The Experts below are selected from a list of 458493 Experts worldwide ranked by ideXlab platform
Andrew H Miller - One of the best experts on this subject based on the ideXlab platform.
-
when not enough is too much the role of insufficient glucocorticoid signaling in the pathophysiology of stress related Disorders
FOCUS, 2011Co-Authors: Charles L Raison, Andrew H MillerAbstract: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 neuropsychitric Disorders were also associated ...
-
when not enough is too much the role of insufficient glucocorticoid signaling in the pathophysiology of stress related Disorders
American Journal of Psychiatry, 2003Co-Authors: Charles L Raison, Andrew H MillerAbstract: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.
-
when not enough is too much the role of insufficient glucocorticoid signaling in the pathophysiology of stress related Disorders
American Journal of Psychiatry, 2003Co-Authors: Charles L Raison, Andrew H MillerAbstract:OBJECTIVE: Previous theories have emphasized the role of excessive glucocorticoid activity in the pathology of chronic stress. Nevertheless, insufficient glucocorticoid signaling (resulting from de...
Kerry J Ressler - One of the best experts on this subject based on the ideXlab platform.
-
developmental pathway genes and neural plasticity underlying emotional learning and stress related Disorders
Learning & Memory, 2017Co-Authors: Marissa Maheu, Kerry J ResslerAbstract:The manipulation of neural plasticity as a means of intervening in the onset and progression of Stress-Related Disorders retains its appeal for many researchers, despite our limited success in translating such interventions from the laboratory to the clinic. Given the challenges of identifying individual genetic variants that confer increased risk for illnesses like depression and post-traumatic stress disorder, some have turned their attention instead to focusing on so-called "master regulators" of plasticity that may provide a means of controlling these potentially impaired processes in psychiatric illnesses. The mammalian homolog of Tailless (TLX), Wnt, and the homeoprotein Otx2 have all been proposed to constitute master regulators of different forms of plasticity which have, in turn, each been implicated in learning and Stress-Related Disorders. In the present review, we provide an overview of the changing distribution of these genes and their roles both during development and in the adult brain. We further discuss how their distinct expression profiles provide clues as to their function, and may inform their suitability as candidate drug targets in the treatment of psychiatric Disorders.
-
stress related Disorders pituitary adenylate cyclase activating peptide pacap ergic system and sex differences
Dialogues in clinical neuroscience, 2016Co-Authors: Teniel S Ramikie, Kerry J ResslerAbstract:Trauma-related Disorders, such as posttraumatic stress disorder (PTSD) are remarkably common and debilitating, and are often characterized by dysregulated threat responses. Across numerous epidemiological studies, females have been found to have an approximately twofold increased risk for PTSD and other Stress-Related Disorders. Understanding the biological mechanisms of this differential risk is of critical importance. Recent data suggest that the pituitary adenylate cyclase-activating polypeptide (PACAP) pathway is a critical regulator of the stress response across species. Moreover, increasing evidence suggests that this pathway is regulated by both stress and estrogen modulation and may provide an important window into understanding mechanisms of sex differences in the stress response. We have recently shown that PACAP and its receptor (PAC1R) are critical mediators of abnormal processes after psychological trauma. Notably, in heavily traumatized human subjects, there appears to be a robust sex-specific association of PACAP blood levels and PAC1R gene variants with fear physiology, PTSD diagnosis, and symptoms, specifically in females. The sex-specific association occurs within a single-nucleotide polymorphism (rs2267735) that resides in a putative estrogen response element involved in PAC1R gene regulation. Complementing these human data, the PAC1R messenger RNA is induced with fear conditioning or estrogen replacement in rodent models. These data suggest that perturbations in the PACAP-PAC1R pathway are regulated by estrogen and are involved in abnormal fear responses underlying PTSD.
-
continuous expression of corticotropin releasing factor in the central nucleus of the amygdala emulates the dysregulation of the stress and reproductive axes
Molecular Psychiatry, 2009Co-Authors: Erin Keenrhinehart, Kerry J Ressler, Vasiliki Michopoulos, Donna Toufexis, Elizabeth I Martin, H Nair, Michael Davis, Michael J Owens, Charles B Nemeroff, Mark L WilsonAbstract:An increase in corticotropin-releasing factor (CRF) is a putative factor in the pathophysiology of Stress-Related Disorders. As CRF expression in the central nucleus of the amygdala (CeA) is important in adaptation to chronic stress, we hypothesized that unrestrained synthesis of CRF in CeA would mimic the consequences of chronic stress exposure and cause dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, increase emotionality and disrupt reproduction. To test this hypothesis, we used a lentiviral vector to increase CRF-expression site specifically in CeA of female rats. Increased synthesis of CRF in CeA amplified CRF and arginine vasopressin peptide concentration in the paraventricular nucleus of the hypothalamus, and decreased glucocorticoid negative feedback, both markers associated with the pathophysiology of depression. In addition, continuous expression of CRF in CeA also increased the acoustic startle response and depressive-like behavior in the forced swim test. Protein levels of gonadotropin-releasing hormone in the medial preoptic area were significantly reduced by continuous expression of CRF in CeA and this was associated with a lengthening of estrous cycles. Finally, sexual motivation but not sexual receptivity was significantly attenuated by continuous CRF synthesis in ovariectomized estradiol-progesterone-primed females. These data indicate that unrestrained CRF synthesis in CeA produces a dysregulation of the HPA axis, as well as many of the behavioral, physiological and reproductive consequences associated with Stress-Related Disorders.
Charles L Raison - One of the best experts on this subject based on the ideXlab platform.
-
when not enough is too much the role of insufficient glucocorticoid signaling in the pathophysiology of stress related Disorders
FOCUS, 2011Co-Authors: Charles L Raison, Andrew H MillerAbstract: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 neuropsychitric Disorders were also associated ...
-
when not enough is too much the role of insufficient glucocorticoid signaling in the pathophysiology of stress related Disorders
American Journal of Psychiatry, 2003Co-Authors: Charles L Raison, Andrew H MillerAbstract: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.
-
when not enough is too much the role of insufficient glucocorticoid signaling in the pathophysiology of stress related Disorders
American Journal of Psychiatry, 2003Co-Authors: Charles L Raison, Andrew H MillerAbstract:OBJECTIVE: Previous theories have emphasized the role of excessive glucocorticoid activity in the pathology of chronic stress. Nevertheless, insufficient glucocorticoid signaling (resulting from de...
Florian Holsboer - One of the best experts on this subject based on the ideXlab platform.
-
long term behavioral and neuroendocrine alterations following chronic social stress in mice implications for stress related Disorders
Hormones and Behavior, 2008Co-Authors: V Sterlemann, Florian Holsboer, K Ganea, C Liebl, D Harbich, S Alam, Marianne B Muller, Mathias V SchmidtAbstract:The period of adolescence is characterized by a high vulnerability to stress and trauma, which might result in long-lasting consequences and an increased risk to develop psychiatric Disorders. Using a recently developed mouse model for chronic social stress during adolescence, we studied persistent neuroendocrine and behavioral effects of chronic social stress obtained 12 months after cessation of the stressor. As a reference, we investigated immediate effects of chronic stress exposure obtained at the end of the chronic stress period. Immediately after the 7 week chronic stress period stressed animals show significantly increased adrenal weights, decreased thymus weight, increased basal corticosterone secretion and a flattened circadian rhythm. Furthermore, stressed animals display an increased anxiety-like behavior in the elevated plus maze and the novelty-induced suppression of feeding test. Hippocampal mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) mRNA levels were significantly decreased. To investigate persistent consequences of this early stressful experience, the same parameters were assessed in aged mice 12 months after the cessation of the stressor. Interestingly, we still found differences between formerly stressed and control mice in important Stress-Related parameters. MR expression levels were significantly lower in stressed animals, suggesting lasting, possibly epigenetic alterations in gene expression regulation. Furthermore, we observed long-term behavioral alterations in animals stressed during adolescence. Thus, we could demonstrate that chronic stress exposure during a crucial developmental time period results in long-term, persistent effects on physiological and behavioral parameters throughout life, which may contribute to an enhanced vulnerability to stress-induced diseases.
-
corticotropin releasing factor receptors 1 and 2 in anxiety and depression
Current Opinion in Pharmacology, 2002Co-Authors: J M H M Reul, Florian HolsboerAbstract:Abstract Corticotropin-releasing factor (CRF) and its related family members are implicated in Stress-Related Disorders such as anxiety and depression. Recently, two new members of this neuropeptide family have been discovered in the brain: urocortin II (also known as stresscopin-related peptide) and urocortin III (also known as stresscopin). These urocortins are selective agonists for the CRF 2 receptor, show a distinct neuroanatomical localization and are involved in stress-coping responses such as anxiolysis. Thus, CRF, the urocortins and their receptors form an intricate network in the brain involved in the acute phase as well as the recovery phase of the stress response.
-
new mode of hypothalamic pituitary adrenocortical axis regulation significance for stress related Disorders
Zeitschrift Fur Rheumatologie, 2000Co-Authors: J M H M Reul, Florian Holsboer, A Bilangbleuel, Susanne K Droste, Astrid C E Linthorst, A GesingAbstract:Two types of corticosteroid receptors have been identified in the brain and pituitary that play an important role in the regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. These glucocorticoid hormone binding receptors are the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). Evidently, a tight control of the concentration and function of these receptors is of prime importance for maintaining and regaining homeostasis after stressful challenges. Here, we describe a novel mechanism revealing a rapid upsurge in MR density in the hippocampus (a limbic structure highly involved in HPA axis regulation) after an acute psychologically stressful challenge. This rise in MR is accompanied by a stronger MR-mediated inhibitory control of the HPA axis. Thus, an acute stressful experience results in a reorganization of the HPA axis involving a principal role of the hippocampal MR. This novel mechanism may be of significance for increasing our understanding of the etiology of Stress-Related Disorders.
Fang Fang - One of the best experts on this subject based on the ideXlab platform.
-
Time-dependent risk of depression, anxiety, and Stress-Related Disorders in patients with invasive and in situ breast cancer
'Wiley', 2020Co-Authors: Yang Haomin, Fang Fang, Brand, Judith S., Chiesa Flaminia, Johansson, Anna L.v., Hall Per, Czene KamilaAbstract:Despite concerns about the mental health of breast cancer patients, little is known regarding the temporal risk pattern and risk factors of common mental Disorders among these patients. We estimated standardized incidence ratios (SIRs) of depression, anxiety and Stress-Related Disorders in a Swedish nationwide cohort of 40,849 women with invasive and 4,402 women with in-situ breast cancer (2001- 2010, median follow-up = 4.5 years). The impact of patient, tumor and treatment characteristics was analyzed using flexible parametric survival models in a regional cohort of 7,940 invasive breast cancer patients (2001-2013, median follow-up = 7.5 years). Women with invasive breast cancer showed increased rates of depression, anxiety and Stress-Related Disorders [overall SIR (95% CI) = 1.57 (1.46- 1.69), 1.55 (1.43-1.68) and 1.77 (1.60-1.95), respectively]. SIRs were highest shortly after diagnosis, but remained increased up to 5 years. Younger age at diagnosis, comorbidity, higher-grade disease, lymph node involvement and chemotherapy were independently associated with the risk of depression and anxiety in invasive cancer patients, with chemotherapy and higher-grade disease conferring short-term risk only, while comorbidities were mainly associated with late-onset events. No clinical risk factors were identified for Stress-Related Disorders except for a greater risk associated with younger age. Patients with in-situ cancer only showed an increased incidence of Stress-Related Disorders during the first six months after diagnosis [SIR (95% CI) = 2.76 (1.31-5.79)]. The time-dependent risk profile of invasive cancer patients may guide health care professionals for timely and targeted psycho-oncologic interventions.Swedish Research CouncilSwedish Cancer SocietyFORTEAccepte
-
Stress related Disorders and risk of cardiovascular disease: population based, sibling controlled cohort study
'BMJ', 2019Co-Authors: Song Huan, Fang Fang, Arnberg Filip, Mataix-cols David, Fernández De La Cruz, Lorena, Almqvist Catarina, Fall Katja, Lichtenstein Paul, Thorgeirsson Gudmundur, Valdimarsdottir UnnurAbstract:Publisher's version (útgefin grein)Objective To assess the association between stress related Disorders and subsequent risk of cardiovascular disease. Design Population based, sibling controlled cohort study. Setting Population of Sweden. Participants 136 637 patients in the Swedish National Patient Register with stress related Disorders, including post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions, from 1987 to 2013; 171 314 unaffected full siblings of these patients; and 1 366 370 matched unexposed people from the general population. Main outcome measures Primary diagnosis of incident cardiovascular disease-any or specific subtypes (ischaemic heart disease, cerebrovascular disease, emboli/thrombosis, hypertensive diseases, heart failure, arrhythmia/conduction disorder, and fatal cardiovascular disease)-and 16 individual diagnoses of cardiovascular disease. Hazard ratios for cardiovascular disease were derived from Cox models, after controlling for multiple confounders. Results During up to 27 years of follow-up, the crude incidence rate of any cardiovascular disease was 10.5, 8.4, and 6.9 per 1000 person years among exposed patients, their unaffected full siblings, and the matched unexposed individuals, respectively. In sibling based comparisons, the hazard ratio for any cardiovascular disease was 1.64 (95% confidence interval 1.45 to 1.84), with the highest subtype specific hazard ratio observed for heart failure (6.95, 1.88 to 25.68), during the first year after the diagnosis of any stress related disorder. Beyond one year, the hazard ratios became lower (overall 1.29, 1.24 to 1.34), ranging from 1.12 (1.04 to 1.21) for arrhythmia to 2.02 (1.45 to 2.82) for artery thrombosis/embolus. Stress related Disorders were more strongly associated with early onset cardiovascular diseases (hazard ratio 1.40 (1.32 to 1.49) for attained age
-
Stress related Disorders and risk of cardiovascular disease : population based, sibling controlled cohort study
'BMJ', 2019Co-Authors: Song Huan, Fang Fang, Arnberg Filip, Mataix-cols David, Fernández De La Cruz, Lorena, Almqvist Catarina, Fall Katja, Lichtenstein Paul, Thorgeirsson Gudmundur, Valdimarsdóttir, Unnur AAbstract:Objective To assess the association between stress related Disorders and subsequent risk of cardiovascular disease. Design Population based, sibling controlled cohort study. Setting Population of Sweden. Participants 136 637 patients in the Swedish National Patient Register with stress related Disorders, including post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions, from 1987 to 2013; 171 314 unaffected full siblings of these patients; and 1 366 370 matched unexposed people from the general population. Main outcome measures Primary diagnosis of incident cardiovascular disease—any or specific subtypes (ischaemic heart disease, cerebrovascular disease, emboli/thrombosis, hypertensive diseases, heart failure, arrhythmia/conduction disorder, and fatal cardiovascular disease)—and 16 individual diagnoses of cardiovascular disease. Hazard ratios for cardiovascular disease were derived from Cox models, after controlling for multiple confounders. Results During up to 27 years of follow-up, the crude incidence rate of any cardiovascular disease was 10.5, 8.4, and 6.9 per 1000 person years among exposed patients, their unaffected full siblings, and the matched unexposed individuals, respectively. In sibling based comparisons, the hazard ratio for any cardiovascular disease was 1.64 (95% confidence interval 1.45 to 1.84), with the highest subtype specific hazard ratio observed for heart failure (6.95, 1.88 to 25.68), during the first year after the diagnosis of any stress related disorder. Beyond one year, the hazard ratios became lower (overall 1.29, 1.24 to 1.34), ranging from 1.12 (1.04 to 1.21) for arrhythmia to 2.02 (1.45 to 2.82) for artery thrombosis/embolus. Stress related Disorders were more strongly associated with early onset cardiovascular diseases (hazard ratio 1.40 (1.32 to 1.49) for attained age <50) than later onset ones (1.24 (1.18 to 1.30) for attained age ≥50; P for difference=0.002). Except for fatal cardiovascular diseases, these associations were not modified by the presence of psychiatric comorbidity. Analyses within the population matched cohort yielded similar results (hazard ratio 1.71 (1.59 to 1.83) for any cardiovascular disease during the first year of follow-up and 1.36 (1.33 to 1.39) thereafter). Conclusion Stress related Disorders are robustly associated with multiple types of cardiovascular disease, independently of familial background, history of somatic/psychiatric diseases, and psychiatric comorbidity
-
Stress related Disorders and subsequent risk of life threatening infections: population based sibling controlled cohort study.
'BMJ', 2019Co-Authors: Song Huan, Fang Fang, Mataix-cols David, Fernández De La Cruz, Lorena, Fall Katja, Lichtenstein Paul, Erlendsdóttir Helga, Lu Donghao, D'onofrio, Brian M, Gottfreðsson MagnúsAbstract:To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadOBJECTIVE: To assess whether severe psychiatric reactions to trauma and other adversities are associated with subsequent risk of life threatening infections. DESIGN: Population and sibling matched cohort study. SETTING: Swedish population. PARTICIPANTS: 144 919 individuals with stress related Disorders (post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions) identified from 1987 to 2013 compared with 184 612 full siblings of individuals with a diagnosed stress related disorder and 1 449 190 matched individuals without such a diagnosis from the general population. MAIN OUTCOME MEASURES: A first inpatient or outpatient visit with a primary diagnosis of severe infections with high mortality rates (ie, sepsis, endocarditis, and meningitis or other central nervous system infections) from the Swedish National Patient Register, and deaths from these infections or infections of any origin from the Cause of Death Register. After controlling for multiple confounders, Cox models were used to estimate hazard ratios of these life threatening infections. RESULTS: The average age at diagnosis of a stress related disorder was 37 years (55 541, 38.3% men). During a mean follow-up of eight years, the incidence of life threatening infections per 1000 person years was 2.9 in individuals with a stress related disorder, 1.7 in siblings without a diagnosis, and 1.3 in matched individuals without a diagnosis. Compared with full siblings without a diagnosis of a stress related disorder, individuals with such a diagnosis were at increased risk of life threatening infections (hazard ratio for any stress related disorder was 1.47 (95% confidence intervals1.37 to 1.58) and for PTSD was 1.92 (1.46 to 2.52)). Corresponding estimates in the population based analysis were similar (1.58 (1.51 to 1.65) for any stress related disorder, P=0.09 for difference between sibling and population based comparison, and 1.95 (1.66 to 2.28) for PTSD, P=0.92 for difference). Stress related Disorders were associated with all studied life threatening infections, with the highest relative risk observed for meningitis (sibling based analysis 1.63 (1.23 to 2.16)) and endocarditis (1.57 (1.08 to 2.30)). Younger age at diagnosis of a stress related disorder and the presence of psychiatric comorbidity, especially substance use Disorders, were associated with higher hazard ratios, whereas use of selective serotonin reuptake inhibitors in the first year after diagnosis of a stress related disorder was associated with attenuated hazard ratios. CONCLUSION: In the Swedish population, stress related Disorders were associated with a subsequent risk of life threatening infections, after controlling for familial background and physical or psychiatric comorbidities.Grant of Excellence, Icelandic Research Fund European Research Council (ERC) Karolinska Institutet Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) West China Hospital, Sichuan University (1.3.5 Project for Disciplines of Excellence
-
Association of Stress-Related Disorders With Subsequent Autoimmune Disease.
JAMA, 2018Co-Authors: Huan Song, Fang Fang, Gunnar Tomasson, Filip K Arnberg, David Mataix-cols, Lorena Fernández De La Cruz, Catarina Almqvist, Katja Fall, Unnur ValdimarsdóttirAbstract:Importance Psychiatric reactions to life stressors are common in the general population and may result in immune dysfunction. Whether such reactions contribute to the risk of autoimmune disease remains unclear. Objective To determine whether there is an association between Stress-Related Disorders and subsequent autoimmune disease. Design, Setting, and Participants Population- and sibling-matched retrospective cohort study conducted in Sweden from January 1, 1981, to December 31, 2013. The cohort included 106 464 exposed patients with Stress-Related Disorders, with 1 064 640 matched unexposed persons and 126 652 full siblings of these patients. Exposures Diagnosis of Stress-Related Disorders, ie, posttraumatic stress disorder, acute stress reaction, adjustment disorder, and other stress reactions. Main Outcomes and Measures Stress-Related disorder and autoimmune diseases were identified through the National Patient Register. The Cox model was used to estimate hazard ratios (HRs) with 95% CIs of 41 autoimmune diseases beyond 1 year after the diagnosis of Stress-Related Disorders, controlling for multiple risk factors. Results The median age at diagnosis of Stress-Related Disorders was 41 years (interquartile range, 33-50 years) and 40% of the exposed patients were male. During a mean follow-up of 10 years, the incidence rate of autoimmune diseases was 9.1, 6.0, and 6.5 per 1000 person-years among the exposed, matched unexposed, and sibling cohorts, respectively (absolute rate difference, 3.12 [95% CI, 2.99-3.25] and 2.49 [95% CI, 2.23-2.76] per 1000 person-years compared with the population- and sibling-based reference groups, respectively). Compared with the unexposed population, patients with Stress-Related Disorders were at increased risk of autoimmune disease (HR, 1.36 [95% CI, 1.33-1.40]). The HRs for patients with posttraumatic stress disorder were 1.46 (95% CI, 1.32-1.61) for any and 2.29 (95% CI, 1.72-3.04) for multiple (≥3) autoimmune diseases. These associations were consistent in the sibling-based comparison. Relative risk elevations were more pronounced among younger patients (HR, 1.48 [95% CI, 1.42-1.55]; 1.41 [95% CI, 1.33-1.48]; 1.31 [95% CI, 1.24-1.37]; and 1.23 [95% CI, 1.17-1.30] for age at ≤33, 34-41, 42-50, and ≥51 years, respectively;Pfor interaction Conclusions and Relevance In this Swedish cohort, exposure to a Stress-Related disorder was significantly associated with increased risk of subsequent autoimmune disease, compared with matched unexposed individuals and with full siblings. Further studies are needed to better understand the underlying mechanisms.
