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Biomedical subjects

S M Southwick

Publications and source records attributed to S M Southwick.

At least 37 records · Page 2Linked to original sources
PubMed1999

Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder.

OBJECTIVE: Childhood sexual abuse is very common in our society, but little is known about the long-term effects of abuse on brain function. The purpose of this study was to measure neural correlates of memories of childhood abuse in sexually abused women with and without the diagnosis of posttraumatic stress disorder (PTSD). METHOD: Twenty-two women with a history of childhood sexual abuse underwent injection of [15O]H2O, followed by positron emission tomography imaging of the brain while they listened to neutral and traumatic (personalized childhood sexual abuse events) scripts. Brain blood flow during exposure to traumatic and neutral scripts was compared for sexually abused women with and without PTSD. RESULTS: Memories of childhood sexual abuse were associated with greater increases in blood flow in portions of anterior prefrontal cortex (superior and middle frontal gyri-areas 6 and 9), posterior cingulate (area 31), and motor cortex in sexually abused women with PTSD than in sexually abused women without PTSD. Abuse memories were associated with alterations in blood flow in medial prefrontal cortex, with decreased blood flow in subcallosal gyrus (area 25), and a failure of activation in anterior cingulate (area 32). There was also decreased blood flow in right hippocampus, fusiform/inferior temporal gyrus, supramarginal gyrus, and visual association cortex in women with PTSD relative to women without PTSD. CONCLUSIONS: These findings implicate dysfunction of medial prefrontal cortex (subcallosal gyrus and anterior cingulate), hippocampus, and visual association cortex in pathological memories of childhood abuse in women with PTSD. Increased activation in posterior cingulate and motor cortex was seen in women with PTSD. Dysfunction in these brain areas may underlie PTSD symptoms provoked by traumatic reminders in subjects with PTSD.

Adult↗
PubMed1999

Anniversary reactions in Gulf War veterans: a follow-up inquiry 6 years after the war.

OBJECTIVE: The goal of this study was to assess the occurrence of anniversary reactions in Gulf War veterans 6 years after the conclusion of the war. METHOD: Subjects were administered questionnaires and asked to identify specific months of best and worst functioning and months of least or most symptoms of posttraumatic stress disorder (PTSD) for the 12 months before the study. Months of negative experiences were compared with previously documented dates of exposure to traumatic events during the war. Similar reports were also obtained from the veterans' spouses in order to assess corroborative evidence for the occurrence of anniversary reactions. RESULTS: Anniversary reactions occurred with a frequency greater than chance and most often in individuals exposed to a greater number of traumatic events. Overall, spouse reports matched the veterans' reports of anniversary reactions. In addition, spouses identified anniversary reactions that were not endorsed by their veterans. CONCLUSIONS: These data suggest that anniversary reactions occur in numbers greater than those expected by chance, are correlated to the occurrence of traumatic events, and may be a part of the syndrome of PTSD.

Adjustment Disorders↗
PubMed1999

Neurotransmitter alterations in PTSD: catecholamines and serotonin.

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.

Animals↗
PubMed1999

Glutamate and post-traumatic stress disorder: toward a psychobiology of dissociation.

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.

Animals↗
PubMed1998

Effects of experimental context and explicit threat cues on acoustic startle in Vietnam veterans with posttraumatic stress disorder.

BACKGROUND: The hypothesis that exaggerated startle in Vietnam veterans with posttraumatic stress disorder (PTSD) reflects an anxiogenic response to stressful contexts was tested. METHODS: Thirty-four nonmedicated Vietnam veterans with PTSD, and 17 combat and 14 civilian non-PTSD controls participated in two testing sessions over separate days. Acoustic startle stimuli were delivered alone or in a test of prepulse inhibition. In the first session, startle was assessed without experimental stress. In the second session, startle was investigated during a stressful "threat of shock" experiment, when subjects anticipated the administration of shocks during threat periods and during safe periods when no shocks were anticipated. RESULTS: The magnitude of startle did not differ significantly among the three groups in the first session, but was increased throughout the threat of shock experiment in the PTSD veterans in the second session. The actual increase in startle in the threat compared to the safe condition did not significantly differ among the three groups. Prepulse inhibition was reduced in the PTSD veterans, compared to the non-PTSD civilians, but not compared to the non-PTSD veterans. CONCLUSION: Exaggerated startle in Vietnam veterans with PTSD reflects an anxiogenic response to an environment that is experienced as stressful.

Acoustic Stimulation↗
PubMed1998

Plasma neuropeptide Y (NPY) increases in humans in response to the alpha 2 antagonist yohimbine.

Previous studies have shown that the intravenous administration of yohimbine, an alpha 2 antagonist, increases norepinephrine turnover and has related anxiogenic effects in humans. We herein report that yohimbine also increases plasma neuropeptide Y (NPY) in healthy human subjects. This finding is consistent with previous reports in animals, but contrasts with a previously reported study in humans. NPY is a 36 amino acid peptide neurotransmitter located in sympathetic and nonsympathetic nerve fibers, as well as in brain structures such as the locus coeruleus, where it is colocalized with norepinephrine. NPY has been shown to inhibit locus coeruleus neuronal firing, decrease norepinephrine release, and increase postsynaptic noradrenergic signal transduction. When administered centrally, NPY also has anxiolytic properties. This study therefore suggests that yohimbine challenge may be useful in assessing NPY and noradrenergic system interactions in neuropsychiatric disorders such as panic disorder or post traumatic stress disorder in which noradrenergic system dysfunction has been observed.

Adrenergic alpha-Antagonists↗
PubMed1998

Measurement of dissociative states with the Clinician-Administered Dissociative States Scale (CADSS).

The purpose of this study was to develop an instrument for the measurement of present-state dissociative symptoms, the Clinician Administered Dissociative States Scale (CADSS). Reported here are interrater reliability and internal consistency of the CADSS, validity as assessed by comparisons with other instruments for the assessment of dissociation, and sensitivity of the CADSS to discriminate patients with dissociative disorders from patients with other psychiatric disorders and healthy subjects. Initial analyses indicated good interrater reliability and construct validity for the CADSS. Scores on the CADSS discriminated patients with dissociative disorders from the other groups.

Adult↗
PubMed1998

Anniversary reactions in Gulf War veterans: a naturalistic inquiry 2 years after the Gulf War.

The goal of this study was to assess the occurrence of anniversary reactions in Gulf War veterans 2 years after the conclusion of Operation Desert Storm. Subjects were administered questionnaires and asked to identify specific months of best and worst functioning, and months of least or most symptoms of posttraumatic stress disorder (PTSD). Negatively experienced months were compared to documented dates of exposure to traumatic events during the war. Anniversary reactions occurred with a frequency greater than chance and were seen most in individuals exposed to a greater number, and to more severe types, of traumatic events. This suggests that anniversary reactions are etiologically linked to traumatic events and may be a part of the syndrome of PTSD.

Chi-Square Distribution↗
PubMed1998

Effect of darkness on acoustic startle in Vietnam veterans with PTSD.

OBJECTIVE: Exaggerated startle is a symptom of posttraumatic stress disorder (PTSD), but empirical studies have not consistently documented elevated baseline startle in PTSD. The authors proposed in a previous study that Vietnam veterans with PTSD exhibit exaggerated startle only under stressful conditions. They reported that darkness facilitated startle in humans, suggesting that the startle reflex is sensitive to the aversive nature of darkness. In the present study they tested the hypothesis that the magnitude of facilitation of startle by darkness would be greater in Vietnam veterans with PTSD than in comparison groups of subjects without PTSD. Prepulse inhibition was also investigated. METHOD: The magnitude of startle and prepulse inhibition were assessed in alternating periods of darkness and light in 19 nonmedicated Vietnam veterans with PTSD, 13 Vietnam veterans without PTSD, and 20 civilians without PTSD. RESULTS: The overall startle level was higher in the veterans with PTSD than in either of the two groups of subjects without PTSD. Startle was facilitated by darkness, and the magnitude of this facilitation was greater in the veterans with PTSD than in the civilians without PTSD, but it was not greater in the veterans without PTSD. Prepulse inhibition was not affected by darkness and did not significantly differ among groups. CONCLUSIONS: Contrary to the hypothesis, elevated sensitivity to darkness was specific to individuals with combat experience, not to individuals with PTSD, perhaps because veterans had become aversively conditioned to darkness during their combat experiences. The more general increase in startle reactivity in the veterans with PTSD is consistent with clinical observations and descriptions of symptoms in DSM-IV.

Acoustic Stimulation↗
PubMed1997

Positron emission tomography measurement of cerebral metabolic correlates of yohimbine administration in combat-related posttraumatic stress disorder.

BACKGROUND: We have previously reported an increase in symptoms of anxiety in patients with posttraumatic stress disorder (PTSD) following administration of the beta 2-antagonist yohimbine, which stimulates brain norepinephrine release. Preclinical studies show decreased metabolism in the neocortex and the caudate nucleus with high-dose yohimbine-induced norepinephrine release, but low levels of norepinephrine release result in an increase in metabolism in these areas. METHODS: We used positron emission tomography and fludeoxyglucose F 18 to measure brain metabolism in Vietnam combat veterans with PTSD (n = 10) and healthy age-matched control subjects (n = 10), following administration of yohimbine (0.4 mg/kg) or placebo in a randomized, double-blind fashion. RESULTS: Yohimbine resulted in a significant increase in anxiety in the patients with PTSD, but not in healthy subjects. There was a significant difference in brain metabolic response to yohimbine in patients with PTSD compared with healthy subjects in prefrontal, temporal, parietal, and orbitofrontal cortexes. Metabolism tended to decrease in patients with PTSD and increase in healthy subjects following administration of yohimbine. CONCLUSION: These findings are consistent with our previous hypothesis of enhanced norepinephrine release in the brain with yohimbine in patients with PTSD.

Anxiety Disorders↗
PubMed1997

Noradrenergic and serotonergic function in posttraumatic stress disorder.

BACKGROUND: Yohimbine hydrochloride produces marked behavioral and cardiovascular effects in combat veterans with posttraumatic stress disorder (PTSD). In the present study, yohimbine was used as a probe of noradrenergic activity, and meta-chlorophenylpiperazine (m-CPP) as a probe of serotonergic activity. To our knowledge, this is the first study to describe the behavioral and cardiovascular effects of meta-CPP in patients with PTSD, and to compare these effects with those of yohimbine. METHOD: Twenty-six patients with PTSD and 14 healthy subjects each received an intravenous infusion of yohimbine hydrochloride (0.4 mg/kg), m-CPP (1.0 mg/kg), or saline solution on 3 separate test days in a randomized balanced order and in double-blind fashion. Behavioral and cardiovascular measurements were determined at multiple times. RESULTS: Eleven (42%) of the patients with PTSD experienced yohimbine-induced panic attacks and had significantly greater increases compared with controls in anxiety, panic, and PTSD symptoms, but not in cardiovascular measurements. Eight patients (31%) with PTSD experienced m-CPP-induced panic attacks and had significantly greater increases compared with controls in anxiety, panic, and PTSD symptoms, and in standing diastolic blood pressure. Yohimbine-induced panic attacks tended to occur in different patients from m-CPP-induced panic attacks. CONCLUSION: These data suggest the presence of 2 neurobiological subgroups of patients with PTSD, one with a sensitized noradrenergic system, and the other with a sensitized serotonergic system.

Adult↗
PubMed1997

Evidence of acoustic startle hyperreflexia in recently detoxified early onset male alcoholics: modulation by yohimbine and m-chlorophenylpiperazine (mCPP).

Preclinical studies suggest that acoustic startle amplitude is increased during ethanol withdrawal. The current study evaluated the effects of intravenous infusion of the alpha 2-adrenergic antagonist, yohimbine (0.4 mg/kg), the serotonin partial agonist m-chlorophenylpiperazine (mCPP, 0.1 mg/kg), and placebo administered to 22 male patients meeting DSM-III-R criteria for alcohol dependence and 13 male healthy subjects. Patients and healthy subjects completed 3 test days under double-blind conditions in a randomized order. Patients were sober for 12-26 days prior to testing. On each test day, participants completed startle testing 80 min following drug infusion. Stimuli with varying intensities (90, 96, 102, 108, 114 dB) were presented in a randomized order balanced across four blocks. Stimuli consisted of 40-ms bursts of white noise administered every 45-60 s for 15-20 min through headphones. Analyses indicated that patients exhibited elevated acoustic startle magnitudes on the placebo day relative to healthy subjects. In patients, the magnitude of startle amplitudes elicited at 90 dB, but not 114 dB, correlated significantly with the number of previous alcohol detoxifications. Yohimbine increased startle magnitudes and reduced startle latencies relative to placebo and mCPP in both patients and healthy subjects. mCPP did not alter startle magnitude in either group. Yohimbine also increased the probability that a 90-dB stimulus produced a startle response in healthy subjects, but not in patients. Blunting of yohimbine effects on startle probability may reflect the baseline elevations in startle probability levels in patients, but may also be consistent with other evidence of reduced postsynaptic, but not presynaptic, noradrenergic function in these same patients. These data replicate and extend previous reports indicating that yohimbine facilitates the acoustic startle response in humans. They also further implicate the number of episodes of ethanol withdrawal as a factor influencing subsequent neurobiological responsivity in chronic alcoholic patients. Based on the current data, future research should explore whether measurement of the acoustic startle response provides an objective quantitative severity measure of ethanol withdrawal.

Acoustic Stimulation↗
PubMed1997

Alexithymia in Holocaust survivors with and without PTSD.

Alexithymia was measured in non-treatment seeking, community-dwelling Holocaust survivors using the Toronto Alexithymia Scale-Twenty Item Version (TAS-20). Scores of survivors with (n = 30) and without (n = 26) posttraumatic stress disorder (PTSD) were compared, and associations among alexithymia, severity of trauma, and severity of PTSD symptoms were determined. Survivors with PTSD had significantly higher scores on the TAS-20 compared to survivors without PTSD. TAS-20 scores were significantly associated with severity of PTSD symptoms, but not with severity of trauma. This study adds to our knowledge of the relationship between alexithymia and trauma by demonstrating that this characteristic is related to the presence of posttraumatic symptoms and not simply exposure to trauma.

Affective Symptoms↗
PubMed1997

Consistency of memory for combat-related traumatic events in veterans of Operation Desert Storm.

OBJECTIVE: The nature of traumatic memories is currently the subject of intense scientific investigation. While some researchers have described traumatic memory as fixed and indelible, others have found it to be malleable and subject to substantial alteration. The current study is a prospective investigation of memory for serious combat-related traumatic events in veterans of Operation Desert Storm. METHOD: Fifty-nine National Guard reservists from two separate units completed a 19-item trauma questionnaire about their combat experiences 1 month and 2 years after their return from the Gulf War. Responses were compared for consistency between the two time points and correlated with level of symptoms of posttraumatic stress disorder (PTSD). RESULTS: There were many instances of inconsistent recall for events that were objective and highly traumatic in nature. Eighty-eight percent of subjects changed their responses on at least one of the 19 items, while 61% changed two or more items. There was a significant positive correlation between score on the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder at 2 years and the number of responses on the trauma questionnaire changed from no at 1 month to yes at 2 years. CONCLUSIONS: These findings do not support the position that traumatic memories are fixed or indelible. Further, the data suggest that as PTSD symptoms increase, so does amplification of memory for traumatic events. This study raises questions about the accuracy of recall for traumatic events, as well as about the well-established but retrospectively determined relationship between level of exposure to trauma and degree of PTSD symptoms.

Adult↗
PubMed1997

Elevated CSF corticotropin-releasing factor concentrations in posttraumatic stress disorder.

OBJECTIVE: Corticotropin-releasing factor (CRF) and somatostatin both play important roles in mediating responses to acute and chronic stress. The purpose of this study was to measure CSF concentrations of CRF and somatostatin in patients with chronic combat-related post-traumatic stress disorder (PTSD) and comparison subjects. METHOD: Lumbar punctures for collection of CSF were performed in Vietnam combat veterans with PTSD (N = 11) and comparison subjects (N = 17). CSF concentrations of CRF and somatostatin were compared between the two groups. RESULTS: CSF concentrations of CRF were higher in the PTSD patients than in the comparison subjects (mean = 29.0 pg/ml, SD = 7.8, versus mean = 21.9 pg/ml, SD = 6.0). This group difference remained significant after covariance for age. CSF somatostatin concentrations in PTSD patients were higher than those of the comparison subjects (mean = 19.9 pg/ml, SD = 5.4, versus mean = 13.7 pg/ml, SD = 8.0). However, covarying for age reduced the level of significance. CONCLUSIONS: Higher CSF CRF concentrations in patients with PTSD may reflect alterations in stress-related neurotransmitter systems. The higher CSF CRF concentrations may play a role in disturbances of arousal in patients with PTSD.

Adult↗
PubMed1997

Startle reflex abnormalities in women with sexual assault-related posttraumatic stress disorder.

OBJECTIVE: This investigation was designed to assess the acoustic startle response in treatment-seeking women with sexual assault-related posttraumatic stress disorder (PTSD). METHOD: Thirteen patients with sexual assault-related PTSD and 16 healthy female comparison subjects were recruited for participation in the study. Each patient met the full criteria for PTSD according to the Structured Clinical Interview for DSM-III-R. All subjects in the study were right-handed. The acoustic stimuli were bursts of white noise (92 dB and 102 dB) with a nearly instantaneous onset delivered binaurally through headphones. RESULTS: The magnitude of the startle response (eye blink) to the first stimulus was asymmetrically distributed in the PTSD patients but not in the comparison subjects: it was greater for the left eye than the right eye in the PTSD patients only. There was a differential asymmetry of startle response in the two subgroups of patients (recent PTSD and long-standing PTSD): the startle reflex was larger for the left eye than the right in the subgroup with recent PTSD but not in the group with long-standing PTSD. CONCLUSIONS: This study provides the first objective evidence of startle abnormalities in women with PTSD. The significantly greater startle responses for the left eye compared with the right in the PTSD subjects suggest a laterality effect. As suggested by the preclinical model of shock sensitization, it is possible that in a subgroup of individuals with PTSD, trauma may sensitize the startle reflex. This model may hold true in humans and is supported by the findings of greater startle response in the patients with recent-onset PTSD.

Acoustic Stimulation↗