Biomedical subjects

Ann M Rasmusson

Publications and source records attributed to Ann M Rasmusson.

11 recordsLinked to original sources

PubMed2006

Decreased cerebrospinal fluid allopregnanolone levels in women with posttraumatic stress disorder.

BACKGROUND: Alterations in the gamma-amino-butyric acid (GABA) neurotransmitter system have been identified in some populations with posttraumatic stress disorder (PTSD). METHODS: To further investigate factors of relevance to GABAergic neurotransmission in PTSD, we measured cerebrospinal fluid (CSF) levels of allopregnanolone and pregnanolone combined (ALLO: congeners that potently and positively modulate effects of GABA at the GABA(A) receptor), 5alpha-dihydroprogesterone (5alpha-DHP: the immediate precursor for allopregnanolone), dehydroepiandrosterone (DHEA: a negative modulator of GABA(A) receptor function), and progesterone with gas chromatography, mass spectrometry in premenopausal women with (n = 9) and without (n = 10) PTSD. Subjects were free of psychotropic medications, alcohol, and illicit drugs; all were in the follicular phase of the menstrual cycle except three healthy and four PTSD subjects receiving oral contraceptives. RESULTS: There were no group differences in progesterone, 5alpha-DHP, or DHEA levels. The PTSD group ALLO levels were < 39% of healthy group levels. The ALLO/DHEA ratio correlated negatively with PTSD re-experiencing symptoms (n = -.82, p < 008; trend) and with Profile of Mood State depression/dejection scores (n = -0.70, p < 0008). CONCLUSION: Low CSF ALLO levels in premenopausal women with PTSD might contribute to an imbalance in inhibitory versus excitatory neurotransmission, resulting in increased PTSD re-experiencing and depressive symptoms.

5-alpha-Dihydroprogesterone↗

PubMed2006

A decrease in the plasma DHEA to cortisol ratio during smoking abstinence may predict relapse: a preliminary study.

RATIONALE: Increases in depressive symptoms during smoking cessation have been associated with risk for relapse. Several studies have linked plasma levels of cortisol and dehydroepiandrosterone (DHEA) or DHEA-sulfate (DHEAS) to depressive symptoms. OBJECTIVES: To determine whether changes in plasma cortisol, DHEA, or DHEAS levels and emergence of depressive symptoms during smoking cessation are associated with smoking relapse. MATERIALS AND METHODS: Subjects were healthy non-medicated men and women, aged 39+/-12 years, who smoked, on average, 22 cigarettes per day. Depressive symptoms, smoking withdrawal symptoms, and plasma steroid levels were measured before and after 8 days of verified smoking abstinence. Relapse status at day 15 was then determined. RESULTS: In the full sample (n=63), there was a trend for changes in depressive symptoms to be associated with relapse. In the subset of 25 subjects with plasma neuroactive steroid data, there was a significant interaction between the change in the plasma DHEA/cortisol ratio from day 0 to day 8 and relapse status at day 15. This ratio was similar before abstinence, but lower at day 8 in relapsed, compared to abstinent, subjects. Changes in the DHEA/cortisol ratio tended to predict changes in depressive symptoms in the women only. CONCLUSION: A decrease in the plasma DHEA/cortisol ratio during 8 days of smoking abstinence was associated with relapse over the following week. Further research is needed to fully characterize sex-specific relationships between abstinence-induced changes in neuroactive steroid levels, depressive or withdrawal symptoms, and relapse. Such research may lead to new interventions for refractory smoking dependence.

Adult↗

PubMed2006

Smoking as a complex but critical covariate in neurobiological studies of posttraumatic stress disorders: a review.

As smoking rates in the general population continue to fall in response to new information and changing social values, the continued high rate of smoking among persons with psychiatric disorders has caught the attention of society at many levels: public health officials, medical and mental health care providers, and concerned family members alike. As a consequence, research studies aimed at quantifying the problem and understanding its cause have increased dramatically over the past several years. The following review first examines epidemiological studies that have revealed a bidirectional causal relationship between tobacco dependence and posttraumatic stress disorder (PTSD), one of several mental health disorders in which tobacco dependence remains prevalent and resistant to intervention. Second, we use a translational neuroscience perspective to discuss possible neurobiological mediators of the relationship between PTSD and tobacco dependence, hoping to spur further human and animal research that will elucidate pathogenetic mechanisms involved and inspire novel treatment interventions. Finally, to enable more effective clinical research in this area, we provide an overview of effective scientific methods for assessing and managing 'smoking status' as an experimental variable in clinical research studies of PTSD as well as other mental health disorders.

Animals↗

PubMed2005

Baseline and modulated acoustic startle responses in adolescent girls with posttraumatic stress disorder.

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.

Acoustic Stimulation↗

PubMed2004

An increased capacity for adrenal DHEA release is associated with decreased avoidance and negative mood symptoms in women with PTSD.

We recently found increased adrenal cortisol responses to adrenocorticotropic hormone (ACTH)1-24 and increased pituitary ACTH and adrenal cortisol responses to corticotropin-releasing factor in premenopausal women with chronic post-traumatic stress disorder (PTSD) compared to healthy nontraumatized subjects. This pattern of hypothalamic-pituitary-adrenal axis (HPA) hyper-reactivity has been previously seen in healthy individuals treated with the antiglucocorticoid mifepristone. We therefore investigated whether endogenous plasma levels of antiglucocorticoids such as dehydroepiandrosteroine (DHEA) and progesterone were increased in premenopausal women with PTSD at baseline or in response to adrenal activation by ACTH1-24. The study revealed that DHEA responses to 250 microg ACTH1-24 were increased in 13 PTSD subjects compared to 13 healthy nontraumatized subjects, while DHEA levels were generally increased in the PTSD subjects compared to seven healthy traumatized subjects. Cortisol responses to ACTH1-24 were also higher in the women with PTSD, while progesterone levels and responses were not different among the three groups. In addition, among the PTSD subjects, the peak change in DHEA in response to ACTH1-24 was negatively correlated with the total Clinician Administered PTSD Scale score, while the peak DHEA to cortisol ratio was inversely associated with negative mood symptoms measured by the Profile of Mood States scale. This work suggests that an increased capacity for DHEA release in response to extreme adrenal activation may influence the pattern of HPA axis adaptation to extreme stress, as well as mitigate the severity of PTSD and negative mood symptoms in premenopausal women with PTSD.

Adrenal Glands↗

PubMed2003

Trauma exposure rather than posttraumatic stress disorder is associated with reduced baseline plasma neuropeptide-Y levels.

BACKGROUND: Exposure to uncontrollable stress reduces baseline plasma neuropeptide-Y levels in animals. We previously reported that baseline plasma neuropeptide-Y levels, as well as neuropeptide-Y responses to yohimbine, were lower in combat veterans with posttraumatic stress disorder, but we were unable to determine whether this was attributable to posttraumatic stress disorder or trauma exposure. The current report addresses this issue. METHODS: A) Baseline plasma neuropeptide-Y levels were measured in 8 healthy combat veterans compared to 18 combat veterans with posttraumatic stress disorder and 8 healthy nontraumatized subjects; and B) Baseline plasma neuropeptide-Y levels, trauma exposure, and posttraumatic stress disorder symptoms were assessed in 41 active military personnel. RESULTS: Plasma neuropeptide-Y was negatively associated with trauma exposure but not posttraumatic stress disorder symptoms in active duty personnel. Baseline neuropeptide-Y was reduced in combat veterans with and without posttraumatic stress disorder. CONCLUSIONS: Trauma exposure rather than posttraumatic stress disorder is associated with reduced baseline plasma neuropeptide-Y levels. Future studies must determine if neuropeptide-Y reactivity differentiates trauma-exposed individuals with and without posttraumatic stress disorder.

Adult↗

PubMed2003

The neuroendocrinology of posttraumatic stress disorder: new directions.

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

Adaptation, Psychological↗

PubMed2003

Salivary cortisol responses to dexamethasone in adolescents with posttraumatic stress disorder.

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.

Adolescent↗

PubMed2003

Posttraumatic stress disorder and substance use in inner-city adolescent girls.

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.

Adolescent↗

PubMed2002

Neuropeptide-Y, cortisol, and subjective distress in humans exposed to acute stress: replication and extension of previous report.

BACKGROUND: We previously reported that stress-related release of cortisol and neuropeptide-Y (NPY) were significantly and positively associated in U.S. Army soldiers participating in survival training. Furthermore, greater levels of NPY were observed in individuals exhibiting fewer psychologic symptoms of dissociation during stress. This study tested whether these findings would be replicated in a sample of U.S. Navy personnel participating in survival school training. METHODS: Psychologic as well as salivary and plasma hormone indices were assessed in 25 active duty personnel before, during, and 24 hours after exposure to U.S. Navy survival school stress. RESULTS: Cortisol and NPY were significantly and positively associated during stress and 24 hours after stress; NPY and norepinephrine (NE) were significantly and positively related during and 24 hours after stress. There was a significant, negative relationship between psychologic distress and NPY release during stress. Finally, psychologic symptoms of dissociation reported at baseline predicted significantly less NPY release during stress. CONCLUSIONS: These data replicate our previous studies demonstrating that acute stress elicits NPY release and that this release is positively associated with cortisol and NE release. These data also replicate our previous finding that greater levels of NPY release are associated with less psychologic distress suggesting that NPY confers anxiolytic activity.

Adult↗

PubMed2002

Downregulation of BDNF mRNA in the hippocampal dentate gyrus after re-exposure to cues previously associated with footshock.

This study examined the effects of footshock stress and re-exposure to cues previously associated with footshock on expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus of male rats. Exposure to twenty 0.5-s 0.4-mA footshocks co-terminating with 70 dB, 5-s long pure tones over 60 min decreased dentate gyrus BDNF mRNA by 21.5%. Baseline BDNF mRNA levels returned to normal by two days after footshock exposure. Re-exposure for 60 min to the chamber and tones previously paired with 0.4 mA footshock decreased BDNF mRNA by 12%. Re-exposure to the conditioning chamber and tones previously paired with 0.6 mA footshock over 60 min decreased BDNF mRNA by 20.8%. The data suggest that psychological, as well as unconditioned physical stress, can decrease hippocampal BDNF mRNA. Possible implications for stress-related and other neuropsychiatric disorders associated with deficits in hippocampal function and volume, such as depression, post-traumatic stress disorder, and Alzheimer's Disease, are discussed.

Acoustic Stimulation↗