anterior cingulate activation during unsuccessful motor inhibition. They also compared activation in medicated versus unmedicated children with bipolar disorder and in children with bipolar disorder and attention deficit hyperactivity disorder (ADHD) versus those with bipolar disorder without ADHD. Method: The authors conducted an event-related functional magnetic resonance imaging study comparing neural activation in children with bipolar disorder and healthy comparison subjects while they performed a motor inhibition task. The study group included 26 children with bipolar disorder (13 unmedicated and 15 with ADHD) and 17 comparison subjects matched by age, gender, and IQ. Results: On failed inhibitory trials, comparison subjects showed greater bilateral striatal and right ventral prefrontal cortex activation than did patients. These deficits were present in unmedicated patients, but the role of ADHD in mediating them was unclear. Conclusions: In relation to comparison subjects, children with bipolar disorder may have deficits in their ability to engage striatal structures and the right ventral prefrontal cortex during unsuccessful inhibition. Further research should ascertain the contribution of ADHD to these deficits and the role that such deficits may play in the emotional and behavioral dysregulation characteristic of bipolar disorder.

Considerable work implicates abnormal neural activation and disrupted attention to facial-threat cues in adult anxiety disorders. However, in pediatric anxiety, no research has examined attention modulation of neural response to threat cues.To determine whether attention modulates amygdala and cortical responses to facial-threat cues differentially in adolescents with generalized anxiety disorder and in healthy adolescents.Case-control study.Government clinical research institute.Fifteen adolescents with generalized anxiety disorder and 20 controls.Blood oxygenation level-dependent signal as measured via functional magnetic resonance imaging. During imaging, participants completed a face-emotion rating task that systematically manipulated attention.While attending to their own subjective fear, patients, but not controls, showed greater activation to fearful faces than to happy faces in a distributed network including the amygdala, ventral prefrontal cortex, and anterior cingulate cortex (P.05, small-volume corrected, for all). Right amygdala findings appeared particularly strong. Functional connectivity analyses demonstrated positive correlations among the amygdala, ventral prefrontal cortex, and anterior cingulate cortex.This is the first evidence in juveniles that generalized anxiety disorder-associated patterns of pathologic fear circuit activation are particularly evident during certain attention states. Specifically, fear circuit hyperactivation occurred in an attention state involving focus on subjectively experienced fear. These findings underscore the importance of attention and its interaction with emotion in shaping the function of the adolescent human fear circuit.

The thickness of the entrainment zone at the top of the atmospheric mixed layer is analyzed using measurements made with a ground-based lidar during the BLX83 and CIRCE field programs. When the entrainment-zone depth normalized by mixed-layer depth is plotted as a function of the entrainment rate normalized by the convective velocity scale, with time as a parameter, a hysteresis curve results. Although portions of the curve can be approximated by diagnostic relationships, the complete hysteresis behavior is better described with a prognostic relationship. A simple thermodynamic model that maps the surface-layer frequency distribution of temperature into a corresponding entrainment zone distribution is shown to approximate the hysteresis evolution to first order.

Highlights • We expand our adolescent re-orientation model to include other developmental periods. • We review neuroimaging literature on social information processing. • We combine human and animal based approaches to social behavior., Social development has been the focus of a great deal of neuroscience based research over the past decade. In this review, we focus on providing a framework for understanding how changes in facets of social development may correspond with changes in brain function. We argue that (1) distinct phases of social behavior emerge based on whether the organizing social force is the mother, peer play, peer integration, or romantic intimacy; (2) each phase is marked by a high degree of affect-driven motivation that elicits a distinct response in subcortical structures; (3) activity generated by these structures interacts with circuits in prefrontal cortex that guide executive functions, and occipital and temporal lobe circuits, which generate specific sensory and perceptual social representations. We propose that the direction, magnitude and duration of interaction among these affective, executive, and perceptual systems may relate to distinct sensitive periods across development that contribute to establishing long-term patterns of brain function and behavior.

The relationships among NASA Space Station operational constraints and logistical requirements are presently investigated. The concepts studied locate organizational, intermediate, and depot maintenance at the Space Station, at the Kennedy Space Center (KSC), and at a depot remote from the KSC. Measures of reliability, maintainability, and availability were selected; a life-cycle study was then conducted to ascertain the optimum Space Station system maintenance concept. The results obtained indicate that orbital replacement unit MTBFs should not be less than 36,000 hours.

Social Anxiety Disorder (SAD) is a common and debilitating condition that typically manifests in adolescence. Here we describe cognitive factors engaged by brain-imaging tasks, which model the peer-based social interactions that evoke symptoms of SAD. We then present preliminary results from the Virtual School paradigm, a novel peer-based social interaction task. This paradigm is designed to investigate the neural mechanisms mediating individual differences in social response flexibility and in participants' responses to uncertainty in social contexts. We discuss the utility of this new paradigm for research on brain function and developmental psychopathology.