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Biomedical subjects

S M Southwick

Publications and source records attributed to S M Southwick.

At least 19 recordsLinked to original sources
PubMed2003

Cortisol response to a cognitive stress challenge in posttraumatic stress disorder (PTSD) related to childhood abuse.

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.

Adolescent↗
PubMed2001

Increased pituitary and adrenal reactivity in premenopausal women with posttraumatic stress disorder.

BACKGROUND: Limited studies of hypothalamic-pituitary-adrenal axis regulation in posttraumatic stress disorder have been performed in premenopausal women. We therefore undertook a study of hypothalamic-pituitary-adrenal axis regulation in this population. METHODS: Outpatient posttraumatic stress disorder subjects were compared with healthy, age- and weight-matched nontraumatized subjects. Subjects were free from psychotropic medications, alcohol and other illicit substances for at least 4 weeks before study. Menstrual cycle phase was determined by monitoring the LH surge and plasma progesterone levels. Corticotropin releasing factor and adrenocorticotropin stimulation tests, as well as 24-hour urinary-free cortisol measurements were performed. RESULTS: Corticotropin releasing factor test: Baseline adrenocorticotropic hormone and cortisol levels did not differ between the 12 PTSD and 11 comparison subjects, but the posttraumatic stress disorder group had greater adrenocorticotropic hormone and cortisol responses to corticotropin releasing factor, as well as a later cortisol peak. Adrenocorticotropic hormone test: Baseline cortisol levels did not differ between the 10 posttraumatic stress disorder subjects and seven controls, but the posttraumatic stress disorder group showed greater cortisol responses to adrenocorticotropic hormone. Peak cortisol responses to corticotropin releasing factor and adrenocorticotropic hormone were correlated with each other and with 24-hour urinary-free cortisol excretion. CONCLUSIONS: Pituitary and adrenal hyperreactivity to exogenous corticotropin releasing factor and adrenocorticotropic hormone is demonstrated in premenopausal women with chronic posttraumatic stress disorder. Cortisol hyperreactivity thus may play a role in the pathophysiology of posttraumatic stress disorder in women.

Adrenocorticotropic Hormone↗
PubMed2001

Substance use disorders in patients with posttraumatic stress disorder: a review of the literature.

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.

Adult↗
PubMed2001

Symptoms of dissociation in humans experiencing acute, uncontrollable stress: a prospective investigation.

OBJECTIVE: Peritraumatic dissociation has been associated with subsequent development of posttraumatic stress disorder, but supporting data have been largely retrospective. The current study was designed to assess the nature and prevalence of dissociative symptoms in healthy humans experiencing acute, uncontrollable stress during U.S. Army survival training. METHOD: In study 1, 94 subjects completed the Clinician-Administered Dissociative States Scale after exposure to the stress of survival training. In study 2, 59 subjects completed the Brief Trauma Questionnaire before acute stress and the dissociative states scale before and after acute stress. A randomly selected group of subjects in study 2 completed a health problems questionnaire after acute stress. RESULTS: In study 1, 96% of subjects reported dissociative symptoms in response to acute stress. Total scores, as well as individual item scores, on the dissociation scale were significantly lower in Special Forces soldiers compared to general infantry troops. In study 2, 42% of subjects reported dissociative symptoms before stress and 96% reported them after acute stress. Dissociative symptoms before and after stress were significantly higher in individuals who reported a perceived threat to life in the past. Forty-one percent of the variance in reported health problems was accounted for by poststress dissociation scores. DISCUSSION: Symptoms of dissociation were prevalent in healthy subjects exposed to high stress. Stress-hardy individuals (Special Forces soldiers) experienced fewer symptoms of dissociation, compared to individuals who were less hardy. These data support the idea that the nature of response to previously experienced threatening events significantly determines the nature of psychological and somatic response to subsequent stress.

Acute Disease↗
PubMed2000

Plasma neuropeptide-Y concentrations in humans exposed to military survival training.

BACKGROUND: Neuropeptide-Y (NPY) is present in extensive neuronal systems of the brain and is present in high concentrations in cell bodies and terminals in the amygdala. Preclinical studies have shown that injections of NPY into the central nucleus of the amygdala function as a central anxiolytic and buffer against the effects of stress. The objective of this study was to assess plasma NPY immunoreactivity in healthy soldiers participating in high intensity military training at the U.S. Army survival school. The Army survival school provides a means of observing individuals under high levels of physical, environmental, and psychological stress, and consequently is considered a reasonable analogue to stress incurred as a result of war or other catastrophic experiences. METHODS: Plasma levels of NPY were assessed at baseline (prior to initiation of training), and 24 hours after the conclusion of survival training in 49 subjects, and at baseline and during the Prisoner of War (P.O.W.) experience (immediately after exposure to a military interrogation) in 21 additional subjects. RESULTS: Plasma NPY levels were significantly increased compared to baseline following interrogations and were significantly higher in Special Forces soldiers, compared to non-Special Forces soldiers. NPY elicited by interrogation stress was significantly correlated to the subjects' behavior during interrogations and tended to be negatively correlated to symptoms of reported dissociation. Twenty-four hours after the conclusion of survival training, NPY had returned to baseline in Special Forces soldiers, but remained significantly lower than baseline values in non-Special Forces soldiers. NPY was positively correlated with both cortisol and behavioral performance under stress. NPY was negatively related to psychological symptoms of dissociation. CONCLUSIONS: These results provide evidence that uncontrollable stress significantly increases plasma NPY in humans, and when extended, produces a significant depletion of plasma NPY. Stress-induced alterations of plasma NPY were significantly different in Special Forces soldiers compared to non-Special Forces soldiers. These data support the idea that NPY may be involved in the enhanced stress resilience seen in humans.

Adult↗
PubMed2000

Hormone profiles in humans experiencing military survival training.

BACKGROUND: Clinical models of the human response to intense, acute stress have been limited to laboratory settings or cross sectional characterizations. As a result, data about the sensitivity of the human neuroendocrine activation to realistic stressors of varying magnitudes are limited. The U.S. Army survival course offers a unique opportunity to examine, in a controlled manner, the human response to acute, realistic, military stress. METHODS: Salivary data were collected in 109 subjects at baseline during four stress exposure time points and at recovery. Serum data was collected at baseline and recovery in 72 subjects and at baseline and during stress exposure in a subgroup of subjects (n = 21). RESULTS: Cortisol significantly increased during the captivity experience and was greatest after subjects' exposure to interrogations. Cortisol remained significantly elevated at recovery. Testosterone was significantly reduced within 12 hours of captivity. Reductions of both total and free T4 and of total and free T3 were observed, as were increases in thyrotropin. CONCLUSIONS: The stress of military survival training produced dramatic alterations in cortisol, percent free cortisol, testosterone, and thyroid indices. Different types of stressors had varying effects on the neuroendocrine indices. The degree of neuroendocrine changes observed may have significant implications for subsequent responses to stress.

Adult↗
PubMed2000

Low baseline and yohimbine-stimulated plasma neuropeptide Y (NPY) levels in combat-related PTSD.

BACKGROUND: Consistent with many studies demonstrating enhanced reactivity of the sympathetic nervous system in posttraumatic stress disorder (PTSD), the administration of yohimbine, a noradrenergic alpha(2)-antagonist, has been shown to increase core symptoms of PTSD and to induce greater increases in plasma 3-methyl-4-hydroxy-phenyl-glycol (MHPG) in subjects with PTSD compared with healthy control subjects. In turn, neuropeptide Y (NPY) has been shown to inhibit the release of norepinephrine from sympathetic noradrenergic neurons. METHODS: In the following study, plasma NPY responses to yohimbine and placebo were measured in a subgroup of 18 subjects with PTSD and 8 healthy control subjects who participated in the previous study of the effect of yohimbine on plasma MHPG. RESULTS: The PTSD subjects had lower baseline plasma NPY and blunted yohimbine-stimulated increases in plasma NPY compared with the healthy control subjects. Within the PTSD group, baseline plasma NPY levels correlated negatively with combat exposure scale scores, baseline PTSD and panic symptoms, and yohimbine-stimulated increases in MHPG and systolic blood pressure. CONCLUSIONS: This study suggests that combat stress-induced decreases in plasma NPY may mediate, in part, the noradrenergic system hyperreactivity observed in combat-related PTSD. The persistence of this decrease in plasma NPY may contribute to symptoms of hyperarousal and the expression of exaggerated alarm reactions, anxiety reactions, or both in combat veterans with PTSD long after war.

Adrenergic alpha-Antagonists↗
PubMed2000

Clinical and functional correlates of posttraumatic stress disorder in urban adolescent girls at a primary care clinic.

OBJECTIVE: To identify clinical and functional correlates of posttraumatic stress disorder (PTSD) in trauma-exposed urban adolescent girls. METHOD: Ninety female adolescents aged 12 to 21 years (mean 17.3 years) who presented for routine medical care at an adolescent primary care clinic were assessed with self-report questionnaires and interviews for trauma exposure, posttraumatic stress symptoms, other psychopathology, and psychosocial, family, and school function. RESULTS: Ninety-two percent (n = 83) endorsed at least one trauma. Witnessing community violence (85.6%) and hearing about a homicide (67.8%) were the most common traumatic events endorsed. Twelve (14.4%) and 10 (11.6%) traumatized girls met DSM-IV symptom criteria for full and partial PTSD, respectively. Compared with traumatized girls without PTSD, girls with PTSD were significantly more depressed, used more cigarettes and marijuana, and were more likely to have failed a school grade, been suspended from school, or been arrested. CONCLUSIONS: Urban adolescent girls are exposed to multiple types of trauma. Whereas most develop at least one posttraumatic stress symptom, girls who meet full symptom criteria for PTSD show evidence of other psychopathology, increased cigarette and marijuana use, and poorer school performance. Further research is needed to identify and treat inner-city girls with PTSD.

Adolescent↗
PubMed2000

Gender differences in the associations between posttraumatic stress symptoms and problematic substance use in psychiatric inpatient adolescents.

This study examined gender differences in the associations between posttraumatic stress symptoms and problematic substance use in psychiatrically hospitalized adolescents. Ninety-five adolescent inpatients (38 boys, 57 girls) were systematically evaluated with a battery of psychometrically well-established self-report measures to assess trauma exposure, posttraumatic stress symptoms, problematic alcohol and drug use, and internalizing and externalizing psychopathology. Twenty-three percent (N = 22) of patients met DSM-IV-based symptom criteria for PTSD, and 37% (N = 35) and 34% (N = 32) of patients endorsed problematic levels of drug and alcohol use, respectively. Posttraumatic stress symptoms were significantly associated with problematic drug and alcohol use in girls but not in boys. There were no significant gender differences in posttraumatic stress symptoms and/or problematic substance use, to account for the gender differences in the association between PTSD and substance use. Our findings suggest that the link between substance abuse and PTSD may be especially salient for female adolescents.

Adolescent↗
PubMed2000

Social sharing of Gulf War experiences: association with trauma-related psychological symptoms.

It commonly is believed that talking with family and friends (social sharing) about stressful or traumatic experiences can be therapeutic with regard to stress-related psychological symptoms. Two years after serving in the Gulf War, 58 National Guard Reservists completed the Mississippi Posttraumatic Stress Disorder Scale (PTSD), the Brief Symptom Inventory, and a measure of social sharing that asked how much they had talked to family and friends about their experiences in the Gulf during the 2-year period since returning from the war. Subjects had a broad range of Mississippi PTSD scores. Six subjects met Mississippi criteria for PTSD. Degree of talking to family and friends about Gulf War experiences did not account for a significant portion of the variance in the prediction of PTSD symptoms but did significantly contribute to prediction of scores for interpersonal sensitivity, depression, and psychoticism. Thus, degree of talking with family and friends was not found to be related to PTSD symptoms, although it may have influenced some symptoms of general psychopathology, such as depression, that are not specific to PTSD.

Adult↗
PubMed2000

Decreased benzodiazepine receptor binding in prefrontal cortex in combat-related posttraumatic stress disorder.

OBJECTIVE: Animals exposed to stress exhibit a decrease in benzodiazepine receptor binding in the frontal cortex. No studies have examined central benzodiazepine receptor binding in patients with posttraumatic stress disorder (PTSD). The purpose of this study was to examine measures of benzodiazepine receptor binding in PTSD. METHOD: From 13 patients with Vietnam combat-related PTSD and 13 case-matched healthy comparison subjects, a quantitative measure related to benzodiazepine receptor binding (distribution volume) was obtained with single photon emission computed tomography (SPECT) imaging of [(123)I]iomazenil binding and measurement of radioligand concentration in plasma. Distribution volume image data were analyzed by means of statistical parametric mapping. RESULTS: Lower distribution volumes were found in the prefrontal cortex (Brodmann's area 9) of PTSD patients than in comparison subjects. CONCLUSIONS: These findings of lower values for the benzodiazepine receptor binding measure of distribution volume are consistent with fewer benzodiazepine receptors and/or reduced affinity of receptor binding in the medial prefrontal cortex in patients with PTSD. Alterations in benzodiazepine receptor function in this area may underlie many of the symptoms of PTSD.

Adult↗
PubMed1999

Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder.

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.

Adrenergic alpha-Agonists↗
PubMed1999

Yohimbine use in a natural setting: effects on posttraumatic stress disorder.

BACKGROUND: Numerous laboratory-based studies have shown that chronic posttraumatic stress disorder (PTSD) is associated with alterations in catecholamines. In a recent neuroendocrine challenge study, IV yohimbine caused exaggerated subjective, behavioral, cardiovascular and catecholamine responses among combat veterans with PTSD compared to healthy controls. Yohimbine is an alpha-2-adrenergic receptor antagonist that activates noradrenergic neurons. METHODS: This report describes the experience of 4 individuals with PTSD who took over-the-counter oral yohimbine that they had purchased from a health food store or pharmacy. RESULTS: All 4 subjects experienced a marked exacerbation of anxiety/panic and PTSD-specific symptoms immediately after ingesting yohimbine in a natural setting. CONCLUSIONS: The response in these individuals closely resembled the response observed after IV yohimbine in combat veterans with PTSD. The present cases occurred in a natural setting and thus complement laboratory-based findings. The authors caution against the recreational or medical use of yohimbine in individuals who have PTSD.

Adrenergic alpha-Antagonists↗
PubMed1999

Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: a positron emission tomography study.

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) show a reliable increase in PTSD symptoms and physiological reactivity following exposure to traumatic pictures and sounds. In this study neural correlates of exposure to traumatic pictures and sounds were measured in PTSD. METHODS: Positron emission tomography and H2[15O] were used to measure cerebral blood flow during exposure to combat-related and neutral pictures and sounds in Vietnam combat veterans with and without PTSD. RESULTS: Exposure to traumatic material in PTSD (but not non-PTSD) subjects resulted in a decrease in blood flow in medial prefrontal cortex (area 25), an area postulated to play a role in emotion through inhibition of amygdala responsiveness. Non-PTSD subjects activated anterior cingulate (area 24) to a greater degree than PTSD patients. There were also differences in cerebral blood flow response in areas involved in memory and visuospatial processing (and by extension response to threat), including posterior cingulate (area 23), precentral (motor) and inferior parietal cortex, and lingual gyrus. There was a pattern of increases in PTSD and decreases in non-PTSD subjects in these areas. CONCLUSIONS: The findings suggest that functional alternations in specific cortical and subcortical brain areas involved in memory, visuospatial processing, and emotion underlie the symptoms of patients with PTSD.

Analysis of Variance↗
PubMed1999

Hospitalized adolescents' reports of sexual and physical abuse: a comparison of two self-report measures.

This study assesses the consistency of adolescents' reports of sexual and physical abuse via two self-report questionnaires with different measurement approaches and examines demographic and psychopathological characteristics that influence abuse reporting. Seventy adolescent inpatients completed the Childhood Trauma Questionnaire (CTQ) (Likert-type items are summed to form dimensional scales, and cutoff scores determine abuse status), the Traumatic Events Questionnaire--Adolescents (multiple-choice items determine abuse status) and measures of depression, suicidal ideation, and dissociative symptoms. Consistent reports of physical and sexual abuse were given by 86% and 71% of youngsters, respectively. Discrepant reporters of sexual abuse were significantly more likely to be male, whereas consistent reporters were significantly more depressed and suicidal and reported higher levels of sexual abuse and emotional and physical neglect. Adolescents, for the most part, were consistent in their responses about sexual and physical abuse on both a Likert scale and a direct-answer-format questionnaire. The CTQ had a lower threshold for detection of sexual abuse, particularly for boys.

Adolescent↗
PubMed1999

Posttraumatic stress disorder in hospitalized adolescents: psychiatric comorbidity and clinical correlates.

OBJECTIVE: To describe the diagnostic comorbidity and clinical correlates of posttraumatic stress disorder (PTSD) in adolescent psychiatric inpatients. METHOD: Seventy-four adolescent inpatients were given a structured diagnostic interview, the revised version of the Diagnostic Interview for Children and Adolescents, and a battery of standard self-report measures to assess general trauma exposure, posttraumatic stress symptoms, suicidal behavior, dissociation, and depression. RESULTS: Ninety-three percent of subjects reported exposure to at least one traumatic event such as being a witness/victim of community violence, witnessing family violence, or being the victim of physical/sexual abuse. Thirty-two percent of subjects met diagnostic criteria for current PTSD, with sexual abuse cited as the most common traumatic stressor in 69% of PTSD cases. Girls were significantly more likely to develop PTSD than boys, although the total number of types of trauma did not differ by gender. Compared with psychiatric controls, male youngsters with PTSD were significantly more likely to have comorbid diagnoses of eating disorders, other anxiety disorders, and somatization disorder. Furthermore, male and female youngsters with PTSD were significantly more likely to have attempted suicide and report greater depressive and dissociative symptoms. CONCLUSION: In clinical populations of hospitalized adolescents exposed to multiple forms of trauma, PTSD is a common, but highly comorbid disorder. Specific multimodal assessments and treatments targeted to both PTSD and its comorbidity profile are warranted.

Adolescent↗
PubMed1999

Perceived abuse and neglect as risk factors for suicidal behavior in adolescent inpatients.

The aim of this study was to assess relative risk of histories of different types of abuse (sexual, physical, and emotional) and neglect (physical and emotional) for suicidal behavior (attempts, ideation, and self-mutilation) in psychiatrically hospitalized adolescents. Seventy-one adolescent inpatients (34 boys, 37 girls) completed self-report measures of abuse and neglect, current suicidal ideation, and lifetime suicide and self-mutilation attempts. The prevalence of sexual and physical abuse was 37.5% and 43.7%, respectively, with 31.3% and 61% of youngsters reporting emotional and physical neglect. Fifty-one percent of youngsters had made suicide attempts, and 39% had self-mutilated. Suicide attempters were significantly more likely to be female, Latino, to report sexual, physical, and emotional abuse, and to endorse emotional neglect. In multivariate analyses, female gender, sexual abuse, and emotional neglect remained significant predictors of self-mutilation and suicidal ideation. Female gender and sexual abuse remained significant predictors of suicide attempts. These findings suggest that emotional neglect is an important and deleterious component of maltreatment experiences and may be a more powerful predictor of suicidal behavior in hospitalized adolescents than physical abuse, emotional abuse, and physical neglect.

Adolescent↗