Anxiety Disorders: Emory University

Raison CL, Demetrashvili M, Capuron L, Miller AH. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322, USA. · CNS Drugs. · Pubmed #15697325 links to  free full text

Abstract: Recombinant preparations of the cytokine interferon (IFN)-alpha are increasingly used to treat a number of medical conditions, including chronic viral hepatitis and several malignancies. Although frequently effective, IFN alpha induces a variety of neuropsychiatric adverse effects, including an acute confusional state that develops rapidly after initiation of high-dose IFN alpha, a depressive syndrome that develops more slowly over weeks to months of treatment, and manic conditions most often characterised by extreme irritability and agitation, but also occasionally by euphoria. Acute IFN alpha-induced confusional states are typically characterised by disorientation, lethargy, somnolence, psychomotor retardation, difficulties with speaking and writing, parkinsonism and psychotic symptoms. Strategies for managing delirium should be employed, including treatment of contributing medical conditions, use of either typical or atypical antipsychotic agents and avoidance of medications likely to worsen mental status. Significant depressive symptoms occur in 21-58% of patients receiving IFN alpha, with symptoms typically manifesting over the first several months of treatment. The most replicated risk factor for developing depression is the presence of mood and anxiety symptoms prior to treatment. Other potential, but less frequently replicated, risk factors include a past history of major depression, being female and increasing IFN alpha dosage and treatment duration. The available data support two approaches to the pharmacological management of IFN alpha-induced depression: antidepressant pretreatment or symptomatic treatment once IFN alpha has been initiated. Pretreatment might be best reserved for patients already receiving antidepressants or for patients who endorse depression or anxiety symptoms of mild or greater severity prior to therapy. Several recent studies demonstrate that antidepressants effectively treat IFN alpha-induced depression once it has developed, allowing the vast majority of subjects to complete treatment successfully. Recent data suggest that IFN alpha-induced depression may be composed of two overlapping syndromes: a depression-specific syndrome characterised by mood, anxiety and cognitive complaints, and a neurovegetative syndrome characterised by fatigue, anorexia, pain and psychomotor slowing. Depression-specific symptoms are highly responsive to serotonergic antidepressants, whereas neurovegetative symptoms are significantly less responsive to these agents. These symptoms may be more effectively treated by agents that modulate catecholaminergic functioning, such as combined serotonin-noradrenaline (norepinephrine) antidepressants, bupropion, psychostimulants or modafinil. Additional factors to consider in selecting an antidepressant include potential drug-drug interactions and adverse effect profile. Finally, IFN alpha appears capable of inducing manic symptoms. Mania, especially when severe, is a clinical emergency. When this occurs, IFN alpha and antidepressants should be stopped, an emergency psychiatric consultation should be obtained, and treatment with a mood stabilizer should be initiated.

Bradley R, Greene J, Russ E, Dutra L, Westen D. · Department of Psychology, Emory University, Atlanta, GA 30322, USA. · Am J Psychiatry. · Pubmed #15677582 links to  free full text

Abstract: OBJECTIVE: The authors present a multidimensional meta-analysis of studies published between 1980 and 2003 on psychotherapy for PTSD. METHOD: Data on variables not previously meta-analyzed such as inclusion and exclusion criteria and rates, recovery and improvement rates, and follow-up data were examined. RESULTS: Results suggest that psychotherapy for PTSD leads to a large initial improvement from baseline. More than half of patients who complete treatment with various forms of cognitive behavior therapy or eye movement desensitization and reprocessing improve. Reporting of metrics other than effect size provides a somewhat more nuanced account of outcome and generalizability. CONCLUSIONS: The majority of patients treated with psychotherapy for PTSD in randomized trials recover or improve, rendering these approaches some of the most effective psychosocial treatments devised to date. Several caveats, however, are important in applying these findings to patients treated in the community. Exclusion criteria and failure to address polysymptomatic presentations render generalizability to the population of PTSD patients indeterminate. The majority of patients posttreatment continue to have substantial residual symptoms, and follow-up data beyond very brief intervals have been largely absent. Future research intended to generalize to patients in practice should avoid exclusion criteria other than those a sensible clinician would impose in practice (e.g., schizophrenia), should avoid wait-list and other relatively inert control conditions, and should follow patients through at least 2 years.

Nemeroff CB. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322-4990, USA. · Psychopharmacol Bull. · Pubmed #15131523 links to  free full text

Abstract: Mechanisms underlying the pathological characteristics of the various anxiety disorders have yet to be fully elucidated. One of the most widely accepted mediators known to play a central role in the pathophysiology of anxiety disorders is the g-aminobutyric acid (GABA) system. Evidence supporting the role of a dysfunctional GABA system has resulted from clinical experience with the benzodiazepines, as well as subsequent determination of mechanism of action, genetic engineering, and neuroimaging studies of the GABA receptor. The concatenation of results suggests a relative deficiency in GABA neurotransmission, which can be augmented by agents acting on different components of the GABA system. Agents such as the benzodiazepines, neuroactive steroids, and barbiturates act as allosteric modulators of the GABAA receptor; b-carboline and the barbiturates function as direct GABA agonists. Valproate, gabapentin, pregabalin, and vigabatrin increase brain GABA levels or neurotransmission at least in part by targeting the metabolic pathways of GABA. Tiagabine selectively increases synaptic GABA availability by blocking the reuptake of GABA via transporter inhibition. Evidence exists, to a greater or lesser extent, that all of these agents possess anxiolytic properties, as would be expected by their mechanisms of action. This article reviews the findings implicating the GABA system in the pathophysiology of anxiety disorders and describes the potential role of agents that modulate GABA neurotransmission in the treatment of these disorders.

Nemeroff CB. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322-4990, USA. · J Clin Psychiatry. · Pubmed #14728093 No free full text.

Abstract: There is considerable evidence to suggest that adverse early-life experiences have a profound effect on the developing brain. Neurobiological changes that occur in response to untoward early-life stress can lead to lifelong psychiatric sequelae. Children who are exposed to sexual or physical abuse or the death of a parent are at higher risk for development of depressive and anxiety disorders later in life. Preclinical and clinical studies have shown that repeated early-life stress leads to alterations in central neurobiological systems, particularly in the corticotropin-releasing factor system, leading to increased responsiveness to stress. Clearly, exposure to early-life stressors leads to neurobiological changes that increase the risk of psychopathology in both children and adults. Identification of the neurobiological substrates that are affected by adverse experiences in early life should lead to the development of more effective treatments for these disorders. The preclinical and clinical studies evaluating the consequences of early-life stress are reviewed.

Bremner JD. · Emory Center for Positron Emission Tomography, Atlanta, Georgia, USA. · Psychopharmacol Bull. · Pubmed #14566211 links to  free full text

Abstract: Seven years ago we wrote a paper about the functional neuroanatomical correlates of the effects of stress on memory; however, at that time there were no data on the effects of stress on the brain in human subjects. Since that time an abundance of research has been carried out using neuroimaging to investigate the neuroanatomical correlates of the effects of stress on memory. These studies have corroborated our initial hypotheses that the functional neuroanatomy of stress involves a circuit of brain areas involved in both stress and memory function, including the hippocampus, amygdala, cingulate and medial prefrontal cortex, and dorsolateral prefrontal cortex. These studies have gone a long way toward advancing our understanding of the neuroanatomical correlates of traumatic stress. This understanding, in turn, will promote the development of future treatment advances for stress-related psychiatric disorders such as posttraumatic stress disorder.

Ninan PT. · Department of Psychiatry, Emory University, Atlanta, GA 30329, USA. · Psychopharmacol Bull. · Pubmed #14566204 links to  free full text

Abstract: Obsessive-compulsive disorder (OCD) is an anxiety disorder that commonly presents comorbidly with other psychiatric disorders. The underlying neurobiology of OCD is associated with circuits involving the basal ganglia, thalamus, and the frontal cortex. Randomized, placebo-controlled trials indicate acute and long-term efficacy of potent selective serotonin reuptake inhibitors (SSRIs), such as paroxetine. There is suggestive evidence that higher doses of paroxetine than those used in major depression are needed for benefit in OCD. Because of their safety and beneficial adverse-event profile, the SSRIs have become the leading choice in the pharmacological management of OCD.

Kilts C. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA. · Psychopharmacol Bull. · Pubmed #14566198 links to  free full text

Abstract: The advent of neuroimaging technology has brought with it a deeper understanding of brain function and structure in health and psychiatric illness. This article overviews pertinent findings from neuroimaging studies in mood and anxiety disorders. Paroxetine is a particularly well-studied psychopharmacologic agent in this regard. The findings of neuroimaging studies of paroxetine will be placed into perspective for a better understanding of the interaction of this selective serotonin reuptake inhibitor (SSRI) with the serotonergic and noradrenergic systems in the brain that mediate clinical efficacy. When considered in the context of a burgeoning literature on neuroimaging research of the pathophysiology of mood and anxiety disorders, the findings of paroxetine studies suggest a neurobiological explanation for the mechanisms whereby chronic administration of paroxetine affects neural systems involved in the pathophysiology of major depression and several anxiety disorders such as obsessive-compulsive disorder, posttraumatic stress disorder, and social anxiety disorder.

Nemeroff CB, Owens MJ. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322, USA. · Psychopharmacol Bull. · Pubmed #14566196 links to  free full text

Abstract: Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with some neuropharmacologic properties unique among this class of compounds. The findings of early in vitro studies demonstrated the potency of paroxetine at inhibiting 5-HT uptake in rat synaptosomes. Paroxetine also has been shown to be a potent and selective inhibitor of the human serotonin transporter (SERT) and has recently been demonstrated to have moderate affinity for the norepinephrine transporter (NET). Because of the affinity and in vitro selectivity of this SSRI, tritiated paroxetine is now widely used as a marker for SERT in laboratory settings, and its use has advanced our understanding of neurotransmitter function in the brain and periphery. The in vivo pharmacologic properties of paroxetine are well characterized, especially following acute administration. However, the pharmacologic effects of chronically administered paroxetine remain an active area of study. Paroxetine administration in laboratory animals has been shown to be associated with decreased SERT density and function, maintenance of normal firing rates and release of 5-HT, and increased activation of postsynaptic 5-HT receptors. Using a novel ex vivo assay, we have demonstrated that paroxetine exhibits dose-related inhibition of the NET in patients treated for depression. At usual clinical doses (ie, 20 mg/d), paroxetine is a potent and selective inhibitor of the SERT; however, at higher doses (ie, 40 mg/d), paroxetine can exhibit marked NET inhibition. The application of these findings of in vivo NET inhibition by paroxetine in the treatment of mood and anxiety disorders will be informed by further clinical studies.

Gutman DA, Nemeroff CB. · Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Drive, Suite 4000 WMRB, Atlanta, GA 30322, USA. · Physiol Behav. · Pubmed #12954441 No free full text.

Abstract: In the search for the underlying biological causes of psychiatric disorders, primary roles for both genetics and environment have been clearly established. A family history of mood or anxiety disorders, representing the genetic component, clearly increases the risk for developing these illnesses in adulthood. The pivotal role of early environmental influences in the pathogenesis of these disorders is also supported by an abundance of both clinical and preclinical data. This review will highlight some of the preclinical and clinical literature that suggests early adverse experience may sensitize corticotropin-releasing factor (CRF) circuitry. The neurobiology of depression highlighting the pathophysiological role of CRF is reviewed. Next, some of the preclinical models of early life stress are discussed; along with a review of the relevant clinical literature that suggests that the functional dysregulation of CRF circuitry in response to early life trauma may contribute to adulthood depression. The discussion will be framed in regards to a stress-diathesis model in which early adverse events result in a sensitized stress axis that predisposes individuals to develop mood disorders.

Marcin MS, Nemeroff CB. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA. · Acta Psychiatr Scand Suppl. · Pubmed #12950436 No free full text.

Abstract: OBJECTIVE: Social anxiety disorder (SAD) is a ubiquitous anxiety disorder. Despite being the third most common psychiatric disorder, little is known about the interaction between genetic predisposition and environmental factors in the development of SAD. The available literature on SAD has been compared with data on the genetics and environmental impact on the phenotypic expression of fear and anxiety, and its implicated neurobiology, in order to explore the neurobiology of SAD as understood through the neurochemical dysregulation expressed in fear and anxiety. METHOD: A systematic review of the literature was employed for the years from 1966 to 2001. RESULTS: SAD does indeed have much overlap with fear and anxiety. This is best demonstrated by the interactions of the noradrenergic and serotonergic systems with each other and the hypothalamic-pituitary-adrenal axis. CONCLUSION: SAD may well be understood as one potential outcome for predisposed individuals who are exposed to the proverbial 'second hit', or environmental insult, in childhood. Behavioral inhibition may be an early expression of this predisposition, with natural progression to SAD occurring via a disruption of neurochemical homeostasis. Through animal and human data it has become evident that fear and anxiety have shared, as well as distinct, neurochemical and neuroanatomical pathways. These similarities are expressed as symptoms and objective signs that are common to many individuals with social anxiety disorder.

Raison CL, Miller AH. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA. · Am J Psychiatry. · Pubmed #12944327 links to  free full text

Abstract: OBJECTIVE: Previous theories have emphasized the role of excessive glucocorticoid activity in the pathology of chronic stress. Nevertheless, insufficient glucocorticoid signaling (resulting from decreased hormone bioavailability or reduced hormone sensitivity) may have equally devastating effects on bodily function. Such effects may be related in part to the role of glucocorticoids in restraining activation of the immune system and other components of the stress response, including the sympathetic nervous system (SNS) and corticotropin-releasing hormone (CRH). METHOD: The literature on neuroendocrine function and glucocorticoid-relevant pathologies in stress-related neuropsychiatric disorders, including posttraumatic stress disorder and major depression, was reviewed. RESULTS: Although not occurring together, both hypocortisolism and reduced responsiveness to glucocorticoids (as determined by dexamethasone challenge tests) were reliably found. Stress-related neuropsychiatric disorders were also associated with immune system activation/inflammation, high SNS tone, and CRH hypersecretion, which are all consistent with insufficient glucocorticoid-mediated regulation of stress hyperresponsiveness. Finally, antidepressants, a mainstay in the treatment of stress-related disorders, were regularly associated with evidence of enhanced glucocorticoid signaling. CONCLUSIONS: Neuroendocrine data provide evidence of insufficient glucocorticoid signaling in stress-related neuropsychiatric disorders. Impaired feedback regulation of relevant stress responses, especially immune activation/inflammation, may, in turn, contribute to stress-related pathology, including alterations in behavior, insulin sensitivity, bone metabolism, and acquired immune responses. From an evolutionary perspective, reduced glucocorticoid signaling, whether achieved at the level of the hormone or its receptor, may foster immune readiness and increase arousal. Emphasis on insufficient glucocorticoid signaling in stress-related pathology encourages development of therapeutic strategies to enhance glucocorticoid signaling pathways.

Hunter RG, Kuhar MJ. · Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA. · Curr Drug Targets CNS Neurol Disord. · Pubmed #12769800 No free full text.

Abstract: CART peptides are relatively novel neuropeptides involved in feeding, drug reward and stress. They are formed from a proCART polypeptide that is 89 amino acids in length in the human version. Fragments 42-89 and 49-89 are behaviorally active in feeding and locomotion as well and other functions. These peptides are highly abundant and widely but discretely distributed in the brain, gut, pituitary, adrenals and pancreas. The presence of CART immunoreactivity in specific nuclei of the hypothalamus has led to an examination of icv-injected CART peptides effects on feeding, which have proven to be significantly anorectic. Studies of transgenic animals and humans have also demonstrated a linkage to both obesity and anorexia. Similarly, the localization of CART to sub-regions of the mesolimbic dopamine system has led to demonstration of the effects of CART peptides on locomotor activity and conditioned place preference when injected into the ventral tegmental area (VTA), which are psychostimulant-like in quality. These findings also suggest that CART has the capacity to modulate mesolimbic dopamine, which could have implications for the treatment not only of psychostimulant abuse but also for the treatment of other disorders with mesolimbic dopamine involvement, such as schizophrenia. Other lines of evidence also show that CART peptides are involved in fear and startle behaviors which may have implications for understanding anxiety and stress. An important part of the development of CART mimetics and related drugs would be the identification of CART receptors. At the present time such receptors have not been identified, and much effort should be directed at this problem. Nonetheless, CART peptides offer interesting targets for new drug development for obesity and, potentially, a number of other disorders.

Nemeroff CB. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Ga 30322, USA. · J Clin Psychiatry. · Pubmed #12662127 No free full text.

Abstract: Although anxiety disorders were classified as neurotic disorders and not systematically studied before DSM-III, researchers and clinicians have been searching for effective, safe agents to treat anxiety symptoms and disorders for over a century. In that time, barbiturates, benzodiazepines, and many classes of antidepressants have been used as anxiolytics, all with side effect profiles that made them less than optimal treatments for anxiety. The recognition of the role of GABA in anxiety disorders has led researchers to develop anxiolytics that target GABA. The long-sought-after class of anxiolytics that are both effective and safe may be found in the new research being conducted with agents that selectively target GABA receptors and their subtypes.

Vermetten E, Bremner JD. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Ga, USA. · J Clin Psychiatry. · Pubmed #12633130 No free full text.

Abstract: BACKGROUND: Memory for odors that are associated with intense emotional experiences is often strongly engraved. Odors are claimed to be more closely connected to affect than other sensory experiences. They can serve as potent contextual cues for memory formation and emotional conditioning and can also serve as cues for olfactory flashbacks. Though trauma-related smells have long been noted by clinicians to be precipitants of traumatic memories in patients with posttraumatic stress disorder (PTSD), very few reports have been published that document this. CASE REPORTS: We review olfactory memories and olfactory flashbacks by presenting 3 cases that illustrate the role of olfaction in PTSD. In these cases olfaction is either a precipitant of PTSD symptoms or an important component of reexperiencing. DISCUSSION: In PTSD, seemingly nonspecific cues have the potential to precipitate traumatic memories with strong emotional components. These conditioned responses in PTSD are hypothesized to be mediated by specific brain areas, i.e., amygdala, hippocampus, and orbitofrontal cortex. Questions about smells as a traumatic reminder should be part of the routine assessment of intrusive memories in PTSD. In addition, smells may have the potential to provide cues to exposure situations in therapy or to facilitate de novo conditioning.

Walker DL, Toufexis DJ, Davis M. · Department of Psychiatry and Behavioral Sciences and The Center for Behavioral Neuroscience, Emory University School of Medicine, 1639 Pierce Drive, Suite 4000, Atlanta, GA 30322, USA. · Eur J Pharmacol. · Pubmed #12600711 No free full text.

Abstract: The bed nucleus of the stria terminalis is a limbic forebrain structure that receives heavy projections from, among other areas, the basolateral amygdala, and projects in turn to hypothalamic and brainstem target areas that mediate many of the autonomic and behavioral responses to aversive or threatening stimuli. Despite its strategic anatomical position, initial attempts to implicate the bed nucleus of the stria terminalis in conditioned fear were largely unsuccessful. Recent studies have shown, however, that the bed nucleus of the stria terminalis does participate in certain types of anxiety and stress responses. In this work, we review these findings and suggest from the emerging pattern of evidence that, although the bed nucleus of the stria terminalis may not be necessary for rapid-onset, short-duration behaviors which occur in response to specific threats, the bed nucleus of the stria terminalis may mediate slower-onset, longer-lasting responses that frequently accompany sustained threats, and that may persist even after threat termination.

Nemeroff CB. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322-4990, USA. · Hum Psychopharmacol. · Pubmed #12404664 No free full text.

Abstract: There have been considerable advances in neurobiology in recent years that are providing new directions for the development of novel classes of antidepressants. For example, the finding that corticotropin-releasing factor (CRF) is hypersecreted in depressed patients and mediates certain symptoms of depression has led to the development of specific antagonists of the CRF(1) receptor. These are expected to prove highly effective for the treatment of mood and anxiety disorders. Another related avenue of research is based on evidence that cortisol is integral to the pathophysiology of major depression with psychotic features. One alternative for treating this subtype of affective disorder is, therefore, to block the action of glucocorticoids using a receptor antagonist such as mifepristone. These are just two of the many new directions that will likely lead to the development of antidepressants in the near future.

Capuron L, Hauser P, Hinze-Selch D, Miller AH, Neveu PJ. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Drive, Suite 4000, Atlanta, GA 30322, USA. · Brain Behav Immun. · Pubmed #12401471 No free full text.

Abstract: A high proportion of cancer and hepatitis C patients who receive cytokine immunotherapy develop symptoms of depression that are indistinguishable from those found in major depressive disorders. These symptoms are alleviated by anti-depressant treatment. Moreover, preventive treatment with anti-depressants, in particular selective serotonin reuptake inhibitors (SSRIs) attenuates IFN-alpha-associated symptoms of depression, anxiety, and neurotoxicity. The intermediate mechanisms of these effects are still unclear. Studies suggest that the state of depression is associated with an increase in plasma levels of various cytokines and soluble cytokine receptors. Furthermore, anti-depressants have been shown to shift the cytokine network towards a decreased production of pro-inflammatory cytokines and an increased production of anti-inflammatory cytokines. Other studies suggest that anti-depressants can also modify immune reactivity by acting on neural structures involved in neuroimmunomodulation. It is possible that anti-depressants could help to normalize the serotoninergic neurotransmission that is likely disrupted during immunotherapy due to the potent effects of cytokines on the metabolism of the amino acid precursor tryptophan. Further work is needed to optimize strategies for preventing neuropsychiatric side effects of cytokine immunotherapy, to clarify the mechanisms involved in the alleviating effects of anti-depressants on cytokine-induced depression, as well as to assess the possible consequences of anti-depressant therapy on the efficacy of immunotherapy on the disease process.

Ninan PT. · Mood and Anxiety Disorders Program, Emory University School of Medicine in Atlanta, GA, USA. · Psychopharmacol Bull. · Pubmed #12397844 links to  free full text

Abstract: The omnipresent worry and anxiety that are characteristic of generalized anxiety disorder (GAD) significantly reduce social and occupational functioning. Yet many clinical investigations of GAD fail to evaluate treatment-related changes in function. As a consequence, many patients who respond to pharmacologic treatment (defined as having a > or = 50% reduction in symptoms) still exhibit subsyndromal symptoms that predispose to relapse. This is particularly true for patients with GAD who have comorbid psychiatric or medical conditions. In recent years, the goal of treatment for anxiety disorders has been set toward the achievement of full remission--that is, a virtually asymptomatic state. Remission indicates an improvement not only of symptoms but also of functionality. Benzodiazepines, azapirones, and antidepressants are the three main classes of agents currently used in the treatment of GAD. Some antidepressants have been shown to better facilitate remission. This article will summarize evidence for the clinical utility of pharmacotherapeutic agents commonly used in the treatment of GAD.

Schwartz AC, Rothbaum BO. · Department of Psychiatry, and Behavioural Sciences, Emory University School of Medicine, Atlanta, GA 30303, USA. · Expert Opin Pharmacother. · Pubmed #12387695 No free full text.

Abstract: Sertraline (Zoloft trade mark, Pfizer) is a selective serotonin re-uptake inhibitor (SSRI) with proven efficacy in the treatment of post-traumatic stress disorder (PTSD). PTSD is a serious, complex and often chronic mental illness that may follow exposure to a traumatic event. The high prevalence of traumatic events and PTSD in the general population and the resulting distress and dysfunction present a need for the systematic study of the efficacy and effectiveness of treatments for PTSD. Sertraline offers advantages over the older antidepressants, including demonstrated efficacy in PTSD, improved tolerability and low risk of lethality in overdose. Sertraline's efficacy, favourable tolerability profile and relatively weak effect on the cytochrome P450 system are factors that contribute to make it a first-line agent of choice in the treatment of PTSD.

Parker KP, Dunbar SB. · Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia, USA. · J Cardiovasc Nurs. · Pubmed #12358091 No free full text.

Abstract: Sleep problems and symptoms of sleep disturbance are very prevalent in patients with heart failure (HF). Numerous contributing factors include sleep-related breathing disorders, increasing age, medications, anxiety and depression, and comorbidities. Thus, the cardiovascular nurse has an important role in the recognition and management of sleep-related problems in persons with HF. This article provides an overview of sleep disturbances in patients with HF, suggests evidence-based strategies for managing the sleep problems, and identifies pertinent areas for future nursing inquiry.

Vermetten E, Bremner JD. · Department of Psychiatry, Emory University School of Medicine, Atlanta, Georgia 30306, USA. · Depress Anxiety. · Pubmed #12203669 No free full text.

Abstract: This paper follows the preclinical work on the effects of stress on neurobiological and neuroendocrine systems and provides a comprehensive working model for understanding the pathophysiology of posttraumatic stress disorder (PTSD). Studies of the neurobiology of PTSD in clinical populations are reviewed. Specific brain areas that play an important role in a variety of types of memory are also preferentially affected by stress, including hippocampus, amygdala, medial prefrontal cortex, and cingulate. This review indicates the involvement of these brain systems in the stress response, and in learning and memory. Affected systems in the neural circuitry of PTSD are reviewed (hypothalamic-pituitary-adrenal axis (HPA-axis), catecholaminergic and serotonergic systems, endogenous benzodiazepines, neuropeptides, hypothalamic-pituitary-thyroid axis (HPT-axis), and neuro-immunological alterations) as well as changes found with structural and functional neuroimaging methods. Converging evidence has emphasized the role of early-life trauma in the development of PTSD and other trauma-related disorders. Current and new targets for systems that play a role in the neural circuitry of PTSD are discussed. This material provides a basis for understanding the psychopathology of stress-related disorders, in particular PTSD.

Newport DJ, Stowe ZN, Nemeroff CB. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA. · Am J Psychiatry. · Pubmed #12153816 links to  free full text

Abstract: OBJECTIVE: This article reviews findings in preclinical research on the adverse impact of parental depression on the development of offspring, with emphasis on the relevance of this research for the psychiatric care of depressed parents. METHOD: The authors reviewed literature from the last 40 years reporting laboratory animal studies pertaining to the persistent effects of parental stress and parenting deficits on neurobehavioral and neurobiological development in offspring. RESULTS: Animal studies indicate that disrupted parenting produces a persistent, deleterious biobehavioral impact on offspring. Stressors, including maternal separation, variable foraging, and a variety of prenatal maternal challenges, produce offspring behaviors reminiscent of the cardinal features of anxiety and affective disorders. The stress paradigms also uniformly produce persistent hyperresponsivity in hypothalamic-pituitary-adrenal axis activity secondary to hypersecretion of corticotropin-releasing hormone. These findings bear striking similarities to findings for stress-related illnesses in humans, including major depression. CONCLUSIONS: Data from research on animal parenting reinforce the idea that parental mental illness may pose the first adverse life event for a child. A thorough risk-benefit assessment for the psychiatric care of parents of young children must consider the impact on the infant of exposure both to treatment and to parental illness. Preclinical data regarding the risk to offspring posed by untreated parental mental illness should be incorporated into clinical decision making in the treatment of parents with mental illness.

Bremner JD. · Department of Psychiatry and Behavioral Sciences, Emory Center for Positron Emission Tomography, Emory University School of Medicine, 1364 Clifton Road, Atlanta, GA 30322, USA. · Curr Psychiatry Rep. · Pubmed #12126593 No free full text.

Abstract: The past decade has seen a rapid advance in understanding of the neural circuits of post-traumatic stress disorder (PTSD), which has largely been due to the application of neuroimaging to the study of this disorder. Based on studies in animals of the effects of stress on the brain, dysfunction of the medial prefrontal cortex, hippocampus, and amygdala have been hypothesized to underlie symptoms of PTSD. Neuroimaging studies in PTSD have been consistent with these hypotheses, with the most replicated findings showing decreased medial prefrontal cortical function in PTSD. Other replicated findings include decreased inferior frontal gyrus function, decreased hippocampal function, increased posterior cingulate function, and, in some behavioral paradigms, increased amygdala function. Several studies have now shown changes in structure (smaller volume) of the hippocampus in PTSD. These studies are beginning to map out a neural circuitry of PTSD that may have future implications for diagnosis and treatment.

Okun MS, McDonald WM, DeLong MR. · Department of Neurology, Emory University, 1639 Pierce Dr, Suite 6000, Atlanta, GA 30322, USA. · Arch Neurol. · Pubmed #12020264 links to  free full text

Abstract: BACKGROUND: Many patients with Parkinson disease (PD) suffer from nonmotor symptoms including depression, anxiety, sexual dysfunction, decreased energy level, and an overall decline in quality of life. Comorbid depression, hypothyroidism, and sleep disorders may account for some, but not all, of these problems. Testosterone deficiency affects 20% to 25% of males over the age of 60 years in the general population and may cause signs and symptoms of the nonmotor symptoms seen in PD. We observed numerous patients with PD whose nonmotor symptoms were refractory to treatment. OBJECTIVE: To determine whether treatment of comorbid testosterone deficiency in male patients with PD can lead to improvements in refractory nonmotor symptoms. METHODS: Case studies were reviewed of the first 5 male patients who had PD with symptoms of testosterone deficiency who were treated in our clinic. All patients had low serum testosterone levels. Screening for testosterone deficiency symptoms using the St Louis Testosterone Deficiency Questionnaire was performed for 4 of the 5 patients. Additionally, to assess the prevalence of PD, total testosterone levels in 68 patients in our PD registry were sent for evaluation. RESULTS: Following testosterone replacement therapy, all 5 patients experienced significant improvements in their refractory nonmotor symptoms. Of 68 male patients with PD enrolled in our PD registry, 24 (35%) had plasma evidence of testosterone deficiency. We also noted that the risk of testosterone deficiency per decade was found to increase 2.8-fold per decade (P<.001), paralleling that which is found in the general elderly male population. CONCLUSIONS: The findings from this study reveal the heretofore unrecognized high prevalence of testosterone deficiency in elderly male patients with PD similar to that found in the general population. These symptoms, which may be refractory to antidepressants, anxiolytics, and antiparkinsonian medications, may respond to treatment with testosterone. More rigorous controlled studies will need to be undertaken to examine the treatment of this common comorbidity in male patients with PD.

Vermetten E, Bremner JD. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA. · Depress Anxiety. · Pubmed #12001181 No free full text.

Abstract: This paper reviews the preclinical literature related to the effects of stress on neurobiological and neuroendocrine systems. Preclinical studies of stress provide a comprehensive model for understanding neurobiological alterations in post-traumatic stress disorder (PTSD). The pathophysiology of stress reflects long-standing changes in biological stress response systems and in systems involved in stress responsivity, learning, and memory. The neural circuitry involved includes systems mediating hypothalamic-pituitary-adrenal (HPA) axis, norepinephrine (locus coeruleus), and benzodiazepine, serotonergic, dopaminergic, neuropeptide, and central amino acid systems. These systems interact with brain structures involved in memory, including hippocampus, amygdala, and prefrontal cortex. Stress responses are of vital importance in living organisms; however excessive and/or repeated stress can lead to long-lasting alterations in these circuits and systems involved in stress responsiveness. Intensity and duration of the stressor, and timing of the stressor in life, have strong impact in this respect.