Anxiety Disorders: Yale University

Stover CS. · Yale University Child Study Center, USA. · J Interpers Violence. · Pubmed #15722500 No free full text.

Abstract: Domestic violence has been an intense area of study in recent decades. Early studies helped with the understanding of the nature of perpetration, the cycle of violence, and the effect of family violence on children. More recently, studies have focused on beginning to evaluate domestic violence interventions and their effects on recidivism. This article acknowledges the importance of what we have learned about the prevalence and impact of domestic violence and explores the need for more focused effort to pinpoint interventions that are effective with perpetrators and victims. Methodological issues relevant to past intervention studies are also discussed and future research directions are outlined.

Rasmusson AM, Vythilingam M, Morgan CA. · Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA. · CNS Spectr. · Pubmed #15079139 No free full text.

Abstract: Studies of the hypothalamic-pituitary-adrenal (HPA) axis in persons with posttraumatic stress disorder (PTSD) have produced variable findings. This review focuses on the factors likely to have affected the outcome of these studies, including population characteristics and experimental design. Also discussed is a possible role for the adrenal neurosteroid dehydroepiandrosterone (DHEA) as a mediator of HPA axis adaptation to extreme stress and the psychiatric symptoms associated with PTSD. The antiglucocorticoid properties of DHEA may contribute to an upregulation of HPA axis responses as well as mitigate possible deleterious effects of high cortisol levels on the brain in some PTSD subpopulations. The neuromodulatory effects of DHEA and its metabolite DHEAS at gamma-aminobutyric acid and N-methyl-D-aspartate receptors in the brain may contribute to psychiatric symptoms associated with PTSD. The possible importance of other neurohormone systems in modulating HPA axis and symptom responses to traumatic stress is also discussed. Understanding the complex interactions of these stress-responsive neurosteroid and peptide systems may help explain the variability in patterns of HPA axis adaptation, brain changes, and psychiatric symptoms observed in PTSD and lead to better targeting of preventive and therapeutic interventions.

Leckman JF. · Child Study Center, Children's Clinical Research Center, and Department of Pediatrics, Yale University, New Haven, CT 06520, USA. · Brain Dev. · Pubmed #14980368 No free full text.

Abstract: Tic symptoms, the hallmark of Tourette's syndrome (TS), may simply be fragments of innate behavior. As such, the sensory urges that precede tics may illuminate some of the normal internal cues that are intimately involved in the assembly of behavioral sequences. The occurrence of tics in time appears to have fractal characteristics that may help to explain the waxing and waning course of tic disorders. Longitudinal studies are currently underway that should permit a close examination of the natural fluctuations in tic severity using valid and reliable clinician-rated scales of tic severity. The natural history of tics typically shows a marked decline during the course of adolescence. However, TS can also be associated with social, emotional, and academic difficulties in early adulthood. Comorbid attention deficit/hyperactivity disorder and obsessive-compulsive disorder are likely to influence the long-term adaptive outcomes of individuals with TS. Future progress may also be expected as endophenotypes, and possibly genetic markers, are identified that are associated with specific comorbid conditions and etiologically distinct forms of TS.

Bailey KP. · Yale University School of Nursing, New Haven, Connecticut, USA. · J Psychosoc Nurs Ment Health Serv. · Pubmed #14682027 No free full text.

Abstract: Most general descriptions of depression that date back to Hippocrates, including the DSM-IV, have listed gastrointestinal problems, sleep disturbances, headaches, appetite changes, and aches and pains of a diffuse nature as common features of the disorder. In addition, physical symptoms have a strong association with psychiatric disorders, and the presence of any physical symptom may increase the likelihood of a mood or anxiety disorder by two-fold or three-fold. A growing body of evidence suggests that serotonin and norepinephrine may share neurochemical mechanisms that tie depression and physical symptoms together. Both selective serotonin reuptake inhibitors alone and antidepressant agents that incorporate both serotonin and norepinephrine reuptake inhibition have shown evidence of relieving physical symptoms. Given the additional disease burden caused by physical symptoms in depression, it is vital that antidepressant agents that effectively treat the physical symptoms and chronic pain associated with depression be used.

Berkowitz SJ, Marans S. · Department of Child and Adolescent Psychiatry, Yale University School of Medicine, Child Study Center, 230 South Frontage Road, New Haven, CT 06520, USA. · Child Adolesc Psychiatr Clin N Am. · Pubmed #14579650 No free full text.

Abstract: The emergency department child and adolescent psychiatrist is in the unique position of informing and helping emergency department providers address the traumatic impact of the cause of a child's emergency presentation and the potential iatrogenic exacerbation of the acute traumatic response. The child and adolescent psychiatrist must become a clinical traumatologist who provides the necessary consultation and education that lead to practice change in emergency department awareness and procedures and performs the optimal evaluation and interventions for children who present in psychiatric crisis.

Franks RP. · Yale Child Study Center, Yale University School of Medicine, 230 South Frontage Road, New Haven, CT 06510, USA. · Child Adolesc Psychiatr Clin N Am. · Pubmed #12910822 No free full text.

Abstract: Children who suffer from childhood seizure disorders, especially epilepsy, have various potential psychiatric issues and concerns that the treating physician and psychiatric consultant should consider. These children are at increased risk of adjustment reactions, anxiety and mood disorders, ADHD, learning difficulties, and familial and social stress. Because of potential risks and vulnerabilities for the development of comorbid psychiatric conditions and the increased risk for individual, familial, and social impairment, a psychiatric consultation to children and families dealing with epilepsy may play an important role in the successful management of this complex disorder.

Szydlo D, van Wattum PJ, Woolston J. · Yale Child Study Center, National Center for Children Exposed to Violence, Yale University School of Medicine, 230 South Frontage Road, New Haven, CT 06520, USA. · Child Adolesc Psychiatr Clin N Am. · Pubmed #12910817 No free full text.

Abstract: Diabetes mellitus (DM) presents itself in two forms: insulin-dependent (type 1 DM) and non-insulin-dependent (type 2 DM). Although type 2 DM usually has an adult onset, in recent years there has been a significant rise in the number of children diagnosed with type 2 DM in the United States. Reasons for this increased frequency are believed to be a larger percentage of children who are overweight, a family history of diabetes, and a considerable increase in the use of psychotropic medication in children. The diagnosis of DM is a significant stressor not only for patients but also for their environment. Children with DM are sometimes stigmatized by their peers and relatives who do not understand the illness or are frightened by it. Some children also may need to alter several of their customary routines and are often scared to participate in activities in which they were previously engaged. The family's response to the diagnosis of DM may have a negative effect on glycemic control. Differences have been found in the way patients with type 1 DM and type 2 DM cope with and adapt to their diagnosis.

Mayes LC. · Yale Child Study Center, Yale University School of Medicine, 230 South Frontage Road, New Haven, CT 06520, USA. · Child Adolesc Psychiatr Clin N Am. · Pubmed #12910815 No free full text.

Abstract: Prematurity and birth defects present parents with a crisis for which they have usually had little preparation and no prior education. Both types of early medical complications may represent a state of suspended animation for most parents. Even large premature infants with good prognoses induce anxiety and symbolize potential death and disability, and children with birth defects may portend years of medical procedures and long-term disability. The fear of serious neurologic impairment or mental retardation presents parents with a long period of ambiguity and chronic anxiety. During this period, they must be helpless observers rather than active participants. Recent research has indicated that the active involvement of parents in the care of their premature infants can be helpful in alleviating the guilt and anxiety related to loss and impairment. Similarly, early physical contact between parents and their severely malformed infant is equally critical. Even if the ultimate complexities of early attachment have yet to be delineated fully, this is a worthwhile practice and useful approach in the nursery. Child mental health professionals have important roles to fulfill in helping staff members deal with increased parental participation and directly managing family members with intense distress related to their infants' fragility. The role of the mental health professional in such consultation may cover five related tasks: 1. Understanding the nature of the biologic issues facing the child and integrating that understanding with an evaluation of the child's neurobehavioral profile. 2. Understanding the family's relationship with the child and their overall level of functioning during an acutely stressful time. 3. Developing an appreciation of the place of the child in his or her family and how the parents understand the nature of the medical problems. 4. Forming a collaborative relationship with the pediatricians and other subspecialists who care for the child so that behavioral and psychological interventions are integrated with the child's biomedical care. 5. Fostering a brief, or sometimes long-term, therapeutic relationship with the family or facilitating the family's finding such a relationship with another clinician. There will never be enough child and adolescent psychiatrists and psychologists to treat all families of medically compromised infants. Knowledge of normative responses has advanced to the point at which basic skills can be used by and transmitted to others who can provide basic services. There is much to be learned about the short- and long-term sequelae of such stressful situations on individuals and family systems with preexisting psychopathology. For such families, child mental health professionals are uniquely suited to play a further role in research and treatment.

Kosten TR, O'Connor PG. · Departments of Psychiatry, Yale University School of Medicine, New Haven, Conn., USA. · N Engl J Med. · Pubmed #12724485 No free full text.

This publication has no abstract.

Santacroce SJ. · Yale University School of Nursing, 100 Church Street South, P.O. Box 9740, New Haven, CT 06536-0740, USA. · J Nurs Scholarsh. · Pubmed #12701526 No free full text.

Abstract: PURPOSE: To explicate the link between parental uncertainty and posttraumatic stress as a way to stimulate advancement in the design and evaluation of nursing interventions for parents of children with serious illness. METHODS: The literature on Mishel's uncertainty in illness theory and its reconceptualization--parental uncertainty in serious childhood illness--and posttraumatic stress are reviewed and synthesized. Pertinent methodological and sociocultural issues are discussed. CONCLUSIONS: The literature indicates support for the theoretical link between parental uncertainty and posttraumatic stress. This linkage provides direction for the design and evaluation of nursing interventions to support parents of children with serious childhood illness.

Abbott BG, Zaret BL. · Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut 06516, USA. · Am J Med. · Pubmed #12586233 No free full text.

This publication has no abstract.

Carroll DH, Scahill L, Phillips KA. · Yale Child Study Center, Yale University School of Nursing, New Haven, CT 06520-7900, USA. · Arch Psychiatr Nurs. · Pubmed #11925574 No free full text.

Abstract: Body dysmorphic disorder (BDD) is a potentially debilitating psychiatric illness characterized by intense preoccupation with an imagined or slight defect in physical appearance. Until recently, it has gone largely unrecognized and did not appear in the Diagnostic and Statistical Manual of Mental Disorders until 1987. Improved methods of assessment and treatment of BDD have increased interest in this disorder. This article reviews current literature on BDD, including the similarities between BDD and obsessive-compulsive disorder (OCD), current assessment and treatment strategies, and implications for clinical practice and future research.

Bessen DE, Lombroso PJ. · Yale University School of Medicine, Department of Epidemiology and Public Health, New Haven, Connecticut, USA. · Adv Neurol. · Pubmed #11530436 No free full text.

This publication has no abstract.

Kaufman J, Charney D. · Department of Psychiatry, Yale University, New Haven, CT 06511, USA. · Dev Psychopathol. · Pubmed #11523843 No free full text.

Abstract: Child abuse is associated with markedly elevated rates of major depression (MDD) in child, adolescentt, and adult cohorts. This article reviews preclinical (e.g., animal) studies of the effects of early stress and studies of the neurobiological correlates of MDD in adults and children, and it highlights differences in the neurobiological correlates of MDD and stress at various developmental stages. The preclinical studies demonstrate that stress early in life can alter the development multiple neurotransmitter systems and promote structural and functional alterations in brain regions similar to those seen in adults with depression. Preclinical and clinical studies suggest, however, that long-term neurobiological changes associated with early stress can be modified by familial/genetic factors, the quality of the subsequent caregiving environment, and pharmacological interventions. Little is known about how developmental factors interact with experiences of early stress and these other modifying factors. Moreover, in cases of child maltreatment, the effects of early abuse are often exacerbated by failures in the child protection system and repeat out-of-home placements. Given the number of factors that impact on the long-term outcome of maltreated children, multidisciplinary research efforts are recommended to address this problem-with foci that span from neurobiology to social policy.

Jacobsen LK, Southwick SM, Kosten TR. · Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06516, USA. · Am J Psychiatry. · Pubmed #11481147 links to  free full text

Abstract: OBJECTIVE: Alcohol use disorders and other substance use disorders are extremely common among patients with posttraumatic stress disorder (PTSD). This article reviews studies pertaining to the epidemiology, clinical phenomenology, and pathophysiology of comorbid PTSD and substance use disorders. METHOD: Studies were identified by means of computerized and manual searches. The review of research on the pathophysiology of PTSD and substance use disorders was focused on studies of the hypothalamic-pituitary-adrenal axis and the noradrenergic system. RESULTS: High rates of comorbidity suggest that PTSD and substance use disorders are functionally related to one another. Most published data support a pathway whereby PTSD precedes substance abuse or dependence. Substances are initially used to modify PTSD symptoms. With the development of dependence, physiologic arousal resulting from substance withdrawal may exacerbate PTSD symptoms, thereby contributing to a relapse of substance use. Preclinical work has led to the proposal that in PTSD, corticotropin-releasing hormone and noradrenergic systems may interact such that the stress response is progressively augmented. Patients may use sedatives, hypnotics, or alcohol in an effort to interrupt this progressive augmentation. CONCLUSIONS: Vigorous control of withdrawal and PTSD-related arousal symptoms should be sought during detoxification of patients with comorbid PTSD and substance use disorders. Inclusion of patients with comorbid PTSD and substance use disorders in neurobiologic research and in clinical trials will be critical for development of effective treatments for this severely symptomatic patient population.

Potenza MN. · Division of Substance Abuse, Department of Psychiatry, Yale University School of Medicine, Connecticut Mental Health Center, New Haven, CT 06519, USA. · Semin Clin Neuropsychiatry. · Pubmed #11447573 No free full text.

Abstract: Despite relatively high prevalence rates and significant morbidity and mortality associated with pathological gambling (PG), our understanding of the neurobiological basis of PG lags in comparison to that for other psychiatric illnesses of comparable magnitude. An improved understanding of the neurobiology of PG would facilitate targeted investigations into more effective treatments. Emerging data suggest shared neurobiological features determine in part pathological gambling and substance use disorders. These findings both challenge current conceptualizations of addictions and provide a substantial basis of knowledge on which to design investigations into the understanding and treatment of pathological gambling. The findings that substance use disorders and the behavioral "addiction" of PG share common causative features raise the question as to what extent other compulsive disorders (eg, compulsive shopping, compulsive sexual behaviors, compulsive computer use) might be biologically related.

Krystal JH, D'Souza DC, Sanacora G, Goddard AW, Charney DS. · Department of Psychiatry, Yale University School of Medicine, Connecticut, USA. · Med Clin North Am. · Pubmed #11349473 No free full text.

Abstract: This article reviews the rapidly changing concepts related to the pathophysiology of major psychiatric disorders. The current era is an exciting one for psychiatric research and the rapidity with which advances are being made is a source of hope to patients with these disorders and for society.

Bremner JD. · Department of Diagnostic Radiology and Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519, USA. · Hippocampus. · Pubmed #11345127 No free full text.

This publication has no abstract.

Howell HB, Brawman-Mintzer O, Monnier J, Yonkers KA. · Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA. · Psychiatr Clin North Am. · Pubmed #11225506 No free full text.

Abstract: Women have a higher prevalence of GAD than do men. This ratio holds true in most clinical and general-population samples. Some variations exist, with evidence to suggest the strong impact of environment and life events. Women are sensitive to lifetime adversity and exacerbation of symptoms in conjunction with their menstrual cycle. Comorbidity is a crucial diagnostic factor when treating anyone with GAD, especially women. Most notably, high comorbidity with other anxiety disorders, MDD and alcohol-abuse disorder occurs for women. Overall, although the prevalence of women with GAD is greater than that of men with GAD, the course of illness and prognosis are not qualitatively different. Across varied methodology, data suggest gender-related differences in the metabolism and potentially in the effects and side effects of the various benzodiazepines and antidepressant psychopharmacologic treatments of GAD. Additional research is needed to better understand these differences.

Kaufman J, Charney D. · Yale University, Department of Psychiatry, New Haven, CT 06511, USA. · Depress Anxiety. · Pubmed #11098417 No free full text.

Abstract: This article reviews data on the prevalence of panic, social phobia, generalized anxiety, and posttraumatic stress disorder, and research documenting the comorbidity of these disorders with major depression (MDD). These anxiety disorders are frequently comorbid with MDD, and 50-60% of individuals with MDD report a lifetime history of one or more of these anxiety disorders. The anxiety disorders are also highly correlated with one another, and approximately one-quarter to one-half of individuals with each of the anxiety disorders report a lifetime history of an alcohol or substance use disorder. Anxiety disorders rarely exist in isolation, with several studies reporting that over 90% of individuals with anxiety disorders have a lifetime history of other psychiatric problems. Implications for research are discussed, including the potential benefit of using combined categorical and dimensional rating scale approaches in future genetic, biochemical, neuroimaging, and treatment studies. The clinical implications of the findings are also discussed, and the results of recent clinical trials summarized. Available data suggests selective serotonin reuptake inhibitors are the first-line pharmacological treatment for these disorders, and that newer serotonin and norepinephrine reuptake inhibitors show significant promise, especially for comorbid cases. Comorbidity among depression and anxiety disorders is associated with greater symptom severity, and a considerably higher incidence of suicidality. Increased public awareness about these disorders and the availability of effective treatments is sorely needed.

Wolff M, Alsobrook JP, Pauls DL. · Child Study Center, Yale University School of Medicine, New Haven, Connecticut, USA. · Psychiatr Clin North Am. · Pubmed #10986726 No free full text.

Abstract: Developments in molecular genetic methods have proved to be powerful tools in the search for genes involved in complex diseases, and they hold the promise of understanding the genetic basis of OCD. The next step in understanding the genetics of OCD is the localization and characterization of the genes that confer susceptibility. A more complete understanding of the genetic basis of OCD and of the interactions between relevant genotypes and relevant environmental factors is important for clarification of the cause, pathogenesis, and treatment of this complex disorder. These genetic methods must be combined with careful clinical and epidemiologic work to correctly elucidate the cause of OCD. Future research also should define subsets of endophenotypes of the disorder. Factors such as neuropsychological functioning, personality testing, comorbidity, and age of onset are extremely useful in the continued study of genetic mechanisms involved in the cause of OCD.

Roberts A. · Yale University, USA. · Clin Psychol Rev. · Pubmed #10860171 No free full text.

Abstract: Research on psychiatric comorbidity among opiate and cocaine addicts has consistently found African-Americans to report fewer symptoms of anxiety and affective disorders than Whites. The current article reviews the research on these racial differences, evaluates various interpretations of these differences, and discusses the limitations of past research. It is concluded that Whites and African-American addicts differ in their underlying reasons for abusing drugs. Drug addiction among Whites appears to be related largely to psychopathology, whereas Black drug abuse is best understood in terms of social and environmental factors. Treatment implications are also discussed.

Southwick SM, Bremner JD, Rasmusson A, Morgan CA, Arnsten A, Charney DS. · Yale University School of Medicine, New Haven, Connecticut, USA. · Biol Psychiatry. · Pubmed #10560025 No free full text.

Abstract: This review focuses on the role of norepinephrine (NE) in traumatic stress. The review is divided into three sections. The first section, "Norepinephrine and Arousal," describes preclinical studies related to norepinephrine's role in arousal, orienting to novel stimuli, selective attention and vigilance. It also contains a brief discussion of NE and its relationship to fear-provoking stimuli followed by preclinical and clinical studies that demonstrate heightened noradrenergic neuronal reactivity, increased alpha 2 receptor sensitivity and exaggerated arousal in organisms that have been exposed to chronic uncontrollable stress. The second section, "Norepinephrine and Memory," describes preclinical and clinical studies related to norepinephrine's role in enhanced encoding of memory for arousing and aversive events and in subsequent re-experiencing symptoms such as, intrusive memories and nightmares. The third section, "Norepinephrine and Pharmacologic Treatment," briefly discusses the use of adrenergic blockers, clonidine and propranol, as well as tricyclic and MAO inhibitors, for the treatment of PTSD. Finally, we attempt to synthesize trauma-related preclinical and clinical studies of norepinephrine. We do this, in part, by focusing on a series of yohimbine studies in subjects with PTSD because data from these studies allow for a discussion that brings together preclinical and clinical findings relevant to trauma-related alterations in arousal and memory.

Chambers RA, Bremner JD, Moghaddam B, Southwick SM, Charney DS, Krystal JH. · Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. · Semin Clin Neuropsychiatry. · Pubmed #10553033 No free full text.

Abstract: Dissociative cognitive and perceptual alterations commonly occur at the time of traumatization and as an enduring feature of post-traumatic stress disorder (PTSD). After stress exposure, dissociative symptoms are a predictor of the development of PTSD. Recent preclinical data suggest that stress stimulates the cortico-limbic release of glutamate. The glutamate that is released during stress in animal models influences behavior, induces a variety of changes in neural plasticity that may have long-lasting effects on brain function and behavior, and contributes to neural toxicity. Antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor also stimulates transient cortico-limbic glutamate release in animals. Further, some of the effects of NMDA antagonists in animals are blocked by drugs that attenuate glutamate release. Clinical studies suggest that NMDA antagonists may transiently stimulate glutamate release and produce symptoms resembling dissociative states in humans. A recent study suggests that a drug that reduces glutamate release also attenuates the perceptual effects of the NMDA antagonist, ketamine, in humans. Because of the possible contributions of hyperglutamatergic states to the acute and long-lasting consequences of traumatic stress exposure, the therapeutic and neuroprotective potential of drugs that attenuate glutamate release should be explored in traumatized individuals with dissociative symptoms.

Bremner JD. · Departments of Diagnostic Radiology and Psychiatry, Yale University School of Medicine, Yale Psychiatric Institute, Yale/VA PET Center, New Haven, CT 06520, USA. · Semin Clin Neuropsychiatry. · Pubmed #10553030 No free full text.

Abstract: Neuroimaging studies in post-traumatic stress disorder (PTSD) have revealed changes in brain structure and function that may underlie the symptoms of PTSD. Two brain areas that have been consistently implicated in PTSD include the hippocampus and prefrontal cortex. Several studies showed that PTSD is associated with reduction in volume of the hippocampus, a brain area involved in learning and memory, as measured with magnetic resonance imaging (MRI). Positron emission tomography (PET) studies showed dysfunction of medial and orbital prefrontal cortex during PTSD symptom provocation and in response to traumatic reminders. Decreased benzodiazepine receptor binding was found in the medial prefrontal cortex as measured with neuroimaging in PTSD. The hippocampus and medial prefrontal cortex play important roles in memory and emotional regulation, and dysfunction in these areas may underlie memory deficits and pathological emotions in PTSD.