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Prior depression, PMDD, and pain: biological mechanisms

The purpose of this study was to examine the extent to which premenstrual dysphoric disorder (PMDD) and major depressive disorder (MDD), two depressive disorders unique or more common to women, exhibit distinct alterations in stress-responsive measures and experimental pain sensitivity. A total of 38 women completed all aspects of testing. Of these women, 17 met strict Diagnostic and Statistical Manual of Mental Disorders criteria for PMDD and were compared with 21 non-PMDD women for PMDD-related differences. For analyses regarding the influence of MDD on dependent measures, a history of MDD was used to model clinical MDD. In our sample, 13 women had a history of MDD and 25 women were classified as never depressed. All women were tested for pain sensitivity to cold pressor and tourniquet ischemic tasks, sympathetic nervous system (SNS) (blood pressure, heart rate, norepinephrine) and hypothalamic pituitary adrenal (HPA)-axis (cortisol and β-endorphin) functioning at baseline, and SNS responses to mental stress tasks. PMDD women displayed decreased threshold and tolerance to the cold pressor task (i.e. greater pain sensitivity), and blunted SNS reactivity to speech stress when compared to non-PMDD women. In addition, while Non-PMDD women showed a more consistent relationship between higher BP levels and decreased pain sensitivity, PMDD women showed a more robust relationship between greater β-endorphin levels and decreased pain sensitivity. Women with prior MDD showed persistent biological disturbances beyond the remission of the depressive episode, reflected in increased cold pressor tolerance (i.e. decreased pain sensitivity), increased premenstrual mood symptoms, greater diastolic blood pressure (BP) responsivity to stress, and an enhanced relationship between BP and pain than never depressed women. Finally, no diagnosis-related differences were found for any baseline HPA-axis factor. These results indicate that dysregulation in pain mechanisms and SNS stress reactivity, as well as in the relationship between pain and stress-related factors in PMDD and prior MDD, may be underlying physiological mechanisms contributing to the etiology of both disorders

Histories of depression, allopregnanolone responses to stress, and premenstrual symptoms in women

Twenty-six women with premenstrual dysphoric disorder (PMDD) and 39 non-PMDD women were tested for allopregnanolone (ALLO) responses to mental stress. Fourteen PMDD and 17 non-PMDD women had a history of depression (DEP), though all were free of current psychiatric illness. Women with prior DEP showed a blunted ALLO stress response and failed to show a decrease from venipuncture to baseline compared to women with no prior DEP. Women with prior DEP did not show the correlation between progesterone and ALLO that was seen in those with no prior DEP. ALLO levels at baseline and blunted ALLO reactivity predicted more severe premenstrual symptoms, but only in PMDD women with prior DEP. These results suggest that prior DEP is associated with a failure of ALLO to be appropriately responsive to challenge, with alterations in the conversion of progesterone to ALLO, and link ALLO to symptoms in PMDD women with prior DEP

Neurosteroids in the context of stress: Implications for depressive disorders

Animal models indicate that the neuroactive steroids 3α,5α-THP (allopregnanolone) and 3α,5α-THDOC (allotetrahydroDOC) are stress responsive, serving as homeostatic mechanisms in restoring normal GABAergic and hypothalamic-pituitary-adrenal (HPA) function following stress. While neurosteroid increases to stress are adaptive in the short term, animal models of chronic stress and depression find lower brain and plasma neurosteroid concentrations and alterations in neurosteroid responses to acute stressors. It has been suggested that disruption in this homeostatic mechanism may play a pathogenic role in some psychiatric disorders related to stress. In humans, neurosteroid depletion is consistently documented in patients with current depression and may reflect their greater chronic stress. Women with the depressive disorder, premenstrual dysphoric disorder (PMDD), have greater daily stress and a greater rate of traumatic stress. While results on baseline concentrations of neuroactive steroids in PMDD are mixed, PMDD women have diminished functional sensitivity of GABAA receptors and our laboratory has found blunted allopregnanolone responses to mental stress relative to non-PMDD controls. Similarly, euthymic women with histories of clinical depression, which may represent a large proportion of PMDD women, show more severe dysphoric mood symptoms and blunted allopregnanolone responses to stress versus never-depressed women. It is suggested that failure to mount an appropriate allopregnanolone response to stress may reflect the price of repeated biological adaptations to the increased life stress that is well documented in depressive disorders and altered allopregnanolone stress responsivity may also contribute to the dysregulation seen in HPA axis function in depression

Menstrual cycle phase does not influence gender differences in experimental pain sensitivity

Influence of menstrual cycle phase on experimental pain sensitivity in women and on gender differences in pain sensitivity was examined in 48 men and 49 women in response to cold pressor, heat, and ischemic pain. Each woman was tested at three points in their menstrual cycle in randomized order, the early follicular, late follicular, and luteal phases, while men were also tested three times, controlling for number of days between test sessions. Cycle phase was confirmed via serum hormone levels. As expected, women were significantly more sensitive to cold pain (p < .01), to heat pain (p < .0001), and to ischemic pain (p < .01) than men. However, pain perception during each task was not influenced by the menstrual cycle in women, nor did the menstrual cycle influence the magnitude of the gender differences in pain sensitivity. These results indicate that although women are more sensitive to a variety of noxious stimuli than men, menstrual cycle phase does not appear to moderate those differences in healthy men and women

Menstrual mood disorders are associated with blunted sympathetic reactivity to stress

AbstractObjectiveFew studies have directly compared women with a menstrually related mood disorder (MRMD) with women who have suffered from depression for stress reactivity phenotypes. It is unclear whether blunted responses to stress in women with a MRMD reflect a unique phenotype of MRMDs or may be explained by a history of depression.MethodsWe assessed cardiovascular reactivity to stress in four groups: 1) Women with a MRMD without a history of depression (n=37); 2) women with a MRMD plus a history of depression (n=26); 3) women without a MRMD and without a history of depression (n=43); and 4) women without a MRMD but with a history of depression (n=20).ResultsWomen with a MRMD showed blunted myocardial (heart rate and cardiac index) reactivity to mental stress compared to non-MRMD women, irrespective of histories of depression. Hypo-reactivity to stress predicted greater premenstrual symptom severity in the entire sample. Women with a MRMD showed blunted norepinephrine and diastolic blood pressure stress reactivity relative to women with no MRMD, but only when no history of depression was present. Both MRMD women and women with depression histories reported greater negative subjective responses to stress relative to their non-MRMD and never depressed counterparts.ConclusionOur findings support the assertion that a blunted stress reactivity profile represents a unique phenotype of MRMDs and also underscore the importance of psychiatric histories to stress reactivity. Furthermore, our results emphasize the clinical relevance of myocardial hypo-reactivity to stress, since it predicts heightened premenstrual symptom severity

Race and Histories of Mood Disorders Modulate Experimental Pain Tolerance in Women

Thirty-two African American and 23 non-Hispanic White women were compared for experimental pain threshold and tolerance to thermal, ischemic, and cold pressor pain. Approximately half of each group had prior mood disorders (17 African Americans, 13 non-Hispanic Whites), though all were free of current mood disturbance. Women with prior mood disorders were less sensitive to ischemic pain than women with no prior mood disorders (p<.05), while African Americans were more sensitive to ischemic pain than non-Hispanic Whites, though only at pain tolerance (p<.001). For cold pressor pain, the effects of race were only seen in women with prior mood disorders, since African Americans with prior mood disorders were more sensitive than non-Hispanic Whites with prior mood disorders (p<.05). These results indicate that experimental pain sensitivity in women is influenced by both race and histories of mood disorders

Histories of major depression and premenstrual dysphoric disorder: Evidence for phenotypic differences

This study examined unique versus shared stress and pain-related phenotypes associated with premenstrual dysphoric disorder (PMDD) and prior major depressive disorder (MDD). Sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA)-axis measures were assessed at rest and during mental stress, as well as sensitivity to cold pressor and tourniquet ischemic pain tasks in four groups of women: (1) non-PMDD with no prior MDD (N=18); (2) non-PMDD with prior MDD (N=9); (3) PMDD with no prior MDD (N=17); (4) PMDD with prior MDD (N=10). PMDD women showed blunted SNS responses to stress compared to non-PMDD women, irrespective of prior MDD; while women with prior MDD showed exaggerated diastolic blood pressure responses to stress versus never depressed women, irrespective of PMDD. However, only in women with histories of MDD did PMDD women have lower cortisol concentrations than non-PMDD women, and only in non-PMDD women was MDD associated with reduced cold pressor pain sensitivity. These results suggest both unique phenotypic differences between women with PMDD and those with a history of MDD, but also indicate that histories of MDD may have special relevance for PMDD

Persistent alterations in biological profiles in women with abuse histories: Influence of premenstrual dysphoric disorder.

To examine dysregulation in biological measures associated with histories of abuse in women and whether women with premenstrual dysphoric disorder (PMDD) differ in their dysregulation

Central Processing of Noxious Somatic Stimuli in Patients With Irritable Bowel Syndrome Compared With Healthy Controls

To compare a central analgesic mechanism known as diffuse noxious inhibitory controls (DNIC) using somatic test stimuli and somatic conditioning stimuli, (CS) in irritable bowel syndrome (IBS) patients and healthy controls