Anxiety Disorders: Southwick SM

Southwick SM, Vythilingam M, Charney DS. · Yale University School of Medicine, National Center for Post-Traumatic Stress Disorder, VA Connecticut Healthcare System, West Haven, Connecticut 06516, USA. · Annu Rev Clin Psychol. · Pubmed #17716089 No free full text.

Abstract: This review discusses neurobiological and psychosocial factors associated with stress-induced depression and compares these factors with those believed to characterize stress resilience. Neurobiological factors that are discussed and contrasted include serotonin, the 5-HT1A receptor, polymorphisms of the 5-HT transporter gene, norepinephrine, alpha-2 adrenergic receptors, neuropeptide Y, polymorphisms of the alpha-2 adrenergic gene, dopamine, corticotropin-releasing hormone (CRH), dehydroepiandrosterone (DHEA), cortisol, and CRH receptors. These factors are described in the context of brain regions believed to be involved in stress, depression, and resilience to stress. Psychosocial factors associated with depression and/or stress resilience include positive emotions and optimism, humor, cognitive flexibility, cognitive explanatory style and reappraisal, acceptance, religion/spirituality, altruism, social support, role models, coping style, exercise, capacity to recover from negative events, and stress inoculation. The review concludes with potential psychological, social, spiritual, and neurobiological approaches to enhancing stress resilience, decreasing the likelihood of developing stress-induced depression/anxiety, and treating stress-induced psychopathology.

Morgan CA, Krystal JH, Southwick SM. · Clinical Neurosciences Division, VA National Center for PTSD, West Haven, Connecticut, USA. · Biol Psychiatry. · Pubmed #12725976 No free full text.

Abstract: In the acute aftermath of exposure to extreme stress, nearly all trauma survivors experience one or more transient symptoms of stress. In the short run, these symptoms may serve an adaptive role and generally remit; in some cases, however, acute stress-related symptoms do not diminish and instead evolve into posttraumatic stress disorder (PTSD). At present it is not clear when and with whom to intervene. On one hand, it is possible that some responses, such as early intrusive memories, effectively recruit support from others and facilitate the psychological processing of trauma; on the other hand, failing to intervene clinically with a recently traumatized individual may permit the subsequent development of PTSD. In this review, we focus on potential pharmacologic interventions aimed at treating early symptoms of extreme arousal or dissociation with the hope of possibly preventing PTSD. To date there is almost no empirical data on effective pharmacologic interventions in the immediate aftermath of extreme psychological trauma. As a result, much of what is discussed in this review is speculative in nature

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.

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.

Southwick SM, Paige S, Morgan CA, Bremner JD, Krystal JH, Charney DS. · Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. · Semin Clin Neuropsychiatry. · Pubmed #10553029 No free full text.

Abstract: In this chapter we review trauma-related studies involving epinephrine (E), norepinephrine (NE), and serotonin (5-HT). Central catecholamine neurons seem to play a critical role in level of alertness, vigilance, orienting, selective attention, memory, fear conditioning, and cardiovascular responses to life-threatening stimuli. Evidence of catecholamine dysregulation in post-traumatic stress disorder (PTSD) includes exaggerated increases in heart rate and blood pressure when exposed to visual and auditory reminders of trauma, elevated 24-hour urine catecholamine excretion, decreased platelet alpha-2 adrenergic receptor number, exaggerated behavioral, cardiovascular, and biochemical responses to IY yohimbine, decreased cortical brain metabolism secondary to IV yohimbine, and clinical efficacy of adrenergic blocking agents. Serotonin seems to play numerous roles in the central nervous system, including regulation of sleep, aggression, appetite, cardiovascular and respiratory activity, motor output, anxiety, mood, neuroendocrine secretion, and analgesia. Evidence of serotonergic dysregulation in PTSD includes frequent symptoms of aggression, impulsivity, depression and suicidality, decreased platelet paroxetine binding, blunted prolactin response to fenfluramine, exaggerated reactivity to m-chloro-phenyl-piperazine, and clinical efficacy of serotonin reuptake inhibitors. It has been suggested that alterations in NE, E, and 5-HT may have relevance for symptoms commonly seen in survivors with PTSD, including hypervigilance, exaggerated startle, irritability, impulsivity, aggression, intrusive memories, depressed mood, and suicidality.

Fujita M, Southwick SM, Denucci CC, Zoghbi SS, Dillon MS, Baldwin RM, Bozkurt A, Kugaya A, Verhoeff NP, Seibyl JP, Innis RB. · Department of Psychiatry, Yale University and Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA. · Biol Psychiatry. · Pubmed #15231441 No free full text.

Abstract: BACKGROUND: A previous single photon emission computed tomography study showed decreased central type benzodiazepine receptors in the prefrontal cortex in Vietnam War veterans with posttraumatic stress disorder. To assess the generalizability of this finding to patients with more recent history, we studied central type benzodiazepine receptors in Gulf War veterans with posttraumatic stress disorder. METHODS: Nineteen Gulf War veterans with posttraumatic stress disorder and 19 age-matched, healthy, nondeployed veterans participated in a single photon emission computed tomography study using [(123)I]iomazenil. Regional total distribution volume (V(T)') was compared between two groups using Statistical Parametric Mapping 99 (Wellcome Department of Imaging Neuroscience, London, United Kingdom) and volumes of interest analysis. RESULTS: Benzodiazepine receptor levels did not show regional differences between the two groups, either with or without global normalization. Average difference in V(T)' was 2% across brain areas; however, by applying global normalization, V(T)' in the patient group showed significant negative correlation with childhood trauma scores in the right superior temporal gyrus. CONCLUSIONS: Less severe symptoms and shorter duration of the illness in the current group than the prior one may be the source of the difference in the results of the two studies.

Bremner JD, Vythilingam M, Vermetten E, Adil J, Khan S, Nazeer A, Afzal N, McGlashan T, Elzinga B, Anderson GM, Heninger G, Southwick SM, Charney DS. · Department of Psychiatry and Behavioral Sciences, Emory Center for Positron Emission Tomography, Emory University School of Medicine, 1364 Briarcliff Road, Atlanta, GA 30322, USA. · Psychoneuroendocrinology. · Pubmed #12812861 No free full text.

Abstract: Preclinical studies show that animals with a history of chronic stress exposure have increased hypothalamic-pituitary-adrenal (HPA) axis reactivity following reexposure to stress. Patients with posttraumatic stress disorder (PTSD) have been found to have normal or decreased function of the HPA axis, however no studies have looked at the HPA response to stress in PTSD. The purpose of this study was to assess cortisol responsivity to a stressful cognitive challenge in patients with PTSD related to childhood abuse. Salivary cortisol levels, as well as heart rate and blood pressure, were measured before and after a stressful cognitive challenge in patients with abuse-related PTSD (N=23) and healthy comparison subjects (N=18). PTSD patients had 61% higher group mean cortisol levels in the time period leading up to the cognitive challenge, and 46% higher cortisol levels during the time period of the cognitive challenge, compared to controls. Both PTSD patients and controls had a similar 66-68% increase in cortisol levels from their own baseline with the cognitive challenge. Following the cognitive challenge, cortisol levels fell in both groups and were similar in PTSD and control groups. PTSD patients appeared to have an increased cortisol response in anticipation of a cognitive challenge relative to controls. Although cortisol has been found to be low at baseline, there does not appear to be an impairment in cortisol response to stressors in PTSD.

Southwick SM, Davis M, Horner B, Cahill L, Morgan CA, Gold PE, Bremner JD, Charney DC. · Department of Psychiatry, Yale University School of Medicine, CT, USA. · Am J Psychiatry. · Pubmed #12153837 links to  free full text

Abstract: OBJECTIVE: The purpose of this study was to investigate the effect of enhanced noradrenergic activity on memory consolidation in humans. METHOD: Thirty healthy subjects (21 men and nine women) viewed a series of 12 slides that depicted an emotionally arousing story. Five minutes after viewing the slides, subjects received either intravenous yohimbine or intravenous placebo in a double-blind randomized fashion. Multiple blood samples were drawn for determining plasma free 3-methoxy-4-hydroxyphenylglycol (MHPG). One week later subjects took a surprise memory test for the slides. RESULTS: There was no significant difference in memory score between yohimbine and placebo groups. Linear regression revealed a significant effect of MHPG on memory score for the group as a whole (subjects who had received yohimbine and those who had received placebo) and for the placebo group alone. CONCLUSIONS: These findings strengthen support for the hypothesis that enhanced memory for emotionally arousing events in humans depends critically on postlearning adrenergic modulation.

Stine SM, Southwick SM, Petrakis IL, Kosten TR, Charney DS, Krystal JH. · Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 2761 E. Jefferson Avenue, Detroit, MI 48207, USA. · Biol Psychiatry. · Pubmed #11955464 No free full text.

Abstract: BACKGROUND: Alteration in noradrenergic regulation as well as alteration in the hypothalamic-pituitary-adrenal (HPA) axis have been associated with opioid dependence and acute abstinence symptoms. METHODS: This double-blind, placebo-controlled study evaluated subjective, physiologic, and biochemical responses to yohimbine (.4 mg/kg, IV) in eight patients receiving methadone and compared results to those from a pool of nine healthy volunteers. All subjects were compared for panic anxiety symptom scale (PASS) scores, systolic and diastolic blood pressure, heart rate, plasma 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol. RESULTS: Yohimbine elicited objective and subjective opioid withdrawal and elevated craving for opioid drugs in methadone patients. Significant yohimbine effects were seen across the combined subject group for PASS, physiologic measures, MHPG, and cortisol. Methadone patients had lower baseline MHPG levels. Methadone group interactions with yohimbine were seen for systolic blood pressure and cortisol levels. CONCLUSIONS: Methadone-maintained patients are sensitive to the postsynaptic effects of noradrenergic-facilitating medications, experiencing greater physiologic and psychological symptoms, including an increase in craving. The effect on cortisol supports the above conclusion and is consistent with HPA axis perturbation in opioid dependence as reported in other studies and extends these observations to stable methadone-maintained patients. Medications that increase synaptic noradrenaline should be used with care in opioid-dependent patients.

Vythilingam M, Nelson EE, Scaramozza M, Waldeck T, Hazlett G, Southwick SM, Pine DS, Drevets W, Charney DS, Ernst M. · Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD, 20892, USA. · Psychiatry Res. · Pubmed #19243926 No free full text.

Abstract: Enhanced brain reward function could contribute to resilience to trauma. Reward circuitry in active duty, resilient special forces (SF) soldiers was evaluated using functional magnetic resonance imaging during a monetary incentive delay task. Findings in this group of resilient individuals revealed unique patterns of activation during expectation of reward in the subgenual prefrontal cortex and nucleus accumbens area, regions pivotal to reward processes.

Haglund ME, aan het Rot M, Cooper NS, Nestadt PS, Muller D, Southwick SM, Charney DS. · Mount Sinai School of Medicine, New York, NY 10029, USA. · Acad Med. · Pubmed #19174682 No free full text.

Abstract: PURPOSE: In the third year of medical school students are exposed to many stressful and potentially traumatic events, including witnessing patient suffering or death, personal mistreatment, and poor role modeling by physicians. These experiences may explain increases in anxiety and depression during medical school. However, to date this has not been studied. METHOD: The present study prospectively measured stressful clerkship events occurring during the 2006-2007 academic year in third-year medical students of the Mount Sinai School of Medicine (n = 125), using surveys completed monthly. Students labeled stressful events traumatic if they met the trauma criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. The authors measured anxiety, depression, and posttraumatic stress symptoms at the beginning and end of the year and twice during the year. At year's end they also measured students' personal growth. RESULTS: Class participation varied from 106 (85%) at baseline to 82 (66%) at endpoint. Most students (101; 81%) completed at least one monthly survey. Many students reported exposure to trauma as well as personal mistreatment and poor role modeling by superiors. Trauma exposure was positively associated with personal growth at year's end. In contrast, exposure to other stressful events was positively associated with endpoint levels of depression and other stress symptoms. CONCLUSIONS: Trauma exposure was common but not associated with poor outcomes by year's end, which suggests that students were resilient. Nonetheless, unprofessional behavior by resident and attending physicians might have adverse effects on the well-being of students.

Vojvoda D, Weine SM, McGlashan T, Becker DF, Southwick SM. · Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. · J Rehabil Res Dev. · Pubmed #18629750 No free full text.

Abstract: This study describes the evolution of trauma-related symptoms over 3 1/2 years in a group of Bosnian refugees. Twenty-one refugees received standardized psychological assessments shortly after arriving in the United States and then 1 year and 3 1/2 years later. Of these refugees, 76% met diagnostic criteria for posttraumatic stress disorder (PTSD) at baseline, 33% at 1 year, and 24% at 3 1/2 years. PTSD severity scores in women refugees were higher than scores in men at all three evaluation time points. At the 3 1/2-year evaluation, 44% of women and 8% of men met criteria for PTSD and no correlation was found between PTSD symptom severity and either age or level of trauma exposure. A significant inverse correlation was found between Global Assessment of Functioning (GAF) scores and PTSD severity scores. Refugees who reported better mastery of the English language had significantly higher GAF scores. Although PTSD symptom severity decreased over time, most refugees continued to have at least one or more trauma-related symptoms and 24% still met criteria for PTSD after 3 1/2 years in the United States. Women refugees and those who had not mastered the English language appeared to be more vulnerable to persisting psychological effects of trauma.

Smith RP, Larkin GL, Southwick SM. · Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA. · J Clin Psychiatry. · Pubmed #18363455 No free full text.

Abstract: OBJECTIVE: To describe trends in anxiety-related mental health visits to U.S. emergency departments, an expanding portal of access for mental health care. METHOD: Data from 1992 through 2001 were obtained from the National Hospital Ambulatory Medical Care Survey using mental health-related ICD-9-CM, E- and V-codes as well as National Center for Health Statistics-assigned Patient Reason-for-Visit classification codes. Population-weighted anxiety-related emergency department visit rates were analyzed over time by age, gender, race, Hispanic ethnicity, insurance status, urban status, region of the country, urgency of presentation, and use of medication. RESULTS: There were 53 million mental health-related visits, increasing from 4.9% to 6.3% of all emergency department visits (p = .003) and from 17.1 to 23.6 per 1000 U.S. population across the decade (p = .000). Anxiety-related visits were common (16% of all mental health visits) and increased significantly from 3.5 to 5.0 visits per 1000 U.S. population over the decade (p = .011). Anxiety-related visits increased significantly among non-Hispanic whites, children (< 15 years), adults younger than 49 years, and the privately insured; changes among Medicare, Medicaid, and self-pay patients were not significant. Overall hospitalization rates declined from 23% to 21% between 1992 and 2001 (p = .037), but they did not change significantly for anxiety-related visits (8%), which remained the least likely visit type to be admitted of all mental health visits for the entire decade. In contrast to rural emergency departments, urban emergency departments witnessed significant increases in anxiety-related visits, rising from 2.9 to 5.2 per 1000 U.S. population across the decade (p trend = 0.007). Regionally, anxiety-related visits were highest in the Northeast, lowest in the West, and increased significantly in only the South and Northeast. CONCLUSION: During the decade, there was an expansion of anxiety-related visits to U.S. emergency departments, reflecting an increase in anxiety-related emergency department care-seeking, an increase in anxiety awareness among patients and practitioners, or both.

Haglund ME, Nestadt PS, Cooper NS, Southwick SM, Charney DS. · Mount Sinai School of Medicine, New York, NY 10029, · Dev Psychopathol. · Pubmed #17705907 No free full text.

Abstract: Resilience refers to the ability to successfully adapt to stressors, maintaining psychological well-being in the face of adversity. Recent years have seen a great deal of research into the neurobiological and psychological factors and mechanisms that characterize resilient individuals. This article draws from that research to outline some of the most important contributors to resilience. The authors hope that by contributing to a growing understanding of the genetic, developmental, neurobiological, and psychological underpinnings of resilience, researchers and clinicians in the field will move closer toward the goal of identifying and treating individuals at risk for developing posttraumatic psychopathology.

Vermetten E, Schmahl C, Southwick SM, Bremner JD. · University Medical Center, Utrecht, The Netherlands. · Psychopharmacol Bull. · Pubmed #17285093 No free full text.

Abstract: OBJECTIVE: Memory for odors is often associated with highly emotional experiences, and odors have long been noted by clinicians to be precipitants of trauma symptoms in posttraumatic stress disorder (PTSD). Primitive brain systems involved in fear responsivity and survival also mediate smell, including the olfactory cortex and amygdala. The purpose of this study was to measure neural correlates of olfaction in PTSD. METHODS: We exposed male combat veterans with PTSD (N = 8) and without PTSD (N = 8) to a set of smells, including diesel (related to traumatic memories of combat), and three other types of smells: odorless air, vanilla/coconut, and hydrogen sulfide (H2S) (respectively, a neutral, positive, and negative hedonic nontraumatic smell) in conjunction with PET imaging of cerebral blood flow and assessment of psychophysiological and behavioral symptoms. All subjects also underwent a baseline of olfactory acuity. RESULTS: PTSD patients rated diesel as unpleasant and distressing, resulting in increased PTSD symptoms and anxiety in PTSD versus combat controls. Exposure to diesel resulted in an increase in regional blood flow (rCBF) in amygdala, insula, medial prefrontal cortex, and anterior cingulate cortex, and decreased rCBF in lateral prefrontal cortex in PTSD in comparison to combat controls. Combat controls showed less rCBF changes on any smell, and did not show amygdala activation upon diesel exposure. CONCLUSIONS: These data support the hypothesis that in PTSD trauma-related smells can serve as strong emotional reminders. The findings indicate the involvement of a neural circuitry that shares olfactory elements and memory processing regions when exposed to trauma-related stimuli.

Southwick SM, Gilmartin R, McDonough P, Morrissey P. · Yale University School of Medicine, USA. · Am J Psychother. · Pubmed #16892952 No free full text.

Abstract: Combat-related Post-traumatic Stress Disorder (PTSD) is often highly debilitating and affects nearly all areas of psychosocial functioning. Veterans with PTSD re-experience their traumas in the form of haunting intrusive memories, nightmares and flashbacks, and have chronic difficulty modulating arousal. As a way to cope with these symptoms, many survivors live isolated and avoidant lives, self-medicate with alcohol and substances of abuse, and numb themselves to emotional experiences and relationships with family and friends. Additionally, many combat veterans report survivor guilt, depression, affect dysregulation, and an altered world view in which fate is seen as uncontrollable and life is viewed as devoid of meaning. In this report we describe the use of logotherapy (healing through meaning) for the treatment of combat-related PTSD

Vermetten E, Vythilingam M, Schmahl C, DE Kloet C, Southwick SM, Charney DS, Bremner JD. · Rudolf Magnus Institute of Neurosciences, Department Psychiatry, University Medical Center, Int mailbox B01206, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. · Ann N Y Acad Sci. · Pubmed #16891570 No free full text.

Abstract: Posttraumatic stress disorder (PTSD) is typically accompanied by both acute and chronic alterations in the stress response. These alterations have mostly been described in individuals under baseline conditions, but studies have also used a challenge model to assess the role of the hypothalamic-pituitary-adrenal (HPA) axis in the stress response. The purpose of this article was to assess the effect of long-term treatment with the selective reuptake inhibitor (SSRI), paroxetine, on stress reactivity in patients with PTSD. We assessed diurnal salivary cortisol and urinary cortisol as well as cortisol, heart rate, and behavioral responses to a standardized cognitive stress challenge, in 13 female patients with chronic PTSD before and after 12 months of paroxetine treatment. Treatment resulted in a significant decrease in PTSD symptoms. Twenty-four-hour urinary cortisol was lower compared to base line after successful treatment. Treatment resulted in a decrease of salivary cortisol levels on all time points on a diurnal curve. Despite similar stress perception, cortisol response to the cognitive stress challenge resulted in a 26.5% relative decrease in stress-induced salivary cortisol with treatment. These results suggest that successful treatment with SSRI in chronic PTSD is associated with a trend for a decrease in baseline diurnal cortisol and with reduced cortisol reactivity to stress.

Lipschitz DS, Mayes LM, Rasmusson AM, Anyan W, Billingslea E, Gueorguieva R, Southwick SM. · Neuroscience Division, National Center for PTSD, and the Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06824, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #16034283 No free full text.

Abstract: OBJECTIVE: To assess baseline and modulated acoustic startle responses in adolescent girls with posttraumatic stress disorder (PTSD). METHOD: Twenty-eight adolescent girls with PTSD and 23 healthy control girls were recruited for participation in the study. Acoustic stimuli were bursts of white noise of 104 dB presented biaurally through headphones. Baseline startle responses as well as prepulse inhibition, a 1,000-Hz prestimulation tone presented 120 milliseconds before the startle stimulus for 30 milliseconds, and prepulse facilitation, a 1000-Hz prestimulation tone presented continuously for 2, 000 milliseconds before the startle stimulus, were compared in these two groups of girls. RESULTS: At baseline and under neutral testing conditions, the magnitude of the startle response (eye blink) did not differ significantly between girls with PTSD and healthy control girls. There were no significant differences in the degree of prepulse inhibition or facilitation between the two groups of girls. CONCLUSIONS: Unlike combat veterans with PTSD, adolescent girls with PTSD who report exaggerated startle may not have exaggerated baseline acoustic startle responses in the laboratory. Further research should explore whether girls with PTSD demonstrate altered startle responses under stress and/or evidence of other types of psychophysiological abnormalities.

Vythilingam M, Luckenbaugh DA, Lam T, Morgan CA, Lipschitz D, Charney DS, Bremner JD, Southwick SM. · Mood and Anxiety Disorders Program, National Institute of Mental Health, MAP, 15K North Drive, Room #111, MSC 2670, Bethesda, MD 20892-2670, USA. · Psychiatry Res. · Pubmed #15967648 No free full text.

Abstract: Reductions in hippocampal volume and impairment in short-term verbal memory have been reported in Vietnam combat veterans with posttraumatic stress disorder (PTSD) and in women with abuse-related PTSD. The present investigation evaluated hippocampal volume and memory in Gulf War veterans. This research is timely given the ongoing war in Iraq and the anticipated high rates of PTSD among returning combat soldiers. Fourteen veterans with PTSD related to traumatic experiences during the Gulf War (1990-1991), 23 deployed veterans without PTSD, 22 non-deployed reservists and 29 healthy civilians were studied. Volumes of the hippocampus, temporal lobe, and whole brain were measured on coronal MRI scans, and hippocampal mediated memory function was evaluated. The head of the hippocampus was the only subregion that was significantly smaller in Gulf War veterans with PTSD than in healthy civilians. Deployed veterans with PTSD, deployed veterans without PTSD, and non-deployed reservists had significantly smaller whole hippocampal volume and lower scores on immediate and delayed verbal and visual retrieval compared with healthy civilians.

Axelrod SR, Morgan CA, Southwick SM. · Department of Psychiatry, Yale University School of Medicine, 425 George St., New Haven, CT 06511, USA. · Am J Psychiatry. · Pubmed #15677590 links to  free full text

Abstract: OBJECTIVE: The present report is part of a follow-along investigation focusing on the evolution of trauma-related symptoms in veterans of Operation Desert Storm. The goal of the current report was to examine three hypotheses on the relationship between severity of war-related trauma, symptoms of posttraumatic stress disorder (PTSD), and symptoms of borderline personality disorder with a mixed retrospective/prospective design. METHOD: Ninety-four National Guard reservists completed self-administered measures of combat-related trauma, PTSD symptoms, and borderline personality disorder features after their Gulf War duty. RESULTS: Consistent with study hypotheses, prewar features of borderline personality disorder predicted variability in postwar PTSD symptoms beyond that predicted by combat exposure, combat exposure predicted variability in postwar features of borderline personality disorder, and PTSD severity assessed shortly after combat exposure accounted for additional variability in subsequent features of borderline personality disorder. CONCLUSIONS: Taken together, the present findings suggest that trauma, symptoms of PTSD, and features of borderline personality disorder are related to one another in a complex fashion that may exceed simple linear models. Clinical and research implications for the relationships among trauma, PTSD, and borderline personality disorder are discussed.

Southwick SM, Charney DS. · Yale Medical School, Yale Child Study Center, and Clinical Neuroscience Division of the National Center for PTSDVA Connecticut, USA. · Psychiatry. · Pubmed #15262585 No free full text.

This publication has no abstract.

Lipschitz DS, Rasmusson AM, Anyan W, Gueorguieva R, Billingslea EM, Cromwell PF, Southwick SM. · Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA. · J Nerv Ment Dis. · Pubmed #14614338 No free full text.

Abstract: The purpose of this study is to examine rates of nicotine, marijuana, and alcohol use as well as patterns of problematic substance use and posttraumatic stress disorder (PTSD) symptoms in inner-city adolescent girls. One hundred four adolescents who obtained medical care at a hospital-based adolescent clinic were systematically surveyed for trauma exposure, posttraumatic stress symptoms, and substance use. A subset (N = 54, 52%) of girls completed a semistructured psychiatric diagnostic interview (K-SADS-PL) to ascertain timing of PTSD symptoms relative to substance use. Compared with traumatized girls without PTSD, girls with full and partial PTSD were significantly more likely to use nicotine, marijuana, and/or alcohol on a regular basis. Fifteen girls met criteria for both PTSD and a substance-use disorder. For 80% of these girls, the age of onset of PTSD was either before or concurrent with the onset of their substance-use disorder. Inner-city adolescent girls with PTSD exhibit problematic substance use and may be at high risk of developing a comorbid substance-use disorder.

Lipschitz DS, Rasmusson AM, Yehuda R, Wang S, Anyan W, Gueoguieva R, Grilo CM, Fehon DC, Southwick SM. · Yale University School of Medicine, 100 York Street, New Haven, CT 06511, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #14566168 No free full text.

Abstract: OBJECTIVE: Previous studies of adults with posttraumatic stress disorder (PTSD) have found various abnormalities in the regulation of the hypothalamic-pituitary-adrenal axis, including enhanced suppression of cortisol following low-dose dexamethasone. The purpose of the present study was to investigate salivary cortisol responses to low-dose dexamethasone in adolescents with PTSD. METHOD: Forty-eight adolescents (20 with current PTSD, 9 trauma controls without PTSD, and 19 healthy nontraumatized controls) were enrolled in the study. On day 1, baseline saliva samples were obtained at 8 a.m. and 0.5 mg of dexamethasone was administered at 11 p.m. Cortisol and dexamethasone levels were assessed at 8 a.m. the following day. RESULTS: Adolescents with current PTSD showed no difference in the suppression of salivary cortisol in response to low-dose (0.5 mg) dexamethasone compared to trauma controls without PTSD and nontraumatized controls. More severely affected PTSD subjects with co-occurring major depression showed higher pre- and post-dexamethasone salivary cortisol levels compared to controls. CONCLUSIONS: The present study did not find evidence for enhanced suppression of salivary cortisol at 8 a.m. following low-dose dexamethasone in multiply traumatized adolescents with PTSD. This result differs from findings in adults with PTSD. Further investigations of hypothalamic-pituitary-adrenal axis abnormalities in traumatized children and adolescents are needed.

Vermetten E, Vythilingam M, Southwick SM, Charney DS, Bremner JD. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA. · Biol Psychiatry. · Pubmed #14512209 No free full text.

Abstract: BACKGROUND: Animal studies have shown that stress is associated with damage to the hippocampus, inhibition of neurogenesis, and deficits in hippocampal-based memory dysfunction. Studies in patients with posttraumatic stress disorder (PTSD) found deficits in hippocampal-based declarative verbal memory and smaller hippocampal volume, as measured with magnetic resonance imaging (MRI). Recent preclinical evidence has shown that selective serotonin reuptake inhibitors promote neurogenesis and reverse the effects of stress on hippocampal atrophy. This study assessed the effects of long-term treatment with paroxetine on hippocampal volume and declarative memory performance in PTSD. METHODS: Declarative memory was assessed with the Wechsler Memory Scale-Revised and Selective Reminding Test before and after 9-12 months of treatment with paroxetine in PTSD. Hippocampal volume was measured with MRI. Of the 28 patients who started the protocol, 23 completed the full course of treatment and neuropsychological testing. Twenty patients were able to complete MRI imaging. RESULTS: Patients with PTSD showed a significant improvement in PTSD symptoms with treatment. Treatment resulted in significant improvements in verbal declarative memory and a 4.6% increase in mean hippocampal volume. CONCLUSIONS: These findings suggest that long-term treatment with paroxetine is associated with improvement of verbal declarative memory deficits and an increase in hippocampal volume in PTSD.