Anxiety Disorders: Pine DS

Pine DS. · No affiliation provided · J Child Psychol Psychiatry. · Pubmed #18093020 No free full text.

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Pine DS, Guyer AE, Leibenluft E. · Mood and Anxiety Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #18931608 No free full text.

This publication has no abstract.

Pine DS, Helfinstein SM, Bar-Haim Y, Nelson E, Fox NA. · Mood and Anxiety Disorders Program, Intramural Research Program, The National Institute of Mental Health, Bethesda, MD 20892-2670, USA. · Neuropsychopharmacology. · Pubmed #18754004 No free full text.

Abstract: Alterations in brain development may contribute to chronic mental disorders. Novel treatments targeted toward the early-childhood manifestations of such chronic disorders may provide unique therapeutic opportunities. However, attempts to develop and deliver novel treatments face many challenges. Work on pediatric anxiety disorders illustrates both the inherent challenges as well as the unusual opportunities for therapeutic advances. The present review summarizes three aspects of translational research on pediatric anxiety disorders as the work informs efforts to develop novel interventions. First, the review summarizes data on developmental conceptualizations of anxiety from both basic neuroscience and clinical perspectives. This summary is integrated with a discussion of the two best-established treatments, cognitive behavioral therapy and selective serotonin reuptake inhibitors. Second, the review summarizes work on attention bias to threat, considering implications for both novel treatments and translational research on neural circuitry functional development. This illustrates the manner in which clinical findings inform basic systems neuroscience research. Finally, the review summarizes work in basic science on fear learning, as studied in fear conditioning, consolidation, and extinction paradigms. This summary ends by describing potential novel treatments, illustrating the manner in which basic neuroscience informs therapeutics.

Lau JY, Pine DS. · Mood and Anxiety Program, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #18343966 No free full text.

Abstract: Recent findings of gene-environment interaction on child and adolescent anxiety generate interest in mechanisms through which genetic risks are expressed. Current findings from neuroscience suggest avenues for exploring putative mechanisms. Specifically recent documentations of abnormality in brain function among anxious adolescents may reflect the end-result of gene expression. In turn these inherited predispositions may increase the likelihood of psychopathology in the presence of stress. The aim of the current article is to consider putative mechanisms reflecting genetic sensitivity to the environment (G x E). Thus we review data implicating biased processing of threat information and anomalies in brain circuitry in the expression of pediatric anxiety. These data suggest that links across development among genes, brain, psychological processes, and behavior are far from established. Accordingly, the article proposes strategies for examining these links. Exploring these relationships during development is crucial, given that these early life processes may potentially shape longer-term patterns of emotional behavior, and therefore life-long trajectories of anxiety.

Pine DS. · Section on Development and Affective Neuroscience, National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA. · J Child Psychol Psychiatry. · Pubmed #17593144 No free full text.

Abstract: Across a range of mammalian species, early developmental variations in fear-related behaviors constrain patterns of anxious behavior throughout life. Individual differences in anxiety among rodents and non-human primates have been shown to reflect early-life influences of genes and the environment on brain circuitry. However, in humans, the manner in which genes and the environment developmentally shape individual differences in anxiety and associated brain circuitry remains poorly specified. The current review presents a conceptual framework that facilitates clinical research examining developmental influences on brain circuitry and anxiety. Research using threat-exposure paradigms might most directly integrate basic and clinical perspectives on pediatric anxiety.

Blair RJ, Peschardt KS, Budhani S, Mitchell DG, Pine DS. · Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Heath, Department of Health and Human Services, Bethesda, MD, USA. · J Child Psychol Psychiatry. · Pubmed #16492259 No free full text.

Abstract: The current review focuses on the construct of psychopathy, conceptualized as a clinical entity that is fundamentally distinct from a heterogeneous collection of syndromes encompassed by the term 'conduct disorder'. We will provide an account of the development of psychopathy at multiple levels: ultimate causal (the genetic or social primary cause), molecular, neural, cognitive and behavioral. The following main claims will be made: (1) that there is a stronger genetic as opposed to social ultimate cause to this disorder. The types of social causes proposed (e.g., childhood sexual/physical abuse) should elevate emotional responsiveness, not lead to the specific form of reduced responsiveness seen in psychopathy; (2) The genetic influence leads to the emotional dysfunction that is the core of psychopathy; (3) The genetic influence at the molecular level remains unknown. However, it appears to impact the functional integrity of the amygdala and orbital/ventrolateral frontal cortex (and possibly additional systems); (4) Disruption within these two neural systems leads to impairment in the ability to form stimulus-reinforcement associations and to alter stimulus-response associations as a function of contingency change. These impairments disrupt the impact of standard socialization techniques and increase the risk for frustration-induced reactive aggression respectively.

Pine DS, Costello J, Masten A. · Section on Development and Affective Neuroscience, National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA. · Neuropsychopharmacology. · Pubmed #16012537 links to  free full text

Abstract: This report summarizes recent literature relevant to the effects of terrorism on children's mental health. The paper addresses three aspects of this topic. In the first section of the paper, data are reviewed concerning the relationships among stress, trauma, and developmental psychopathology. A particular emphasis is placed on associations with indirect forms of trauma, given that terrorism involves high levels of indirect trauma. Second, the paper delineates a set of key principles to be considered when considering ways in which the effects of terrorism on children's mental health can be minimized. Third, data are reviewed from studies in developmental psychobiology. These data are designed to illustrate the mechanisms through which children exhibit unique effects in the wake of traumatic circumstances.

Nelson EE, Leibenluft E, McClure EB, Pine DS. · Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD 20892, USA. · Psychol Med. · Pubmed #15841674 No free full text.

Abstract: BACKGROUND: Many changes in social behavior take place during adolescence. Sexuality and romantic interests emerge during this time, and adolescents spend more time with peers and less time with parents and family. While such changes in social behavior have been well documented in the literature, relatively few neurophysiological explanations for these behavioral changes have been presented. METHOD: In this article we selectively review studies documenting (a) the neuronal circuits that are dedicated to the processing of social information; (b) the changes in social behavior that take place during adolescence; (c) developmental alterations in the adolescent brain; and (d) links between the emergence of mood and anxiety disorders in adolescence and changes in brain physiology occurring at that time. RESULTS: The convergence of evidence from this review indicates a relationship between development of brain physiology and developmental changes in social behavior. Specifically, the surge of gonadal steroids at puberty induces changes within the limbic system that alters the emotional attributions applied to social stimuli while the gradual maturation of the prefrontal cortex enables increasingly complex and controlled responses to social information. CONCLUSIONS: Observed alterations in adolescent social behavior reflect developmental changes in the brain social information processing network. We further speculate that dysregulation of the social information processing network in this critical period may contribute to the onset of mood and anxiety disorders during adolescence.

Pine DS. · Section on Development and Affective Neuroscience, National Institutes of Health, National Institute of Mental Health/Mood and Anxiety Program, Bethesda, Maryland 20892, USA. · Biol Psychiatry. · Pubmed #12725972 No free full text.

Abstract: Interest in developmental and psychobiological aspects of trauma has grown with recent research in adults with mood and anxiety disorders reporting histories of trauma during childhood. Studies conducted directly in children and adolescents could add much to ongoing research in this area. This review summarizes data in three areas of developmental science that might inform future studies. First, the review briefly summarizes current data on clinical aspects of trauma in juveniles, focusing on associations with psychopathology and moderators of outcome. Second, the review summarizes data from the basic sciences delineating experiential and developmental changes in brain systems involved in threat perception and response. This review incorporates knowledge gained from research examining the effects of rearing manipulations on regulation of the stress response in rodents and primates. Third, the review summarizes data from cognitive neuroscience studies among both adults and children, again focusing on studies examining aspects of the threat response. This summary includes a review from studies in patients with posttraumatic stress disorder.

Leibenluft E, Charney DS, Towbin KE, Bhangoo RK, Pine DS. · Mood and Anxiety Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1255, USA. · Am J Psychiatry. · Pubmed #12611821 links to  free full text

Abstract: OBJECTIVE: The authors suggest criteria for a range of narrow to broad phenotypes of bipolar disorder in children, differentiated according to the characteristics of the manic or hypomanic episodes, and present methods for validation of the criteria. METHOD: Relevant literature describing bipolar disorder in both children and adults was reviewed critically, and the input of experts was sought. RESULTS: Areas of controversy include whether the diagnosis of bipolar disorder should require clearly demarcated affective episodes and, if so, of what duration, and whether specific hallmark symptoms of mania should be required for the diagnosis. The authors suggest a phenotypic system of juvenile mania consisting of a narrow phenotype, two intermediate phenotypes, and a broad phenotype. The narrow phenotype is exhibited by patients who meet the full DSM-IV diagnostic criteria for hypomania or mania, including the duration criterion, and also have hallmark symptoms of elevated mood or grandiosity. The intermediate phenotypes include 1) hypomania or mania not otherwise specified, in which the patient has clear episodes and hallmark symptoms, but the episodes are between 1 and 3 days in duration, and 2) irritable hypomania or mania, in which the patient has demarcated episodes with irritable, but not elevated, mood. The broad phenotype is exhibited by patients who have a chronic, nonepisodic illness that does not include the hallmark symptoms of mania but shares with the narrower phenotypes the symptoms of severe irritability and hyperarousal. CONCLUSIONS: The presence of distinct episodes and hallmark symptoms can be used to differentiate clinical phenotypes of juvenile mania. The utility and validity of this system can be tested in subsequent research.

Pine DS. · National Institute of Mental Health, Intramural Research Program, Bethesda, Maryland 20892-1381, USA. · J Child Adolesc Psychopharmacol. · Pubmed #12427293 No free full text.

Abstract: This article addresses a key question on the use of selective serotonin reuptake inhibitors (SSRIs) among children and adolescents. As briefly reviewed, recent randomized controlled trials have established the safety and efficacy of SSRIs in the acute treatment of major depression and anxiety disorders among children and adolescents. Major questions emerge in light of these data concerning the potential risks and benefits of long-term SSRI use among children and adolescents who receive significant short-term benefits from SSRI treatment. The current review summarizes research on longitudinal outcomes, neuroscience, and psychopharmacology to formulate a set of preliminary recommendations on long-term SSRI use. A review of data in these areas supports three conclusions. First, for children who achieve marked reduction in anxiety or depressive symptoms on an SSRI, clinicians should consider recommending a medication-free trial. Second, when indicated, this medication-free trial should coincide with the first low-stress period occurring after 1 year of continual SSRI treatment. Third, SSRI treatment should be reinitiated in children who exhibit signs of relapse during this medication-free trial.

Pine DS. · Section on Development and Affective Neuroscience, Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD 20892-1381, USA. · Semin Clin Neuropsychiatry. · Pubmed #12382205 No free full text.

Abstract: Research in mood disorder pathophysiology has stimulated considerable interest in clinical and biologic aspects of mood disorders among children and adolescents. From the clinical perspective, developmental aspects of psychiatric disorders have crystallized in the relatively new theoretical school known as developmental psychopathology. This school attempts to understand the nature of developmental changes in behavior, with the goal of differentiating normal from abnormal stage-related behavior. This perspective has exerted major impact on conceptualizations of psychiatric disorders. From the basic science perspective, biologic findings in emotion have stimulated an integration of basic and clinical approaches to mood disorders. The term emotion is often used to refer to brain states elicited by stimuli for which an organism will extend effort to obtain (rewards) or avoid (punishments). Imaging studies suggest that brain regions engaged by rewarding and punishing stimuli in lower mammals are also implicated in mood disorders. Other studies suggest that environmental factors exert profound effects on the development of these brain regions. The impact of 4 areas of research on our understanding of depression pathophysiology is reviewed: (1) mood disorder onset, (2) structural magnetic resonance imaging (MRI), (3) behavioral or cognitive correlates of major depression, and (4) functional MRI of brain regions engaged across development. This is a US government work. There are no restrictions on its use.

Monk CS, Pine DS, Charney DS. · Section on Development and Affective Neuroscience, Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD 20892, USA. · Semin Clin Neuropsychiatry. · Pubmed #11953938 No free full text.

Abstract: Basic and clinical research documents associations between stress and a set of related psychobiologic perturbations, including dysfunction of the hypothalamic-pituitary-adrenal axis, alterations in the structure and function of the medial temporal lobe, and impairments in explicit memory. Although these associations are thought to emerge developmentally, insufficient clinical research elucidates the manner in which early trauma relates to these abnormalities. To gain a better understanding of relevant processes, we propose the use of a developmental and neurobiological approach, where data in animal models are used to inform studies in traumatized children who will be followed longitudinally. This approach will help clarify how early traumatic events have the capacity to lead to psychopathology or a healthy outcome.

Pine DS, Cohen JA. · Intramural Research Program, National Institute of Mental Health, 15K North Drive, Room 110 MSC 2670, Bethesda, MD 20892-1670, USA. · Biol Psychiatry. · Pubmed #11950454 No free full text.

Abstract: The recent wave of terrorism affecting the United States and other countries raises concerns about the welfare of children and adolescents. This review is designed to address such concerns by summarizing data from two scientific areas. First, a series of recent studies examine psychiatric outcomes over time in children exposed to various forms of trauma. This review summarizes data on the various psychiatric consequences of childhood exposure to trauma, with specific emphasis on identifying factors that predict psychiatric outcome. Prior studies suggest that level of exposure, evidence of psychopathology before trauma exposure, and disruption in social support networks consistently emerge as strong predictors of psychopathology following exposure to trauma. Hence, clinicians might monitor children exposed to trauma most closely when they present with these risk factors. Second, a series of randomized controlled trials documents the beneficial effects of cognitive behavioral therapy (CBT) in children exposed to sexual abuse. When combined with other data from open studies and controlled trials in nontraumatized children, these studies suggest that CBT represents a logical therapeutic option for children developing anxiety symptoms following the recent wave of terrorism. In terms of psychopharmacological treatments, data from randomized controlled trials in traumatized children have not been generated, but recent studies in other groups of children exhibiting symptoms of anxiety or depression suggest the utility of selective serotonin reuptake inhibitors.

Pine DS. · Section on Development and Affective Neuroscience, Intramural Research Program and Program on Mood and Anxiety Disorders, National Institute of Mental Health, Bethesda, Maryland, USA. · Psychiatr Clin North Am. · Pubmed #11723628 No free full text.

Abstract: Recent studies on the familial distribution and longitudinal outcome of SAD emphasize developmental aspects of the syndrome, consistent with the developmental psychopathology perspective. Key questions in this area concern factors that mediate familial transmission and that predict outcome. Prior studies provide incomplete answers to these questions. Recent studies in affective neuroscience suggest potential avenues for answering these questions. As reviewed in the current article, fMRI studies of face processing provide examples of such potentially informative research directions.

Pine DS. · Division of Child Psychiatry, New York State Psychiatric Institute, NY 10032, USA. · Biol Psychiatry. · Pubmed #10599483 No free full text.

Abstract: Prior reviews on the pathophysiology of anxiety consistently note the need for more research on biological aspects of childhood social phobia, separation anxiety disorder, and generalized anxiety disorder. The current review summarizes biological research that is relevant to these three disorders. In the first part of the review, barriers that have prevented progress in this area are delineated, and recent developments are discussed that set the stage for major advances in research on childhood anxiety disorders. In the second part of the review, studies are discussed that provide insights on the pathophysiology of childhood social phobia, separation anxiety disorder, and generalized anxiety disorder. Research on each specific disorder illustrates the manner in which recent developments in biological research facilitate novel research approaches uniquely suited for answering essential clinical questions in research on both childhood and adult anxiety disorders. For example, in research on social phobia, biological studies might enhance understandings of the longitudinal associations between individual childhood and adult disorders. In research on separation anxiety disorder, biological studies might enhance understanding on family-genetic associations between childhood and adult disorders. Finally, in research on generalized anxiety disorder, biological studies might enhance understandings of comorbidities among distinct childhood and adult disorders, particularly with respect to the relationship between anxiety and depressive disorders.

Pine DS, Grun J. · Division of Child Psychiatry, New York State Psychiatric Institute, New York 10032, USA. · J Child Adolesc Psychopharmacol. · Pubmed #10357513 No free full text.

Abstract: This article reviews progress in research on childhood phobia, generalized anxiety, and separation anxiety disorders from the perspectives of developmental psychopathology and affective neuroscience. These perspectives represent two organizing theoretical schools in the realms of clinical and basic science research. Studies in developmental psychopathology suggest the need to identify specific subgroups of children with one of these anxiety disorders who are particularly at risk for anxiety disorders in adulthood. Studies in affective neuroscience suggest potential neurobiological avenues for identifying such children who face a particularly high risk for chronic anxiety disorders.

Marsh AA, Finger EC, Buzas B, Soliman N, Richell RA, Vythilingham M, Pine DS, Goldman D, Blair RJ. · Mood and Anxiety Program, National Institute of Mental Health,National Institutes of Health, Bethesda, MD 20892, USA. · Psychopharmacology (Berl). · Pubmed #17013635 No free full text.

Abstract: RATIONALE: Genotype at the 5' promoter region (5-HTTLPR) of the serotonin transporter has been implicated in moderating the effects of acute tryptophan depletion on neurocognitive functioning. Acute tryptophan depletion has been associated with the processing of fear-relevant cues, such as emotional expressions, but the effect of genotype at the 5-HTTLPR has not been assessed. OBJECTIVE: The present study investigated the effects of acute tryptophan depletion on the recognition of standardized facial expressions of emotions in healthy volunteers classified as ll homozygotes or s carriers. MATERIALS AND METHODS: A double-blind between-groups design was used with volunteers randomly selected to ingest capsules containing an amino acid mixture specifically lacking tryptophan, or placebo capsules containing lactose. 5 h after capsule ingestion, subjects were required to identify anger, disgust, fear, happiness, sadness, and surprise expressions that progressed from neutral to each full emotional expression in 5% steps. RESULTS: Tryptophan depletion significantly impaired the recognition of fearful facial expressions in s carriers but not ll homozygotes. This impairment was specific to fear expressions. No significant differences in the recognition of other expressions were found. Free tryptophan levels were correlated with fear recognition in s carriers but not ll homozygotes. CONCLUSIONS: The effects of acute tryptophan depletion on the processing of emotional expressions varies as a function of genotype at the 5-HTTLPR. Depletion impairs the recognition of fear in s carriers but not ll homozygotes. This finding reinforces the importance of considering genotype when assessing the behavioral effects of pharmacologic modulation.

Grillon C, Levenson J, Pine DS. · Mood and Anxiety Disorders Program, National Institute of Mental Health, NIH, Bethesda, MD 20892-2670, USA. · Neuropsychopharmacology. · Pubmed #16971899 links to  free full text

Abstract: Serotonin reuptake inhibitors may increase symptoms of anxiety immediately following treatment initiation. The present study examined whether acute citalopram increased fear-potentiated startle to predictable and/or unpredictable shocks in healthy subjects. Eighteen healthy subjects each received two treatments, placebo and 20 mg citalopram in a crossover design. Participants were exposed to three conditions including one in which predictable aversive shocks were signaled by a cue, a second in which unpredictable shocks were anticipated, and a third in which no shocks were administered. Changes in aversive states were investigated using acoustic startle stimuli. Citalopram did not affect baseline startle. However, the phasic startle potentiation to the threat cue in the predictable condition was robustly increased by acute citalopram. The sustained startle potentiation in the unpredictable conditions was also increased by citalopram, but only when the drug was given during the first session. These results indicate that a single dose of citalopram is not anxiogenic in itself, but can exacerbate the expression of fear and anxiety.

Finger EC, Marsh AA, Buzas B, Kamel N, Rhodes R, Vythilingham M, Pine DS, Goldman D, Blair JR. · Mood and Anxiety Disorders Program, Unit on Affective Cognitive Neuroscience, National Institute of Mental Health, Bethesda, MD 20892, USA. · Neuropsychopharmacology. · Pubmed #16900105 links to  free full text

Abstract: Transient reductions in serotonin levels during tryptophan depletion (TD) are thought to impair reward processing in healthy volunteers, while another facet of the serotonergic system, the serotonin transporter (5-HTTLPR) short allele polymorphism, is implicated in augmented processing of aversive stimuli. We examined the impact and interactions of TD and the serotonin promoter polymorphism genotype on reward and punishment via two forms of instrumental learning: passive avoidance and response reversal. In this study, healthy volunteers (n=35) underwent rapid TD or control procedures and genotyping (n=26) of the 5-HTTLPR for long and short allele variants. In the passive avoidance task, tryptophan-depleted volunteers failed to respond sufficiently to rewarded stimuli compared to the control group. Additionally, long allele homozygous individuals (n=11) were slower to learn to avoid punished stimuli compared to short allele carriers (n=15). TD alone did not produce measurable deficits in probabilistic response reversal errors. However, a significant drug group by genotype interaction was found indicating that in comparison to short allele carriers, tryptophan-depleted individuals homozygous for the long allele failed to appropriately use punishment information to guide responding. These findings extend prior reports of impaired reward processing in TD to include instrumental learning. Furthermore, they demonstrate behavioral differences in responses to punishing stimuli between long allele homozygotes and short allele carriers when serotonin levels are acutely reduced.

Easter J, McClure EB, Monk CS, Dhanani M, Hodgdon H, Leibenluft E, Charney DS, Pine DS, Ernst M. · Section on Development and Affective Neuroscience, Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, Maryland 20892-2670, USA. · J Child Adolesc Psychopharmacol. · Pubmed #16190788 No free full text.

Abstract: INTRODUCTION: Anxiety disorders in adults involve aberrant processing of emotional information that is hypothesized to reflect perturbations in the amygdala. This study examines the relationship between face-emotion recognition and anxiety in a sample of children and adolescents participating in a brain-imaging study of amygdala structure and function. METHODS: This study recruited 15 children and adolescents with ongoing anxiety disorders and 11 psychiatrically healthy comparisons group-matched on age, gender, and IQ. Face-emotion recognition was assessed using the Diagnostic Analysis of Nonverbal Accuracy Scale (DANVA). RESULTS: Children and adolescents with anxiety disorders exhibited significantly poorer performance on the face-emotion recognition task compared to healthy controls (z = 2.2; p < 0.05). This difference was found only for expressions posed by adults but not children. Discussion: Reduced accuracy on a face-emotion recognition test is consistent with perturbed amygdala function in pediatric anxiety disorders. CONCLUSION: As this study was conducted in a sample undergoing a neuroimaging investigation of amygdala integrity, future analyses will examine associations among amygdala function, clinical anxiety, and face-recognition abilities.

Jazbec S, McClure E, Hardin M, Pine DS, Ernst M. · Section of Developmental and Affective Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. · Biol Psychiatry. · Pubmed #16018983 No free full text.

Abstract: BACKGROUND: Emotion-related perturbations in cognitive control characterize adult mood and anxiety disorders. Fewer data are available to confirm such deficits in youth. Studies of cognitive control and error processing can provide an ideal template to examine these perturbations. Antisaccade paradigms are particularly well suited for this endeavor because they provide exquisite behavioral measures of modulation of response errors. METHODS: A new monetary reward antisaccade task was used with 28 healthy, 11 anxious, and 12 depressed adolescents. Performance accuracy, saccade latency, and peak velocity of incorrect responses were analyzed. RESULTS: Performance accuracy across all groups was improved by incentives (obtain reward, avoid punishment). However, modulation of saccade errors by incentives differed by groups. In incentive trials relative to neutral trials, inhibitory efficiency (saccade latency) was enhanced in healthy, unaffected in depressed, and diminished in anxious adolescents. Modulation of errant actions (saccade peak velocity) was improved in the healthy group and unchanged in both the anxious and depressed groups. CONCLUSIONS: These findings provide grounds for testing hypotheses related to the impact of motivation deficits and emotional interference on directed action in adolescents with mood and anxiety disorders. Furthermore, neural mechanisms can now be examined by using this task paired with functional neuroimaging.

Ernst M, Nelson EE, McClure EB, Monk CS, Munson S, Eshel N, Zarahn E, Leibenluft E, Zametkin A, Towbin K, Blair J, Charney D, Pine DS. · Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, 15K North Drive, Bethesda, MD 20892-2670, USA. · Neuropsychologia. · Pubmed #15327927 No free full text.

Abstract: We examined neural activations during decision-making using fMRI paired with the wheel of fortune task, a newly developed two-choice decision-making task with probabilistic monetary gains. In particular, we assessed the impact of high-reward/risk events relative to low-reward/risk events on neural activations during choice selection and during reward anticipation. Seventeen healthy adults completed the study. We found, in line with predictions, that (i) the selection phase predominantly recruited regions involved in visuo-spatial attention (occipito-parietal pathway), conflict (anterior cingulate), manipulation of quantities (parietal cortex), and preparation for action (premotor area), whereas the anticipation phase prominently recruited regions engaged in reward processes (ventral striatum); and (ii) high-reward/risk conditions relative to low-reward/risk conditions were associated with a greater neural response in ventral striatum during selection, though not during anticipation. Following an a priori ROI analysis focused on orbitofrontal cortex, we observed orbitofrontal cortex activation (BA 11 and 47) during selection (particularly to high-risk/reward options), and to a more limited degree, during anticipation. These findings support the notion that (1) distinct, although overlapping, pathways subserve the processes of selection and anticipation in a two-choice task of probabilistic monetary reward; (2) taking a risk and awaiting the consequence of a risky decision seem to affect neural activity differently in selection and anticipation; and thus (3) common structures, including the ventral striatum, are modulated differently by risk/reward during selection and anticipation.

Monk CS, McClure EB, Nelson EE, Zarahn E, Bilder RM, Leibenluft E, Charney DS, Ernst M, Pine DS. · Section on Development and Affective Neuroscience and Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. · Neuroimage. · Pubmed #14527602 No free full text.

Abstract: Selective attention, particularly during the processing of emotionally evocative events, is a crucial component of adolescent development. We used functional magnetic resonance imagining (fMRI) with adolescents and adults to examine developmental differences in activation in a paradigm that involved selective attention during the viewing of emotionally engaging face stimuli. We evaluated developmental differences in neural activation for three comparisons: (1) directing attention to subjective responses to fearful facial expressions relative to directing attention to a nonemotional aspect (nose width) of fearful faces, (2) viewing fearful relative to neutral faces while attending to a nonemotional aspect of the face, and (3) viewing fearful relative to neutral faces while attention was unconstrained (passive viewing). The comparison of activation across attention tasks revealed greater activation in the orbital frontal cortex in adults than in adolescents. Conversely, when subjects attended to a nonemotional feature, fearful relative to neutral faces influenced activation in the anterior cingulate more in adolescents than in adults. When attention was unconstrained, adolescents relative to adults showed greater activation in the anterior cingulate, bilateral orbitofrontal cortex, and right amygdala in response to the fearful relative to neutral faces. These findings suggest that adults show greater modulation of activity in relevant brain structures based on attentional demands, whereas adolescents exhibit greater modulation based on emotional content.

Walkup J, Labellarte M, Riddle MA, Pine DS, Greenhill L, Fairbanks J, Klein R, Davies M, Sweeney M, Abikoff H, Hack S, Klee B, Bergman RL, Lynn D, McCracken J, March J, Gammon P, Vitiello B, Ritz L, Roper M, Anonymous00127. · Johns Hopkins University, USA. · J Child Adolesc Psychopharmacol. · Pubmed #12427292 No free full text.

Abstract: BACKGROUND: An 8-week placebo-controlled study, the Research Units on Pediatric Psychopharmacology Anxiety Study, documented beneficial effects of fluvoxamine in the treatment of pediatric social anxiety, separation anxiety, or generalized anxiety disorders. Following completion of this study, participants were invited to enter a 6-month open-label treatment phase designed to examine three issues: (a) long-term maintenance of response in fluvoxamine responders, (b) acute response to fluoxetine in fluvoxamine nonresponders, and (c) acute response to fluvoxamine in placebo nonresponders. METHODS: Participants aged 6-17 years meeting criteria for social anxiety, separation anxiety, or generalized anxiety disorders previously treated in an 8-week placebo-controlled trial (n = 128) were offered open treatment. Changes in symptoms of anxiety during open treatment were assessed in three groups: (a) fluvoxamine responders maintained on fluvoxamine, (b) fluvoxamine nonresponders changed to fluoxetine, and (c) placebo nonresponders changed to fluvoxamine. Response was defined based on Clinical Global Impression criteria. RESULTS: During 6 months of continued open treatment, anxiety symptoms remained low in 33 of 35 (94%) subjects who initially responded to fluvoxamine. Among 14 fluvoxamine nonresponders switched to fluoxetine, anxiety symptoms appeared significantly improved in 10 (71%) subjects. Finally, among 48 placebo nonresponders, 27 (56%) showed clinically significant improvement in anxiety on fluvoxamine. CONCLUSION: The current findings concerning extended treatment of pediatric anxiety disorders are only preliminary, because treatment was uncontrolled. Results suggest that an initial fluvoxamine response is likely to be retained with continued treatment, that some fluvoxamine nonresponders may respond to fluoxetine, and that some placebo nonresponders may respond to fluvoxamine.