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Biomedical subjects

Margaret Altemus

Publications and source records attributed to Margaret Altemus.

17 recordsLinked to original sources
PubMed2006

Salivary cortisol and psychopathology in children bereaved by the september 11, 2001 terror attacks.

BACKGROUND: Studies suggest that stressful events increase risk for childhood anxiety and depression and hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This prospective longitudinal study evaluated relationships among severe psychosocial stress, psychiatric morbidity, and HPA axis function in children. METHODS: Forty-five children (mean age: 8.9 +/- 2.9 years) suffering parent death from September 11, 2001 terror attacks and 34 nonbereaved children (mean age: 9.3 +/- 2.5 years) were evaluated prospectively at 6-month intervals in this 2-year study. Assessments involved diagnostic interviews (Child Schedule for Affective Disorders and Schizophrenia [K-SADS]) for psychopathology and 3 days of baseline salivary cortisol and a salivary dexamethasone suppression test for HPA axis function. RESULTS: Bereaved children, but not nonbereaved children, had significantly increased rates of psychiatric disorders involving anxiety disorders, especially posttraumatic stress disorder (PTSD), after September 11, 2001 compared with retrospective assessments before September 11, 2001. Morning (AM) and 4:00 pm baseline cortisol were significantly and persistently higher for bereaved than nonbereaved children. Compared with bereaved children without psychopathology, bereaved children with PTSD had significantly lower 4:00 pm baseline cortisol and significantly greater 4:00 pm cortisol suppression. Children with generalized anxiety disorder had significantly less AM cortisol suppression than children without psychopathology. CONCLUSIONS: Children bereaved by sudden, unexpected parent death had persistent psychological dysfunction and HPA axis dysregulation in this study.

Adolescent↗
PubMed2006

Sex differences in depression and anxiety disorders: potential biological determinants.

The phenomenon of higher rates of affective disorders in women illustrates many of the difficulties as well as promises of translating preclinical models to human disorders. Abnormalities in the regulation of the hypothalamic-pituitary adrenal axis and the sympathoadrenomedullary system have been identified in depression and anxiety disorders, and these disorders are clearly precipitated and exacerbated by stress. Despite the striking sex difference in the prevalence of depression and anxiety disorders, attempts to identify corresponding sex differences in stress response reactivity in animal models have met with limited success. Processes which may contribute to increased rates of affective disorders in women are greater fluxes in reproductive hormones across the life span, and increased sensitivity to catecholamine augmentation of emotional memory consolidation.

Animals↗
PubMed2006

Romantic love and sexual desire in close relationships.

Drawing on recent claims in the study of relationships, attachment, and emotion, the authors hypothesized that romantic love serves a commitment-related function and sexual desire a reproduction-related function. Consistent with these claims, in Study 1, brief experiences of romantic love and sexual desire observed in a 3-min interaction between romantic partners were related to distinct feeling states, distinct nonverbal displays, and commitment- and reproductive-related relationship outcomes, respectively. In Study 2, the nonverbal display of romantic love was related to the release of oxytocin. Discussion focuses on the place of romantic love and sexual desire in the literature on emotion.

Adult↗
PubMed2006

Immune function in PTSD.

Disturbed regulation of both the hypothalamic-pituitary-adrenal (HPA) axis and sympathoadrenomedullary system in posttraumatic stress disorder (PTSD) suggests that immune function, which is modulated by these systems, may also be dysregulated. Two dermatologic, in vivo measures of immune function, delayed-type hypersensitivity (DTH) and skin barrier function recovery, were examined in female subjects with PTSD and compared to measures in healthy female comparison subjects. In addition, at the time of DTH test placement, circulating numbers of lymphocyte subtypes were assessed. In separate studies, the effects of acute psychological stress on DTH and skin barrier function recovery were examined in healthy volunteer subjects. Both DTH and barrier function recovery were enhanced in women with PTSD. These findings contrast with the effects of acute stress in healthy control subjects, which was associated with suppression of DTH responses and skin barrier function recovery. There was no difference between subjects with PTSD and healthy control subjects in proportions of circulating lymphocyte subsets or in expression of the lymphocyte markers CD62, CD25, and CD45RO/CD45RA. These results suggest that cell-mediated immune function is enhanced in individuals with PTSD, a condition that imposes chronic physiologic and mental stress on sufferers. These findings contrast with suppression of DTH and skin barrier function recovery in healthy volunteers in response to acute psychological stress.

Adrenocorticotropic Hormone↗
PubMed2006

Maternal-infant response to variable foraging demand in nonhuman primates: effects of timing of stressor on cerebrospinal fluid corticotropin-releasing factor and circulating glucocorticoid concentrations.

The maternal stress response may vary as a function of infant developmental phase. Using a median split, 13 bonnet macaque (M. radiata) mother-infant dyads were exposed to early initiation of variable foraging demand (VFD), a prolonged stressor, whereas 11 dyads were exposed to late VFD onset. Cerebrospinal fluid (CSF) and plasma samples were obtained from mothers and infants prior to and following VFD. Increases in maternal CSF corticotropin-releasing factor (CRF) concentrations were evident in response to late, but not early, VFD. Mothers exhibited either increased or decreased cortisol concentrations in response to VFD. However, absolute cortisol change was greater in early versus late VFD. Timing of the VFD stressor differentially affects maternal neuroendocrine response, with potential implications for the offspring's developmental trajectory.

Agonistic Behavior↗
PubMed2005

Orbitofrontal cortex activity related to emotional processing changes across the menstrual cycle.

The orbitofrontal cortex (OFC) has been implicated in the representation of emotional stimuli, assignment of emotional valence/salience to stimuli, stimulus-reinforcement association learning, motivation, and socio-emotional control. Using functional magnetic resonance imaging in female subjects without premenstrual mood symptoms, we found that OFC activity to emotional linguistic stimuli varies depending on the menstrual cycle phase. Specifically, anterior-medial OFC activity for negative vs. neutral stimuli was increased premenstrually and decreased postmenstrually. The inverse pattern was seen in the lateral OFC. These findings suggest that specific subregional OFC activity to emotional stimuli is modulated across the menstrual cycle. The data also demonstrate that menstrual cycle phase is an important consideration in further studies attempting to elucidate the neural substrates of affective representation.

Adult↗
PubMed2005

Sex-related differences in stimulated hypothalamic-pituitary-adrenal axis during induced gonadal suppression.

CONTEXT: Sex-related differences in the stress response are well described in the animal literature but in humans are inconsistent and appear to reflect both the method used to stimulate the hypothalamic-pituitary-adrenal (HPA) axis and the age of the subjects. Sex-related differences in reproductive steroid levels further confound efforts to define the specific role of the sex of the individual in stress axis responsivity. OBJECTIVE: The aim of this study was to address this role independent of differences in reproductive steroid levels. We compared HPA axis response to pharmacological (CRH) and physiological (exercise) stressors in two groups of young to middle-aged (18-45 yr) men (n = 10 and 8) and women (n = 12 and 13) undergoing gonadal suppression with leuprolide acetate (monthly im injection of 7.5 mg in men and 3.75 mg in women). DESIGN: Exercise and CRH stimulation tests were performed during induced hypogonadal conditions. SETTING: The study was conducted at a National Institutes of Health Clinical Center Outpatient Clinic. PATIENT OR OTHER PARTICIPANTS: Male and female normal volunteers participated in the study. MAIN OUTCOME MEASURES: The main outcome measures were stimulated ACTH and cortisol levels. RESULTS: Both CRH (1 microg/kg) stimulation and graded treadmill exercise stimulation occurred in the month after the second leuprolide injection to ensure gonadal suppression. Despite the absence of sex differences in estradiol or testosterone at the time of testing, men showed increased stimulated ACTH (repeated-measures ANOVA for CRH, P < 0.005) and cortisol (repeated-measures ANOVA for exercise, P < 0.05) compared with women. Among the summary measures, area under the curve (AUC) for cortisol was significantly greater in men than women after exercise. Although the AUC for ACTH was not significantly different across sexes, the initial AUC (0-30 min) was significantly greater in men for both procedures. No significant sex differences were found in a measure of adrenal responsivity, the cortisol to ACTH ratio, for either procedure. Cortisol-binding globulin levels did not differ between men and women and were not correlated with stimulated HPA axis measures. These data confirm earlier reports of sex differences in stimulated HPA axis activity and demonstrate that these differences exist even under induced hypogonadal conditions (i.e. in the absence of characteristic differences in reproductive steroids).

Adolescent↗
PubMed2005

Synchronized maternal-infant elevations of primate CSF CRF concentrations in response to variable foraging demand.

BACKGROUND: The study of environment-gene interactions during neurodevelopment may facilitate our understanding of the origins of psychiatric disorders. Environmental contribution to the neurobiology of psychopathology is perhaps most relevant during infancy, where vulnerability to early-life stressors is particularly evident. OBJECTIVES: In the current study, we wished to examine if central corticotropin-releasing factor (CRF) would provide a plausible biological vehicle for synchronized increases in mothers and their infant. METHODS: Twenty-four mother-infant bonnet macaques (Macaca radiata) dyads, of known age and weight served as subjects. The subjects were group-housed in four pens of 5-7 dyads each, stabilized for several weeks prior to the study period. Although adequate food was always available, mothers faced uncertainty of food availability for 16 weeks within the first year of infant life, through a procedure dubbed "variable foraging demand" (VFD). Pre- and post-VFD cerebrospinal fluid (CSF) samples were obtained simultaneously on mothers and infants. RESULTS: Maternal CSF CRF concentrations exhibited a significant mean elevation of 26% from pre-VFD to post-VFD; there was no effect of number of days postpartum on maternal pre-VFD CSF CRF levels. There was a significant mean increase (45%) in infant CSF CRF concentrations over the 16-week period of the VFD paradigm. No infant sex differences were evident. Post-VFD minus pre-VFD differences in infant CSF CRF concentrations were positively correlated (r = .52; N = 16; P = .0384) with the magnitude of maternal CRF response to VFD, providing evidence of synchronized CSF CRF expression by the dyad. CONCLUSION: This parallel response within the dyad suggests, as one testable hypothesis, that maternal responsivity to the stress of the VFD condition is "communicated" between mother and infant via a CRF-mediated mechanism. The VFD stressor produces a parallel activation of the central CRF system in both mothers and their infants.

Animals↗
PubMed2004

Changes in cerebrospinal fluid neurochemistry during pregnancy.

BACKGROUND: Little is known about changes in brain function that may occur during pregnancy. Studies in rodents and sheep suggest that several brain neurotransmitter and neurohormonal systems known to modulate anxiety may be altered during pregnancy. METHODS: Cerebrospinal fluid (CSF) and plasma samples were obtained from 21 women (during weeks 38-39 of pregnancy) who were undergoing elective cesarean section and from 22 healthy nonpregnant women. RESULTS: The CSF levels of g-aminobutyric acid (GABA) and 3-methoxy-4-hydroxyphenylglycolwere reduced in pregnant women. There were no changes in CSF glutamate, 5-hydroxyindoleactic acid, and homovanillic acid. There was a large increase in CSF prolactin in pregnant women and also a trend toward an elevation in CSF oxytocin. Levels of prolactin, but not oxytocin, in CSF and plasma were correlated in pregnant women. CONCLUSIONS: These results suggest that pregnancy alters regulation of brain GABA, norepinephrine, and prolactin, which may play a role in changes in vulnerability to anxiety and depression during pregnancy and postpartum. Prolactin circulating in the bloodstream seems to be the major source of CSF prolactin during pregnancy.

Adult↗
PubMed2004

HPA axis activation in major depression and response to fluoxetine: a pilot study.

Hypothalamic-pituitary-adrenal (HPA) axis activation is a frequently observed phenomenon in major depression. However, whether this activation has any implications for treatment is unknown. To address this question, we examined baseline response to metyrapone and 6-week response to fluoxetine. Premenopausal women (n = 20) who met criteria for major depression with no other confounding Axis I disorders, medications, or medical illnesses and were not taking hormonal contraceptives were evaluated with an evening metyrapone challenge before the onset of treatment. Twenty-one normal women were also studied with the evening metyrapone challenge. The depressed patients then entered an open label treatment with fluoxetine for 6 weeks. Subjects were classified as responders if they demonstrated a 50% or greater decrease in Hamilton Depression Rating Scale rating. As a group, the depressed women demonstrated significantly increased ACTH secretion compared to control women before the onset of treatment, during the metyrapone challenge. Before treatment, women who were non-responders to fluoxetine showed increased HPA axis activation compared to controls, while the fluoxetine responders did not differ significantly from normal subjects in their ACTH levels during metyrapone challenge. These results suggest that overactivity of the HPA axis may be one factor associated with slower response to fluoxetine. This may reflect the greater severity of subjects with HPA axis dysregulation or the need to normalize the HPA axis with medications for optimal response.

Adolescent↗
PubMed2004

Puberty, ovarian steroids, and stress.

Puberty is accompanied by a number of changes, among them increased risk for development of major depression. The most common etiology of major depression is stressful life events, being present in approximately 90% of first episodes of depression. The hypothalamic-pituitary-adrenal (HPA) axis is one of the major systems involved in responses to stress, and this system is clearly influenced by ovarian hormones. Normal women demonstrate resistance to negative feedback of both cortisol in the fast-feedback paradigm and dexamethasone in the standard delayed-feedback paradigm. Depressed premenopausal women show greater increases in baseline cortisol than postmenopausal depressed women and than depressed men. Studies in rodents suggest a similar resistance to glucocorticoid feedback but suggest that estradiol can function to inhibit stress responsiveness. Studies of premenopausal depressed women demonstrate lower estradiol, which suggests that there is less inhibitory feedback of estradiol on the HPA axis, while normal progesterone continues to augment stress responses further. The onset of these reproductive hormonal changes modulating stress systems at puberty may sensitize girls to stressful life events, which become more frequent at the transition to puberty and young adulthood.

Animals↗
PubMed2003

Enhanced cellular immune response in women with PTSD related to childhood abuse.

OBJECTIVE: Disturbed regulation of both the hypothalamic-pituitary-adrenal (HPA) axis and the sympathoadrenomedullary system in posttraumatic stress disorder (PTSD) suggests that immune function, which is modulated by these systems, also may be dysregulated in individuals with PTSD. METHOD: Delayed-type hypersensitivity skin test responses were measured in 16 women with PTSD due to childhood sexual or physical abuse and 15 women who did not have a history of abuse, other trauma, or psychiatric disorders. HPA axis activity was assessed by examination of circadian salivary cortisol levels and a single time point measurement of plasma cortisol. RESULTS: Delayed-type hypersensitivity was enhanced in women with PTSD. Cortisol measures did not differ between PTSD and healthy comparison subjects. CONCLUSIONS: These results suggest that cell-mediated inflammatory reactions are greater in individuals with PTSD.

Adult↗
PubMed2003

Differential menstrual cycle regulation of hypothalamic-pituitary-adrenal axis in women with premenstrual syndrome and controls.

Previous studies in animals indicate that reproductive steroids are potent modulators of the hypothalamic-pituitary-adrenal (HPA) axis, a physiologic system that is typically dysregulated in affective disorders, such as major depression. Determination of the role of reproductive steroids in HPA axis regulation in humans is of importance when attempting to understand the pathophysiology of premenstrual syndrome (PMS), a disorder characterized by affective symptoms during the luteal phase of the menstrual cycle. We performed two studies using treadmill exercise stress testing to determine the effect of menstrual cycle phase and diagnosis on the HPA axis in women with PMS and controls and the role of gonadal steroids in HPA axis modulation in control women. The results of these studies indicate that women with PMS fail to show the normal increased HPA axis response to exercise during the luteal phase and that progesterone, not estradiol, produces increased HPA axis response to treadmill stress testing in control women. These data demonstrate that women with PMS, when symptomatic, appear to have an abnormal response to progesterone and, furthermore, do not display the HPA axis abnormalities characteristic of major depression.

Adrenocorticotropic Hormone↗
PubMed2002

Replication of a premenstrual decrease in right-ear advantage on language-related dichotic listening tests of cerebral laterality.

Five fused dichotic word tasks measured perceptual asymmetry in 30 women at 4 weekly intervals. The five tasks varied according to whether the stimuli presented were word-word pairs or nonsense word-pairs, or whether they consisted of neutral words paired with positive emotion-evoking words (e.g. hug-tug), neutral words paired with negative emotion-evoking words (e.g. till-kill), or neutral words paired with neutral words (e.g. bean-dean). Overall right-ear advantage (REA) decreased in the premenstrual week relative to the postmenstrual week, replicating previous results using identical measures. In addition, REA scores were similar at menstrual, postmenstrual and midcycle weeks. Additional data from 12 men suggests sex differences in task performance were small or non-existent. In both women and men, there were no effects of repeated testing on REA, but emotional proclivity indices, defined as the tendency to recall words of positive or negative affective tone, increased across the four test sessions. As found previously, there was a trend for women to hear fewer positive words during the premenstrual week. These data are consistent with other research suggesting that a progesterone-mediated decrease in functional asymmetry occurs in the luteal phase. Future research manipulating task demands (e.g. memory load) or the affective valence of the stimuli may be useful in understanding the observed changes in hemispheric advantage.

Adolescent↗
PubMed2002

Differing concentrations of corticotropin-releasing factor and oxytocin in the cerebrospinal fluid of bonnet and pigtail macaques.

The two neuropeptides corticotropin-releasing-factor (CRF) and oxytocin (OT) may produce opposing behavioral effects - elevations of the former have been associated with anxiety and social vigilance and reductions of the latter with reduced social affiliation. We sought to test the hypothesis that, within the primate macaque genus, the more gregarious, affiliative, and affectively stable bonnet species (Macaca radiata) would exhibit lower cerebrospinal fluid (CSF) CRF and higher CSF OT concentrations in comparison to its close relative, the temperamentally volatile and socially distant pigtail (Macaca nemestrina). Cisternal CSF samples were obtained from young adult male and female pigtail and bonnet macaques, and CRF and OT concentrations were measured by radioimmunoassay. Pigtail macaques exhibited significantly higher concentrations of CSF CRF and significant lower concentrations of CSF OT than bonnet macaques. Results were not attributable to age or sex differences in group composition. When included together in a multiple regression, CRF and OT showed a multiple R of 0.76, accounting for more than half of the species variance. Although species differences in the bioeffectiveness of these peptides may possibly confound the observed biobehavioral relationships, in the absence of any existing data to that effect, the current findings appear in accordance with the hypothesis and consistent with previously reported species-typical behaviors observed in these macaques.

Animals↗
PubMed2002

Effects of emotion on oxytocin, prolactin, and ACTH in women.

Research on both non-human mammals and humans has raised interest in the role that oxytocin may play in human attachment and attachment-related emotions. This study examined changes in plasma oxytocin, prolactin, and ACTH concentrations in response to laboratory-induced positive and negative emotions related to close, interpersonal relationships. Participants were 32 female volunteers recruited from university communities. During positive emotion induction, oxytocin decreased over time (F(1,3) = 4.41, p < 0.007), prolactin increased (F(1,3) = 4.80, p < 0.004) and ACTH remained constant. During negative emotion induction, prolactin levels increased (F(1,3) = 2.81, p < 0.05), ACTH decreased only after the induction terminated (F(1,3) = 4.02, p < 0.01) and oxytocin remained constant. While oxytocin decreased during positive emotion, this finding contrasted previous research that showed decreases in response to negative emotion. In conclusion, plasma oxytocin levels were not reliably altered by positive or negative emotion induction. While prolactin and ACTH were expected to decrease over time due to diurnal variation, they instead either increased or remained level during emotion induction, or decreased only after the induction. Overall, the degree of change in circulating hormones in response to happy and sad emotions was very small and possibly not functionally significant.

Adrenocorticotropic Hormone↗