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M Altemus

Publications and source records attributed to M Altemus.

At least 37 records · Page 2Linked to original sources
PubMed1997

Integrative functions of lactational hormones in social behavior and stress management.

For mammalian reproduction to succeed, self-defense and asociality must be subjugated to positive social behaviors, at least during birth, lactation, and sexual behavior. Perhaps the important task of regulating the interaction between social and agonistic behaviors is managed, in part, by interactions between two related neurochemical systems that incorporate oxytocin and vasopressin in their functions. The neuropeptides oxytocin and vasopressin participate in important reproductive functions, such as parturition and lactation, and homeostatic responses, including modulation of the adrenal axis. Recent evidence also implicates these hormones in social aspects of reproductive behaviors. For example, oxytocin is important for a variety of positive social behaviors, including the regulation of maternal-infant interactions. In adult animals, oxytocin may facilitate both social contact and selective social interactions associated with social attachment and pair bonding, and it participates in the regulation of parasympathetic functions. Vasopressin, in contrast, is associated with behaviors that might be broadly classified as "defensive" including enhanced arousal, attention, or vigilance, increased aggressive behavior, and a general increase in sympathetic functions. On the basis of the literature on the functions of these hormones and our own recent findings, we propose that dynamic interactions between oxytocin and vasopressin are components of a larger system which integrates the neuroendocrine and autonomic changes associated with mammalian social behaviors and the concurrent regulation of the stress axis. In addition, studies of lactating females provide a valuable model for understanding the more general neuroendocrinology of the stress axis. Peptide hormones, including oxytocin and vasopressin, do not readily cross the blood-brain barrier and must be administered centrally (i.c.v.) to reach the brain. Nasal sprays have been used to promote milk let down and have been used in some behavioral studies, but the extent to which such compounds reach the brain is not known. Therefore, virtually nothing is known regarding the effects in humans of centrally administered oxytocin. The study of human lactation, in conjunction with animal research, provides an opportunity to begin to develop viable hypotheses regarding the behavioral effects of oxytocin.

Adrenal Glands↗
PubMed1997

Reduced sensitivity to glucocorticoid feedback and reduced glucocorticoid receptor mRNA expression in the luteal phase of the menstrual cycle.

We examined the effects of the menstrual cycle on hypothalamic-pituitary adrenal axis regulation in healthy women with no history of psychiatric illness by measuring plasma cortisol responses to a low-dose (0.25 mg) of dexamethasone (N = 23) and by measuring glucocorticoid receptor (type II) mRNA expression in lymphocytes using Northern blotting (N = 19). Both measures were performed in the early follicular and mid-luteal phases of the menstrual cycle. Dexamethasone suppression of plasma cortisol was greater in the follicular phase of the menstrual cycle compared to the mid-luteal phase (p < .01). In addition, type II glucocorticoid receptor mRNA expression in lymphocytes was 78% higher in the follicular phase compared to the mid-luteal phase (p < .02). These results indicate that glucocorticoid feedback regulation of the hypothalamic-pituitary-adrenal axis is reduced in the mid-luteal phase of the menstrual cycle. Reduced feedback regulation of central stress response systems may play a role in generation of common premenstrual symptoms of irritability and dysphoria.

Adult↗
PubMed1997

Central nervous system actions of oxytocin and modulation of behavior in humans.

The posterior pituitary hormone oxytocin has modulatory effects on neural functioning that are significant to the regulation of behavior. Basic research in animals has established the importance of oxytocin in affiliation, including mating, pair bonding and parenting behaviors. It is also an important regulator of feeding, grooming and responses to stress. The actions of oxytocin in the brain are regulated by gonadal steroid hormones, particularly estrogen. Oxytocin might also influence normal behavior in humans, and dysfunctions in the oxytocin system might be involved in the etiology and expression of neuropsychiatric disorders.

Amino Acid Sequence↗
PubMed1997

Effect of prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a preliminary study.

OBJECTIVE: Prefrontal mechanisms are implicated in obsessive-compulsive disorder. The authors investigated whether prefrontal repetitive transcranial magnetic stimulation influenced obsessive-compulsive disorder symptoms. METHOD: Twelve patients with obsessive-compulsive disorder were given repetitive transcranial magnetic stimulation (80% motor threshold, 20 Hz/2 seconds per minute for 20 minutes) to a right lateral prefrontal, a left lateral prefrontal, and a midoccipital (control) site on separate days, randomized. The patients' symptoms and mood were rated for 8 hours afterward. RESULTS: Compulsive urges decreased significantly for 8 hours after right lateral prefrontal repetitive transcranial magnetic stimulation, but there were nonsignificant increases in compulsive urges after repetitive transcranial magnetic stimulation of the midoccipital site. A shorter-lasting (30 minutes), modest, and nonsignificant reduction in compulsive urges occurred after left lateral prefrontal repetitive transcranial magnetic stimulation. Mood improved during and 30 minutes after right lateral prefrontal stimulation. CONCLUSIONS: These preliminary results suggest that right prefrontal repetitive transcranial magnetic stimulation might affect prefrontal mechanisms involved in obsessive-compulsive disorder.

Adult↗
PubMed1996

Intact coding region of the serotonin transporter gene in obsessive-compulsive disorder.

Epidemiologic studies indicate that obsessive-compulsive disorder is genetically transmitted in some families, although no genetic abnormalities have been identified in individuals with this disorder. The selective response of obsessive-compulsive disorder to treatment with agents which block serotonin reuptake suggests the gene coding for the serotonin transporter as a candidate gene. The primary structure of the serotonin-transporter coding region was sequenced in 22 patients with obsessive-compulsive disorder, using direct PCR sequencing of cDNA synthesized from platelet serotonin-transporter mRNA. No variations in amino-acid sequence were found among the obsessive-compulsive disorder patients or healthy controls. These results do not support a role for alteration in the primary structure of the coding region of the serotonin-transporter gene in the pathogenesis of obsessive-compulsive disorder.

Adult↗
PubMed1996

Comparison of obsessions and compulsions in patients with anorexia nervosa and obsessive compulsive disorder.

Patients with anorexia nervosa (n = 18) and patients with obsessive-compulsive disorder (OCD) (n = 16) had similar scores on the Yale-Brown Obsessive Compulsive Scale (19 + or - 9 vs. 22 + or - 6). This suggests that these disorders have similar magnitude of impairment from obsessions and compulsions; however, OCD patients endorsed a wide variety of obsessions and compulsions, whereas anorexics tended to endorse symptoms that were related to symmetry and order.

Adolescent↗
PubMed1996

Hypervigilance in patients with obsessive-compulsive disorder.

The hypothesis that patients with obsessive-compulsive disorder (OCD) suffer from hypervigilant attention was investigated via explicit memory (incidental recall and recognition) and priming (reading speed) measures. OCD patients did not differ from normal controls on explicit measures of memory; specifically, recognition of unusual words (experiment 1) and recall and recognition of words and feature-specific information (experiment 2). Although both normal controls and OCD patients showed priming, the pattern of priming differed for the two groups (experiment 2). Specifically, patients with OCD failed to show feature-specific priming, suggesting they may have attended more focally on the priming task than did normal controls. These findings support previous reports of normal performance in OCD on explicit memory tasks, but suggest more sensitive measures may reflect differences in processing information.

Adult↗
PubMed1996

Effects of serotonergic agents on food-restriction-induced hyperactivity.

Rats that are fed for 90 min per day can stabilize their weight after an initial drop; however, if rats on this feeding schedule are also given access to a running wheel, they run excessively, eat less, lose weight, and often die. To investigate this phenomenon as a possible animal model of obsessive-compulsive disorder (OCD), rats were treated for 5 weeks with fluoxetine, an antidepressant that relieves OCD symptoms in humans (5 mg/kg, 2.5 mg/kg), or imipramine, an antidepressant that does not affect OCD symptoms (5 mg/kg), or saline prior to exposure to food restriction and the running wheel. In addition, because chronic fluoxetine treatment is thought to enhance serotonergic neurotransmission, for contrast an additional group of rats were treated with parachlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor that depletes serotonin. Rats treated with fluoxetine lost significantly less weight, ran significantly less, and increased food intake more rapidly during restriction of food availability than saline-treated rats. Rats treated with imipramine did not differ from those treated with saline on these parameters. Compared to saline-treated rats, rats treated with PCPA lost more weight, ate less food, and increased running more rapidly. These effects of pharmacological treatment indicate an inverse relationship between central serotonergic activity and vulnerability to develop food-restriction-induced anorexia and compulsive running. In addition, like OCD in humans, this phenomenon in rats seems to be blocked by chronic treatment with a serotonin selective reuptake inhibitor but not a less selective monoamine reuptake inhibitor.

Animals↗
PubMed1996

Thyroid function in bulimia nervosa.

Basal thyroid-stimulating hormone (TSH) and thyroid hormone levels were evaluated in 18 women with bulimia nervosa during a period of active binging and vomiting and again after 7 weeks of abstinence from these behaviors and compared to measures in 27 control women. In 10 of the patients and 11 of the controls, the TSH nocturnal surge was calculated from hourly TSH measurements obtained in the afternoon from 1500 to 1900 h and in the night from 2300 to 0400 h. During the binging phase of the illness patients had lower total triiodothyronine (T3) values than controls (p < .001). After 7 weeks without binge eating or purging, patients had lower T3, total thyroxine (T4), free triiodothyronine, free thyroxine (FT4), reverse triiodothyronine and thyroid-binding globulin (TBG) values compared to controls (p < .01) and significant reductions in T3, T4, FT4 and TBG compared to themselves in the active phase of the illness (p < .02). The reduction in thyroid hormone levels was not due to a reduction in the nocturnal thyrotropin surge, since surge values did not differ between normals and patients at either phase of the illness. Bulimics in the binging phase of the illness showed a positive correlation between caloric intake and TSH values (p < .01), suggesting that food binging may stimulate thyroid activity. In sum, these results show a substantial reduction in thyroid hormone levels after 7 weeks of abstinence from binging and vomiting behaviors.

Adult↗
PubMed1996

Naloxone-induced pituitary-adrenal activation does not differ in patients with depression, obsessive compulsive disorder, and healthy controls.

Adrenocorticotropic hormone (ACTH) and cortisol secretion have been shown to be abnormal in approximately half of depressed patients. Information from pituitary and adrenal studies suggests that the locus of this dysregulation is at or above the level of the hypothalamus; however, direct evidence from provocative studies of the hypothalamic corticotropin releasing hormone (CRH) neuron does not exist. The current study was designed to stimulate hypothalamic CRH release using the opiate antagonist naloxone in patients with depression and elevated urinary-free cortisols as well as healthy and psychiatric controls. All subjects received naloxone and placebo on separate days in a double-blinded, randomized fashion at a dose determined previously to reliably induce significant increases in ACTH and cortisol secretion. No significant differences were noted among groups. We conclude that although naloxone is an effective central stimulant of the hypothalamic CRH neuron, stimulation of the hypothalamic CRH neuron with naloxone does not provide evidence of dysregulation of the HPA axis in depression.

Adrenocorticotropic Hormone↗
PubMed1995

Stress and antidepressants differentially regulate neurotrophin 3 mRNA expression in the locus coeruleus.

The mechanisms by which stress and anti-depressants exert opposite effects on the course of clinical depression are not known. However, potential candidates might include neurotrophic factors that regulate the development, plasticity, and survival of neurons. To explore this hypothesis, we examined the effects of stress and antidepressants on neurotrophin expression in the locus coeruleus (LC), which modulates many of the behavioral and physiological responses to stress and has been implicated in mood disorders. Using in situ hybridization, we demonstrate that neurotrophin 3 (NT-3) is expressed in noradrenergic neurons of the LC. Recurrent, but not acute, immobilization stress increased NT-3 mRNA levels in the LC. In contrast, chronic treatment with antidepressants decreased NT-3 mRNA levels. The effect occurred in response to antidepressants that blocked norepinephrine uptake, whereas serotonin-specific reuptake inhibitors did not alter NT-3 levels. Electroconvulsive seizures also decreased NT-3 expression in the LC as well as the hippocampus. Ntrk3 (neurotrophic tyrosine kinase receptor type 3; formerly TrkC), the receptor for NT-3, is expressed in the LC, but its mRNA levels did not change with stress or antidepressant treatments. Because, NT-3 is known to be trophic for LC neurons, our results raise the possibility that some of the effects of stress and antidepressants on LC function and plasticity could be mediated through NT-3. Moreover, the coexpression of NT-3 and its receptor in the LC suggests the potential for autocrine mechanisms of action.

Animals↗
PubMed1995

Cerebrospinal fluid levels of kynurenine pathway metabolites in patients with eating disorders: relation to clinical and biochemical variable.

In brain, most L-tryptophan is metabolized to indoleamines, whereas in systemic tissues L-tryptophan is catabolized to kynurenine pathway metabolites. Among these latter compounds are: quinolinic acid, an N-methyl-D-aspartate receptor agonist; kynurenic acid, an antagonist of excitatory amino acid receptors that also reduces quinolinic acid-mediated neurotoxicity; and L-kynurenine, a possible convulsant. Because the metabolism of L-tryptophan through the kynurenine pathway is dependent upon adequate nutrition, we sought to determine whether the impaired nutrition characteristic of eating-disordered patients might be associated with specific disturbances in this metabolic pathway. Cerebrospinal fluid levels of L-tryptophan, quinolinic acid, kynurenic acid, L-kynurenine, and 5-hydroxyindoleacetic acid were measured in medication-free female patients meeting DSM-III-R criteria for either anorexia nervosa (n = 10) or normal-weight bulimia nervosa (n = 22), studied at varying stages of nutritional recovery. Eight healthy, normal-weight females served as a comparison group. Cerebrospinal fluid levels of kynurenic acid were significantly reduced in underweight anorectics, compared to normal females, but returned to normal values with restoration of normal body weight. Although cerebrospinal fluid quinolinic acid levels were not different from controls, the ratio of quinolinic acid to kynurenic acid was significantly increased during the underweight phase of anorexia nervosa. Furthermore, in the eating-disordered patients, kynurenic acid levels in cerebrospinal fluid correlated positively with percent-of-population average body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Working memory as assessed by subject-ordered tasks in patients with obsessive-compulsive disorder.

We tested patients with obsessive-compulsive disorder (OCD) and normal subjects (n = 18 per group) on a self-paced, working memory task that, based on studies of patients with focal brain lesions and functional brain imaging studies of normals, is largely mediated by prefrontal cortex. The OCD patients had normal working memory spans and normal recognition memory for all types of material tested (abstract words, common objects, and novel nonsense objects). The patients, however, were slow (p < .005), and the time they took to complete the tasks was significantly correlated with ratings of OCD symptoms (r = .539, p < .05) and depression (r = .643, p < .01), but not anxiety. Slowed performance on this self-paced task was discussed in relation to normal response times by OCD patients under typical laboratory conditions. It was suggested that this discrepancy may be related to a broader dissociation between real-world and laboratory performance as seen in some patients with prefrontal lobe dysfunction.

Adult↗
PubMed1995

Suppression of hypothalmic-pituitary-adrenal axis responses to stress in lactating women.

In the rat, lactation suppresses a variety of physiological responses to stress. We investigated whether stress-responsive neurohormonal systems are also restrained during breast feeding in humans. We chose treadmill exercise as a stressor because this stimulus produces an exercise intensity-dependent activation of the hypothalamic-pituitary-adrenal axis and the sympathomedullary system that is independent of differences in physical conditioning among subjects. Ten lactating and ten nonlactating women who were between 7 and 18 weeks postpartum performed 20 min of graded treadmill exercise. The final 5 min of exercise was set to elicit 90% of the maximal oxygen uptake of each subject. Plasma ACTH, cortisol, and glucose responses to exercise were significantly attenuated in lactating women (P < 0.001, P < 0.05, and P < 0.001, respectively). Basal norepinephrine levels were also reduced in lactating women (P < 0.05). These results indicate that stress-responsive neurohormonal systems are restrained in lactating women.

Adrenocorticotropic Hormone↗
PubMed1994

Changes in cerebrospinal fluid neurochemistry during treatment of obsessive-compulsive disorder with clomipramine.

BACKGROUND: This study examined the effect of long-term (mean, 19 months) treatment with clomipramine hydrochloride on cerebrospinal fluid (CSF) levels of several neuropeptides and monoamine metabolites in children and adolescents with obsessive-compulsive disorder. METHODS: The CSF levels of corticotropin-releasing hormone, vasopressin, somatostatin, and oxytocin and of the monoamine metabolites 5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were measured in 17 children and adolescents with obsessive-compulsive disorder before and after long-term treatment with clomipramine. RESULTS: Treatment resulted in significant decreases in CSF levels of corticotropin-releasing hormone (mean +/- SD, 175 +/- 32 vs 152 +/- 25 pmol/L, P < .03) and vasopressin (mean +/- SD, 1.30 +/- 0.57 vs 0.86 +/- 0.54 pmol/L, P < .02) and a trend toward a decrease in somatostatin levels (mean +/- SD, 21.3 +/- 8.5 vs 15.3 +/- 9.8 pmol/L, P < .06). Treatment also significantly increased CSF oxytocin levels (mean +/- SD, 6.05 +/- 1.60 vs 6.70 +/- 1.44 pmol/L, P < .01). Significant changes in CSF monoamine metabolite levels with treatment included significant decreases in CSF levels of 5-hydroxyindoleacetic acid (mean +/- SD, 109 +/- 31 vs 77 +/- 23 pmol/mL, P < .001), CSF homovanillic acid (mean +/- SD, 273 +/- 111 vs 237 +/- 101 pmol/mL, P < .04), and 3-methoxy-4-hydroxyphenylglycol (mean +/- SD, 42.4 +/- 10.2 vs 36.1 +/- 4.8 pmol/L, P < .02) and a significant increase in the homovanillic acid-5-hydroxyindoleacetic acid ratio (mean +/- SD, 2.44 +/- 0.46 vs 3.42 +/- 0.84, P < .0001). CONCLUSIONS: These neuropeptide results coupled with evidence that central administration of corticotropin-releasing hormone, vasopressin, and somatostatin to laboratory animals increases arousal and acquisition of conditioned behaviors whereas central administration of oxytocin has opposite behavioral effects are consistent with a role for these neuropeptides in the pathophysiologic processes and pharmacologic treatment of obsessive-compulsive disorder.

Adolescent↗