Anxiety Disorders: University of Michigan

Marcus SM. · Child and Adolescent Psychiatry, Perinatal Mood Disorders Program, University of Michigan, Ann Arbor, Michigan, USA. · Can J Clin Pharmacol. · Pubmed #19164843 links to  free full text

Abstract: Affective illness is common in women, and the puerperium is a time of particular vulnerability. Gender differences in the expression of affective disorders have been attributed to the impact of hormonal influence, socialization, and genetics. Dramatic fluctuations in gonadal hormones that occur following childbirth, influences the increased incidence of mood disorders during this time. Numerous tools including the Edinburgh Postpartum Depression Scale can be used to screen for depression during pregnancy and postpartum. While screening tools may assist with appropriately identifying women who should be further assessed, their use alone does not significantly increase treatment seeking in women, even when their providers are notified about risk. Many studies demonstrate that only a small number (18%) of women who meet criteria for major depressive disorder seek treatment during pregnancy and postpartum. Additionally, common symptoms of depression (sleep, energy and appetite change) may be misinterpreted as normative experiences of pregnancy.Treatment engagement is important as untreated depression during pregnancy may have unfavorable outcomes for both women and children. Complications of pregnancy associated with depression include: inadequate weight gain,under utilization of prenatal care, increased substance use, and premature birth. Human studies demonstrate that perceived life-event stress, as well as depression and anxiety predicted lower birth weight, decreased Apgar scores, and smaller head circumference, and small for gestational age babies. Postpartum depression (PPD) is a common clinical disorder occurring in 15% of deliveries,making it one of the most frequent conditions to complicate pregnancy. Risk factors include past personal or family history of depression, sing marital status, poor health functioning, lower SES, and alcohol use. Women who have a prior history of postpartum depression, particularly with features of bipolarity or psychosis may be at particularly high risk.

Maren S. · Department of Psychology and Neuroscience Program, University of Michigan, Ann Arbor, MI 48109-1043, USA. · Eur J Neurosci. · Pubmed #18973583 No free full text.

Abstract: Pavlovian fear conditioning has become an important model for investigating the neural substrates of learning and memory in rats, mice and humans. The hippocampus and amygdala are widely believed to be essential for fear conditioning to contexts and discrete cues, respectively. Indeed, this parsing of function within the fear circuit has been used to leverage fear conditioning as a behavioral assay of hippocampal and amygdala function, particularly in transgenic mouse models. Recent work, however, blurs the anatomical segregation of cue and context conditioning and challenges the necessity for the hippocampus and amygdala in fear learning. Moreover, nonassociative factors may influence the performance of fear responses under a variety of conditions. Caution must therefore be exercised when using fear conditioning as a behavioral assay for hippocampal- and amygdala-dependent learning.

Monk CS. · Department of Psychology and the Center for Human Growth and Development, 2000 East Hall, 530 Church Street, University of Michigan, Ann Arbor, MI 48109-1043, USA. · Dev Psychopathol. · Pubmed #18838040 No free full text.

Abstract: Disturbances in the detection of, response to, and interpretation of emotion are common in many forms of psychopathology. The amygdala, striatum, and structures within the prefrontal cortex are highly involved in mediating these stages of emotion processing, and evidence indicates that these regions show structural and functional alterations in different types of psychopathology, including anxiety, depression, and autism spectrum disorders. However, we do not know how genes and the environment interact to alter development of these brain regions in ways that give rise to emotion-related psychopathology. This review discusses the current understanding of brain regions that are involved in emotional functioning, how they develop, and how they are altered in three forms of psychopathology: anxiety, depression, and autism spectrum disorders. Following this, a framework is described that may facilitate the integration of investigations of genetic variation and brain function with symptom and diagnostic measures. The framework involves three components: (a) a greater emphasis on simultaneously analyzing multiple levels (genes, brain function, behavior, symptoms, and diagnoses); (b) further integration of developmental considerations, including timing of environmental events, adaptations (or maladaptations), and disorder-related trajectories that guide some children toward atypical experiences; and (c) greater cross-talk between animal and human investigations to take advantage of biological measures that cannot be acquired in humans.

Cerdá M, Sagdeo A, Galea S. · Robert Wood Johnson Foundation Health and Society Scholars Program, Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109-2029, USA. · Epidemiol Rev. · Pubmed #18621743 No free full text.

Abstract: The purpose of this review is to systematically appraise the peer-reviewed literature about clustered forms of psychopathology and to present a framework that can be useful for studying comorbid psychiatric disorders. The review focuses on four of the most prevalent types of mental health problems: anxiety, depression, conduct disorder, and substance abuse. The authors summarize existing empirical research on the distribution of concurrent and sequential comorbidity in children and adolescents and in adults, and they review existing knowledge about exogenous risk factors that influence comorbidity. The authors include articles that used a longitudinal study design and used psychiatric definitions of the disorders. A total of 58 articles met the inclusion criteria and were assessed. Current evidence demonstrates a reciprocal, sequential relation between most comorbid pairs, although the mechanisms that mediate such links remain to be explained. Methodological concerns include the inconsistency of measurement of the disorders across studies, small sample sizes, and restricted follow-up times. Given the significant mental health burden placed by comorbid disorders, and their high prevalence across populations, research on the key risk factors for clustering of psychopathology is needed.

Zivin K, Kales HC. · National VA Serious Mental Illness Treatment, Research & Evaluation Center (SMITREC), Ann Arbor, Michigan 48109, USA. · Drugs Aging. · Pubmed #18582145 No free full text.

Abstract: Depression in older adults has been detected, diagnosed and treated more frequently in recent years. However, substantial gaps in effective treatment remain. Adherence to depression treatment can be viewed as the 'next frontier' in the treatment of late-life depression. Using the Theory of Reasoned Action, a model of health behaviours, this paper conceptualizes and reviews the current evidence for key patient-level factors associated with depression treatment adherence among older adults. We categorize these factors according to how their impact on adherence might be affected by specialized treatment approaches or interventions as: (i) modifiable; (ii) potentially modifiable; and (iii) non-modifiable. Based on current evidence, modifiable factors associated with depression treatment adherence include patient attitudes, beliefs and social norms. Patient attitudes include perceptions of the effectiveness of depression treatment, preferences for the type of depression treatment and concepts regarding the aetiology of depression (e.g. resistance to viewing depression as a medical illness). There is also evidence from the literature that spiritual and religious beliefs may be important determinants of adherence to depression care. Social norms such as the impact of caregiver agreement with treatment recommendations and stigma may also affect adherence to depression treatment. Other factors may be less modifiable per se, but they may have an impact on adherence that is potentially modifiable by specialized interventions. Based upon a review of the current literature, potentially modifiable factors associated with adherence to depression treatment include co-morbid anxiety, substance use, cognitive status, polypharmacy and medical co-morbidity, social support and the cost of treatment. Finally, non-modifiable factors include patient gender and race. Importantly, non-modifiable factors may interact with modifiable factors to affect health behavioural intent (e.g. race and spiritual beliefs). Thus, adherence to depression treatment in older adults is associated with multiple factors. Strategies to improve patient adherence need to be multidimensional, including consideration of age-related cognitive and co-morbidity factors, environmental and social factors, functional status and belief systems. Evidence-based interventions involving greater patient, caregiver, provider and public health education should be developed to decrease stigma, negative attitudes and other modifiable barriers to detection, diagnosis, treatment and adherence to depression treatment. These interventions should also be tailored to the individual as well as to the treatment setting. While important progress has been made in increasing detection of depression in older adults, greater focus now needs to be placed on treatment engagement and continuation of improvements in quality of life, reducing suffering and achieving better outcomes.

Glass JM. · Substance Abuse Section, Department of Psychiatry, University of Michigan Medical School, Ann Arbor, USA. · J Clin Psychiatry. · Pubmed #18537459 No free full text.

Abstract: Patients with fibromyalgia frequently complain of cognitive problems or "fibrofog." The existence of these symptoms has been confirmed by studies of the incidence of cognitive problems in fibromyalgia patients and by the results of objective tests of metamemory, working memory, semantic memory, everyday attention, task switching, and selective attention. The results of these tests show that fibromyalgia patients have impairments in working, episodic, and semantic memory that mimic about 20 years of aging. These patients have particular difficulty with memory when tasks are complex and their attention is divided. Cognitive symptoms in these patients may be exacerbated by the presence of depression, anxiety, sleep problems, endocrine disturbances, and pain, but the relationship of these factors to cognitive problems in fibromyalgia patients is unclear. Standardized tests and treatment have not yet been established for cognitive problems in fibromyalgia patients.

Kerman IA. · Molecular and Behavioral Neuroscience Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI 48109, USA. · Exp Brain Res. · Pubmed #18369609 No free full text.

Abstract: Numerous physiological and emotionally motivated behaviors require concomitant activation of somatomotor and sympathetic efferents. Likewise, adaptive and maladaptive responses to stress are often characterized by simultaneous recruitment of these efferent systems. This review describes recent literature that outlines the organization of somatomotor-sympathetic circuitry in the rat. These circuits were delineated by employing recombinant pseudorabies (PRV) viral vectors as retrograde trans-synaptic tract tracers. In these studies PRV-152, a strain that expresses enhanced green fluorescent protein, was injected into sympathectomized hindlimb muscle, while PRV-BaBlu, which expresses beta-galactosidase, was injected into the adrenal gland in the same animals. Immunofluorescent methods were then used to determine the presence of putative dual-function neurons that were infected with both viral strains. These somatomotor-sympathetic neurons (SMSNs) were detected in a number of brain regions. However, the most prominent nodes in this circuitry included the paraventricular, dorsomedial, and lateral nuclei of the hypothalamus, ventrolateral periaqueductal grey and ventromedial medulla. Phenotypic studies revealed subsets of SMSNs to be capable of synthesizing serotonin, or to contain neuroactive peptides vasopressin, oxytocin, orexins, or melanin-concentrating hormone. Based on these data and the results of studies employing monosynaptic tracers a central somatomotor-sympathetic circuit is proposed. This circuitry is likely recruited in diverse situations, including stress responses, cold defense, exercise and sleep. Furthermore, activation of specific classes of SMSNs likely shapes distinct stress-coping strategies. Dysregulation in the organization and function of this circuit may also contribute to the expression of physical symptoms of affective disorders, such as major depression, anxiety and panic.

Liberzon I, Sripada CS. · Department of Psychiatry, University of Michigan, MCHC, F6135, Ann Arbor, MI 48109, USA. · Prog Brain Res. · Pubmed #18037013 No free full text.

Abstract: Neuroimaging provides an opportunity to understand core processes that mediate the experience of emotions in healthy individuals as well as dysregulation of these processes in conditions such as posttraumatic stress disorder (PTSD). The first decade of neuroimaging research produced symptom provocation, cognitive activation, and functional connectivity studies that highlighted the role of the medial prefrontal cortex (mPFC), amygdala, sublenticular extended amygdala (SLEA), and hippocampus, in mediating symptom formation in PTSD. There is a growing realization that a number of other psychological processes are relevant to PTSD, and they are emerging as a new focus of neuroimaging research. These include fear conditioning, habituation, and extinction; cognitive-emotional interactions; and self-related and social emotional processing. Neuroimaging findings are reviewed that suggest that the mPFC is implicated in a number of these processes. It is proposed that the mPFC plays a role in the "contextualization" of stimuli, and dysregulation of contextualization processes might play a key role in the generation of PTSD symptoms.

Cameron OG. · Department of Psychiatry, University of Michigan Medical Center, Ann Arbor, MI 48103-9735, USA. · Crit Care Clin. · Pubmed #17964368 No free full text.

Abstract: Understanding relevant psychosocial (neural, behavioral, psychiatric) issues is essential to optimal care of individuals who have cardiovascular disorders. Delirium, a condition of diffuse cerebral dysfunction caused by underlying systemic or central nervous system pathology, and often requiring measures of acute neurobehavioral management with nonpharmacological and pharmacological means, in addition to treatment of the underlying medical disorder, often occurs in association with severe cardiovascular disease. Depression is a psychiatric disorder known to be associated with cardiovascular disease. Substantial improvement in understanding the nature of this association has occurred in the past 10 to 20 years, including very preliminary data suggesting that pharmacological treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants might improve postmyocardial infarction cardiac prognosis. Numerous other factors-anxiety, stress, social support, anger, and other personality factors-also are implicated in the relationship of psychosocial issues to cardiovascular disease.

Cameron OG. · University of Michigan Medical Center, Ann Arbor, USA. · Essent Psychopharmacol. · Pubmed #16989290 No free full text.

Abstract: Psychiatric comorbidity is all too common. An important example is the high comorbidity frequency of depressive and anxiety disorders, 25%-50%, much higher than the 5% or less expected by chance. Possible reasons for this comorbidity include definitional, environmental, and biological factors. Few previous studies have assessed, with proper methodology, potential biological changes associated with this co-occurrence. We assessed both hypothalamic-pituitary-adrenocortical axis (HPA) responses to the Trier Social Stress Test and growth hormone (GH) responses to clonidine, a centrally active alpha-2 adrenoreceptor agonist, in 15 persons with major depression without anxiety, 15 with an anxiety disorder without depression, 18 comorbid for anxiety and depression, and 48 individually matched control subjects. Individuals with depression only were normal on both tests, while those with anxiety only had normal HPA responses but blunted GH responses. Comorbid individuals showed elevated HPA responses and only those comorbid persons with anxiety symptoms predominant also showed blunted GH responses. Controls and anxiety-only subjects showed significant correlations between the results of the two tests. This association was disrupted by the presence of depression with or without comorbidity. Comorbidity is fundamental to understanding the pathophysiologies of depression and anxiety.

Galea S, Acierno R, Ruggiero K, Resnick H, Tracy M, Kilpatrick D. · Department of Epidemiology, University of Michigan School of Public Health, 1214 S. University, Ann Arbor, MI 48104, USA. · Ann N Y Acad Sci. · Pubmed #16891574 No free full text.

Abstract: A growing body of research is identifying the molecular and genetic correlates of psychopathology and holds tremendous promise in suggesting the biologic mechanisms that may explain emergent posttraumatic stress disorder (PTSD) phenotypes. Another body of research has begun to consider how elements of the social context may influence the risk of PTSD. It is likely that the social context and molecular/genetic factors jointly determine the risk of PTSD and as such scientific inquiry that considers the interrelationship of these factors stands to advance the field. However, there are particular conceptual and methodologic challenges to conducting and designing studies that adequately assess both the social context and the biologic determinants of PTSD. Much of the current research exploring the biology of PTSD is conducted with highly selective samples that were recruited on the basis of strict phenotypic or medical history criteria. In contrast, population-based sampling represents an opportunity to obtain heterogeneous samples that better represent the population distribution of relevant molecular, genotypic, and phenotypic parameters of interest. These sampling strategies also allow researchers to consider the role of the social context and in turn, how the social context influences the molecular determinants of PTSD. An example of our own work illustrates the feasibility of the population-based sampling approach.

Liberzon I, Martis B. · Trauma Stress and Anxiety Research Group, Department of Psychiatry, Ann Arbor VA Healthcare System, University of Michigan, 1500 E. Medical Center Drive UH9D 0118, Ann Arbor, MI 48109-0118, USA. · Ann N Y Acad Sci. · Pubmed #16891565 No free full text.

Abstract: Neuroimaging research offers a powerful and noninvasive means to understand healthy as well as dysregulated emotional processing in healthy subjects and PTSD patients. Functional neuroimaging findings suggest specific roles for subregions of the medial prefrontal (mPFC), orbito frontal (OFC), anterior cingulate (ACC), and insular cortices as well as the sublenticular extended amygdala (SLEA) and hippocampus in various components of emotional processing. Some of the same regions appear to be associated with emotional response to trauma, and with symptom formation in PTSD. Neuroimaging findings of emotional processing in healthy subjects and PTSD patients are discussed, addressing the specific roles of cortical regions like mPFC, ACC, and insula, and their potential contribution to PTSD pathophysiology. Processes of cognitive-emotional interactions and social emotions are discussed in an attempt to synthesize the prefrontal findings in healthy subjects and PTSD patients. Further links between functional neuroanatomy of emotional responses and neuroendocrine stress regulation are proposed.

Abelson JL, Khan S, Liberzon I, Young EA. · Department of Psychiatry and Molecular and Behavioral Neuroscience Institute, Trauma, Stress and Anxiety Research Group, University of Michigan, Ann Arbor, Michigan 48109-0118, USA. · Depress Anxiety. · Pubmed #16845643 No free full text.

Abstract: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may play a role in panic disorder. HPA studies in patients with panic disorder, however, have produced inconsistent results. Seeking to understand the inconsistencies, we reexamined endocrine data from four studies of patients with panic disorder, in light of animal data highlighting the salience of novelty, control, and social support to HPA axis activity. Patients with panic disorder were studied (1) at rest over a full circadian cycle, (2) before and after activation by a panicogenic respiratory stimulant (doxapram) that does not directly stimulate the HPA axis, and (3) before and after a cholecystokinin B (CCK-B) agonist that is panicogenic and does directly stimulate the HPA axis. Patients with panic disorder had elevated overnight cortisol levels, which correlated with sleep disruption. ACTH and cortisol levels were higher in a challenge paradigm (doxapram) than in a resting state study, and paradigm-related ACTH secretion was exaggerated in patients with panic disorder. Panic itself could be elicited without HPA axis activation. Patients with panic disorder showed an exaggerated ACTH response to pentagastrin stimulation, but this response was normalized by prior exposure to the experimental context or psychological preparation to reduce novelty and enhance sense of control. Novelty is one of a number of contextual cues known from animal work to activate the HPA axis. The HPA axis abnormalities seen in patients with panic disorder in the four experiments reviewed here might all be due to exaggerated HPA axis reactivity to novelty cues. Most of the published panic/HPA literature is consistent with the hypothesis that HPA axis dysregulation in panic is due to hypersensitivity to contextual cues. This hypothesis requires experimental testing.

Louis DS, Doro C, Hayden RJ. · Division of Hand Elbow and Microsurgery, Department of Orthopaedic Surgery, University of Michigan Medical Center, 2098 South Main Street, Ann Arbor, MI 48103, USA. · Clin Occup Environ Med. · Pubmed #16647660 No free full text.

Abstract: Factitious disorders reside under the broad umbrella of dysfunctional syndromes. This article is meant specifically to focus on common patterns of upper extremity factitious illness. It is intended to emphasize recognition, differential diagnosis, and problems related to misdiagnosis. It is not devoted to treatment, which is a separate issue.

Hanna GL, Fischer DJ, Fluent TE. · Section of Child and Adolescent Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan, USA. · Pediatr Rev. · Pubmed #16452275 No free full text.

This publication has no abstract.

McLean SA, Clauw DJ, Abelson JL, Liberzon I. · Department of Emergency Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA. · Psychosom Med. · Pubmed #16204439 links to  free full text

Abstract: OBJECTIVES: Persistent pain and psychological sequelae are common after motor vehicle collision (MVC), but their etiology remains poorly understood. Such common sequelae include whiplash-associated disorders (WAD), fibromyalgia, and posttraumatic stress disorder (PTSD). Increasing evidence suggests that these disorders share overlapping epidemiologic and clinical features. A model is proposed in which central neurobiological systems, including physiologic systems and neuroanatomical structures involved in the stress response, are an important substrate for the development of all 3 disorders and interact with psychosocial and other factors to influence chronic symptom development. METHODS: Epidemiologic and clinical characteristics regarding the development of these disorders after MVC are reviewed. Evidence suggesting a role for stress response systems in the development of these disorders is presented. RESULTS: Contemporary evidence supports a model of chronic symptom development that incorporates the potential for interactions between past experience, acute stress responses to trauma, post-MVC behavior, and cognitive/psychosocial consequences to alter activity within brain regions which process pain and to result in persistent pain, as well as psychological sequelae, after MVC. Such a model incorporates factors identified in prior biopsychosocial theories and places them in the landscape of our rapidly developing understanding of stress systems and CNS pain-modulating pathways. CONCLUSION: New models are needed to stimulate deeper examination of the interacting influences of initial tissue damage, acute pain, psychosocial contingencies, and central stress pathways during chronic symptom development after MVC. Deeper understanding could contribute to improved treatment approaches to reduce the immense personal and societal burdens of common trauma-related disorders.

Liberzon I, Phan KL. · Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA. · CNS Spectr. · Pubmed #15079138 No free full text.

Abstract: Brain-imaging studies of posttraumatic stress disorder (PTSD) have rapidly increased in recent years. Structural studies have identified potential smaller volumes of the hippocampus of traumatized and/or PTSD subjects. Functional activation studies have implicated hyperactive or altered functioning of brain regions, such as the amygdala and the insula, and a failure to engage emotional regulatory structures, such as the medial prefrontal and anterior cingulate cortex. Recent neurochemical investigations have suggested that neuromodulatory systems (eg, gamma-aminobutyric acid, micro-opioid) may underlie these aberrant brain activation patterns. This article reviews the literature on structural, functional, and neurochemical brain-imaging studies of PTSD.

Brower KJ. · University of Michigan Addiction Research Center, Ann Arbor, MI 48108, USA. · Sleep Med Rev. · Pubmed #15018094 No free full text.

Abstract: Insomnia and alcoholism are significantly associated in community surveys and patient samples. Insomnia occurs in 36-72% of alcoholic patients and may last for weeks to months after initiating abstinence from alcohol. Some correlates of insomnia in alcoholic patients are identical to those observed in non-alcoholic insomniacs, including anxiety and depression, tobacco smoking, and the use of alcohol to aid sleep. Other studies suggest that as the severity of alcoholism increases, so does the likelihood of insomnia in alcoholic patients. In the sleep laboratory, alcoholic patients who complain of insomnia have disrupted sleep continuity when compared to alcoholic patients without insomnia complaints. Recently sober alcoholics are also more likely than non-alcoholics to have sleep-disordered breathing and increased periodic leg movements, which might contribute to insomnia in some alcoholic patients. The co-occurrence of insomnia and alcoholism is clinically significant because alcoholism can exacerbate the adverse consequences of insomnia (e.g. mood changes and performance decrements) and because insomnia among patients entering treatment for alcoholism has been significantly associated with subsequent alcoholic relapse. Baseline polysomnographic correlates of subsequent relapse include prolonged sleep latency, decreased sleep efficiency and total sleep time, increased rapid eye movement sleep pressure, and decreased slow wave sleep. Whether treatment of insomnia in alcoholic patients reduces relapse rates is unknown, but preliminary treatment guidelines that accommodate the special characteristics of alcoholic patients are provided, with a goal to reduce daytime impairment and psychological distress.

Anderson DK, Saunders DG. · University of Michigan, USA. · Trauma Violence Abuse. · Pubmed #14697121 No free full text.

Abstract: Four facets of leaving an abusive relationship are reviewed: (a). factors related to initially leaving an abusive partner; (b). the process of leaving an abusive relationship; (c). the psychological well-being of survivors after leaving; and (d). the predictors of this well-being. The conceptual and methodological limitations of studies in each of these areas are presented. Consistently found predictors of leaving include both material and psychological factors. Because battered women typically undergo several shifts in their thinking about the abuse before leaving permanently, research on leaving as a process is highlighted. A stress-process framework is used to explain the seemingly paradoxical finding that some women just out of the abusive relationship may have greater psychological difficulties than those who are still in it. For those experiencing the most stress, psychological health can worsen over time. Researchers and practitioners need to pay more attention to the plight of women who have left abusive partners.

Geisser ME, Robinson ME, Miller QL, Bade SM. · Department of Physical Medical Medicine and Rehabilitation, University of Michigan Health System, Spine Program, Eisenhower Parkway, Ann Arbor, Michigan, USA. · J Occup Rehabil. · Pubmed #14671990 No free full text.

Abstract: Psychosocial factors have been found to have a significant impact on functional activity, particularly among persons with chronic pain. While various systems have been developed to assess functional limitations through functional capacity evaluation (FCE), assessment of psychosocial factors that may impact function have been largely ignored. This paper examines the existing literature on psychosocial factors and FCE performance. Given that there are few studies that have directly addressed this issue, the paper also examines psychosocial factors that have been found to influence function in persons with pain. The results of the literature review indicate that few psychosocial factors have been found to be directly associated with FCE and functional measures, although many are related to various measures of disability. The strongest evidence that psychosocial factors are related to functional performance is based on the studies examining the association between functional activity and pain-related fear, self-efficacy, and illness behavior. Psychosocial factors have also been shown to influence measures of sincerity of effort often obtained during FCE. Proposals for modifying FCE assessment are given based on the available data, as well as suggestions for future research.

Clauw DJ, Engel CC, Aronowitz R, Jones E, Kipen HM, Kroenke K, Ratzan S, Sharpe M, Wessely S. · Department of Medicine, University of Michigan School of Medicine, USA. · J Occup Environ Med. · Pubmed #14534444 No free full text.

Abstract: Twelve years of concern regarding a possible "Gulf War syndrome" has now given way to societal concerns of a "World Trade Center syndrome" and efforts to prevent unexplained symptoms following the most recent war in Iraq. These events serve to remind us that unexplained symptoms frequently occur after war and are likely after terrorist attacks. An important social priority is to recognize, define, prevent, and care for individuals with unexplained symptoms after war and related events (eg, terrorism, natural or industrial disasters). An international, multidisciplinary, and multiinstitutional consensus project was completed to summarize current knowledge on unexplained symptoms after terrorism and war.

Liberzon I, Britton JC, Phan KL. · Psychiatry Service, Ann Arbor Veterans Affairs Medical Center, MI 48109, USA. · Stress. · Pubmed #13129808 No free full text.

Abstract: Functional activation studies of posttraumatic stress disorder (PTSD) using symptom provocation paradigms have implicated dysfunction in limbic and paralimbic brain regions. Increased or altered cerebral blood flow has been observed in amygdala and insula. Decreased or absent activity has been seen in medial prefrontal and anterior cingulate cortex (ACC). These brain regions comprise a neural circuit that has been demonstrated as important for emotional processing and emotional regulation. We studied combat veterans with PTSD (n=16), combat veterans without PTSD (combat controls, n=15), and age-matched healthy control subjects (n=15) with [O-15] H2O PET under a script-driven imagery paradigm of personalized traumatic/stressful and emotionally neutral events. Preliminary findings show that PTSD patients and combat controls had differential blood flow patterns during emotional recall in amygdala, insula and medial prefrontal cortex. Consistent with and extending prior findings, these preliminary results replicate differential patterns of activation in limbic and paralimbic regions of PTSD patients and trauma exposed controls suggesting that these neural substrates may be involved in the deficits in emotional processing in PTSD on one hand, and in resilience to trauma on the other.

Villafuerte S, Burmeister M. · Mental Health Research Institute, University of Michigan, Ann Arbor, Michigan MI 48109-0720, USA. · Genome Biol. · Pubmed #12914652 links to  free full text

Abstract: As is the case for normal individual variation in anxiety levels, the conditions panic disorder, agoraphobia and other phobias have a significant genetic basis. Recent reports have started to untangle the genetic relationships between predispositions to anxiety and anxiety disorders.

Seng JS. · University of Michigan School of Nursing, Division II, Ann Arbor, 48109-0482, USA. · Clin Nurse Spec. · Pubmed #12544119 No free full text.

Abstract: Many people in our society have been exposed to overwhelming trauma, including abuse and assault. Posttraumatic stress can persist and become a chronic disorder, with behavioral and physiologic alterations affecting health across the lifespan. Often the etiologic role of trauma in a health problem remains undiscerned and unacknowledged. Acknowledging the effects of trauma is a caring intervention in itself, and it can lead to more effective healthcare and better relationships with patients. This article describes the process of acknowledging the effects of trauma in clinical reasoning, in dialogue with the patient, and in planning care and interventions.

Caamaño CA, Morano MI, Akil H. · Mental Health Research Institute, University of Michigan Medical School, Ann Arbor, MI, USA. · Psychopharmacol Bull. · Pubmed #12397867 links to  free full text

Abstract: Glucocorticoids are key elements in the maintenance of an organism's homeostasis, a dynamic balance that is constantly challenged by internal and external stressors. Chronic exposure to elevated glucocorticoids may induce profound effects on an individual's physical and mental well-being. Therefore, a complex neuroendocrine system, the limbic-hypothalamo-pituitary-adrenocortical (LHPA) axis, exists to regulate glucocorticoid homeostasis. Dysregulation of the LHPA axis has been linked to numerous psychiatric disorders, including eating disorders, anxiety, depression, posttraumatic stress disorder, memory impairment, neurodegenerative disorders, and even Alzheimer disease. At a molecular level, the actions of glucocorticoids are mediated by two different cytoplasmic receptors, the mineralocorticoid receptor and the glucocorticoid receptor. These corticosteroid receptors are heteromeric complexes found in dynamic association with a still growing number of chaperone proteins and other factors mediating their actions. Because this dynamic association is extremely sensitive to changes in cellular environment, energy, and metabolic state, we hypothesize that these corticosteroid receptors act as "sensor" signal transducers critical for homeostasis. In this review, we focus on the interplay among protein folding, transport, and function of the corticosteroid receptors at the cellular level, which provides a foundation for understanding the pathogenesis of glucocorticoid resistance or hypersensitivity, causing imbalances in the LHPA axis, and possibly triggering psychiatric disorders.