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Biomedical subjects

Meir Steiner

Publications and source records attributed to Meir Steiner.

At least 19 recordsLinked to original sources

Early deprivation, but not maternal separation, attenuates rise in corticosterone levels after exposure to a novel environment in both juvenile and adult female rats.

Separation from the maternal nest alters the hypothalamic-pituitary-adrenal (HPA) axis stress response in adult male rats, but little research has addressed how separation affects female rats. The following experiments investigated how early maternal separation from postnatal day (PND) 2 to 14 affected stress-induced corticosterone and ACTH after exposure to an open field in juvenile and adult female rats. Female rats were separated for 5 h daily from mother and littermates (early deprivation: ED), separated from mother but not littermates (maternal separation: MS), or animal facility reared (AFR). Male siblings were left with the mother rat during separation. Female rats were exposed to an open field arena either during the juvenile period (PND 30) or during adulthood (PND 80-100). Results show that ED juvenile female rats showed a lower corticosterone stress response than MS and AFR female rats when measured at 5 min post-stress, but no difference at 20 or 60 min post-stress. In adulthood, ED female rats showed comparable elevations of corticosterone as MS and AFR rats at 5 min post-stress but lower elevations at 20 min. In terms of behavior, there were no significant effects of early experience. However, in adulthood, ED and MS rats tended to show a decreased proportion of inner grid crossings of the open field compared to AFR rats, suggesting a tendency for increased anxiety in these two separation groups.

Adrenocorticotropic Hormone↗

Women and reproductive-related trauma.

Women are at higher risk for developing posttraumatic stress disorder (PTSD) than men, leading to significant psychosocial burden and healthcare-related costs. Research has shown an association between the negative impact of traumatic experiences and the reproductive life cycle in women. Pregnant women with a history of abuse/trauma frequently report intrusive reemergence of symptoms. Women who experience miscarriage may present with even higher prevalence rates of PTSD symptoms. Both psychologic and physiologic factors are believed to be relevant to the development of peripartum posttraumatic stress symptoms. Much less is known, however, about treatment. A case series of patients who presented with PTSD symptoms in the context of reproductive-related traumatic events (e.g., miscarriage, stillbirth) or who experienced reemergence of symptoms during pregnancy is presented, including treatment strategies.

Abortion, Spontaneous↗

The effects of adrenalectomy and corticosterone replacement on maternal memory in postpartum rats.

Hormones associated with parturition prime rats to behave maternally, although hormonal changes are not necessary for these behaviors to occur. Experience with pups after birth enhances maternal responsiveness after a period of isolation, creating a maternal memory. The purpose of this study was to determine the role of corticosterone in the formation of maternal memory. Adrenalectomy or sham surgeries were performed in late gestation with corticosterone or vehicle pellets being given to adrenalectomized rats. Pups were removed immediately following parturition, and half of the rats received 4 h of pup experience, while the other half received only brief pup experience associated with parturition. Ten days following pup experience, foster pups were given to all rats. Latency to become maternal and maternal behaviors on the first 2 days of re-exposure and the first two maternal days were recorded. Among adrenalectomized rats given corticosterone, 4-h experience with pups decreased maternal latency when compared to brief experience with pups. This maternal experience effect was not found in comparisons between adrenalectomized rats not given corticosterone. In addition, corticosterone decreased latencies regardless of pup experience. Corticosterone also increased maternal behavior upon initial exposure to foster pups. In conclusion, corticosterone enhanced maternal memory and initial maternal behavior in postpartum rats.

Adrenalectomy↗

The effects of adrenalectomy and corticosterone replacement on induction of maternal behavior in the virgin female rat.

Maternal behavior of the sensitized virgin rat is affected by approach-avoidance systems as well as by hypothalamic-pituitary-adrenal (HPA) axis, which is also activated during stress. The present experiments investigated the effects of adrenalectomy and of varying corticosterone concentrations on the onset and expression of maternal behavior in sensitized virgin rats. In the first experiment, latency to onset of maternal behavior and time spent licking once maternal were positively related to endogenous levels of corticosterone. However, few rats showed licking. In the second experiment, virgin rats were adrenalectomized or given sham surgeries before being sensitized and being given 0, 25, 100, 300, or 500 microg/mL of corticosterone in their drinking water. In the third experiment, virgin rats were adrenalectomized or given sham surgeries and given either control or corticosterone time-release pellets after being sensitized. Maternal behavior was then tested. Adrenalectomy increased licking in the second experiment and time over pups in the third experiment. Corticosterone replacement reduced licking in the second experiment and both licking and time over pups in the third experiment. In conclusion, exogenous corticosterone had an inhibitory effect on the expression of maternal behavior in the sensitized virgin rat, unlike the facilitatory effect previously found in the postpartum rat.

Administration, Oral↗

[Trauma & the reproductive lifecycle in women].

Women are at significantly higher risk for developing post-traumatic stress disorder (PTSD) than men, resulting in increased psychosocial burden and healthcare related costs. Recent research has shown complex interactions between the impact of traumatic experiences, and the reproductive lifecycle in women. For example, women suffering from premenstrual dysphoric disorder (PMDD) who also report a history of sexual or physical abuse are more likely to present with different neuroendocrine reactivity to stressors, when compared to premenstrual dysphoric disorder subjects without prior history of trauma or abuse or non-premenstrual dysphoric disorder subjects. In addition, women with a history of abuse or trauma may experience re-emergence of symptoms during pregnancy. Lastly, females who experience miscarriage may present with even higher prevalence rates of post-traumatic stress disorder symptoms. In this manuscript we examine the existing data on gender differences in post-traumatic stress disorder, with particular focus on psychological and physiological factors that might be relevant to the development of symptoms after exposure to traumatic events associated with the reproductive life cycle. Current options available for the treatment of such symptoms, including group and counselling therapies and debriefing are critically reviewed.

Abortion, Spontaneous↗

Gender differences in clinical presentation and response to sertraline treatment of generalized anxiety disorder.

OBJECTIVE: To evaluate gender differences in the clinical presentation of generalized anxiety disorder (GAD) and response to sertraline treatment. METHODS: Adult outpatients who met DSM-IV criteria for GAD with a minimum Hamilton rating scale for anxiety (HAM-A) total score>or=18 were randomized to 12 weeks of double-blind treatment with flexible doses (50-150 mg) of sertraline (n=182; female, 59%) or placebo (n=188; female, 51%). RESULTS: Clinical presentation of GAD was very similar in men and women in terms of the severity of the HAM-A psychic factor, severity of concomitant depression symptoms, duration of GAD, quality of life and impairment in physical health. Women had an earlier age of onset and higher HAM-A somatic factor scores compared with men. For both men and women, treatment with sertraline resulted in greater change from baseline to endpoint on the HAM-A compared with placebo (adjusted change+/-SE: men:-12.1+/-0.9 vs -8.8+/-0.9; women: -11.4+/-0.8 vs -7.1+/-0.9, p<0.001); the interaction between gender and treatment group was not significant, nor was there a significant difference between the average change from baseline for men compared with women. Similarly, responder rates based upon clinical global impression-improvement (CGI-I) scores at endpoint showed no significant interaction between gender and treatment, nor was there a significant difference in the response rates by gender; however, the response rate of sertraline compared with placebo was significantly different (p<0.0001) (men: 64% vs 40%; women: 62% vs 34%). Similar findings were evident at week 4 assessment and for completers (week 12). Overall, sertraline was well tolerated by both men and women. DISCUSSION: Women and men with GAD showed similar clinical presentations, with the exception that women had an earlier age of onset and reported more somatic anxiety symptoms. Sertraline was an effective and well tolerated treatment for GAD in both men and women.

Antidepressive Agents↗

Luteal phase dosing with paroxetine controlled release (CR) in the treatment of premenstrual dysphoric disorder.

OBJECTIVE: This clinical trial evaluated luteal phase dosing with paroxetine controlled release (CR) (12.5 mg and 25 mg) in the treatment of premenstrual dysphoric disorder (PMDD). STUDY DESIGN: A multicenter, randomized, double-blind, placebo-controlled, 3-arm, fixed-dose study of luteal phase dosing with paroxetine CR in the treatment of PMDD. Three hundred seventy-three patients with PMDD were randomly assigned into the study. The primary measure of efficacy was the change from baseline in the mean luteal visual analogue scale (VAS)-Mood score. Secondary efficacy measures included disorder-specific evaluations, global assessments of disease severity, and assessments of functional impairment. Adverse events were recorded throughout the trial. RESULTS: Patients treated with either dose of paroxetine CR demonstrated significantly greater improvements on the primary efficacy measure (change from baseline in mean luteal phase VAS-Mood scores) and on the majority of secondary efficacy measures compared with patients randomly assigned to placebo. CONCLUSION: For the treatment of PMDD, luteal phase dosing with 12.5 mg and 25 mg of paroxetine CR is effective and generally well tolerated.

Adolescent↗

Child maltreatment and HPA axis dysregulation: relationship to major depressive disorder and post traumatic stress disorder in females.

A history of child maltreatment increases the vulnerability to the development of Major Depressive Disorder (MDD) and/or Posttraumatic Stress Disorder (PTSD), especially in females. Both MDD and PTSD are associated with a dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. Dysregulation of the HPA axis may be an important etiological link between child maltreatment and subsequent psychiatric disorder, yet little is known about the relationship between exposure and outcome. The aim of this review is to explore the role of HPA axis dysregulation in the link between child maltreatment and MDD/PTSD among women. Studies of females with MDD frequently indicate a hyperactivity of the HPA axis, and contribute to our understanding of the underlying mechanisms involved in mood dysregulation. Evidence for HPA axis dysregulation in PTSD is less convincing and suggests that timing of the stressful experience as well as the type of the trauma may influence the outcome. The strongest evidence to date suggesting that the development of the HPA axis may be affected by early life stressful experiences comes from pre-clinical animal studies. Together these studies add to our understanding of the role of the HPA axis in psychiatric disorders in relation to stress. The literature on HPA axis function in both children and adults following child maltreatment further highlights the potential relevance of early stress to later onset of major psychiatric disorders. Such knowledge may also contribute to the development of early interventions targeted at primary prevention.

Adolescent↗

Experiential and hormonal correlates of maternal behavior in teen and adult mothers.

This study explores the role of cortisol and early life experiences in the regulation of maternal behavior and mood in teen and adult mothers. Primiparous mothers (n=119) (teen mothers < 19 years, n=42), young mothers (19-25 years, n= 4), and mature mothers, (>25 years, n=43) were assessed for their maternal behavior, mood, and hormonal profile at approximately 6 weeks postpartum. Outcome measures were analyzed as a function of age and early life experience. Results showed an interaction between age and type of maternal behavior, where teen mothers engaged in more instrumental (e.g. changing diapers, adjusting clothes) less affectionate (e.g., stroking, kissing, patting) behavior, and mature mothers engaged in more affectionate and less instrumental behavior. When groups were reassessed based on early life experience (consistency of care during the first 12 years of life: consistent care; having at least one consistent caregiver, inconsistent care; having multiple and changing caregivers), an interaction was also found between consistency of care and type of behavior shown, where mothers who received inconsistent care engaged in more instrumental and less affectionate behavior. Compared to mature mothers, teen mothers who were breast feeding also had higher salivary cortisol levels, and high cortisol in teen mothers related to decreased fatigue and increased energy. These results suggest that early life experiences are linked to mothering behavior and are consistent with the emerging human and animal literature on intergenerational effects of mothering style.

Adolescent↗

Treatment of menopause-related mood disturbances.

More than 1.7 million American women are expected to reach menopause each year. Recent Canadian statistics show that a 50-year-old woman can now expect to live until her mid-80s, which implies living at least one-third of her life after menopause. The menopausal transition is typically marked by intense hormonal fluctuations, accompanied by vasomotor symptoms (eg, hot flashes, night sweats), sleeps disturbance, and changes in sexual function, as well as increased risk for osteoporosis, cardiovascular disease, and cognitive decline. More importantly, recent studies have demonstrated a significant association between menopausal transition and a higher risk for developing depression. In the post-Women's Health Initiative Study era, physicians and patients are questioning the safety and efficacy of long-term hormone therapy use. This article reviews the current literature on the benefits and risks of using hormone therapy for the treatment of menopause-related mood disturbances and alternate strategies currently available for the management of menopause-related problems, including antidepressants, complementary and alternative medicine, and selective estrogen receptor modulators.

Estrogen Replacement Therapy↗

Validation of a revised visual analog scale for premenstrual mood symptoms: results from prospective and retrospective trials.

OBJECTIVE: Previous studies have demonstrated that visual analog scales (VASs) are valid and reliable instruments for measuring the severity of premenstrual symptoms. Most of these studies, though, predate the introduction of DSM-IV diagnostic criteria for premenstrual dysphoric disorder (PMDD). Our objective was to assess the reliability and validity of VASs that were revised to better reflect the DSM-IV definition of PMDD. METHODS: Concurrent information from the well-validated Premenstrual Tension Syndrome-Observer (PMTS-O) rating scale was used to evaluate the revised VASs. Data from 4 randomized controlled trials (n = 1208) evaluating the efficacy of paroxetine for the treatment of PMDD were used. Cronbach's alpha coefficient was used to evaluate the internal consistency of the core VAS mood items. Pearson's correlation between scores from the 2 scales was used to assess reliability. RESULTS: The internal consistency among the core VAS mood items (Cronbach's alpha > 0.90 across trials) was high. Luteal VAS scores and corresponding PMTS-O scores were moderately correlated at baseline (P < 0.01). Luteal VAS change scores and corresponding PMTS-O change scores were strongly correlated (P < 0.01). These results did not differ regardless of whether the PMTS-O data were collected prospectively or retrospectively. CONCLUSION: The revised VASs, which approximate the current DSM-IV definition of PMDD, provide a valid and reliable measure of the severity of premenstrual symptoms when evaluated against the validated PMTS-O scale. Our results also suggest that, whether observers assessed severity of PMDD symptoms retrospectively or prospectively using the PMTS-O scale, the correlations with the patient-reported VAS scores were comparable.

Adult↗

Paroxetine Controlled Release for Premenstrual Dysphoric Disorder: Remission Analysis Following a Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: To compare the efficacy and safety of paroxetine controlled release (CR) (12.5 mg/day or 25 mg/day) versus placebo in premenstrual dysphoric disorder (PMDD).Method: A double-blind, randomized, placebo-controlled trial was conducted over 3 menstrual cycles in women aged 18-45 years with confirmed DSM-IV PMDD in 47 outpatient centers across the United States and Canada from November 1999 to January 2002. The primary efficacy measure was the visual analog scale (VAS)-Mood, which is the mean of 4 core symptoms: irritability, tension, depressed mood, and affective lability.Results: A statistically significant difference was observed in favor of paroxetine CR 25 mg versus placebo on the VAS-Mood (adjusted mean difference = -12.58 mm, 95% CI = -18.40 to -6.76; p < .001) and for paroxetine CR 12.5 mg versus placebo (adjusted mean difference = -7.51 mm, 95% CI = -13.40 to -1.62; p = .013). Paroxetine CR was generally well tolerated.Conclusion: Paroxetine CR doses of 12.5 mg/day and 25 mg/day are effective in treating PMDD and are well tolerated.

Journal Article↗

Sleep and perinatal mood disorders: a critical review.

Pregnancy and the postpartum period are recognized as times of vulnerability to mood disorders, including postpartum depression and psychosis. Recently, changes in sleep physiology and sleep deprivation have been proposed as having roles in perinatal psychiatric disorders. In this article we review what is known about changes in sleep physiology and behaviour during the perinatal period, with a focus on the relations between sleep and postpartum "blues," depression and psychosis and on sleep-based interventions for the treatment and prevention of perinatal mood disorders. The interaction between sleep and perinatal mood disorders is significant, but evidence-based research in this field is limited. Studies that measure both sleep and mood during the perinatal period, particularly those that employ objective measurement tools such as polysomnography and actigraphy, will provide important information about the causes, prevention and treatment of perinatal mood disorders.

Depression, Postpartum↗

Strategies and methods for research on sex differences in brain and behavior.

Female and male brains differ. Differences begin early during development due to a combination of genetic and hormonal events and continue throughout the lifespan of an individual. Although researchers from a myriad of disciplines are beginning to appreciate the importance of considering sex differences in the design and interpretation of their studies, this is an area that is full of potential pitfalls. A female's reproductive status and ovarian cycle have to be taken into account when studying sex differences in health and disease susceptibility, in the pharmacological effects of drugs, and in the study of brain and behavior. To investigate sex differences in brain and behavior there is a logical series of questions that should be answered in a comprehensive investigation of any trait. First, it is important to determine that there is a sex difference in the trait in intact males and females, taking into consideration the reproductive cycle of the female. Then, one must consider whether the sex difference is attributable to the actions of gonadal steroids at the time of testing and/or is sexually differentiated permanently by the action of gonadal steroids during development. To answer these questions requires knowledge of how to assess and/or manipulate the hormonal condition of the subjects in the experiment appropriately. This article describes methods and procedures to assist scientists new to the field in designing and conducting experiments to investigate sex differences in research involving both laboratory animals and humans.

Animals↗

The effects of adrenalectomy and corticosterone replacement on maternal behavior in the postpartum rat.

It is well known that the hypothalamic-pituitary-adrenal (HPA) axis is activated during stress. Recent work suggests it is also implicated in the regulation of "normal" behaviors. The present studies investigated the effects of adrenalectomy and of varying glucocorticoid concentrations on adult maternal behavior in primiparous rats. In two studies, rats in late pregnancy were adrenalectomized or given sham surgeries and were tested for maternal behavior. In the first study, primiparous rats were given 0, 25, 100, 300, or 500 microg/ml of corticosterone in their drinking water. In the second study, primiparous rats were given either control or corticosterone time-release pellets. Blood samples were taken to ensure that rats demonstrated levels of corticosterone in blood that were relative to doses received. In studies one and two, primiparous adrenalectomized rats showed slightly, but significantly, lower levels of some maternal behaviors, including licking and time in nest, than primiparous sham rats. Primiparous rats given higher doses of corticosterone replacement showed higher levels of these maternal behaviors than primiparous rats given lower doses of corticosterone. In conclusion, adrenalectomy decreases, but does not abolish, maternal behavior. Corticosterone replacement reverses these effects. Corticosterone is not necessary for the initiation or maintenance of maternal behavior but plays a role in the modulation of ongoing maternal behavior.

Administration, Oral↗

Burden of dysthymia and comorbid illness in adults in a Canadian primary care setting: high rates of psychiatric illness in the offspring.

BACKGROUND: The burden of comorbid dysthymia and other comorbid psychiatric illnesses in a Canadian primary care setting was measured. Two groups of primary care patients: those who scored positive for comorbid dysthymia versus those who scored negative for any psychiatric disorder were compared. METHODS: This was a cross-sectional survey in a Health Service Organization (HSO) in Ontario, Canada. The subjects were patients of the HSO. The main outcome measures were: health status, mood, social adjustment, coping ability, children's psychiatric disorders, child development, family function, and health and social service utilization. RESULTS: Of the 6280 eligible adults who were patients at the HSO, 68.9% consented to be screened for psychiatric disorders; 5.1% screened positive for dysthymia, of which 90% had at least one comorbid psychiatric disorder. The following statistically significant differences were found between people with dysthymia and other comorbid psychiatric disorders versus people without any psychiatric disorder. People with dysthymia were more likely to have worse health status, worry more about their health, and report levels of pain that impaired their function; they had higher MADRS depression scores, lower social role function scores, lower social adjustment scores, and lower coping ability. More children of people with comorbid dysthymia met criteria for one or more childhood psychiatric disorders and there were more families with a parent with dysthymia that were dysfunctional. People with dysthymia used a greater proportion of health and social services, had higher per person annual health care costs (excluding hospital services), and had higher per person annual indirect costs (lost wages). CONCLUSION: This analysis demonstrated the burden of illness and costs that this disorder imposes on individuals, their families, and society as a whole.

Adaptation, Psychological↗