Macrophage Migration Inhibitory Factor and microRNA-451a in Response to Mindfulness-based Therapy or Treatment as Usual in Patients with Depression, Anxiety, or Stress and Adjustment Disorders.

Background: Macrophage migration inhibitory factor is a proinflammatory cytokine that has been associated with various psychiatric disorders. MicroRNA-451a can directly target macrophage migration inhibitory factor and downregulate its expression in cells. However, the role of macrophage migration inhibitory factor and microRNA-451a in psychiatric patients treated with psychotherapeutic interventions is unknown. In this study, our aim was to investigate levels of macrophage migration inhibitory factor and its regulating microRNA-451a in patients with depression, anxiety, or stress and adjustment disorders who underwent mindfulness-based therapy or treatment as usual. Methods: A total of 168 patients with psychiatric disorders were included from a randomized controlled trial that compared mindfulness-based therapy with treatment as usual. Plasma levels of macrophage migration inhibitory factor and microRNA-451a were measured at baseline and after the 8-week follow-up using Luminex assay and qPCR. Results: Macrophage migration inhibitory factor levels decreased significantly in patients posttreatment, whereas microRNA-451a levels showed a nonsignificant change. Macrophage migration inhibitory factor levels were inversely associated with microRNA-451a expression levels at baseline (ß=-0.04, P=.008). The change in macrophage migration inhibitory factor levels (follow-up levels minus baseline levels) was associated with the change in microRNA-451a (follow-up levels minus baseline levels) (ß=-0.06, P < .0001). The change in either macrophage migration inhibitory factor or microRNA-451a was not associated with improvement in psychiatric symptoms. Conclusion: We demonstrate that the levels of macrophage migration inhibitory factor decreased after psychotherapeutic interventions in patients with psychiatric disorders. However, this reduction was not associated with an improvement in psychiatric symptoms in response to the treatment. We also found an association between macrophage migration inhibitory factor and its regulating microRNA. However, this association needs to be further examined in future studies.

Psychiatric symptoms and proinflammatory cytokines in pregnancy.

OBJECTIVE: Clinical studies suggest that psychiatric symptoms, particularly depression, anxiety, and trauma, may be associated with inflammation, as indexed by proinflammatory cytokines. Such a link may be especially significant in pregnancy and may shed additional light on the etiology of perinatal mood disorders. METHODS: We prospectively observed 145 women selected from a community obstetric clinic serving a primarily low-income, high-psychosocial risk population. Women without evidence of medical high-risk pregnancies were screened (including psychiatric and trauma histories) and then assessed in detail (e.g., mood symptoms) at approximately 18 and 32 weeks' gestation. Blood was drawn to measure key proinflammatory markers, interleukin 6 and tumor necrosis factor α (TNF-α). Data on pregnancy and obstetric outcome were derived from medical records. RESULTS: There was considerable stability of cytokine levels within individuals and a significant mean increase across pregnancy observed for interleukin 6 (p < .001) and TNF-α (p < .001). History of trauma was associated with significantly elevated TNF-α levels (F(1,135) = 4.43, p < .05), controlling for psychosocial and obstetric covariates. In contrast, elevated measures of depression and anxiety were unrelated to proinflammatory cytokines (p > .1). Exploratory analyses indicated that neither psychiatric symptoms nor proinflammatory cytokines predicted birth weight, gestational age, or obstetric complications. CONCLUSIONS: These findings suggest that antecedent trauma may be associated with persistently elevated TNF-α levels during pregnancy. The evidence that a generalized proinflammatory state was associated with symptoms of depression or anxiety in pregnant women was not found.

Serum melatonin concentration in the child with non-organic failure to thrive: comparison with other types of stress.

Human beings must adapt both to novel, unfavourable conditions and to circumstances of physical or psychological isolation. The initial response to stress depends fundamentally on the activation of the HPA axis. In regaining homeostatic equilibrium, melatonin plays a role due to its synchronising and anti-stress properties. To study the role of melatonin and the pineal gland in the organic and/or behavioural response to acute or chronic stress, 311 children were divided into two large groups: 1) Control Group - 121 healthy children classified, in turn, into 4 control subgroups, one for each pathology being studied; 2) Problem Groups, classified as traumatic stress (n=58), surgical stress (n=38), psychic stress (n=64) and febrile stress (n=30), according to pre-established clinical criteria. These groups were sub-classified according to the degree (low or high) and duration (acute or chronic) of the stress. This study used a case controlled, cross sectional design. Serum melatonin was measured by radioimmunoassay (RIA). In all the situations of acute stress, melatonin increased at a rate directly proportional to the severity and/or duration of the stress-causing stimulus. In contrast, in chronic stress, i.e. the Affective Deprivation Syndrome (or Psychological Dwarfism) with or without non-organic failure to thrive, resulted in the opposite response with a significant reduction of melatonin. In conclusion, in acute stress an increase in the bioavailability of melatonin could contribute to maintaining homeostatic balance. The lack of an appropriate response to acute stress could make some groups of patients (Affective deprivation syndrome with or without growth failure) predisposed to suffer depressive symptoms associated with a wide range of neurological, endocrinological or immunological consequences.

The relationship of thyroid hormone status with myocardial function in stress cardiomyopathy.

OBJECTIVE: This study aimed to investigate thyroid hormone (TH) status and its relationship with myocardial function as well as clinical and biochemical parameters in stress cardiomyopathy (CMP). METHODS: Forty-five patients with stress CMP (the patient group), 31 patients without stress CMP (the control II group), and 58 healthy subjects (the control I group) were included. Sick euthyroid syndrome (SES) was defined as low total triiodothyronine (T(3)) with normal TSH levels. RESULTS: In the patient group at admission, prevalence of SES was 62.2%. Compared with the control I group, the patient group had a decrease in left ventricular ejection fraction (LVEF) and systolic blood pressure (BP) and an increase in troponin-I, CK-MB, and B-type natriuretic peptide (BNP) levels. Total T(3) levels were reduced, and anti-thyroid peroxidase antibody (anti-TPO Ab) positivity, C-reactive protein (CRP) and cortisol levels were elevated. Total T(3) levels were associated with acute physiology and chronic health evaluation II (APACHE II) score, LVEF, systolic BP, and cortisol levels in multivariate analysis. In the control II group, total T(3) levels were not associated with any variables. In the SES (n=28) and myocardial dysfunction (MDys, n=27) subgroups, increased APACHE II score and BNP levels as well as decreased LVEF and systolic BP were significant. Total T(3) levels were reduced, and CRP, cortisol and catecholamines levels were elevated. In the MDys subgroup, anti-TPO Ab positivity and titer were increased. CONCLUSION: These results suggest that total T(3) levels may be associated with myocardial contractility, clinical severity, and cortisol levels. Thyroid autoimmunity may influence myocardial contractility in stress CMP.

[Variants of the course of early noncomplicated postoperative period following excision of hypothalamo-hypophysial region tumors in children]. / Osnovnye varianty techeniia rannego neoslozhnennogo posleoperatsionnogo perioda posle udaleniia opukholei gipotalamo-gipofizarnoi oblasti u detei.

A study of non-specific and specific reactions in neurosurgical patients as conducted in the early postoperative period revealed three main variations of an early postoperative clinical course, i.e. with a normal stress-reaction, with a normal stress-reaction concomitant with diabetes insi pidus, and with a lower reactivity to surgical intervention. The treatment algorithms were appropriately amended (the preventive component was added) with due respect to the above circumstances.

When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders.

OBJECTIVE: Previous theories have emphasized the role of excessive glucocorticoid activity in the pathology of chronic stress. Nevertheless, insufficient glucocorticoid signaling (resulting from decreased hormone bioavailability or reduced hormone sensitivity) may have equally devastating effects on bodily function. Such effects may be related in part to the role of glucocorticoids in restraining activation of the immune system and other components of the stress response, including the sympathetic nervous system (SNS) and corticotropin-releasing hormone (CRH). METHOD: The literature on neuroendocrine function and glucocorticoid-relevant pathologies in stress-related neuropsychiatric disorders, including posttraumatic stress disorder and major depression, was reviewed. RESULTS: Although not occurring together, both hypocortisolism and reduced responsiveness to glucocorticoids (as determined by dexamethasone challenge tests) were reliably found. Stress-related neuropsychiatric disorders were also associated with immune system activation/inflammation, high SNS tone, and CRH hypersecretion, which are all consistent with insufficient glucocorticoid-mediated regulation of stress hyperresponsiveness. Finally, antidepressants, a mainstay in the treatment of stress-related disorders, were regularly associated with evidence of enhanced glucocorticoid signaling. CONCLUSIONS: Neuroendocrine data provide evidence of insufficient glucocorticoid signaling in stress-related neuropsychiatric disorders. Impaired feedback regulation of relevant stress responses, especially immune activation/inflammation, may, in turn, contribute to stress-related pathology, including alterations in behavior, insulin sensitivity, bone metabolism, and acquired immune responses. From an evolutionary perspective, reduced glucocorticoid signaling, whether achieved at the level of the hormone or its receptor, may foster immune readiness and increase arousal. Emphasis on insufficient glucocorticoid signaling in stress-related pathology encourages development of therapeutic strategies to enhance glucocorticoid signaling pathways.